C-JUN N-TERMINAL KINASES MAPK SIGNALING PATHWAY (PW:0000313)
Description
The c-Jun N-terminal
kinase pathway (Jnk), known as a stress activated protein kinase pathway
(SAPK), responds to inflammatory cytokines and various stresses and to a lesser
degree to growth factors. Jnk displays the characteristic three-tier core
cascade MAPK architecture. The downstream and effector MAPK tier (here Jnk1-3
represented by Mapk8-10) is activated by phosphorylation of threonine and
tyrosine residues within the conserved TPY motif in the activation loop by dual
specificity kinases of the middle MAP2K tier (here Mkk4 and Mkk7 - Map2k4 and 7,
respectively), in turn activated by the upstream MAP3K tier. Interestingly, 14
out of about 20 Map3ks can activate the Mkk4/7 middle tier. While some are
specific for Jnk pathway, others can activate both Jnk and the p38 MAPK pathway
(the other SAPK), a few activate both Jnk and either Raf/Mek/Erk or Erk5 MAPK
pathways. Some of Map3ks may be activated by small monomeric G-proteins,
particularly by members of the
Rho
family (eg. Rac1 and Cdc42); others by interaction with adapter bound proteins
downstream of cytokine receptors (eg. Traf2). Out of the three Jnk genes of the
MAPK tier, two are ubiquitously expressed (Mapk8/Jnk1 and Mapk9/Jnk2) while
Mapk10/Jnk3 appears to be restricted only to certain tissues. The MAPKs are
serine/threonine kinases with a broad repertoire of targets that include
transcription factors and other nuclear proteins; among the non-nuclear targets
there are members of the intrinsic apoptotic pathway and structural proteins.
Several scaffold proteins mediate the organization of components and regulate the
functioning of the pathway. The family of Jip proteins has been shown to act as
scaffolds for Jnk; the second member might also act as a scaffold for p38 Mapk
cascade. They use their C-terminal regions to interact with kinases of the
first and second tier and N-terminal regions to interact with Mapks of the last
tier (schematically represented in the diagram). Dual specificity phosphatases
such as Dusp8/M3/6, Dusp10/Mkp-5, Dusp16/Mkp-7 and possibly Dusp1/Mkp-1
negatively regulate the pathway but the exact mechanisms thereby this is
accomplished are still elusive. Some Mkp members are inactive in the absence of
the substrate. Binding of the substrate alters the structure of the DUSP (
DSPc
domain ) phosphatase domain, rendering the enzyme catalytically active. Dusp8,
10 and 16 are type III family members that localize both in the cytoplasm and
nucleus. Processes regulated by JNK pathway include proliferation, motility,
inflammatory response, apoptosis; deregulation of the pathway is associated
with several human diseases.
To see the ontology report for annotations, GViewer and
download, click here [click to see related GO term ¿
GO:0007254 and KEGG map ¿
map04010 ...(less)
Pathway Diagram:
Genes in Pathway:
G
Cdc42 cell division cycle 42
ISO RGD
PMID:8910292 PMID:9305638 RGD:2293876 , RGD:2293879
NCBI chr 5:149,555,069...149,593,239
G
Dusp1 dual specificity phosphatase 1
ISO RGD
PMID:17208316 RGD:2293881
NCBI chr10:16,680,478...16,683,275
G
Dusp10 dual specificity phosphatase 10
ISO RGD
PMID:17208316 RGD:2293881
NCBI chr13:95,613,716...95,651,716
G
Dusp16 dual specificity phosphatase 16
ISO RGD
PMID:17208316 RGD:2293881
NCBI chr 4:167,546,780...167,630,173
G
Dusp19 dual specificity phosphatase 19
ISO RGD
PMID:11959862 RGD:2314491
NCBI chr 3:65,538,424...65,554,465
G
Dusp8 dual specificity phosphatase 8
ISO RGD
PMID:17208316 RGD:2293881
NCBI chr 1:197,167,392...197,184,285
G
Map2k4 mitogen activated protein kinase kinase 4
ISO IDA RGD
PMID:17306896 PMID:17064355 PMID:10051439 RGD:2293875 , RGD:2298577 , RGD:2298561
NCBI chr10:50,343,227...50,447,956
G
Map2k7 mitogen activated protein kinase kinase 7
ISO IDA RGD
PMID:17306896 PMID:17064355 PMID:15680699 PMID:10051439 RGD:2293875 , RGD:2298577 , RGD:2298567 , RGD:2298561
NCBI chr12:2,591,312...2,600,534
G
Map3k1 mitogen-activated protein kinase kinase kinase 1
ISO RGD
PMID:9305638 PMID:17306896 RGD:2293879 , RGD:2293875
NCBI chr 2:43,348,572...43,414,706
G
Map3k10 mitogen activated protein kinase kinase kinase 10
ISO RGD
PMID:17306896 RGD:2293875
NCBI chr 1:82,955,784...82,974,084
G
Map3k11 mitogen-activated protein kinase kinase kinase 11
ISO IDA RGD
PMID:8910292 PMID:17064355 PMID:15680699 PMID:17306896 RGD:2293876 , RGD:2298577 , RGD:2298567 , RGD:2293875
NCBI chr 1:202,975,353...202,988,655
G
Map3k12 mitogen activated protein kinase kinase kinase 12
ISO RGD
PMID:17306896 RGD:2293875
NCBI chr 7:133,630,267...133,648,464
G
Map3k13 mitogen-activated protein kinase kinase kinase 13
ISO RGD PMID:17306896 RGD:2293875
NCBI chr11:79,094,087...79,235,181
G
Map3k2 mitogen activated protein kinase kinase kinase 2
ISO RGD
PMID:9305638 PMID:17306896 RGD:2293879 , RGD:2293875
NCBI chr18:23,807,218...23,879,722
G
Map3k20 mitogen-activated protein kinase kinase kinase 20
ISO RGD PMID:17306896 RGD:2293875
NCBI chr 3:57,130,539...57,289,943
G
Map3k21 mitogen-activated protein kinase kinase kinase 21
ISO RGD PMID:17306896 RGD:2293875
NCBI chr19:53,880,032...53,913,560
G
Map3k3 mitogen activated protein kinase kinase kinase 3
ISO RGD
PMID:9305638 PMID:17306896 RGD:2293879 , RGD:2293875
NCBI chr10:91,020,174...91,088,852
G
Map3k4 mitogen activated protein kinase kinase kinase 4
ISO RGD
PMID:9305638 PMID:17306896 RGD:2293879 , RGD:2293875
NCBI chr 1:48,431,801...48,519,358
G
Map3k5 mitogen-activated protein kinase kinase kinase 5
ISO RGD PMID:12215209 PMID:17306896 RGD:2293875 RGD:2296020
NCBI chr 1:14,685,776...14,904,935
G
Map3k7 mitogen activated protein kinase kinase kinase 7
ISO RGD
PMID:17306896 RGD:2293875
NCBI chr 5:46,356,973...46,415,597
G
Map3k9 mitogen-activated protein kinase kinase kinase 9
ISO RGD
PMID:17306896 RGD:2293875
NCBI chr 6:101,423,754...101,488,822
G
Mapk10 mitogen activated protein kinase 10
ISO IDA RGD
PMID:17306896 PMID:15680699 PMID:10051439 RGD:2293875 , RGD:2298567 , RGD:2298561
NCBI chr14:6,497,662...6,790,109
G
Mapk8 mitogen-activated protein kinase 8
ISO IDA RGD
PMID:17306896 PMID:17064355 PMID:10051439 RGD:2293875 , RGD:2298577 , RGD:2298561
NCBI chr16:8,638,897...8,721,960
G
Mapk8ip1 mitogen-activated protein kinase 8 interacting protein 1
ISO IDA RGD
PMID:17726577 PMID:15816852 RGD:2293880 , RGD:1579811
NCBI chr 3:78,355,051...78,372,946
G
Mapk8ip2 mitogen-activated protein kinase 8 interacting protein 2
ISO RGD
PMID:17726577 RGD:2293880
NCBI chr 7:120,526,732...120,536,982
G
Mapk8ip3 mitogen-activated protein kinase 8 interacting protein 3
ISO RGD
PMID:17726577 RGD:2293880
NCBI chr10:13,918,417...13,958,335
G
Mapk9 mitogen-activated protein kinase 9
ISO IDA RGD
PMID:17306896 PMID:17064355 PMID:10051439 RGD:2293875 , RGD:2298577 , RGD:2298561
NCBI chr10:34,169,661...34,211,138
G
Rac1 Rac family small GTPase 1
ISO RGD
PMID:8910292 PMID:9305638 RGD:2293876 , RGD:2293879
NCBI chr12:11,037,028...11,057,251
G
Rapgef1 Rap guanine nucleotide exchange factor 1
IMP RGD
PMID:10811109 RGD:11534984
NCBI chr 3:12,898,349...13,016,234
G
Spp1 secreted phosphoprotein 1
ISO RGD
PMID:15757900 RGD:1581337
NCBI chr14:5,308,885...5,315,120
G
Traf2 Tnf receptor-associated factor 2
ISO RGD
PMID:12215209 RGD:2296020
NCBI chr 3:8,341,950...8,366,609
Pathway Gene Annotations
Disease Annotations Associated with Genes in the c-Jun N-terminal kinases MAPK signaling pathway
Cdc42 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency , Adrenal Gland Neoplasms , Alzheimer's disease , Animal Mammary Neoplasms , bipolar disorder , carcinoma , cleft palate , congenital disorder of glycosylation Ir , Experimental Arthritis , Experimental Mammary Neoplasms , fibrosarcoma , genetic disease , human immunodeficiency virus infectious disease , hyperprolinemia type 2 , microvillus inclusion disease , Necrosis , Neurodevelopmental Disorders , Noonan Like Syndrome , pancreatic cancer , Parkinson's disease 6 , Reperfusion Injury , rhinitis , Spinal Cord Injuries , Takenouchi-Kosaki Syndrome , temporal lobe epilepsy Dusp1 Amyloid Neuropathies , anti-basement membrane glomerulonephritis , arteriosclerosis , atrial heart septal defect 7 , Atrial Septal Defect with Atrioventricular Conduction Defects , breast cancer , Carotid Artery Injuries , colitis , contact dermatitis , COVID-19 , diabetic encephalopathy , endometriosis , Experimental Diabetes Mellitus , Experimental Mammary Neoplasms , Fetal Growth Retardation , glucose intolerance , Huntington's disease , hydrocephalus , Hyperalgesia , hypertension , Intimal Hyperplasia , juvenile rheumatoid arthritis , Left Ventricular Hypertrophy , leishmaniasis , major depressive disorder , Myocardial Ischemia , obesity , otitis media , ovarian carcinoma , pancreatitis , portal hypertension , prostate cancer , psoriasis , Retina Reperfusion Injury , Spinal Cord Injuries , Spine Osteoarthritis , squamous cell carcinoma , transient cerebral ischemia , type 1 diabetes mellitus , urinary bladder cancer , visual epilepsy Dusp10 Experimental Autoimmune Encephalomyelitis , gastrointestinal stromal tumor , Inflammation , Loeys-Dietz syndrome 4 , pancreatitis , parathyroid carcinoma , Usher syndrome Dusp16 autosomal dominant intellectual developmental disorder 6 , Experimental Liver Cirrhosis , transient cerebral ischemia Dusp19 amenorrhea Dusp8 delta beta-thalassemia , developmental and epileptic encephalopathy , early infantile epileptic encephalopathy , immunodeficiency 39 , neuronal ceroid lipofuscinosis , Segawa Syndrome, Autosomal Recessive Map2k4 Brain Death , Breast Neoplasms , Cardiac Arrhythmias , chronic obstructive pulmonary disease , colorectal adenoma , colorectal cancer , gastric adenocarcinoma , hepatocellular carcinoma , invasive ductal carcinoma , laryngeal squamous cell carcinoma , lung adenocarcinoma , lung cancer , lung non-small cell carcinoma , nasopharynx carcinoma , Neoplasm Metastasis , neuroblastoma , Ovarian Neoplasms , ovarian serous carcinoma , pancreatic cancer , papilloma , prostate carcinoma in situ , Prostatic Neoplasms , Retina Reperfusion Injury , Skin Neoplasms , Sleep Deprivation , tongue squamous cell carcinoma , transient cerebral ischemia , urinary bladder cancer Map2k7 breast cancer , Breast Neoplasms , colon adenocarcinoma , colon cancer , congestive heart failure , esophageal carcinoma , Experimental Mammary Neoplasms , familial hemophagocytic lymphohistiocytosis 5 , Fibrosis , larynx cancer , Liver Metastasis , lung adenocarcinoma , lung carcinoma , Lung Neoplasms , lung non-small cell carcinoma , lung squamous cell carcinoma , mucolipidosis type IV , neuroblastoma , Ovarian Neoplasms , pre-malignant neoplasm , prostate cancer , prostate carcinoma in situ , Prostatic Neoplasms , schizophrenia , stomach cancer , urinary bladder cancer 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 Map3k10 Carpenter Syndrome 2 , congenital hypoplastic anemia , craniosynostosis , Diamond-Blackfan anemia , maple syrup urine disease , maturity-onset diabetes of the young type 1 , type 2 diabetes mellitus Map3k11 Aicardi-Goutieres Syndrome 3 , Bardet-Biedl syndrome , glycogen storage disease V , high grade glioma , intellectual disability , Recurrent Infections, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations Map3k12 Neurodevelopmental Disorders Map3k13 Currarino syndrome , gastroesophageal adenocarcinoma Map3k2 autosomal dominant thrombophilia due to protein C deficiency , autosomal recessive limb-girdle muscular dystrophy type 2W , centronuclear myopathy 2 Map3k20 centronuclear myopathy 6 with fiber-type disproportion , genetic disease , split hand-foot malformation , split hand-foot malformation 1 , split hand-foot malformation 5 , Split-Foot Malformation with Mesoaxial Polydactyly Map3k21 gastrointestinal stromal tumor , parathyroid carcinoma Map3k3 Esophageal Neoplasms , verrucous keratotic hemangioma Map3k4 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome , Endometrial Neoplasms , nephroblastoma Map3k5 amyotrophic lateral sclerosis , Arterial Injury , Brain Hypoxia-Ischemia , cardiomyopathy , Carotid Artery Injuries , cerebral infarction , Chemical and Drug Induced Liver Injury , Chronic Cerebral Hypoperfusion , cognitive disorder , congestive heart failure , diabetes mellitus , Experimental Arthritis , Experimental Diabetes Mellitus , Familial Behcet-Like Autoinflammatory Syndrome , Huntington's disease , immunodeficiency 27A , Kidney Reperfusion Injury , melanoma , membranous glomerulonephritis , myocardial infarction , Myocardial Reperfusion Injury , Neointima , Parkinson's disease , perinatal necrotizing enterocolitis , Spinal Cord Injuries , Subarachnoid Hemorrhage , transient cerebral ischemia , Ventilator-Induced Lung Injury , Ventricular Remodeling , visual epilepsy Map3k7 arteriosclerosis , benign hypertensive renal disease , brain edema , Brain Hypoxia-Ischemia , Brain Injuries , brain ischemia , Cachexia , Cardiac Fibrosis , Cardiomegaly , chronic kidney disease , chronic obstructive pulmonary disease , congestive heart failure , coronary artery disease , Diabetic Cardiomyopathies , dilated cardiomyopathy , Embryo Loss , extrahepatic cholestasis , Forney Robinson Pascoe Syndrome , frontometaphyseal dysplasia , frontometaphyseal dysplasia 2 , genetic disease , hypertrophic cardiomyopathy , Liver Reperfusion Injury , Mitral Regurgitation, Conductive Deafness, and Fusion of Cervical Vertebrae and of Carpal and Tarsal Bones , myocardial infarction , Opsismodysplasia , pancreatic ductal carcinoma , prostate cancer , Prostatic Neoplasms , Pulmonary Arterial Hypertension , Stroke , Subarachnoid Hemorrhage , transient cerebral ischemia , Wolff-Parkinson-White syndrome Map3k9 melanoma Mapk10 Alzheimer's disease , congestive heart failure , Generalized Epilepsy , Lennox-Gastaut syndrome , pancreatic adenocarcinoma , prostate cancer Mapk8 abdominal aortic aneurysm , Acute Liver Failure , Acute Otitis Media , alcohol use disorder , Alzheimer's disease , Animal Disease Models , anogenital venereal wart , anti-basement membrane glomerulonephritis , Arenaviridae infectious disease , atopic dermatitis , bacterial pneumonia , brain ischemia , candidiasis , Cardiomegaly , chronic mucocutaneous candidiasis , chronic obstructive pulmonary disease , Cockayne syndrome B , Colonic Neoplasms , colorectal adenocarcinoma , colorectal adenoma , Contrast-Induced Nephropathy , dengue disease , endometriosis , Endotoxemia , extrahepatic cholestasis , Helicobacter Infections , hepatitis , hepatocellular carcinoma , Hyperalgesia , hypertension , Infectious Ectromelia , influenza A , Intestinal Neoplasms , Kuhnt-Junius degeneration , Liver Reperfusion Injury , megacolon , metabolic dysfunction-associated steatotic liver disease , myocardial infarction , Myocardial Reperfusion Injury , Neoplastic Cell Transformation , Oxygen-Induced Retinopathy , pancreatic adenocarcinoma , pancreatic ductal adenocarcinoma , Parkinsonism , pre-malignant neoplasm , Pseudomonas Infections , rectal benign neoplasm , Reperfusion Injury , schizophrenia , Sepsis , steatotic liver disease , Stomach Neoplasms , Stroke , trigeminal neuralgia , type 2 diabetes mellitus Mapk8ip1 congenital disorder of glycosylation type IIc , infantile Refsum disease , intellectual disability , maturity-onset diabetes of the young type 1 , type 2 diabetes mellitus , Zellweger syndrome Mapk8ip2 autism spectrum disorder , chromosome 22q13 duplication syndrome , congenital disorder of glycosylation Ig , intellectual disability , metachromatic leukodystrophy , Phelan-McDermid syndrome Mapk8ip3 autistic disorder , developmental and epileptic encephalopathy 4 , Developmental Disabilities , Developmental Disease , epilepsy , genetic disease , idiopathic generalized epilepsy , NEURODEVELOPMENTAL DISORDER WITH OR WITHOUT VARIABLE BRAIN ABNORMALITIES , Neurodevelopmental Disorders , polycystic ovary syndrome , Reperfusion Injury , short-rib thoracic dysplasia 9 with or without polydactyly , tuberous sclerosis 2 Mapk9 Alzheimer's disease , Animal Disease Models , arteriosclerosis , colorectal cancer , extrahepatic cholestasis , hepatitis , Hyperalgesia , ischemia , Neoplasm Metastasis , pancreatic adenocarcinoma , pre-malignant neoplasm , Prostatic Neoplasms , Reperfusion Injury , trigeminal neuralgia , type 2 diabetes mellitus Rac1 autosomal dominant intellectual developmental disorder 48 , breast cancer , Cardiomegaly , Cardiotoxicity , colon adenocarcinoma , colon adenoma , colorectal adenocarcinoma , colorectal cancer , colorectal carcinoma , congestive heart failure , Developmental Disabilities , Developmental Disease , diabetes mellitus , dilated cardiomyopathy , extrahepatic bile duct adenocarcinoma , gallbladder carcinoma , gastric adenocarcinoma , genetic disease , head and neck squamous cell carcinoma , hepatocellular carcinoma , Left Ventricular Hypertrophy , liver disease , lung adenocarcinoma , lung cancer , melanoma , nasopharynx carcinoma , Neoplasm Metastasis , Neoplastic Cell Transformation , neurodevelopmental disorder with dysmorphic facies and distal limb anomalies , pancreatic adenocarcinoma , pancreatic ductal adenocarcinoma , Sepsis , skin melanoma , stomach cancer , uterine cancer , Ventricular Dysfunction, Left Rapgef1 anti-basement membrane glomerulonephritis , Ehlers-Danlos syndrome classic type 1 , mesangial proliferative glomerulonephritis , Monoclonal B-Cell Lymphocytosis , primary coenzyme Q10 deficiency 7 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 Traf2 Adams-Oliver Syndrome 5 , autosomal dominant intellectual developmental disorder 8 , autosomal dominant nocturnal frontal lobe epilepsy 5 , developmental and epileptic encephalopathy 14 , epilepsy , Joubert syndrome 1 , Kleefstra syndrome 1 , Leigh disease , primary coenzyme Q10 deficiency 7 , Rafiq syndrome , Transplant Rejection , tuberous sclerosis 1
3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency Cdc42 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome Map3k4 46,XY sex reversal 6 Map3k1 abdominal aortic aneurysm Mapk8 acute kidney failure Spp1 Acute Liver Failure Mapk8 Acute Otitis Media Mapk8 Adams-Oliver Syndrome 5 Traf2 adenocarcinoma Spp1 Adrenal Gland Neoplasms Cdc42 Aicardi-Goutieres Syndrome 3 Map3k11 Albuminuria Spp1 alcohol use disorder Mapk8 Alcoholic Liver Diseases Spp1 allergic contact dermatitis Spp1 allergic disease Spp1 Alzheimer's disease Cdc42 , Mapk10 , Mapk8 , Mapk9 amenorrhea Dusp19 Amyloid Neuropathies Dusp1 amyotrophic lateral sclerosis Map3k5 Aneurysm Spp1 Angina Pectoris Spp1 Animal Disease Models Mapk8 , Mapk9 Animal Mammary Neoplasms Cdc42 anogenital venereal wart Mapk8 anti-basement membrane glomerulonephritis Dusp1 , Mapk8 , Rapgef1 , Spp1 aortic aneurysm Spp1 aortic dissection Spp1 Arenaviridae infectious disease Mapk8 Arterial Injury Map3k5 arteriosclerosis Dusp1 , Map3k7 , Mapk9 asbestosis Spp1 atopic dermatitis Mapk8 atrial heart septal defect 7 Dusp1 Atrial Septal Defect with Atrioventricular Conduction Defects Dusp1 autism spectrum disorder Mapk8ip2 autistic disorder Mapk8ip3 autosomal dominant intellectual developmental disorder 48 Rac1 autosomal dominant intellectual developmental disorder 6 Dusp16 autosomal dominant intellectual developmental disorder 8 Traf2 autosomal dominant nocturnal frontal lobe epilepsy 5 Traf2 autosomal dominant polycystic kidney disease Spp1 autosomal dominant thrombophilia due to protein C deficiency Map3k2 autosomal recessive limb-girdle muscular dystrophy type 2W Map3k2 bacterial pneumonia Mapk8 Bardet-Biedl syndrome Map3k11 benign hypertensive renal disease Map3k7 biliary atresia Spp1 bipolar disorder Cdc42 Brain Death Map2k4 brain edema Map3k7 Brain Hypoxia-Ischemia Map3k5 , Map3k7 Brain Injuries Map3k7 brain ischemia Map3k7 , Mapk8 Brain Neoplasms Spp1 breast cancer Dusp1 , Map2k7 , Map3k1 , Rac1 Breast Neoplasms Map2k4 , Map2k7 , Map3k1 , Spp1 Cachexia Map3k7 calcinosis Spp1 candidiasis Mapk8 carcinoma Cdc42 Cardiac Arrhythmias Map2k4 Cardiac Fibrosis Map3k7 Cardiomegaly Map3k7 , Mapk8 , Rac1 , Spp1 cardiomyopathy Map3k5 Cardiotoxicity Rac1 Carotid Artery Injuries Dusp1 , Map3k5 carotid stenosis Spp1 Carpenter Syndrome 2 Map3k10 centronuclear myopathy 2 Map3k2 centronuclear myopathy 6 with fiber-type disproportion Map3k20 Cerebral Hemorrhage Spp1 cerebral infarction Map3k5 Chemical and Drug Induced Liver Injury Map3k5 , Spp1 chromosome 22q13 duplication syndrome Mapk8ip2 Chronic Cerebral Hypoperfusion Map3k5 Chronic Hepatitis C Spp1 chronic kidney disease Map3k7 chronic mucocutaneous candidiasis Mapk8 chronic obstructive pulmonary disease Map2k4 , Map3k7 , Mapk8 cleft palate Cdc42 Cockayne syndrome B Mapk8 cognitive disorder Map3k5 colitis Dusp1 colon adenocarcinoma Map2k7 , Rac1 colon adenoma Rac1 colon cancer Map2k7 Colonic Neoplasms Mapk8 colorectal adenocarcinoma Mapk8 , Rac1 colorectal adenoma Map2k4 , Mapk8 colorectal cancer Map2k4 , Mapk9 , Rac1 colorectal carcinoma Rac1 congenital disorder of glycosylation Ig Mapk8ip2 congenital disorder of glycosylation Ir Cdc42 congenital disorder of glycosylation type IIc Mapk8ip1 congenital hypoplastic anemia Map3k10 congestive heart failure Map2k7 , Map3k5 , Map3k7 , Mapk10 , Rac1 contact dermatitis Dusp1 Contrast-Induced Nephropathy Mapk8 coronary artery disease Map3k7 , Spp1 coronary restenosis Spp1 COVID-19 Dusp1 craniosynostosis Map3k10 Currarino syndrome Map3k13 Cystic, Mucinous, and Serous Neoplasms Spp1 delta beta-thalassemia Dusp8 dengue disease Mapk8 developmental and epileptic encephalopathy Dusp8 developmental and epileptic encephalopathy 14 Traf2 developmental and epileptic encephalopathy 4 Mapk8ip3 Developmental Disabilities Mapk8ip3 , Rac1 Developmental Disease Mapk8ip3 , Rac1 diabetes mellitus Map3k5 , Rac1 Diabetic Cardiomyopathies Map3k7 , Spp1 diabetic encephalopathy Dusp1 Diabetic Nephropathies Spp1 Diamond-Blackfan anemia Map3k10 diffuse gastric cancer Map3k1 dilated cardiomyopathy Map3k7 , Rac1 disease of cellular proliferation Spp1 disorder of sexual development Map3k1 Drug-Related Side Effects and Adverse Reactions Spp1 early infantile epileptic encephalopathy Dusp8 Ehlers-Danlos syndrome classic type 1 Rapgef1 Embryo Loss Map3k7 encephalomyelitis Spp1 Endometrial Neoplasms Map3k4 Endometrioid Carcinomas Spp1 endometriosis Dusp1 , Mapk8 Endotoxemia Mapk8 epilepsy Mapk8ip3 , Traf2 esophageal carcinoma Map2k7 Esophageal Neoplasms Map3k3 esophagus squamous cell carcinoma Map3k1 Experimental Arthritis Cdc42 , Map3k5 Experimental Autoimmune Encephalomyelitis Dusp10 Experimental Autoimmune Neuritis Spp1 Experimental Diabetes Mellitus Dusp1 , Map3k5 , Spp1 Experimental Liver Cirrhosis Dusp16 , Spp1 Experimental Liver Neoplasms Spp1 Experimental Mammary Neoplasms Cdc42 , Dusp1 , Map2k7 , Spp1 Experimental Neoplasms Spp1 extrahepatic bile duct adenocarcinoma Rac1 extrahepatic cholestasis Map3k7 , Mapk8 , Mapk9 Familial Behcet-Like Autoinflammatory Syndrome Map3k5 familial hemophagocytic lymphohistiocytosis 5 Map2k7 Fetal Growth Retardation Dusp1 fibrosarcoma Cdc42 Fibrosis Map2k7 , Spp1 focal segmental glomerulosclerosis Spp1 Foreign-Body Reaction Spp1 Forney Robinson Pascoe Syndrome Map3k7 frontometaphyseal dysplasia Map3k7 frontometaphyseal dysplasia 2 Map3k7 gallbladder carcinoma Rac1 gastric adenocarcinoma Map2k4 , Rac1 gastroesophageal adenocarcinoma Map3k13 gastrointestinal stromal tumor Dusp10 , Map3k21 Generalized Epilepsy Mapk10 genetic disease Cdc42 , Map3k1 , Map3k20 , Map3k7 , Mapk8ip3 , Rac1 glomerulonephritis Spp1 glomerulosclerosis Spp1 glucose intolerance Dusp1 glycogen storage disease V Map3k11 head and neck squamous cell carcinoma Rac1 Hearing Loss Map3k1 heart disease Spp1 heart valve disease Spp1 Helicobacter Infections Mapk8 hepatitis Mapk8 , Mapk9 , Spp1 hepatocellular carcinoma Map2k4 , Map3k1 , Mapk8 , Rac1 , Spp1 Hereditary Neoplastic Syndromes Map3k1 high grade glioma Map3k11 , Spp1 human immunodeficiency virus infectious disease Cdc42 Huntington's disease Dusp1 , Map3k5 hydrocephalus Dusp1 Hyperalgesia Dusp1 , Mapk8 , Mapk9 hyperprolinemia type 2 Cdc42 hypertension Dusp1 , Mapk8 hypertrophic cardiomyopathy Map3k7 idiopathic generalized epilepsy Mapk8ip3 immunodeficiency 27A Map3k5 immunodeficiency 39 Dusp8 infantile Refsum disease Mapk8ip1 Infectious Ectromelia Mapk8 Inflammation Dusp10 , Spp1 influenza A Mapk8 intellectual disability Map3k11 , Mapk8ip1 , Mapk8ip2 Intestinal Neoplasms Mapk8 Intimal Hyperplasia Dusp1 invasive ductal carcinoma Map2k4 ischemia Mapk9 Joubert syndrome 1 Traf2 juvenile rheumatoid arthritis Dusp1 Kidney Calculi Spp1 kidney disease Spp1 kidney failure Spp1 Kidney Reperfusion Injury Map3k5 Kleefstra syndrome 1 Traf2 Kuhnt-Junius degeneration Mapk8 Laryngeal Neoplasms Spp1 laryngeal squamous cell carcinoma Map2k4 larynx cancer Map2k7 Left Ventricular Hypertrophy Dusp1 , Rac1 Leigh disease Traf2 leishmaniasis Dusp1 Lennox-Gastaut syndrome Mapk10 Leukoencephalopathies Spp1 liver cirrhosis Spp1 liver disease Rac1 Liver Metastasis Map2k7 Liver Reperfusion Injury Map3k7 , Mapk8 Loeys-Dietz syndrome 4 Dusp10 lung adenocarcinoma Map2k4 , Map2k7 , Rac1 lung cancer Map2k4 , Rac1 lung carcinoma Map2k7 lung metastasis Map3k1 Lung Neoplasms Map2k7 , Spp1 lung non-small cell carcinoma Map2k4 , Map2k7 , Map3k1 , Spp1 lung squamous cell carcinoma Map2k7 major depressive disorder Dusp1 malaria Spp1 maple syrup urine disease Map3k10 maturity-onset diabetes of the young type 1 Map3k10 , Mapk8ip1 megacolon Mapk8 melanoma Map3k5 , Map3k9 , Rac1 , Spp1 membranous glomerulonephritis Map3k5 mesangial proliferative glomerulonephritis Rapgef1 Mesothelioma Spp1 metabolic dysfunction-associated steatotic liver disease Mapk8 metachromatic leukodystrophy Mapk8ip2 microvillus inclusion disease Cdc42 Mitral Regurgitation, Conductive Deafness, and Fusion of Cervical Vertebrae and of Carpal and Tarsal Bones Map3k7 Monoclonal B-Cell Lymphocytosis Rapgef1 mucolipidosis type IV Map2k7 multiple myeloma Spp1 multiple sclerosis Spp1 myocardial infarction Map3k5 , Map3k7 , Mapk8 , Spp1 Myocardial Ischemia Dusp1 Myocardial Reperfusion Injury Map3k5 , Mapk8 , Spp1 myocarditis Spp1 nasopharynx carcinoma Map2k4 , Rac1 Necrosis Cdc42 Neointima Map3k5 Neoplasm Metastasis Map2k4 , Mapk9 , Rac1 , Spp1 Neoplastic Cell Transformation Mapk8 , Rac1 Neovascularization, Pathologic Spp1 nephroblastoma Map3k4 Nervous System Trauma Spp1 neuroblastoma Map2k4 , Map2k7 neurodevelopmental disorder with dysmorphic facies and distal limb anomalies Rac1 NEURODEVELOPMENTAL DISORDER WITH OR WITHOUT VARIABLE BRAIN ABNORMALITIES Mapk8ip3 Neurodevelopmental Disorders Cdc42 , Map3k1 , Map3k12 , Mapk8ip3 neuronal ceroid lipofuscinosis Dusp8 Noonan Like Syndrome Cdc42 obesity Dusp1 Opsismodysplasia Map3k7 Osteolysis Spp1 otitis media Dusp1 ovarian carcinoma Dusp1 Ovarian Neoplasms Map2k4 , Map2k7 , Map3k1 , Spp1 ovarian serous carcinoma Map2k4 Oxygen-Induced Retinopathy Mapk8 pancreas disease Spp1 pancreatic adenocarcinoma Mapk10 , Mapk8 , Mapk9 , Rac1 pancreatic cancer Cdc42 , Map2k4 , Spp1 pancreatic ductal adenocarcinoma Mapk8 , Rac1 pancreatic ductal carcinoma Map3k7 pancreatitis Dusp1 , Dusp10 papilloma Map2k4 parathyroid carcinoma Dusp10 , Map3k21 Parkinson's disease Map3k5 Parkinson's disease 6 Cdc42 Parkinsonism Mapk8 perinatal necrotizing enterocolitis Map3k5 Phelan-McDermid syndrome Mapk8ip2 Pleural Neoplasms Spp1 pneumonia Spp1 polycystic ovary syndrome Mapk8ip3 portal hypertension Dusp1 pre-malignant neoplasm Map2k7 , Mapk8 , Mapk9 primary coenzyme Q10 deficiency 7 Rapgef1 , Traf2 progressive osseous heteroplasia Spp1 prostate cancer Dusp1 , Map2k7 , Map3k7 , Mapk10 prostate carcinoma Spp1 prostate carcinoma in situ Map2k4 , Map2k7 Prostatic Neoplasms Map2k4 , Map2k7 , Map3k1 , Map3k7 , Mapk9 , Spp1 proteinuria Spp1 Pseudomonas Infections Mapk8 psoriasis Dusp1 Pulmonary Arterial Hypertension Map3k7 pulmonary fibrosis Spp1 radiculopathy Spp1 Rafiq syndrome Traf2 rectal benign neoplasm Mapk8 rectum cancer Map3k1 Recurrent Infections, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations Map3k11 renovascular hypertension Spp1 Reperfusion Injury Cdc42 , Mapk8 , Mapk8ip3 , Mapk9 , Spp1 Retina Reperfusion Injury Dusp1 , Map2k4 rheumatoid arthritis Spp1 rhinitis Cdc42 schizophrenia Map2k7 , Mapk8 scrapie Spp1 Segawa Syndrome, Autosomal Recessive Dusp8 Sepsis Mapk8 , Rac1 short-rib thoracic dysplasia 9 with or without polydactyly Mapk8ip3 skin melanoma Rac1 Skin Neoplasms Map2k4 Sleep Deprivation Map2k4 Spinal Cord Injuries Cdc42 , Dusp1 , Map3k5 , Spp1 Spine Osteoarthritis Dusp1 split hand-foot malformation Map3k20 split hand-foot malformation 1 Map3k20 split hand-foot malformation 5 Map3k20 Split-Foot Malformation with Mesoaxial Polydactyly Map3k20 squamous cell carcinoma Dusp1 steatotic liver disease Mapk8 stomach cancer Map2k7 , Map3k1 , Rac1 Stomach Neoplasms Mapk8 , Spp1 Stroke Map3k7 , Mapk8 Subarachnoid Hemorrhage Map3k5 , Map3k7 syndromic microphthalmia 5 Map3k1 Takenouchi-Kosaki Syndrome Cdc42 temporal lobe epilepsy Cdc42 Thyroid Neoplasms Spp1 tongue squamous cell carcinoma Map2k4 transient cerebral ischemia Dusp1 , Dusp16 , Map2k4 , Map3k5 , Map3k7 Transplant Rejection Traf2 trigeminal neuralgia Mapk8 , Mapk9 tuberculosis Spp1 tuberous sclerosis 1 Traf2 tuberous sclerosis 2 Mapk8ip3 type 1 diabetes mellitus Dusp1 type 2 diabetes mellitus Map3k10 , Mapk8 , Mapk8ip1 , Mapk9 uremia Spp1 urinary bladder cancer Dusp1 , Map2k4 , Map2k7 , Spp1 Urinary Calculi Spp1 Usher syndrome Dusp10 uterine cancer Rac1 Vascular System Injuries Spp1 Ventilator-Induced Lung Injury Map3k5 Ventricular Dysfunction, Left Rac1 Ventricular Remodeling Map3k5 verrucous keratotic hemangioma Map3k3 visual epilepsy Dusp1 , Map3k5 , Spp1 Wolff-Parkinson-White syndrome Map3k7 Wounds and Injuries Spp1 Zellweger syndrome Mapk8ip1
