THE EXTRACELLULAR SIGNAL-REGULATED RAF/MEK/ERK SIGNALING PATHWAY (PW:0000102)
Description
The
extracellular signal regulated MAP kinase pathway (Raf/Mek/Erk) couples signals
reverberating from activated cell surface receptors via their downstream
effectors, to many cytoplasmic and nuclear targets. Raf/Mek/Erk displays the
characteristic three-tier core cascade MAPK architecture. The downstream and
effector MAPK tier (here Erk represented by Mapk1 and 3) is activated by
phosphorylation of threonine and tyrosine residues within the conserved TEY
motif in the activation loop by dual specificity kinases of the middle MAP2K
tier (here Mek represented by Map2k1 and 2), in turn activated by the upstream
MAP3K tier (here Raf). While the Raf proteins are the main MAP3Ks, other MAP3Ks
can activate this and other MAPK signaling (e.g. Map3k1/Mekk1 also acting as a
MAP3K for JNK pathway). Downstream of growth factors activated receptor
tyrosine kinases, various effectors and adapters lead to activation of small
monomeric G proteins of the Ras family. Activated Ras bind to and recruit the
Raf proteins to the plasma membrane where through a series of phosphorylation,
dephosphorylation and other events they get activated. Of the several members
of Ras, Kras appears to be a more potent inducer of the Raf/Mek/Erk cascade.
The three mammalian Raf proteins - Araf, Braf and Raf1/Craf are
serine/threonine kinases whose primary targets are the Map2k1/Mek1 and
Map2k2/Mek2 members of the MAP2K tier. Mapk1/Erk2 and Mapk3/Erk1 are
serine/threonine kinases whose targets include transcription factors, cytoplasmic
proteins as well as other kinases referred to as MAPKAPK. The latter can be considered a fourth tier which further transmits
the signal through the many targets it controls. Phosphorylated MAPKs are the targets of many phosphatases such as
Pp2a - a serine/threonine phosphatase complex, Ptprr (known as PTP-SL) - a
tyrosine phosphatase, or by members of the dual specificity phosphatases of the
MKP/Dusp family, eg. Dusp6. Pp2a dephosphorylates and downregulates the
activity of Mek while dephosphorylation of Raf helps rescue it from an inactive
state leading to its activation. Pp2a activity is stimulated by kinases and
appears to be a target of p38 MAPK raising the possibility that Erk signaling
is negatively regulated by p38 MAPK pathway. Raf is negatively regulated by
phosphorylation within the regulatory domain, eg. Akt, or through the
interaction with Pebp1/Rkip that inhibits its kinase activity. Scaffold
proteins, such as Ksr1 and KSR2 (human, help organize the core modules and shape their activity. Ksr1 and KSR2 form ternary complexes with Raf and Mek and display kinase activity towards Mek (not shown). The scaffolding and catalytic attributes promote and/
or facilitate Raf activity towards Mek.
The MAPKs can also provide feedback regulatory loops to the upstream components
of the pathway. Raf/Mek/Erk pathway regulates processes such as proliferation,
differentiation. Deregulation of the pathway either through mutations in the
core or upstream components (eg B-Raf, Ras) or other pathways that regulate it
(eg PI3K/Akt) has been implicated in human cancer.
To see the ontology report for annotations, GViewer and
download, click here
[click to see related GO term -
GO:0070371 ,
KEGG map -
map04010
and entries at Reactome -
REACT_962.4 ;
REACT_1482.4 ]
...(less)
Pathway Diagram:
Genes in Pathway:
G
Araf
A-Raf proto-oncogene, serine/threonine kinase
ISO
RGD
PMID:22177953
RGD:5686410
NCBI chr X:1,227,392...1,292,356
Ensembl chr X:1,227,392...1,239,073
G
Braf
B-Raf proto-oncogene, serine/threonine kinase
IMP ISO
RGD
PMID:16508002 PMID:22177953 PMID:17310240
RGD:1580106 , RGD:5686410 , RGD:1626216
NCBI chr 4:68,375,484...68,510,652
Ensembl chr 4:68,384,649...68,510,463
G
Dusp6
dual specificity phosphatase 6
ISO
RGD
PMID:17208316
RGD:2293881
NCBI chr 7:34,092,848...34,097,186
Ensembl chr 7:34,092,943...34,097,185
G
Gper1
G protein-coupled estrogen receptor 1
IMP
RGD
PMID:20445128
RGD:4892084
NCBI chr12:15,217,217...15,222,679
Ensembl chr12:15,217,442...15,221,889
G
Hras
HRas proto-oncogene, GTPase
ISO
RGD
PMID:22177953
RGD:5686410
NCBI chr 1:196,290,127...196,299,823
Ensembl chr 1:196,296,263...196,300,615
G
Kras
KRAS proto-oncogene, GTPase
IDA ISO
RGD
PMID:12388314 PMID:22177953
RGD:628557 , RGD:5686410
NCBI chr 4:178,185,418...178,218,484
G
Ksr1
kinase suppressor of ras 1
ISO
RGD
PMID:17726577 PMID:22177953
RGD:2293880 , RGD:5686410
NCBI chr10:63,961,771...64,098,076
Ensembl chr10:63,961,759...64,098,076
G
Ksr2
kinase suppressor of ras 2
ISO
RGD
PMID:22177953
RGD:5686410
NCBI chr12:38,802,796...39,187,809
Ensembl chr12:38,802,004...39,188,375
G
Map2k1
mitogen activated protein kinase kinase 1
TAS IMP
RGD
PMID:9779826 PMID:17310240
RGD:70317 , RGD:1626216
NCBI chr 8:64,683,449...64,754,900
Ensembl chr 8:64,683,449...64,755,147
G
Map2k2
mitogen activated protein kinase kinase 2
NAS IMP
RGD
PMID:8462694 PMID:17310240
RGD:729046 , RGD:1626216
NCBI chr 7:8,590,729...8,610,279
Ensembl chr 7:8,580,905...8,610,243
G
Map3k1
mitogen-activated protein kinase kinase kinase 1
ISS ISO
RGD
PMID:12835716 PMID:9305638
RGD:1357969 , RGD:2293879
NCBI chr 2:43,348,572...43,414,706
Ensembl chr 2:43,350,098...43,414,463
G
Map3k2
mitogen activated protein kinase kinase kinase 2
NAS
RGD
PMID:11359865
RGD:724475
NCBI chr18:23,807,218...23,879,722
Ensembl chr18:23,807,218...23,871,433
G
Mapk1
mitogen activated protein kinase 1
IDA IMP
RGD
PMID:12097495 PMID:16955078 PMID:17310240
RGD:628468 , RGD:8553011 , RGD:1626216
NCBI chr11:83,957,813...84,023,629
Ensembl chr11:83,957,813...84,023,616
G
Mapk3
mitogen activated protein kinase 3
IDA ISO IMP
RGD
PMID:12097495 PMID:20080775 PMID:16955078 PMID:17310240
RGD:628468 , RGD:5508172 , RGD:8553011 , RGD:1626216
NCBI chr 1:181,366,646...181,372,863
Ensembl chr 1:181,366,637...181,372,863
G
Mknk1
MAPK interacting serine/threonine kinase 1
ISO IMP
RGD
PMID:16421520 PMID:16955078
RGD:2315047 , RGD:8553011
NCBI chr 5:129,318,128...129,357,641
Ensembl chr 5:129,318,170...129,357,639
G
Mknk2
MAPK interacting serine/threonine kinase 2
ISO
RGD
PMID:16421520
RGD:2315047
NCBI chr 7:9,039,771...9,050,832
Ensembl chr 7:9,039,728...9,050,827
G
Nras
NRAS proto-oncogene, GTPase
ISO
RGD
PMID:22177953
RGD:5686410
NCBI chr 2:190,582,885...190,593,509
Ensembl chr 2:190,582,918...190,591,626
G
Pebp1
phosphatidylethanolamine binding protein 1
TAS IMP
RGD
PMID:17126425 PMID:10490027
RGD:2293882 , RGD:2302807
NCBI chr12:39,302,864...39,307,064
Ensembl chr12:39,302,840...39,307,862
G
Prkcd
protein kinase C, delta
IMP
RGD
PMID:12790799
RGD:1642529
NCBI chr16:5,769,217...5,799,380
Ensembl chr16:5,769,215...5,799,352
G
Ptk2b
protein tyrosine kinase 2 beta
IMP
RGD
PMID:15096502
RGD:1642630
NCBI chr15:40,360,722...40,481,235
Ensembl chr15:40,360,723...40,481,282
G
Raf1
Raf-1 proto-oncogene, serine/threonine kinase
TAS ISO IMP
RGD
PMID:9779826 PMID:22177953 PMID:17310240 PMID:16508002
RGD:70317 , RGD:5686410 , RGD:1626216 , RGD:1580106
NCBI chr 4:148,679,534...148,740,265
Ensembl chr 4:148,679,530...148,740,317
G
Rps6ka1
ribosomal protein S6 kinase A1
ISO
RGD
PMID:16421520
RGD:2315047
NCBI chr 5:146,079,018...146,118,272
Ensembl chr 5:146,079,021...146,118,272
G
Rps6ka2
ribosomal protein S6 kinase A2
ISO
RGD
PMID:16421520
RGD:2315047
NCBI chr 1:52,631,582...52,906,739
Ensembl chr 1:52,631,736...52,906,739
G
Rps6ka3
ribosomal protein S6 kinase A3
ISO
RGD
PMID:16421520
RGD:2315047
NCBI chr X:35,517,306...35,623,296
Ensembl chr X:35,517,306...35,623,207
G
Rps6ka4
ribosomal protein S6 kinase A4
ISO
RGD
PMID:16421520
RGD:2315047
NCBI chr 1:204,021,805...204,032,781
Ensembl chr 1:204,021,806...204,032,761
G
Rps6ka5
ribosomal protein S6 kinase A5
ISO
RGD
PMID:16421520
RGD:2315047
NCBI chr 6:119,828,823...120,006,190
Ensembl chr 6:119,828,846...120,006,224
G
Rps6ka6
ribosomal protein S6 kinase A6
ISO
RGD
PMID:16421520
RGD:2315047
NCBI chr X:76,353,316...76,454,502
Ensembl chr X:76,353,760...76,454,484
G
S1pr1
sphingosine-1-phosphate receptor 1
IMP
RGD
PMID:14711826
RGD:1304283
NCBI chr 2:203,624,752...203,629,110
Ensembl chr 2:203,621,587...203,629,681
G
Shc1
SHC adaptor protein 1
IEP
RGD
PMID:16699171
RGD:1643182
NCBI chr 2:174,837,937...174,849,538
Ensembl chr 2:174,837,930...174,849,536
G
Smad1
SMAD family member 1
IMP
RGD
PMID:16427075
RGD:1643230
NCBI chr19:28,513,130...28,573,665
Ensembl chr19:28,513,131...28,573,651
G
Spp1
secreted phosphoprotein 1
ISO
RGD
PMID:15757900
RGD:1581337
NCBI chr14:5,308,885...5,315,120
Ensembl chr14:5,308,885...5,315,162
G
Tsc2
TSC complex subunit 2
ISO
RGD
PMID:15150271
RGD:1580097
NCBI chr10:13,621,135...13,655,773
Ensembl chr10:13,621,136...13,655,951
G
Braf
B-Raf proto-oncogene, serine/threonine kinase
ISO
RGD
PMID:17126425 PMID:18098337 PMID:20951313 PMID:21277552
RGD:2293882 , RGD:2298531 , RGD:5133242 , RGD:5133243
NCBI chr 4:68,375,484...68,510,652
Ensembl chr 4:68,384,649...68,510,463
G
Kras
KRAS proto-oncogene, GTPase
TAS ISO
RGD
PMID:16112461 PMID:18772397 PMID:19506583 PMID:20951313 PMID:19078924
RGD:2306732 , RGD:5490966 , RGD:5490965 , RGD:5133242 , RGD:4143515
NCBI chr 4:178,185,418...178,218,484
G
Map2k1
mitogen activated protein kinase kinase 1
ISO
RGD
PMID:20951313 PMID:21277552
RGD:5133242 , RGD:5133243
NCBI chr 8:64,683,449...64,754,900
Ensembl chr 8:64,683,449...64,755,147
G
Raf1
Raf-1 proto-oncogene, serine/threonine kinase
ISO
RGD
PMID:17126425
RGD:2293882
NCBI chr 4:148,679,534...148,740,265
Ensembl chr 4:148,679,530...148,740,317
Pathway Gene Annotations
Disease Annotations Associated with Genes in the the extracellular signal-regulated Raf/Mek/Erk signaling pathway
Araf autistic disorder , Breast Neoplasms , congenital disorder of glycosylation type IIm , high grade glioma , immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome , lung adenocarcinoma , lung non-small cell carcinoma , neurodegeneration with brain iron accumulation 5 , papillary renal cell carcinoma , skin melanoma , Sporadic Papillary Renal Cell Carcinoma , syndromic X-linked intellectual disability Lubs type , X-linked epilepsy with variable learning disabilities and behavior disorders , X-linked severe congenital neutropenia Braf adrenocortical carcinoma , ameloblastoma , Aortic Aneurysm, Giant Congenital , arteriovenous malformations of the brain , ataxia telangiectasia , B-Cell Chronic Lymphocytic Leukemia , bile duct adenoma , Brain Neoplasms , Breast Neoplasms , cancer , Carcinogenesis , cardiofaciocutaneous syndrome , cardiofaciocutaneous syndrome 1 , cardiomyopathy , cholangiocarcinoma , chronic lymphocytic leukemia , chronic myelogenous leukemia, BCR-ABL1 positive , chronic myeloid leukemia , colon carcinoma , Colonic Neoplasms , colorectal adenocarcinoma , colorectal cancer , Colorectal Neoplasms , Costello syndrome , craniopharyngioma , Dandy-Walker syndrome , Developmental Disabilities , diffuse large B-cell lymphoma , dilated cardiomyopathy , disease of cellular proliferation , dysembryoplastic neuroepithelial tumor , dysplastic nevus syndrome , endometrial carcinoma , Experimental Melanoma , Experimental Neoplasms , familial melanoma , Follicular Thyroid Cancer , gallbladder cancer , ganglioglioma , gastric adenocarcinoma , gastrointestinal stromal tumor , genetic disease , germinoma , glioblastoma , head and neck squamous cell carcinoma , hepatocellular carcinoma , high grade glioma , hypertrophic cardiomyopathy , hypertrophic cardiomyopathy 4 , intellectual disability , intrahepatic cholangiocarcinoma , Kidney Neoplasms , Langerhans-cell histiocytosis , Liver Metastasis , Liver Neoplasms , lung adenocarcinoma , lung cancer , lung carcinoma , Lung Neoplasms , lung non-small cell carcinoma , lung squamous cell carcinoma , lymphangioma , Lymphatic Metastasis , malignant astrocytoma , Mandibular Neoplasms , melanoma , Microsatellite Instability , multiple myeloma , myoepithelioma , Neoplasm Metastasis , nephroblastoma , neuroendocrine tumor , Nevus , newborn respiratory distress syndrome , non-Hodgkin lymphoma , Nonseminomatous Germ Cell Tumor , Noonan syndrome , Noonan syndrome 1 , Noonan syndrome 7 , Noonan syndrome with multiple lentigines , Noonan syndrome with multiple lentigines 3 , Ovarian Neoplasms , ovarian serous cystadenocarcinoma , pancreatic acinar cell adenocarcinoma , pancreatic cancer , papillary renal cell carcinoma , Paraproteinemias , PHACE Association , plasma cell neoplasm , pleomorphic xanthoastrocytoma , Premature Birth , primary cutaneous T-cell non-Hodgkin lymphoma , prostate adenocarcinoma , Prostate Cancer, Hereditary, 1 , Prostatic Neoplasms , pulmonary valve stenosis , RASopathy , Sezary's disease , skin melanoma , Sporadic Papillary Renal Cell Carcinoma , tethered spinal cord syndrome , thyroid gland papillary carcinoma , Thyroid Neoplasms , transitional cell carcinoma , type 2 diabetes mellitus , uterine cancer , Vascular Malformations , ventricular septal defect Dusp6 Animal Mammary Neoplasms , brain ischemia , breast cancer , carcinoma , Experimental Liver Cirrhosis , Experimental Mammary Neoplasms , genetic disease , glioblastoma , Hyperalgesia , hypogonadotropic hypogonadism 19 with or without anosmia , hypogonadotropic hypogonadism 7 with or without anosmia , leishmaniasis , Myocardial Ischemia , pancreatitis , Postoperative Pain , visual epilepsy Gper1 Breast Neoplasms , COVID-19 , Dysbiosis , endometriosis , generalized anxiety disorder , Hepatomegaly , Hyperalgesia , interstitial lung disease 2 , leiomyoma , Liver Neoplasms , melanoma , Multiple Abnormalities , Spinal Cord Injuries Hras acute myeloid leukemia , adenoid cystic carcinoma , Alzheimer's disease , angiosarcoma , Animal Mammary Neoplasms , autistic disorder , autoimmune hepatitis , B-Cell Chronic Lymphocytic Leukemia , bladder carcinoma , Brain Neoplasms , Breast Neoplasms , carcinoma , cardiofaciocutaneous syndrome , Chanarin-Dorfman syndrome , chronic lymphocytic leukemia , Colorectal Neoplasms , complex cortical dysplasia with other brain malformations , congenital fibrosis of the extraocular muscles , Congenital Myopathy with Excess of Muscle Spindles , Costello syndrome , delta beta-thalassemia , developmental and epileptic encephalopathy , diabetic retinopathy , disease of cellular proliferation , Disease Progression , early infantile epileptic encephalopathy , endometrial carcinoma , epidermal nevus , esophageal carcinoma , Experimental Diabetes Mellitus , Experimental Liver Neoplasms , Experimental Mammary Neoplasms , Experimental Neoplasms , Follicular Thyroid Cancer , gastric adenocarcinoma , genetic disease , glioblastoma , head and neck squamous cell carcinoma , hepatocellular adenoma , hepatocellular carcinoma , Hereditary Neoplastic Syndromes , high grade glioma , Hydrops Fetalis , Hypophosphatemic Rickets , immunodeficiency 39 , intellectual disability , large congenital melanocytic nevus , Leber congenital amaurosis , linear nevus sebaceous syndrome , liver cancer , liver carcinoma , liver cirrhosis , Liver Neoplasms , lung adenocarcinoma , Lung Neoplasms , lung non-small cell carcinoma , lung squamous cell carcinoma , malignant astrocytoma , melanoma , Mouth Neoplasms , multiple myeloma , myelodysplastic syndrome , Nasopharyngeal Neoplasms , Neoplasm Invasiveness , Neoplastic Cell Transformation , Neoplastic Processes , neuroblastoma , neuronal ceroid lipofuscinosis , Noonan syndrome , Noonan syndrome 1 , Noonan syndrome 3 , obsessive-compulsive disorder , ovarian cancer , Ovarian Neoplasms , ovarian serous cystadenocarcinoma , pancreatic adenocarcinoma , papillary renal cell carcinoma , papilloma , Paraproteinemias , parathyroid adenoma , Penile Neoplasms , phobic disorder , Pigmented Nevus , plasma cell neoplasm , pre-malignant neoplasm , prostate adenocarcinoma , Prostate Cancer, Hereditary, 1 , Prostatic Neoplasms , pulmonary valve stenosis , RASopathy , Recurrence , rhabdomyosarcoma , Salivary Gland Neoplasms , Sebaceous Nevus Syndrome and Hemimegalencephaly , seminoma , skin benign neoplasm , skin melanoma , Skin Neoplasms , spermatocytoma , Splenic Neoplasms , Sporadic Papillary Renal Cell Carcinoma , squamous cell carcinoma , Stomach Neoplasms , T-cell non-Hodgkin lymphoma , thymoma , Thyroid Neoplasms , Tongue Neoplasms , transitional cell carcinoma , Trichilemmoma , urinary bladder cancer , Urinary Bladder Neoplasm , uterine cancer , uterine carcinosarcoma , Uterine Cervical Neoplasms Kras Acute Experimental Pancreatitis , acute lymphoblastic leukemia , acute myeloid leukemia , adenocarcinoma , adenoid cystic carcinoma , adenoma , anaplastic astrocytoma , anemia , angiosarcoma , Animal Disease Models , arteriovenous malformations of the brain , autoimmune lymphoproliferative syndrome type 4 , B-Cell Chronic Lymphocytic Leukemia , breast adenocarcinoma , breast cancer , Breast Cancer, Familial , Breast Neoplasms , bronchiolo-alveolar adenocarcinoma , Capillary Malformation-Arteriovenous Malformation 1 , Carcinogenesis , carcinoma , cardiofaciocutaneous syndrome , cardiofaciocutaneous syndrome 1 , cardiofaciocutaneous syndrome 2 , cardiomyopathy , Cecal Neoplasms , cholangiocarcinoma , chronic lymphocytic leukemia , chronic myelogenous leukemia, BCR-ABL1 positive , chronic myeloid leukemia , Colonic Neoplasms , colorectal cancer , Colorectal Neoplasms , Costello syndrome , dilated cardiomyopathy , disease of cellular proliferation , Disease Progression , Encephalocraniocutaneous Lipomatosis , endometrial adenocarcinoma , endometrial carcinoma , endometrial hyperplasia , Endometrial Hyperplasia without Atypia , Endometrial Intraepithelial Neoplasia , Endometrial Neoplasms , Endometrioid Carcinomas , endometriosis , epidermal nevus , esophageal carcinoma , Experimental Liver Neoplasms , Experimental Neoplasms , Experimental Sarcoma , fibrillary astrocytoma , gallbladder cancer , Gallbladder Neoplasms , gastric adenocarcinoma , gastrointestinal stromal tumor , genetic disease , glioblastoma , hepatocellular adenoma , hepatocellular carcinoma , hereditary breast ovarian cancer syndrome , hereditary diffuse gastric cancer , high grade glioma , Hodgkin's lymphoma , Hydrops Fetalis , hypertension , intellectual disability , intrahepatic cholangiocarcinoma , juvenile myelomonocytic leukemia , juvenile rheumatoid arthritis , Kidney Neoplasms , Klatskin's tumor , Leukocytosis , linear nevus sebaceous syndrome , Liver Neoplasms , lung adenocarcinoma , lung cancer , lung carcinoma , Lung Neoplasms , lung non-small cell carcinoma , Lung Reperfusion Injury , lung sarcomatoid carcinoma , lung squamous cell carcinoma , lymphoma , Lynch syndrome , malignant astrocytoma , melanoma , Mouth Neoplasms , Multiple Abnormalities , multiple myeloma , muscular atrophy , myelodysplastic syndrome , myeloid neoplasm , myeloid sarcoma , Neoplasm Metastasis , Neoplastic Cell Transformation , neuroblastoma , Noonan syndrome , Noonan syndrome 1 , Noonan syndrome 3 , oculoectodermal syndrome , Ovarian Neoplasms , ovary serous adenocarcinoma , pancreatic adenocarcinoma , pancreatic cancer , pancreatic carcinoma , pancreatic ductal carcinoma , pancreatic mucinous cystadenoma , Paraproteinemias , Parasitic Liver Diseases , Penile Neoplasms , pilocytic astrocytoma , plasma cell neoplasm , prostate cancer , Prostate Cancer, Hereditary, 1 , prostate carcinoma in situ , Prostatic Neoplasms , RASopathy , Recurrence , renal cell carcinoma , renal fibrosis , Sebaceous Nevus Syndrome and Hemimegalencephaly , seminoma , skin melanoma , Splenomegaly , squamous cell carcinoma , stomach cancer , stomach carcinoma , Stomach Neoplasms , T-cell acute lymphoblastic leukemia , teratoma , Thyroid Carcinoma, Nonmedullary 1 , thyroid gland follicular carcinoma , thyroid gland medullary carcinoma , Thyroid Neoplasms , transitional cell carcinoma , Triple Negative Breast Neoplasms , urinary bladder cancer , Urinary Bladder Neoplasm , uterine cancer , Uterine Cervical Neoplasms , Uterine Neoplasms , Vascular Malformations Ksr1 breast adenocarcinoma , breast cancer Ksr2 maturity-onset diabetes of the young type 1 , morbid obesity , type 2 diabetes mellitus Map2k1 autism spectrum disorder , Bloom syndrome , brain ischemia , breast cancer , cardiofaciocutaneous syndrome , cardiofaciocutaneous syndrome 3 , Cardiovascular Abnormalities , cataract , colorectal cancer , Colorectal Neoplasms , congestive heart failure , Costello syndrome , disease of cellular proliferation , Experimental Liver Neoplasms , Familial Prostate Cancer , gastric adenocarcinoma , genetic disease , hairy cell leukemia , head and neck squamous cell carcinoma , high grade glioma , lung adenocarcinoma , lung non-small cell carcinoma , lung squamous cell carcinoma , melanoma , melorheostosis , neuronal ceroid lipofuscinosis , non-Hodgkin lymphoma , Noonan syndrome , Noonan syndrome 1 , ovarian carcinoma , Ovarian Neoplasms , pancreatic adenocarcinoma , pancreatitis , prostate adenocarcinoma , Prostatic Neoplasms , RASopathy , renal cell carcinoma , skin melanoma , small intestine adenocarcinoma , spermatogenic failure 57 , Sturge-Weber syndrome , transitional cell carcinoma , uterine cancer , Vascular Malformations Map2k2 adenoid cystic carcinoma , amenorrhea , breast cancer , cardiofaciocutaneous syndrome , cardiofaciocutaneous syndrome 1 , cardiofaciocutaneous syndrome 4 , colorectal cancer , Costello syndrome , gastric adenocarcinoma , glioblastoma , head and neck squamous cell carcinoma , hepatocellular carcinoma , hypertrophic cardiomyopathy , lung non-small cell carcinoma , melanoma , Metabolic Syndrome , migraine , multicentric Castleman disease , neurofibromatosis-Noonan syndrome , Noonan syndrome , Noonan syndrome 1 , Noonan syndrome with multiple lentigines , Ovarian Neoplasms , pancreatic adenocarcinoma , Prostatic Neoplasms , RASopathy , skin melanoma , small intestine adenocarcinoma , Smith-Magenis syndrome Map3k1 46,XY sex reversal 6 , breast cancer , Breast Neoplasms , diffuse gastric cancer , disorder of sexual development , esophagus squamous cell carcinoma , genetic disease , Hearing Loss , hepatocellular carcinoma , Hereditary Neoplastic Syndromes , lung metastasis , lung non-small cell carcinoma , Neurodevelopmental Disorders , Ovarian Neoplasms , Prostatic Neoplasms , rectum cancer , stomach cancer , syndromic microphthalmia 5 Map3k2 autosomal dominant thrombophilia due to protein C deficiency , autosomal recessive limb-girdle muscular dystrophy type 2W , centronuclear myopathy 2 Mapk1 Aberrant Crypt Foci , alcohol dependence , alcohol use disorder , Alzheimer's disease , Animal Disease Models , autism spectrum disorder , brain ischemia , breast cancer , Cardiomegaly , cardiomyopathy , childhood pilocytic astrocytoma , chromosome 22q11.2 deletion syndrome, distal , cocaine abuse , cocaine dependence , Cocaine-Related Disorders , colon adenocarcinoma , colon cancer , colorectal adenocarcinoma , Colorectal Neoplasms , congenital heart disease , coronary restenosis , Coronavirus infectious disease , demyelinating disease , depressive disorder , Diabetic Cardiomyopathies , Diabetic Nephropathies , DiGeorge syndrome , Dwarfism , endometrial adenocarcinoma , endometrial carcinoma , Endometrioid Carcinomas , Experimental Colitis , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , Experimental Liver Neoplasms , Experimental Mammary Neoplasms , Experimental Radiation Injuries , extrahepatic cholestasis , Female Infertility , gastric ulcer , genetic disease , Gliosis , glomerulonephritis , Head and Neck Neoplasms , head and neck squamous cell carcinoma , Hemorrhagic Shock , hepatocellular carcinoma , Hodgkin's lymphoma , Hyperalgesia , Hypertrophy , intellectual disability , Intimal Hyperplasia , juvenile rheumatoid arthritis , kidney disease , Kidney Neoplasms , Left Ventricular Hypertrophy , Lung Neoplasms , melanoma , Memory Disorders , middle cerebral artery infarction , morphine dependence , Multiple Organ Failure , myocardial infarction , Myocardial Reperfusion Injury , Neoplasm Invasiveness , Neoplasm Metastasis , Nerve Degeneration , neuronal ceroid lipofuscinosis 6A , Noonan syndrome 13 , obesity , Ovarian Neoplasms , pancreatic adenocarcinoma , Parkinson's disease , Pneumococcal Pneumonia , portal hypertension , Postoperative Cognitive Dysfunction , prostate adenocarcinoma , pulmonary hypertension , renal cell carcinoma , renal fibrosis , Sepsis , severe acute respiratory syndrome , Sezary's disease , Shock , squamous cell carcinoma , Stomach Neoplasms , Testis Reperfusion Injury , thyroid cancer , Thyroid Neoplasms , transitional cell carcinoma , trigeminal neuralgia , type 2 diabetes mellitus , ureteral obstruction , urethral obstruction , Urinary Incontinence , Uterine Cervical Neoplasms , vascular dementia , velocardiofacial syndrome , Weissenbacher-Zweymuller syndrome , withdrawal disorder Mapk3 Aberrant Crypt Foci , alcohol dependence , alcohol use disorder , Alzheimer's disease , Animal Disease Models , Atrophy , autism spectrum disorder , autistic disorder , brain ischemia , cardiomyopathy , chromosome 16p11.2 deletion syndrome, 593-kb , chromosome 16p11.2 duplication syndrome , cocaine abuse , cocaine dependence , Cocaine-Related Disorders , colon adenocarcinoma , colorectal adenocarcinoma , Colorectal Neoplasms , Coronavirus infectious disease , coronin-1A deficiency , Developmental Disabilities , Diabetic Cardiomyopathies , endometrial adenocarcinoma , endometrial carcinoma , Endometrial Neoplasms , Endometrioid Carcinomas , Episodic Kinesigenic Dyskinesia , episodic kinesigenic dyskinesia 1 , Experimental Colitis , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , Experimental Liver Neoplasms , Experimental Mammary Neoplasms , Experimental Radiation Injuries , extrahepatic cholestasis , Female Infertility , gastric ulcer , Gliosis , Glycogen Storage Disease XII , Head and Neck Neoplasms , high grade glioma , Hyperalgesia , Hypertrophy , Insulin Resistance , Kidney Neoplasms , Lung Neoplasms , Memory Disorders , middle cerebral artery infarction , morphine dependence , Myocardial Reperfusion Injury , Neoplasm Invasiveness , Neoplasm Metastasis , Nerve Degeneration , Neurodevelopmental Disorders , neuronal ceroid lipofuscinosis 6A , obesity , Osteoarthritis, Experimental , Ovarian Neoplasms , pancreatic ductal carcinoma , Parkinson's disease , Pneumococcal Pneumonia , Postoperative Cognitive Dysfunction , Prostatic Neoplasms , pulmonary hypertension , schizophrenia , Sepsis , severe acute respiratory syndrome , Shock , spondylocostal dysostosis 5 , squamous cell carcinoma , Stomach Neoplasms , Testis Reperfusion Injury , trigeminal neuralgia , type 2 diabetes mellitus , ureteral obstruction , withdrawal disorder Mknk1 substance-related disorder Mknk2 cyclic hematopoiesis , Neurodevelopmental Disorders , progressive myoclonus epilepsy 9 Nras acute lymphoblastic leukemia , acute myeloid leukemia , acute promyelocytic leukemia , adrenocortical carcinoma , adult T-cell leukemia/lymphoma , anemia , autoimmune lymphoproliferative syndrome , autoimmune lymphoproliferative syndrome type 4 , B-Cell Chronic Lymphocytic Leukemia , B-cell lymphoma , Brain Neoplasms , cervical cancer , cholangitis , chronic lymphocytic leukemia , chronic myelogenous leukemia, BCR-ABL1 positive , chronic myeloid leukemia , chronic myelomonocytic leukemia , colon carcinoma , colorectal cancer , Colorectal Neoplasms , disease of cellular proliferation , epidermal nevus , Experimental Arthritis , Experimental Leukemia , Experimental Liver Neoplasms , Experimental Neoplasms , Experimental Sarcoma , focal epilepsy , Follicular Thyroid Cancer , gastric adenocarcinoma , glioblastoma , hepatocellular carcinoma , hereditary spastic paraplegia 47 , juvenile myelomonocytic leukemia , large congenital melanocytic nevus , leukemia , Leukocytosis , linear nevus sebaceous syndrome , liver carcinoma , Liver Metastasis , lung adenocarcinoma , lung non-small cell carcinoma , lymphoma , medulloblastoma , melanoma , Mouth Neoplasms , multiple myeloma , myelodysplastic syndrome , myeloid leukemia associated with Down Syndrome , myeloid neoplasm , Nasopharyngeal Neoplasms , neuroblastoma , Neurocutaneous Melanosis , Neurodevelopmental Disorders , neurofibrosarcoma , non-Hodgkin lymphoma , Noonan syndrome , Noonan syndrome 1 , Noonan syndrome 6 , ovarian serous cystadenocarcinoma , Paraproteinemias , Pigmented Nevus , plasma cell neoplasm , prostate cancer , Prostate Cancer, Hereditary, 1 , Pyogenic Granuloma , RASopathy , rectal benign neoplasm , renal cell carcinoma , Renal Cell Carcinoma 1 , Sebaceous Nevus Syndrome and Hemimegalencephaly , skin melanoma , Splenomegaly , Stomach Neoplasms , Thyroid Neoplasms , transitional cell carcinoma , uterine cancer Pebp1 Alzheimer's disease , Animal Mammary Neoplasms , carcinoma , congenital heart disease , congestive heart failure , Experimental Mammary Neoplasms , Lymphatic Metastasis , myocardial infarction , Myocardial Ischemia , Neoplasm Metastasis , ovarian cancer , pre-malignant neoplasm , prostate cancer , renal cell carcinoma Prkcd autoimmune lymphoproliferative syndrome type 3 , brain ischemia , Burns , Cardiomegaly , Chemical and Drug Induced Liver Injury , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , Fever , genetic disease , hyperinsulinism , hypertension , Hypothermia , Insulin Resistance , Intestinal Neoplasms , Left Ventricular Hypertrophy , metabolic dysfunction-associated steatotic liver disease , muscular disease , Myocardial Ischemia , Myocardial Reperfusion Injury , obesity , Parkinsonism , portal hypertension , restrictive cardiomyopathy , Right Ventricular Hypertrophy , steatotic liver disease , Stroke , toxic encephalopathy Ptk2b Alzheimer's disease , anti-basement membrane glomerulonephritis , bone disease , brain ischemia , breast cancer , diabetic angiopathy , glomerulonephritis , hypertension , Insulin Resistance , Left Ventricular Hypertrophy , melanoma , Neointima , nephritis , Postmenopausal Osteoporosis , prostate cancer , Reperfusion Injury , Skin Neoplasms , status epilepticus Raf1 Breast Neoplasms , Cardiomegaly , colorectal adenocarcinoma , colorectal adenoma , Colorectal Neoplasms , dilated cardiomyopathy , dilated cardiomyopathy 1B , dilated cardiomyopathy 1NN , Dilated Cardiomyopathy with Left Ventricular Noncompaction , familial hypertrophic cardiomyopathy , gastric adenocarcinoma , genetic disease , high grade glioma , Hyperalgesia , hypertrophic cardiomyopathy , hypertrophic cardiomyopathy 1 , ischemia , Kidney Neoplasms , Liver Neoplasms , lung adenocarcinoma , Lung Neoplasms , lung non-small cell carcinoma , Lymphangiectasis , malignant mesothelioma , melanoma , Noonan syndrome , Noonan syndrome 1 , Noonan syndrome 3 , Noonan syndrome 5 , Noonan syndrome with multiple lentigines , Noonan syndrome with multiple lentigines 2 , ovarian carcinoma , pancreatic adenocarcinoma , pancreatic carcinoma , Pituitary Stalk Interruption Syndrome , prostate adenocarcinoma , prostate cancer , Prostatic Neoplasms , RASopathy , skin melanoma , Stroke , Ventricular Tachycardia Rps6ka1 fetal alcohol spectrum disorder , retinitis pigmentosa 59 , Sezary's disease Rps6ka2 autism spectrum disorder , bipolar disorder Rps6ka3 autistic disorder , bone development disease , Coffin-Lowry syndrome , developmental and epileptic encephalopathy 2 , Developmental Disabilities , genetic disease , glycogen storage disease IXA , hepatocellular carcinoma , Hirsutism , Hypertelorism , intellectual disability , Nance-Horan syndrome , Neoplasm Invasiveness , Neoplasm Metastasis , Neurodevelopmental Disorders , non-syndromic X-linked intellectual disability 19 , Psychomotor Disorders , syndromic X-linked intellectual disability Lubs type Rps6ka4 high grade glioma , intellectual disability , leukocyte adhesion deficiency 3 Rps6ka5 achondrogenesis type IA , Cocaine-Related Disorders , COVID-19 Rps6ka6 autistic disorder , syndromic X-linked intellectual disability Lubs type S1pr1 Animal Mammary Neoplasms , carcinoma , Cardiomegaly , COVID-19 , epilepsy , Experimental Liver Cirrhosis , Experimental Mammary Neoplasms , hypertension , maple syrup urine disease , Neointima , Reperfusion Injury , Vascular System Injuries Shc1 Albuminuria , Alzheimer's disease , amyotrophic lateral sclerosis type 1 , Breast Neoplasms , Cardiomegaly , Charcot-Marie-Tooth disease type 2 , Chemical and Drug Induced Liver Injury , Chronic Hepatitis , familial hyperlipidemia , gastrointestinal stromal tumor , glomerulosclerosis , hepatocellular carcinoma , hyperglycemia , Hypertensive Nephropathy , immunodeficiency 42 , Insulin Resistance , Left Ventricular Hypertrophy , liver cirrhosis , MHC class II deficiency , parathyroid carcinoma , severe congenital neutropenia 3 , severe congenital neutropenia 5 , steatotic liver disease Smad1 Cocaine-Related Disorders , COVID-19 , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , glomerulonephritis , granulosa cell tumor , Hypoglossal Nerve Injuries , male infertility , Myocardial Reperfusion Injury , nephrotic syndrome , Primary Pulmonary Hypertension, 1 , pulmonary hypertension , Testicular Neoplasms , withdrawal disorder Spp1 acute kidney failure , adenocarcinoma , Albuminuria , Alcoholic Liver Diseases , allergic contact dermatitis , allergic disease , Aneurysm , Angina Pectoris , anti-basement membrane glomerulonephritis , aortic aneurysm , aortic dissection , asbestosis , autosomal dominant polycystic kidney disease , biliary atresia , Brain Neoplasms , Breast Neoplasms , calcinosis , Cardiomegaly , carotid stenosis , Cerebral Hemorrhage , Chemical and Drug Induced Liver Injury , Chronic Hepatitis C , coronary artery disease , coronary restenosis , Cystic, Mucinous, and Serous Neoplasms , Diabetic Cardiomyopathies , Diabetic Nephropathies , disease of cellular proliferation , Drug-Related Side Effects and Adverse Reactions , encephalomyelitis , Endometrioid Carcinomas , Experimental Autoimmune Neuritis , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , Experimental Liver Neoplasms , Experimental Mammary Neoplasms , Experimental Neoplasms , Fibrosis , focal segmental glomerulosclerosis , Foreign-Body Reaction , glomerulonephritis , glomerulosclerosis , heart disease , heart valve disease , hepatitis , hepatocellular carcinoma , high grade glioma , Inflammation , Kidney Calculi , kidney disease , kidney failure , Laryngeal Neoplasms , Leukoencephalopathies , liver cirrhosis , Lung Neoplasms , lung non-small cell carcinoma , malaria , melanoma , Mesothelioma , multiple myeloma , multiple sclerosis , myocardial infarction , Myocardial Reperfusion Injury , myocarditis , Neoplasm Metastasis , Neovascularization, Pathologic , Nervous System Trauma , Osteolysis , Ovarian Neoplasms , pancreas disease , pancreatic cancer , Pleural Neoplasms , pneumonia , progressive osseous heteroplasia , prostate carcinoma , Prostatic Neoplasms , proteinuria , pulmonary fibrosis , radiculopathy , renovascular hypertension , Reperfusion Injury , rheumatoid arthritis , scrapie , Spinal Cord Injuries , Stomach Neoplasms , Thyroid Neoplasms , tuberculosis , uremia , urinary bladder cancer , Urinary Calculi , Vascular System Injuries , visual epilepsy , Wounds and Injuries Tsc2 Acute Hepatitis , acute myeloid leukemia , Alzheimer's disease , angiomyolipoma , Arthralgia , astroblastoma, MN1-altered , autism spectrum disorder , autistic disorder , bone osteosarcoma , brain disease , Brain Neoplasms , breast cancer , Cafe-au-Lait Spots , developmental and epileptic encephalopathy 1 , endometrial carcinoma , epilepsy , Experimental Diabetes Mellitus , familial adenomatous polyposis 3 , Female Infertility , Fever , Focal Cortical Dysplasia of Taylor , genetic disease , Hamartoma , hemangioma , hepatic angiomyolipoma , hepatocellular carcinoma , Hereditary Neoplastic Syndromes , Hirschsprung Disease 1 , Hirschsprung's disease , idiopathic generalized epilepsy , Inflammation , intellectual disability , Joint Instability , Kidney Neoplasms , leiomyoma , Lung Neoplasms , lymphangioleiomyomatosis , Lymphatic Metastasis , medulloblastoma , Mouth Neoplasms , Nerve Degeneration , Nervous System Malformations , neuroblastoma , Neurodevelopmental Disorders , ovarian cancer , pancreatic cancer , pancreatic ductal carcinoma , polycystic kidney disease , pre-malignant neoplasm , renal cell carcinoma , Rhabdomyoma , short-rib thoracic dysplasia 9 with or without polydactyly , squamous cell carcinoma , tuberous sclerosis , tuberous sclerosis 1 , tuberous sclerosis 2 , uterine fibroid , vascular dementia , West syndrome
46,XY sex reversal 6 Map3k1 Aberrant Crypt Foci Mapk1 , Mapk3 achondrogenesis type IA Rps6ka5 Acute Experimental Pancreatitis Kras Acute Hepatitis Tsc2 acute kidney failure Spp1 acute lymphoblastic leukemia Kras , Nras acute myeloid leukemia Hras , Kras , Nras , Tsc2 acute promyelocytic leukemia Nras adenocarcinoma Kras , Spp1 adenoid cystic carcinoma Hras , Kras , Map2k2 adenoma Kras adrenocortical carcinoma Braf , Nras adult T-cell leukemia/lymphoma Nras Albuminuria Shc1 , Spp1 alcohol dependence Mapk1 , Mapk3 alcohol use disorder Mapk1 , Mapk3 Alcoholic Liver Diseases Spp1 allergic contact dermatitis Spp1 allergic disease Spp1 Alzheimer's disease Hras , Mapk1 , Mapk3 , Pebp1 , Ptk2b , Shc1 , Tsc2 ameloblastoma Braf amenorrhea Map2k2 amyotrophic lateral sclerosis type 1 Shc1 anaplastic astrocytoma Kras anemia Kras , Nras Aneurysm Spp1 Angina Pectoris Spp1 angiomyolipoma Tsc2 angiosarcoma Hras , Kras Animal Disease Models Kras , Mapk1 , Mapk3 Animal Mammary Neoplasms Dusp6 , Hras , Pebp1 , S1pr1 anti-basement membrane glomerulonephritis Ptk2b , Spp1 aortic aneurysm Spp1 Aortic Aneurysm, Giant Congenital Braf aortic dissection Spp1 arteriovenous malformations of the brain Braf , Kras Arthralgia Tsc2 asbestosis Spp1 astroblastoma, MN1-altered Tsc2 ataxia telangiectasia Braf Atrophy Mapk3 autism spectrum disorder Map2k1 , Mapk1 , Mapk3 , Rps6ka2 , Tsc2 autistic disorder Araf , Hras , Mapk3 , Rps6ka3 , Rps6ka6 , Tsc2 autoimmune hepatitis Hras autoimmune lymphoproliferative syndrome Nras autoimmune lymphoproliferative syndrome type 3 Prkcd autoimmune lymphoproliferative syndrome type 4 Kras , Nras autosomal dominant polycystic kidney disease Spp1 autosomal dominant thrombophilia due to protein C deficiency Map3k2 autosomal recessive limb-girdle muscular dystrophy type 2W Map3k2 B-Cell Chronic Lymphocytic Leukemia Braf , Hras , Kras , Nras B-cell lymphoma Nras bile duct adenoma Braf biliary atresia Spp1 bipolar disorder Rps6ka2 bladder carcinoma Hras Bloom syndrome Map2k1 bone development disease Rps6ka3 bone disease Ptk2b bone osteosarcoma Tsc2 brain disease Tsc2 brain ischemia Dusp6 , Map2k1 , Mapk1 , Mapk3 , Prkcd , Ptk2b Brain Neoplasms Braf , Hras , Nras , Spp1 , Tsc2 breast adenocarcinoma Kras , Ksr1 breast cancer Dusp6 , Kras , Ksr1 , Map2k1 , Map2k2 , Map3k1 , Mapk1 , Ptk2b , Tsc2 Breast Cancer, Familial Kras Breast Neoplasms Araf , Braf , Gper1 , Hras , Kras , Map3k1 , Raf1 , Shc1 , Spp1 bronchiolo-alveolar adenocarcinoma Kras Burns Prkcd Cafe-au-Lait Spots Tsc2 calcinosis Spp1 cancer Braf Capillary Malformation-Arteriovenous Malformation 1 Kras Carcinogenesis Braf , Kras carcinoma Dusp6 , Hras , Kras , Pebp1 , S1pr1 cardiofaciocutaneous syndrome Braf , Hras , Kras , Map2k1 , Map2k2 cardiofaciocutaneous syndrome 1 Braf , Kras , Map2k2 cardiofaciocutaneous syndrome 2 Kras cardiofaciocutaneous syndrome 3 Map2k1 cardiofaciocutaneous syndrome 4 Map2k2 Cardiomegaly Mapk1 , Prkcd , Raf1 , S1pr1 , Shc1 , Spp1 cardiomyopathy Braf , Kras , Mapk1 , Mapk3 Cardiovascular Abnormalities Map2k1 carotid stenosis Spp1 cataract Map2k1 Cecal Neoplasms Kras centronuclear myopathy 2 Map3k2 Cerebral Hemorrhage Spp1 cervical cancer Nras Chanarin-Dorfman syndrome Hras Charcot-Marie-Tooth disease type 2 Shc1 Chemical and Drug Induced Liver Injury Prkcd , Shc1 , Spp1 childhood pilocytic astrocytoma Mapk1 cholangiocarcinoma Braf , Kras cholangitis Nras chromosome 16p11.2 deletion syndrome, 593-kb Mapk3 chromosome 16p11.2 duplication syndrome Mapk3 chromosome 22q11.2 deletion syndrome, distal Mapk1 Chronic Hepatitis Shc1 Chronic Hepatitis C Spp1 chronic lymphocytic leukemia Braf , Hras , Kras , Nras chronic myelogenous leukemia, BCR-ABL1 positive Braf , Kras , Nras chronic myeloid leukemia Braf , Kras , Nras chronic myelomonocytic leukemia Nras cocaine abuse Mapk1 , Mapk3 cocaine dependence Mapk1 , Mapk3 Cocaine-Related Disorders Mapk1 , Mapk3 , Rps6ka5 , Smad1 Coffin-Lowry syndrome Rps6ka3 colon adenocarcinoma Mapk1 , Mapk3 colon cancer Mapk1 colon carcinoma Braf , Nras Colonic Neoplasms Braf , Kras colorectal adenocarcinoma Braf , Mapk1 , Mapk3 , Raf1 colorectal adenoma Raf1 colorectal cancer Braf , Kras , Map2k1 , Map2k2 , Nras Colorectal Neoplasms Braf , Hras , Kras , Map2k1 , Mapk1 , Mapk3 , Nras , Raf1 complex cortical dysplasia with other brain malformations Hras congenital disorder of glycosylation type IIm Araf congenital fibrosis of the extraocular muscles Hras congenital heart disease Mapk1 , Pebp1 Congenital Myopathy with Excess of Muscle Spindles Hras congestive heart failure Map2k1 , Pebp1 coronary artery disease Spp1 coronary restenosis Mapk1 , Spp1 Coronavirus infectious disease Mapk1 , Mapk3 coronin-1A deficiency Mapk3 Costello syndrome Braf , Hras , Kras , Map2k1 , Map2k2 COVID-19 Gper1 , Rps6ka5 , S1pr1 , Smad1 craniopharyngioma Braf cyclic hematopoiesis Mknk2 Cystic, Mucinous, and Serous Neoplasms Spp1 Dandy-Walker syndrome Braf delta beta-thalassemia Hras demyelinating disease Mapk1 depressive disorder Mapk1 developmental and epileptic encephalopathy Hras developmental and epileptic encephalopathy 1 Tsc2 developmental and epileptic encephalopathy 2 Rps6ka3 Developmental Disabilities Braf , Mapk3 , Rps6ka3 diabetic angiopathy Ptk2b Diabetic Cardiomyopathies Mapk1 , Mapk3 , Spp1 Diabetic Nephropathies Mapk1 , Spp1 diabetic retinopathy Hras diffuse gastric cancer Map3k1 diffuse large B-cell lymphoma Braf DiGeorge syndrome Mapk1 dilated cardiomyopathy Braf , Kras , Raf1 dilated cardiomyopathy 1B Raf1 dilated cardiomyopathy 1NN Raf1 Dilated Cardiomyopathy with Left Ventricular Noncompaction Raf1 disease of cellular proliferation Braf , Hras , Kras , Map2k1 , Nras , Spp1 Disease Progression Hras , Kras disorder of sexual development Map3k1 Drug-Related Side Effects and Adverse Reactions Spp1 Dwarfism Mapk1 Dysbiosis Gper1 dysembryoplastic neuroepithelial tumor Braf dysplastic nevus syndrome Braf early infantile epileptic encephalopathy Hras Encephalocraniocutaneous Lipomatosis Kras encephalomyelitis Spp1 endometrial adenocarcinoma Kras , Mapk1 , Mapk3 endometrial carcinoma Braf , Hras , Kras , Mapk1 , Mapk3 , Tsc2 endometrial hyperplasia Kras Endometrial Hyperplasia without Atypia Kras Endometrial Intraepithelial Neoplasia Kras Endometrial Neoplasms Kras , Mapk3 Endometrioid Carcinomas Kras , Mapk1 , Mapk3 , Spp1 endometriosis Gper1 , Kras epidermal nevus Hras , Kras , Nras epilepsy S1pr1 , Tsc2 Episodic Kinesigenic Dyskinesia Mapk3 episodic kinesigenic dyskinesia 1 Mapk3 esophageal carcinoma Hras , Kras esophagus squamous cell carcinoma Map3k1 Experimental Arthritis Nras Experimental Autoimmune Neuritis Spp1 Experimental Colitis Mapk1 , Mapk3 Experimental Diabetes Mellitus Hras , Mapk1 , Mapk3 , Prkcd , Smad1 , Spp1 , Tsc2 Experimental Leukemia Nras Experimental Liver Cirrhosis Dusp6 , Mapk1 , Mapk3 , Prkcd , S1pr1 , Smad1 , Spp1 Experimental Liver Neoplasms Hras , Kras , Map2k1 , Mapk1 , Mapk3 , Nras , Spp1 Experimental Mammary Neoplasms Dusp6 , Hras , Mapk1 , Mapk3 , Pebp1 , S1pr1 , Spp1 Experimental Melanoma Braf Experimental Neoplasms Braf , Hras , Kras , Nras , Spp1 Experimental Radiation Injuries Mapk1 , Mapk3 Experimental Sarcoma Kras , Nras extrahepatic cholestasis Mapk1 , Mapk3 familial adenomatous polyposis 3 Tsc2 familial hyperlipidemia Shc1 familial hypertrophic cardiomyopathy Raf1 familial melanoma Braf Familial Prostate Cancer Map2k1 Female Infertility Mapk1 , Mapk3 , Tsc2 fetal alcohol spectrum disorder Rps6ka1 Fever Prkcd , Tsc2 fibrillary astrocytoma Kras Fibrosis Spp1 Focal Cortical Dysplasia of Taylor Tsc2 focal epilepsy Nras focal segmental glomerulosclerosis Spp1 Follicular Thyroid Cancer Braf , Hras , Nras Foreign-Body Reaction Spp1 gallbladder cancer Braf , Kras Gallbladder Neoplasms Kras ganglioglioma Braf gastric adenocarcinoma Braf , Hras , Kras , Map2k1 , Map2k2 , Nras , Raf1 gastric ulcer Mapk1 , Mapk3 gastrointestinal stromal tumor Braf , Kras , Shc1 generalized anxiety disorder Gper1 genetic disease Braf , Dusp6 , Hras , Kras , Map2k1 , Map3k1 , Mapk1 , Prkcd , Raf1 , Rps6ka3 , Tsc2 germinoma Braf glioblastoma Braf , Dusp6 , Hras , Kras , Map2k2 , Nras Gliosis Mapk1 , Mapk3 glomerulonephritis Mapk1 , Ptk2b , Smad1 , Spp1 glomerulosclerosis Shc1 , Spp1 glycogen storage disease IXA Rps6ka3 Glycogen Storage Disease XII Mapk3 granulosa cell tumor Smad1 hairy cell leukemia Map2k1 Hamartoma Tsc2 Head and Neck Neoplasms Mapk1 , Mapk3 head and neck squamous cell carcinoma Braf , Hras , Map2k1 , Map2k2 , Mapk1 Hearing Loss Map3k1 heart disease Spp1 heart valve disease Spp1 hemangioma Tsc2 Hemorrhagic Shock Mapk1 hepatic angiomyolipoma Tsc2 hepatitis Spp1 hepatocellular adenoma Hras , Kras hepatocellular carcinoma Braf , Hras , Kras , Map2k2 , Map3k1 , Mapk1 , Nras , Rps6ka3 , Shc1 , Spp1 , Tsc2 Hepatomegaly Gper1 hereditary breast ovarian cancer syndrome Kras hereditary diffuse gastric cancer Kras Hereditary Neoplastic Syndromes Hras , Map3k1 , Tsc2 hereditary spastic paraplegia 47 Nras high grade glioma Araf , Braf , Hras , Kras , Map2k1 , Mapk3 , Raf1 , Rps6ka4 , Spp1 Hirschsprung Disease 1 Tsc2 Hirschsprung's disease Tsc2 Hirsutism Rps6ka3 Hodgkin's lymphoma Kras , Mapk1 Hydrops Fetalis Hras , Kras Hyperalgesia Dusp6 , Gper1 , Mapk1 , Mapk3 , Raf1 hyperglycemia Shc1 hyperinsulinism Prkcd Hypertelorism Rps6ka3 hypertension Kras , Prkcd , Ptk2b , S1pr1 Hypertensive Nephropathy Shc1 hypertrophic cardiomyopathy Braf , Map2k2 , Raf1 hypertrophic cardiomyopathy 1 Raf1 hypertrophic cardiomyopathy 4 Braf Hypertrophy Mapk1 , Mapk3 Hypoglossal Nerve Injuries Smad1 hypogonadotropic hypogonadism 19 with or without anosmia Dusp6 hypogonadotropic hypogonadism 7 with or without anosmia Dusp6 Hypophosphatemic Rickets Hras Hypothermia Prkcd idiopathic generalized epilepsy Tsc2 immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome Araf immunodeficiency 39 Hras immunodeficiency 42 Shc1 Inflammation Spp1 , Tsc2 Insulin Resistance Mapk3 , Prkcd , Ptk2b , Shc1 intellectual disability Braf , Hras , Kras , Mapk1 , Rps6ka3 , Rps6ka4 , Tsc2 interstitial lung disease 2 Gper1 Intestinal Neoplasms Prkcd Intimal Hyperplasia Mapk1 intrahepatic cholangiocarcinoma Braf , Kras ischemia Raf1 Joint Instability Tsc2 juvenile myelomonocytic leukemia Kras , Nras juvenile rheumatoid arthritis Kras , Mapk1 Kidney Calculi Spp1 kidney disease Mapk1 , Spp1 kidney failure Spp1 Kidney Neoplasms Braf , Kras , Mapk1 , Mapk3 , Raf1 , Tsc2 Klatskin's tumor Kras Langerhans-cell histiocytosis Braf large congenital melanocytic nevus Hras , Nras Laryngeal Neoplasms Spp1 Leber congenital amaurosis Hras Left Ventricular Hypertrophy Mapk1 , Prkcd , Ptk2b , Shc1 leiomyoma Gper1 , Tsc2 leishmaniasis Dusp6 leukemia Nras leukocyte adhesion deficiency 3 Rps6ka4 Leukocytosis Kras , Nras Leukoencephalopathies Spp1 linear nevus sebaceous syndrome Hras , Kras , Nras liver cancer Hras liver carcinoma Hras , Nras liver cirrhosis Hras , Shc1 , Spp1 Liver Metastasis Braf , Nras Liver Neoplasms Braf , Gper1 , Hras , Kras , Raf1 lung adenocarcinoma Araf , Braf , Hras , Kras , Map2k1 , Nras , Raf1 lung cancer Braf , Kras lung carcinoma Braf , Kras lung metastasis Map3k1 Lung Neoplasms Braf , Hras , Kras , Mapk1 , Mapk3 , Raf1 , Spp1 , Tsc2 lung non-small cell carcinoma Araf , Braf , Hras , Kras , Map2k1 , Map2k2 , Map3k1 , Nras , Raf1 , Spp1 Lung Reperfusion Injury Kras lung sarcomatoid carcinoma Kras lung squamous cell carcinoma Braf , Hras , Kras , Map2k1 Lymphangiectasis Raf1 lymphangioleiomyomatosis Tsc2 lymphangioma Braf Lymphatic Metastasis Braf , Pebp1 , Tsc2 lymphoma Kras , Nras Lynch syndrome Kras malaria Spp1 male infertility Smad1 malignant astrocytoma Braf , Hras , Kras malignant mesothelioma Raf1 Mandibular Neoplasms Braf maple syrup urine disease S1pr1 maturity-onset diabetes of the young type 1 Ksr2 medulloblastoma Nras , Tsc2 melanoma Braf , Gper1 , Hras , Kras , Map2k1 , Map2k2 , Mapk1 , Nras , Ptk2b , Raf1 , Spp1 melorheostosis Map2k1 Memory Disorders Mapk1 , Mapk3 Mesothelioma Spp1 metabolic dysfunction-associated steatotic liver disease Prkcd Metabolic Syndrome Map2k2 MHC class II deficiency Shc1 Microsatellite Instability Braf middle cerebral artery infarction Mapk1 , Mapk3 migraine Map2k2 morbid obesity Ksr2 morphine dependence Mapk1 , Mapk3 Mouth Neoplasms Hras , Kras , Nras , Tsc2 multicentric Castleman disease Map2k2 Multiple Abnormalities Gper1 , Kras multiple myeloma Braf , Hras , Kras , Nras , Spp1 Multiple Organ Failure Mapk1 multiple sclerosis Spp1 muscular atrophy Kras muscular disease Prkcd myelodysplastic syndrome Hras , Kras , Nras myeloid leukemia associated with Down Syndrome Nras myeloid neoplasm Kras , Nras myeloid sarcoma Kras myocardial infarction Mapk1 , Pebp1 , Spp1 Myocardial Ischemia Dusp6 , Pebp1 , Prkcd Myocardial Reperfusion Injury Mapk1 , Mapk3 , Prkcd , Smad1 , Spp1 myocarditis Spp1 myoepithelioma Braf Nance-Horan syndrome Rps6ka3 Nasopharyngeal Neoplasms Hras , Nras Neointima Ptk2b , S1pr1 Neoplasm Invasiveness Hras , Mapk1 , Mapk3 , Rps6ka3 Neoplasm Metastasis Braf , Kras , Mapk1 , Mapk3 , Pebp1 , Rps6ka3 , Spp1 Neoplastic Cell Transformation Hras , Kras Neoplastic Processes Hras Neovascularization, Pathologic Spp1 nephritis Ptk2b nephroblastoma Braf nephrotic syndrome Smad1 Nerve Degeneration Mapk1 , Mapk3 , Tsc2 Nervous System Malformations Tsc2 Nervous System Trauma Spp1 neuroblastoma Hras , Kras , Nras , Tsc2 Neurocutaneous Melanosis Nras neurodegeneration with brain iron accumulation 5 Araf Neurodevelopmental Disorders Map3k1 , Mapk3 , Mknk2 , Nras , Rps6ka3 , Tsc2 neuroendocrine tumor Braf neurofibromatosis-Noonan syndrome Map2k2 neurofibrosarcoma Nras neuronal ceroid lipofuscinosis Hras , Map2k1 neuronal ceroid lipofuscinosis 6A Mapk1 , Mapk3 Nevus Braf newborn respiratory distress syndrome Braf non-Hodgkin lymphoma Braf , Map2k1 , Nras non-syndromic X-linked intellectual disability 19 Rps6ka3 Nonseminomatous Germ Cell Tumor Braf Noonan syndrome Braf , Hras , Kras , Map2k1 , Map2k2 , Nras , Raf1 Noonan syndrome 1 Braf , Hras , Kras , Map2k1 , Map2k2 , Nras , Raf1 Noonan syndrome 13 Mapk1 Noonan syndrome 3 Hras , Kras , Raf1 Noonan syndrome 5 Raf1 Noonan syndrome 6 Nras Noonan syndrome 7 Braf Noonan syndrome with multiple lentigines Braf , Map2k2 , Raf1 Noonan syndrome with multiple lentigines 2 Raf1 Noonan syndrome with multiple lentigines 3 Braf obesity Mapk1 , Mapk3 , Prkcd obsessive-compulsive disorder Hras oculoectodermal syndrome Kras Osteoarthritis, Experimental Mapk3 Osteolysis Spp1 ovarian cancer Hras , Pebp1 , Tsc2 ovarian carcinoma Map2k1 , Raf1 Ovarian Neoplasms Braf , Hras , Kras , Map2k1 , Map2k2 , Map3k1 , Mapk1 , Mapk3 , Spp1 ovarian serous cystadenocarcinoma Braf , Hras , Nras ovary serous adenocarcinoma Kras pancreas disease Spp1 pancreatic acinar cell adenocarcinoma Braf pancreatic adenocarcinoma Hras , Kras , Map2k1 , Map2k2 , Mapk1 , Raf1 pancreatic cancer Braf , Kras , Spp1 , Tsc2 pancreatic carcinoma Kras , Raf1 pancreatic ductal carcinoma Kras , Mapk3 , Tsc2 pancreatic mucinous cystadenoma Kras pancreatitis Dusp6 , Map2k1 papillary renal cell carcinoma Araf , Braf , Hras papilloma Hras Paraproteinemias Braf , Hras , Kras , Nras Parasitic Liver Diseases Kras parathyroid adenoma Hras parathyroid carcinoma Shc1 Parkinson's disease Mapk1 , Mapk3 Parkinsonism Prkcd Penile Neoplasms Hras , Kras PHACE Association Braf phobic disorder Hras Pigmented Nevus Hras , Nras pilocytic astrocytoma Kras Pituitary Stalk Interruption Syndrome Raf1 plasma cell neoplasm Braf , Hras , Kras , Nras pleomorphic xanthoastrocytoma Braf Pleural Neoplasms Spp1 Pneumococcal Pneumonia Mapk1 , Mapk3 pneumonia Spp1 polycystic kidney disease Tsc2 portal hypertension Mapk1 , Prkcd Postmenopausal Osteoporosis Ptk2b Postoperative Cognitive Dysfunction Mapk1 , Mapk3 Postoperative Pain Dusp6 pre-malignant neoplasm Hras , Pebp1 , Tsc2 Premature Birth Braf primary cutaneous T-cell non-Hodgkin lymphoma Braf Primary Pulmonary Hypertension, 1 Smad1 progressive myoclonus epilepsy 9 Mknk2 progressive osseous heteroplasia Spp1 prostate adenocarcinoma Braf , Hras , Map2k1 , Mapk1 , Raf1 prostate cancer Kras , Nras , Pebp1 , Ptk2b , Raf1 Prostate Cancer, Hereditary, 1 Braf , Hras , Kras , Nras prostate carcinoma Spp1 prostate carcinoma in situ Kras Prostatic Neoplasms Braf , Hras , Kras , Map2k1 , Map2k2 , Map3k1 , Mapk3 , Raf1 , Spp1 proteinuria Spp1 Psychomotor Disorders Rps6ka3 pulmonary fibrosis Spp1 pulmonary hypertension Mapk1 , Mapk3 , Smad1 pulmonary valve stenosis Braf , Hras Pyogenic Granuloma Nras radiculopathy Spp1 RASopathy Braf , Hras , Kras , Map2k1 , Map2k2 , Nras , Raf1 rectal benign neoplasm Nras rectum cancer Map3k1 Recurrence Hras , Kras renal cell carcinoma Kras , Map2k1 , Mapk1 , Nras , Pebp1 , Tsc2 Renal Cell Carcinoma 1 Nras renal fibrosis Kras , Mapk1 renovascular hypertension Spp1 Reperfusion Injury Ptk2b , S1pr1 , Spp1 restrictive cardiomyopathy Prkcd retinitis pigmentosa 59 Rps6ka1 Rhabdomyoma Tsc2 rhabdomyosarcoma Hras rheumatoid arthritis Spp1 Right Ventricular Hypertrophy Prkcd Salivary Gland Neoplasms Hras schizophrenia Mapk3 scrapie Spp1 Sebaceous Nevus Syndrome and Hemimegalencephaly Hras , Kras , Nras seminoma Hras , Kras Sepsis Mapk1 , Mapk3 severe acute respiratory syndrome Mapk1 , Mapk3 severe congenital neutropenia 3 Shc1 severe congenital neutropenia 5 Shc1 Sezary's disease Braf , Mapk1 , Rps6ka1 Shock Mapk1 , Mapk3 short-rib thoracic dysplasia 9 with or without polydactyly Tsc2 skin benign neoplasm Hras skin melanoma Araf , Braf , Hras , Kras , Map2k1 , Map2k2 , Nras , Raf1 Skin Neoplasms Hras , Ptk2b small intestine adenocarcinoma Map2k1 , Map2k2 Smith-Magenis syndrome Map2k2 spermatocytoma Hras spermatogenic failure 57 Map2k1 Spinal Cord Injuries Gper1 , Spp1 Splenic Neoplasms Hras Splenomegaly Kras , Nras spondylocostal dysostosis 5 Mapk3 Sporadic Papillary Renal Cell Carcinoma Araf , Braf , Hras squamous cell carcinoma Hras , Kras , Mapk1 , Mapk3 , Tsc2 status epilepticus Ptk2b steatotic liver disease Prkcd , Shc1 stomach cancer Kras , Map3k1 stomach carcinoma Kras Stomach Neoplasms Hras , Kras , Mapk1 , Mapk3 , Nras , Spp1 Stroke Prkcd , Raf1 Sturge-Weber syndrome Map2k1 substance-related disorder Mknk1 syndromic microphthalmia 5 Map3k1 syndromic X-linked intellectual disability Lubs type Araf , Rps6ka3 , Rps6ka6 T-cell acute lymphoblastic leukemia Kras T-cell non-Hodgkin lymphoma Hras teratoma Kras Testicular Neoplasms Smad1 Testis Reperfusion Injury Mapk1 , Mapk3 tethered spinal cord syndrome Braf thymoma Hras thyroid cancer Mapk1 Thyroid Carcinoma, Nonmedullary 1 Kras thyroid gland follicular carcinoma Kras thyroid gland medullary carcinoma Kras thyroid gland papillary carcinoma Braf Thyroid Neoplasms Braf , Hras , Kras , Mapk1 , Nras , Spp1 Tongue Neoplasms Hras toxic encephalopathy Prkcd transitional cell carcinoma Braf , Hras , Kras , Map2k1 , Mapk1 , Nras Trichilemmoma Hras trigeminal neuralgia Mapk1 , Mapk3 Triple Negative Breast Neoplasms Kras tuberculosis Spp1 tuberous sclerosis Tsc2 tuberous sclerosis 1 Tsc2 tuberous sclerosis 2 Tsc2 type 2 diabetes mellitus Braf , Ksr2 , Mapk1 , Mapk3 uremia Spp1 ureteral obstruction Mapk1 , Mapk3 urethral obstruction Mapk1 urinary bladder cancer Hras , Kras , Spp1 Urinary Bladder Neoplasm Hras , Kras Urinary Calculi Spp1 Urinary Incontinence Mapk1 uterine cancer Braf , Hras , Kras , Map2k1 , Nras uterine carcinosarcoma Hras Uterine Cervical Neoplasms Hras , Kras , Mapk1 uterine fibroid Tsc2 Uterine Neoplasms Kras vascular dementia Mapk1 , Tsc2 Vascular Malformations Braf , Kras , Map2k1 Vascular System Injuries S1pr1 , Spp1 velocardiofacial syndrome Mapk1 ventricular septal defect Braf Ventricular Tachycardia Raf1 visual epilepsy Dusp6 , Spp1 Weissenbacher-Zweymuller syndrome Mapk1 West syndrome Tsc2 withdrawal disorder Mapk1 , Mapk3 , Smad1 Wounds and Injuries Spp1 X-linked epilepsy with variable learning disabilities and behavior disorders Araf X-linked severe congenital neutropenia Araf