REELIN SIGNALING PATHWAY (PW:0000388)
Description
The Reelin signaling pathway controls neuronal migration and positioning in central nervous system (CNS) development, as well as synaptic plasticity and memory, operating through different receptors, probably depending on context. Defects in the Reelin gene lead to the reeler phenotype in mice, exhibiting neural positioning defects, and to lissencephaly in humans, with malformation of the cerebrum and cerebellum. Reelin signaling is also thought to be involved in Alzheimer's disease, autism and other neurological disorders. Reelin expression is regulated epigenetically, and transcriptionally by thyroid hormone and, along with NMDA (N-methyl-D-aspartate) receptor subunits, by nuclear proteins CASK, CINAP and Tbr-1. The two best-studied receptors for Reelin are the apolipoprotein E receptor 2 (ApoER2; Lrp8) and the very low density lipoprotein receptor (VLDLR). Competing ligands for these receptors, such as ApoE and RAP, can interfere with Reeling signaling. The secreted glycoprotein Reelin is processed, probably by metalloproteases, into fragments less effective at signaling. Acting as an oligomer, full-length Reelin more effectively binds to the high-affinity receptors ApoER2 and VLDLR, causing clustering. This causes the membrane- and receptor-associated cytosolic Disabled-1 (Dab1) adapter protein to be tyrosine-phosphorylated by src-family kinases such as Fyn. Reelin-induced phosphorylated Dab1 (Dab1-P) stimulates further Src kinase activation, as well as a phosphatidylinositol 3-kinase (PI3K) pathway that activates protein kinase B (Akt) and inhibits glycogen synthase kinase-3beta,which is involved in modulating antiapoptotic, neuroprotective pathways of cell growth and survival. Stimulation of the PI3K pathway also results in reduced phosphorylation of Tau protein, involved in microtubule organization. Dab1-P can alternatively signal through Lis1 (Pafah1b1) and the alpha subunits of the Pafah1b complex to control CNS layer formation. Fine tuning of Reelin signaling may occur via phosphorylation-dependent ubiquitination of Dab1-P, thought to be associated with endocytosis of the reeling signaling complex and receptor recycling. There is evidence that alpha3beta1 integrins (Itga3, Itgb1) are also involved alongside ApoER2s and VLDLRs in transmitting Reelin signals to control neuronal positioning. Cadherin-related neuronal receptors bind Reelin and Src kinases as well, and serve as functional Reelin receptors. In adults, Reelin is thought to mediate synaptic plasticity , memory and learning through Dab1-P, via src kinases and NMDA receptors (e. g. Grin2a, Grin2b), or via PI3K and tetrameric AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate) receptors (e. g. Gria1).
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Pathway Diagram:
Genes in Pathway:
G
Akt1 AKT serine/threonine kinase 1
ISO PID PID:200062
NCBI chr 6:131,713,716...131,735,319
G
Arhgef2 Rho/Rac guanine nucleotide exchange factor 2
ISO PID PID:200062
NCBI chr 2:174,061,126...174,118,355
G
Cbl Cbl proto-oncogene
ISO PID PID:200062
NCBI chr 8:44,487,824...44,571,620
G
Cdk5 cyclin-dependent kinase 5
ISO PID PID:200062
NCBI chr 4:10,754,682...10,760,110
G
Cdk5r1 cyclin-dependent kinase 5 regulatory subunit 1
ISO PID PID:200062
NCBI chr10:65,484,266...65,485,467
G
Crkl CRK like proto-oncogene, adaptor protein
ISO PID PID:200062
NCBI chr11:83,528,788...83,563,214
G
Dab1 DAB adaptor protein 1
TAS ISO PID PMID:12670697 PID:200062, RGD:727518
NCBI chr 5:118,392,953...119,513,625
G
Fyn FYN proto-oncogene, Src family tyrosine kinase
ISO PID PMID:12778121 PID:200062, RGD:2324970
NCBI chr20:42,767,733...42,960,903
G
Gria1 glutamate ionotropic receptor AMPA type subunit 1
TAS RGD
PMID:18237558 RGD:2325284
NCBI chr10:41,210,713...41,527,283
G
Grin2a glutamate ionotropic receptor NMDA type subunit 2A
TAS ISO PID PMID:18237558 PID:200062, RGD:2325284
NCBI chr10:5,629,683...6,053,262
G
Grin2b glutamate ionotropic receptor NMDA type subunit 2B
TAS ISO PID PMID:18237558 PID:200062, RGD:2325284
NCBI chr 4:168,580,824...169,044,110
G
Gsk3b glycogen synthase kinase 3 beta
ISO PID PID:200062
NCBI chr11:62,498,997...62,648,665
G
Itga3 integrin subunit alpha 3
ISO RGD
PMID:15583703 RGD:2325851
NCBI chr10:79,990,160...80,022,206
G
Itgb1 integrin subunit beta 1
ISO PID PMID:15583703 PID:200062, RGD:2325851
NCBI chr19:56,705,123...56,753,199
G
Lrp8 LDL receptor related protein 8
ISO PID PMID:19846452 PID:200062, RGD:2324974
NCBI chr 5:122,563,468...122,635,434
G
Lrpap1 LDL receptor related protein associated protein 1
ISO PID PID:200062
NCBI chr14:75,651,371...75,663,380
G
Map1b microtubule-associated protein 1B
ISO PID PID:200062
NCBI chr 2:30,817,261...30,910,458
G
Map2k7 mitogen activated protein kinase kinase 7
ISO PID PID:200062
NCBI chr12:2,591,312...2,600,534
G
Map3k11 mitogen-activated protein kinase kinase kinase 11
ISO PID PID:200062
NCBI chr 1:202,975,353...202,988,655
G
Mapk8 mitogen-activated protein kinase 8
ISO PID PID:200062
NCBI chr16:8,638,897...8,721,960
G
Mapt microtubule-associated protein tau
ISO PID PID:200062
NCBI chr10:89,138,644...89,236,137
G
Nck2 NCK adaptor protein 2
ISO PID PID:200062
NCBI chr 9:45,713,979...45,840,330
G
Pafah1b1 platelet-activating factor acetylhydrolase 1b, regulatory subunit 1
ISO PID PMID:17330141 PID:200062, RGD:4107040
NCBI chr10:59,533,042...59,591,808
G
Pafah1b2 platelet-activating factor acetylhydrolase 1b, catalytic subunit 2
ISO RGD
PMID:17330141 RGD:4107040
NCBI chr 8:46,260,069...46,312,073
G
Pafah1b3 platelet-activating factor acetylhydrolase 1b, catalytic subunit 3
ISO RGD
PMID:17330141 RGD:4107040
NCBI chr 1:80,881,263...80,883,789
G
Pik3ca phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha
ISO PID PID:200062
NCBI chr 2:115,175,275...115,249,034
G
Pik3r1 phosphoinositide-3-kinase regulatory subunit 1
ISO PID PMID:17167084 PID:200062, RGD:4108507
NCBI chr 2:32,878,942...32,963,668
G
Rap1a RAP1A, member of RAS oncogene family
ISO PID PID:200062
NCBI chr 2:193,208,631...193,286,513
G
Rapgef1 Rap guanine nucleotide exchange factor 1
ISO PID PID:200062
NCBI chr 3:12,898,349...13,016,234
G
Reln reelin
TAS ISO PID PMID:12670697 PID:200062, RGD:727518
NCBI chr 4:12,736,177...13,162,956
G
Src SRC proto-oncogene, non-receptor tyrosine kinase
ISO RGD
PMID:18237558 RGD:2325284
NCBI chr 3:146,091,969...146,139,492
G
Vldlr very low density lipoprotein receptor
TAS ISO PID PMID:12670697 PID:200062, RGD:727518
NCBI chr 1:224,813,539...224,850,400
G
Dab1 DAB adaptor protein 1
TAS RGD
PMID:12670697 RGD:727518
NCBI chr 5:118,392,953...119,513,625
G
Fyn FYN proto-oncogene, Src family tyrosine kinase
ISO RGD
PMID:12778121 RGD:2324970
NCBI chr20:42,767,733...42,960,903
G
Itga3 integrin subunit alpha 3
ISO RGD
PMID:15583703 RGD:2325851
NCBI chr10:79,990,160...80,022,206
G
Itgb1 integrin subunit beta 1
ISO RGD
PMID:15583703 RGD:2325851
NCBI chr19:56,705,123...56,753,199
G
Lrp8 LDL receptor related protein 8
ISO RGD
PMID:19846452 RGD:2324974
NCBI chr 5:122,563,468...122,635,434
G
Pafah1b1 platelet-activating factor acetylhydrolase 1b, regulatory subunit 1
ISO RGD
PMID:17330141 RGD:4107040
NCBI chr10:59,533,042...59,591,808
G
Pafah1b2 platelet-activating factor acetylhydrolase 1b, catalytic subunit 2
ISO RGD
PMID:17330141 RGD:4107040
NCBI chr 8:46,260,069...46,312,073
G
Pafah1b3 platelet-activating factor acetylhydrolase 1b, catalytic subunit 3
ISO RGD
PMID:17330141 RGD:4107040
NCBI chr 1:80,881,263...80,883,789
G
Reln reelin
TAS RGD
PMID:12670697 RGD:727518
NCBI chr 4:12,736,177...13,162,956
G
Src SRC proto-oncogene, non-receptor tyrosine kinase
ISO RGD
PMID:18237558 RGD:2325284
NCBI chr 3:146,091,969...146,139,492
G
Vldlr very low density lipoprotein receptor
ISS RGD
PMID:12764038 RGD:1358468
NCBI chr 1:224,813,539...224,850,400
Pathway Gene Annotations
Disease Annotations Associated with Genes in the Reelin signaling pathway
Akt1 Acute Lung Injury , acute promyelocytic leukemia , adenocarcinoma , Alzheimer's disease , amphetamine abuse , amyotrophic lateral sclerosis , Animal Disease Models , atherosclerosis , autosomal recessive polycystic kidney disease , bipolar disorder , bone osteosarcoma , Brain Injuries , brain ischemia , breast adenocarcinoma , breast cancer , Breast Cancer, Familial , Breast Neoplasms , Calcification of Aortic Valve , cannabis abuse , Carcinogenesis , cardiac arrest , Cardiomegaly , cardiomyopathy , Charcot-Marie-Tooth disease axonal type 2O , chronic myeloid leukemia , colon cancer , colon carcinoma , colorectal cancer , Colorectal Neoplasms , coronary artery disease , Cowden syndrome 6 , Diabetic Cardiomyopathies , diabetic retinopathy , Endometrioid Carcinomas , Endotoxemia , epilepsy , esophageal cancer , esophagus squamous cell carcinoma , Experimental Arthritis , Experimental Colitis , Experimental Diabetes Mellitus , Experimental Mammary Neoplasms , familial adenomatous polyposis , Fibrosis , focal segmental glomerulosclerosis 5 , gastric adenocarcinoma , genetic disease , glioblastoma , head and neck squamous cell carcinoma , hepatocellular carcinoma , Hepatomegaly , Hereditary Neoplastic Syndromes , Hyperplasia , hypertension , Hypertriglyceridemia , impotence , in situ carcinoma , Inflammation , intermediate coronary syndrome , interstitial lung disease 2 , Intervertebral Disc Displacement , invasive ductal carcinoma , Kidney Neoplasms , lung adenocarcinoma , Lung Neoplasms , lung non-small cell carcinoma , lung oat cell carcinoma , lung small cell carcinoma , lung squamous cell carcinoma , Macrocephaly Mesodermal Hamartoma Spectrum , malignant astrocytoma , melanoma , Memory Disorders , Meningeal Neoplasms , meningioma , muscular atrophy , myocardial infarction , Myocardial Reperfusion Injury , Neointima , obesity , osteosarcoma , ovarian cancer , Ovarian Neoplasms , Pain , pancreatic cancer , pancreatic intraductal papillary-mucinous neoplasm , paraplegia , Parkinson's disease , pre-malignant neoplasm , prostate adenocarcinoma , prostate cancer , Prostatic Neoplasms , Proteus syndrome , pulmonary tuberculosis , renal cell carcinoma , Reperfusion Injury , Right Ventricular Hypertrophy , schizophrenia , skin melanoma , Skin Neoplasms , Spinal Cord Injuries , squamous cell carcinoma , Staphylococcal Pneumonia , steatotic liver disease , Stroke , substance-induced psychosis , T-cell non-Hodgkin lymphoma , Thyroid Neoplasms , transitional cell carcinoma , type 2 diabetes mellitus , ureteral obstruction , urinary bladder cancer , Uterine Cervical Neoplasms , Ventilator-Induced Lung Injury , vulva cancer Arhgef2 Charcot-Marie-Tooth disease type 2 , gastrointestinal stromal tumor , immunodeficiency 42 , MHC class II deficiency , microcephaly , myoepithelioma , neurodevelopmental disorder with midbrain and hindbrain malformations , Noonan syndrome 8 , parathyroid carcinoma , severe congenital neutropenia 3 , severe congenital neutropenia 5 Cbl acute myeloid leukemia , B-Cell Chronic Lymphocytic Leukemia , B-lymphoblastic leukemia/lymphoma with hyperdiploidy , Carotid Artery Injuries , CD3epsilon deficiency , Chromosome 11, Partial Trisomy 11q , colorectal cancer , congenital diaphragmatic hernia , congenital disorder of glycosylation Ij , congenital myasthenic syndrome 13 , congestive heart failure , cryptorchidism , Developmental Disabilities , Dilated Cardiomyopathy with Left Ventricular Noncompaction , Dwarfism , Experimental Arthritis , Experimental Leukemia , genetic disease , Growth Disorders , hematologic cancer , Hematologic Neoplasms , hepatocellular carcinoma , hyperglycemia , immunodeficiency 17 , immunodeficiency 18 , immunodeficiency 19 , inflammatory bowel disease 28 , isolated microphthalmia 5 , juvenile myelomonocytic leukemia , long QT syndrome 10 , lung non-small cell carcinoma , Lymphatic Metastasis , lymphopenia , male infertility , malignant ovarian germ cell neoplasm , microcephaly , multiple myeloma , myeloid neoplasm , Myocardial Reperfusion Injury , Neurodevelopmental Disorders , Noonan Like Syndrome , Noonan syndrome , Noonan syndrome 1 , Noonan Syndrome-Like Disorder with or without Juvenile Myelomonocytic Leukemia , osteosarcoma , ovarian germ cell cancer , Peripheral Nerve Injuries , RASopathy , rhabdomyosarcoma , schizophrenia , Stroke , transient cerebral ischemia , type 1 diabetes mellitus , vasculitis Cdk5 Alzheimer's disease , amphetamine abuse , amyotrophic lateral sclerosis , brain ischemia , Cocaine-Related Disorders , COVID-19 , depressive disorder , HIV Encephalitis , Inflammation , lethal congenital glycogen storage disease of heart , lissencephaly 7 with cerebellar hypoplasia , long QT syndrome , middle cerebral artery infarction , Neuralgia , Spinal Cord Reperfusion Injury , tauopathy , transient cerebral ischemia , trigeminal neuralgia , vascular dementia Cdk5r1 Alzheimer's disease , attention deficit hyperactivity disorder , brain disease , Brain Hypoxia-Ischemia , cognitive disorder , depressive disorder , hypothyroidism , Nerve Degeneration , Spinal Cord Reperfusion Injury , trigeminal neuralgia Crkl autistic disorder , Breast Neoplasms , chromosome 22q11.2 deletion syndrome, distal , chromosome 22q11.2 microduplication syndrome , chronic myeloid leukemia , colon carcinoma , DiGeorge syndrome , epilepsy , intellectual disability , invasive ductal carcinoma , lung carcinoma , megacolon , Neurodevelopmental Disorders , ovarian cancer , primary immunodeficiency disease , prostate carcinoma , schizophrenia , skin cancer , velocardiofacial syndrome Dab1 autistic disorder , Peters anomaly , spastic ataxia , spinocerebellar ataxia type 37 , status epilepticus Fyn adult T-cell leukemia/lymphoma , Alzheimer's disease , Burns , Catalepsy , Experimental Liver Cirrhosis , peripheral T-cell lymphoma , primary ovarian insufficiency , pulmonary fibrosis , schizophrenia , Sepsis , skin disease , skin squamous cell carcinoma , Stomach Neoplasms , temporal lobe epilepsy Gria1 alcohol dependence , alcohol use disorder , alcohol withdrawal syndrome , allergic rhinitis , amphetamine abuse , autism spectrum disorder , autistic disorder , Autosomal Dominant Intellectual Developmental Disorder 67 , autosomal recessive intellectual developmental disorder 76 , Central Nervous System Viral Diseases , cocaine abuse , cocaine dependence , Cocaine-Related Disorders , cognitive disorder , epilepsy , familial adenomatous polyposis 1 , Fetal Growth Retardation , genetic disease , hepatic encephalopathy , Hereditary Neoplastic Syndromes , heroin dependence , Hyperalgesia , hyperhomocysteinemia , Hyperkinesis , Hypotension , intellectual disability , learning disability , morphine dependence , morphine withdrawal syndrome , Neurodevelopmental Disorders , non-syndromic intellectual disability , Olfaction Disorders , Reperfusion Injury , schizoaffective disorder , sexual health disorder , status epilepticus , traumatic brain injury , visual epilepsy , withdrawal disorder Grin2a alcohol dependence , Alzheimer's disease , autistic disorder , autosomal dominant intellectual developmental disorder 21 , benign epilepsy with centrotemporal spikes , bipolar disorder , Brain Hypoxia-Ischemia , Central Nervous System Viral Diseases , Charcot-Marie-Tooth disease type 1C , cognitive disorder , colorectal cancer , Colorectal Neoplasms , Developmental Disabilities , epilepsy , Episodic Ataxia Type 9 , familial temporal lobe epilepsy 1 , Fetal Growth Retardation , focal epilepsy , Focal Epilepsy with Speech Disorder and with or without Mental Retardation , GABA aminotransferase deficiency , Generalized Epilepsy , genetic disease , heroin dependence , Huntington's disease , Hyperalgesia , hyperhomocysteinemia , intellectual disability , Landau-Kleffner syndrome , Language Development Disorders , melanoma , MHC class II deficiency , microcephaly , morphine dependence , nasopharynx carcinoma , neonatal abstinence syndrome , Neuralgia , NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, ARTHROGRYPOSIS, AND STRUCTURAL BRAIN ANOMALIES , Neurodevelopmental Disorders , opioid abuse , placental insufficiency , post-traumatic stress disorder , pyridoxine-dependent epilepsy , Reperfusion Injury , schizophrenia , Sepsis , speech disorder , status epilepticus , Tinnitus , transient cerebral ischemia , vascular dementia , withdrawal disorder Grin2b alcohol use disorder , Alzheimer's disease , astigmatism , Ataxia , attention deficit hyperactivity disorder , autism spectrum disorder , autistic disorder , autosomal dominant intellectual developmental disorder , autosomal dominant intellectual developmental disorder 6 , bipolar disorder , Brain Hypoxia-Ischemia , cerebral palsy , chronic obstructive pulmonary disease , cognitive disorder , Craniosynostosis Syndrome, Autosomal Recessive , developmental and epileptic encephalopathy 27 , Developmental Disabilities , Developmental Disease , dystonia , egg allergy , epilepsy , Episodic Ataxia Type 9 , Experimental Diabetes Mellitus , fetal alcohol spectrum disorder , Fetal Growth Retardation , Generalized Epilepsy , genetic disease , Huntington's disease , Hyperalgesia , hyperhomocysteinemia , hypoglycemia , Hypotension , Hypoxia , intellectual disability , Landau-Kleffner syndrome , Nervous System Trauma , Neurodevelopmental Disorders , nicotine dependence , opioid abuse , phenylketonuria , placental insufficiency , Reperfusion Injury , retinitis pigmentosa , schizophrenia , sciatic neuropathy , Sleep Deprivation , temporal lobe epilepsy , transient cerebral ischemia , vascular dementia , withdrawal disorder Gsk3b Aberrant Crypt Foci , acute kidney failure , acute myocardial infarction , Alzheimer's disease , amyotrophic lateral sclerosis , bipolar disorder , Brain Injuries , Breast Neoplasms , Burns , Cardiomegaly , cognitive disorder , colon cancer , Colonic Neoplasms , colorectal adenocarcinoma , congestive heart failure , degenerative disc disease , depressive disorder , diabetic encephalopathy , Diabetic Nephropathies , dilated cardiomyopathy , Drug-Induced Dyskinesia , endometrial carcinoma , Endometrial Neoplasms , Experimental Arthritis , Experimental Mammary Neoplasms , Hearing Loss, Cisplatin-Induced , heart disease , hypertension , Intestinal Neoplasms , Liver Reperfusion Injury , mantle cell lymphoma , middle cerebral artery infarction , Multiple Abnormalities , muscular atrophy , myocardial infarction , Myocardial Reperfusion Injury , Neoplastic Cell Transformation , neuronal ceroid lipofuscinosis 6A , oral squamous cell carcinoma , Ovarian Neoplasms , Parkinson's disease , peritonitis , Poisoning , Prostatic Neoplasms , schizophrenia , sciatic neuropathy , Sepsis , status epilepticus , Subarachnoid Hemorrhage , substance-related disorder , Tachycardia , tauopathy , type 2 diabetes mellitus , urinary bladder cancer , vascular dementia Itga3 anemia , bronchopulmonary dysplasia , Cardiomegaly , Eczema , Experimental Diabetes Mellitus , gastroesophageal reflux disease , genetic disease , glomerulonephritis , Hyperalgesia , Junctional Epidermolysis Bullosa 7, with Interstitial Lung Disease and Nephrotic Syndrome , myocardial infarction , nephrotic syndrome , osteogenesis imperfecta type 1 , Penoscrotal Transposition , phimosis , respiratory failure , trichodontoosseous syndrome Itgb1 calcinosis , cardiomyopathy , congestive heart failure , dilated cardiomyopathy , endometriosis , esophageal atresia , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , Gliosis , glomerulonephritis , Hirschsprung's disease , hydrocephalus , Hyperalgesia , lung non-small cell carcinoma , lung small cell carcinoma , Lymphatic Metastasis , myocardial infarction , Neoplasm Invasiveness , Neoplasm Metastasis , neural tube defect , squamous cell carcinoma , traumatic brain injury Lrp8 Alzheimer's disease , coronary artery disease , dementia , genetic disease , myocardial infarction , Nerve Degeneration , schizophrenia , thrombosis Lrpap1 Alzheimer's disease , dementia , Ellis-Van Creveld syndrome , membranous glomerulonephritis , Metabolic Syndrome , myocardial infarction , Myopia 23, Autosomal Recessive , Osteoarthritis, Experimental , prostate cancer Map1b autism spectrum disorder , Autosomal Dominant Nonsyndromic Deafness 83 , Brain Injuries , Developmental Disabilities , epilepsy , genetic disease , hypothyroidism , Macrocephaly , Neurodevelopmental Disorders , periventricular nodular heterotopia , Periventricular Nodular Heterotopia 9 , Spinal Cord Injuries , visual epilepsy 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 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 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 Mapt Alzheimer's disease , Animal Disease Models , anxiety disorder , Ataxia , atrial fibrillation , Brain Hypoxia-Ischemia , brain ischemia , breast cancer , cardiomyopathy , cognitive disorder , Cognitive Dysfunction , Creutzfeldt-Jakob disease , dementia , Drug-Induced Dyskinesia , epilepsy , essential tremor , Experimental Autoimmune Encephalomyelitis , Experimental Diabetes Mellitus , frontotemporal dementia , genetic disease , Gliosis , hepatocellular carcinoma , intellectual disability , Iron Overload , Koolen de Vries syndrome , late onset Parkinson's disease , learning disability , Memory Disorders , middle cerebral artery infarction , multiple system atrophy , Multiple System Atrophy (MSA) with Orthostatic Hypotension , neurodegenerative disease , obesity , Osteoarthritis, Hip , Parkinson's disease , Parkinsonism , Pick's disease , Premature Aging , progressive supranuclear palsy , Progressive Supranuclear Palsy Atypical , prostate cancer , Psychomotor Agitation , respiratory failure , semantic dementia , Shy-Drager Syndrome , Spinal Cord Injuries , Splenomegaly , Sporadic Creutzfeldt-Jakob Disease , syndromic intellectual disability , tauopathy , temporal lobe epilepsy , traumatic brain injury , vascular dementia , Weight Gain , Weight Loss Nck2 Albuminuria , Alzheimer's disease , nephrotic syndrome , proteinuria Pafah1b1 Abnormal Cortical Gyration , Carcinogenesis , chromosome 15q11.2 deletion syndrome , Classical Lissencephalies and Subcortical Band Heterotopias , developmental coordination disorder , genetic disease , hepatocellular carcinoma , intellectual disability , learning disability , lissencephaly , lissencephaly 1 , Miller-Dieker lissencephaly syndrome , Nervous System Malformations , NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, ARTHROGRYPOSIS, AND STRUCTURAL BRAIN ANOMALIES , schizophrenia , subcortical band heterotopia , visual epilepsy Pafah1b2 CD3epsilon deficiency , Chromosome 11, Partial Trisomy 11q , Dwarfism , immunodeficiency 17 , immunodeficiency 18 , immunodeficiency 19 , inflammatory bowel disease 28 , intellectual disability , isolated microphthalmia 5 , lymphoma , nephronophthisis 15 , RASopathy Pafah1b3 autism spectrum disorder , autosomal dominant intellectual developmental disorder 45 , Carpenter Syndrome 2 , congenital hypoplastic anemia , craniosynostosis , Diamond-Blackfan anemia , INTELLECTUAL DEVELOPMENTAL DISORDER WITH PERSISTENCE OF FETAL HEMOGLOBIN , maple syrup urine disease , schizophrenia Pik3ca adenocarcinoma , adenoid cystic carcinoma , adrenocortical carcinoma , Agenesis of Corpus Callosum , autosomal recessive polycystic kidney disease , Bannayan-Riley-Ruvalcaba syndrome , basal cell carcinoma , Brain Neoplasms , breast adenocarcinoma , breast angiosarcoma , breast cancer , Breast Cancer, Familial , breast carcinoma , Breast Neoplasms , Cardiovascular Abnormalities , Cerebral Cavernous Malformation 4 , CLAPO Syndrome , CLOVES syndrome , colon adenocarcinoma , colon carcinoma , colorectal cancer , colorectal carcinoma , Colorectal Neoplasms , complex cortical dysplasia with other brain malformations , Cowden syndrome , Cowden syndrome 5 , Currarino syndrome , cutaneous Paget's disease , Developmental Disabilities , Diabetic Cardiomyopathies , diaphragmatic eventration , diffuse large B-cell lymphoma , disease of cellular proliferation , Disease Progression , Down syndrome , endometrial carcinoma , Endometrial Neoplasms , epidermal nevus , esophageal cancer , esophageal carcinoma , esophagus adenocarcinoma , estrogen-receptor positive breast cancer , Facial Asymmetry , familial multiple nevi flammei , gallbladder cancer , gallbladder carcinoma , gastric adenocarcinoma , Gastrointestinal Neoplasms , genetic disease , glioblastoma , glycogen storage disease II , Growth Disorders , head and neck cancer , Head and Neck Neoplasms , head and neck squamous cell carcinoma , Hemimegalencephaly , hepatocellular carcinoma , Hereditary Neoplastic Syndromes , high grade glioma , Hyperplasia , Hypertelorism , keratoacanthoma , Klippel-Trenaunay syndrome , liver cancer , lung adenocarcinoma , lung cancer , lung carcinoma , Lung Neoplasms , lung non-small cell carcinoma , lung oat cell carcinoma , lung small cell carcinoma , lung squamous cell carcinoma , Lymphatic Metastasis , Macrocephaly , medulloblastoma , Megalencephaly - Cutis Marmorata Telangiectatica Congenita , Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome , Megalodactyly , melanoma , Mouth Neoplasms , multiple myeloma , Nasopharyngeal Neoplasms , Neoplasm Metastasis , neuroblastoma , NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, ARTHROGRYPOSIS, AND STRUCTURAL BRAIN ANOMALIES , non-Hodgkin lymphoma , Noonan syndrome 8 , ovarian cancer , Ovarian Neoplasms , ovarian serous cystadenocarcinoma , pancreatic adenocarcinoma , papillary renal cell carcinoma , Paraproteinemias , Penile Neoplasms , plasma cell neoplasm , polycystic kidney disease , prostate adenocarcinoma , prostate cancer , Prostatic Neoplasms , PTEN hamartoma tumor syndrome , rectal benign neoplasm , renal cell carcinoma , Renal Cell Carcinoma 1 , rosette-forming glioneuronal tumor , sarcoma , seborrheic keratosis , skin melanoma , Sporadic Papillary Renal Cell Carcinoma , squamous cell carcinoma , stomach cancer , Stomach Neoplasms , Stroke , Thyroid Neoplasms , transitional cell carcinoma , urinary bladder cancer , uterine cancer , uterine carcinosarcoma , Uterine Cervical Neoplasms , Vascular Malformations , Ventricular Dysfunction, Left , Weight Gain Pik3r1 agammaglobulinemia 7 , Alzheimer's disease , Animal Mammary Neoplasms , astroblastoma , Brain Neoplasms , Breast Neoplasms , Burkitt lymphoma , carcinoma , CLOVES syndrome , Colonic Neoplasms , colorectal cancer , Colorectal Neoplasms , disease of cellular proliferation , endometrial adenocarcinoma , endometrial cancer , endometrial carcinoma , Experimental Diabetes Mellitus , Experimental Mammary Neoplasms , genetic disease , glioblastoma , glucose intolerance , hepatocellular carcinoma , hypertension , hypoglycemia , immunodeficiency 36 , Insulin Resistance , lung adenocarcinoma , lung small cell carcinoma , Megalencephaly - Cutis Marmorata Telangiectatica Congenita , melanoma , Nematode Infections , Neurodevelopmental Disorders , obesity , osteoarthritis , Ovarian Neoplasms , portal hypertension , primary immunodeficiency disease , prostate cancer , Prostatic Neoplasms , renal cell carcinoma , Reperfusion Injury , rheumatoid arthritis , Septic Peritonitis , SHORT syndrome , skin melanoma , Smith-Kingsmore Syndrome , type 2 diabetes mellitus , uterine cancer , uterine carcinosarcoma , Vascular Malformations , vitiligo , X-linked agammaglobulinemia Rap1a Hyperoxaluria , Myocardial Reperfusion Injury Rapgef1 anti-basement membrane glomerulonephritis , Ehlers-Danlos syndrome classic type 1 , mesangial proliferative glomerulonephritis , Monoclonal B-Cell Lymphocytosis , primary coenzyme Q10 deficiency 7 Reln Alzheimer's disease , Ataxia , autism spectrum disorder , autistic disorder , benign epilepsy with centrotemporal spikes , bipolar disorder , depressive disorder , Down syndrome , epilepsy , Experimental Liver Cirrhosis , familial temporal lobe epilepsy 1 , familial temporal lobe epilepsy 7 , genetic disease , hypothyroidism , intellectual disability , lissencephaly , liver cirrhosis , major depressive disorder , middle cerebral artery infarction , Nervous System Malformations , Norman-Roberts syndrome , pleomorphic xanthoastrocytoma , Sacroiliac Arthritis , schizophrenia , status epilepticus , temporal lobe epilepsy Src Aicardi-Goutieres Syndrome 5 , autosomal recessive polycystic kidney disease , brain ischemia , Breast Neoplasms , Cardiomegaly , colitis , colon adenocarcinoma , colon cancer , colon carcinoma , Colonic Neoplasms , colorectal cancer , colorectal carcinoma , Colorectal Neoplasms , disease of cellular proliferation , ductal carcinoma in situ , focal epilepsy , Hearing Loss, Noise-Induced , hepatocellular carcinoma , hypertension , Kidney Reperfusion Injury , Liver Metastasis , lung adenocarcinoma , lung metastasis , lung squamous cell carcinoma , Lymphatic Metastasis , myelofibrosis , nasopharynx carcinoma , Neoplasm Invasiveness , Neoplasm Metastasis , Neuralgia , pancreatic acinar cell adenocarcinoma , Parkinsonism , prostate cancer , Reperfusion Injury , sensorineural hearing loss , status epilepticus , stomach cancer , Stroke , Thrombocytopenia 6 , Trauma and Stressor Related Disorders , type 2 diabetes mellitus , urinary bladder cancer , Williams-Beuren syndrome Vldlr age related macular degeneration 1 , Alzheimer's disease , amenorrhea , arteriosclerosis , autistic disorder , Cardiomegaly , cerebellar ataxia, mental retardation and dysequlibrium syndrome , Cerebellar Ataxia, Mental Retardation, and Dysequilibrium Syndrome 1 , cerebellar hypoplasia , chromosome 9p deletion syndrome , dementia , Experimental Diabetes Mellitus , familial hyperlipidemia , focal segmental glomerulosclerosis , genetic disease , Hypercholesterolemia , Hypertriglyceridemia , intellectual disability , metabolic dysfunction-associated steatotic liver disease , microcephaly , nephrotic syndrome , Nervous System Malformations , obesity
abdominal aortic aneurysm Mapk8 Aberrant Crypt Foci Gsk3b Abnormal Cortical Gyration Pafah1b1 acute kidney failure Gsk3b Acute Liver Failure Mapk8 Acute Lung Injury Akt1 acute myeloid leukemia Cbl acute myocardial infarction Gsk3b Acute Otitis Media Mapk8 acute promyelocytic leukemia Akt1 adenocarcinoma Akt1 , Pik3ca adenoid cystic carcinoma Pik3ca adrenocortical carcinoma Pik3ca adult T-cell leukemia/lymphoma Fyn agammaglobulinemia 7 Pik3r1 age related macular degeneration 1 Vldlr Agenesis of Corpus Callosum Pik3ca Aicardi-Goutieres Syndrome 3 Map3k11 Aicardi-Goutieres Syndrome 5 Src Albuminuria Nck2 alcohol dependence Gria1 , Grin2a alcohol use disorder Gria1 , Grin2b , Mapk8 alcohol withdrawal syndrome Gria1 allergic rhinitis Gria1 Alzheimer's disease Akt1 , Cdk5 , Cdk5r1 , Fyn , Grin2a , Grin2b , Gsk3b , Lrp8 , Lrpap1 , Mapk8 , Mapt , Nck2 , Pik3r1 , Reln , Vldlr amenorrhea Vldlr amphetamine abuse Akt1 , Cdk5 , Gria1 amyotrophic lateral sclerosis Akt1 , Cdk5 , Gsk3b anemia Itga3 Animal Disease Models Akt1 , Mapk8 , Mapt Animal Mammary Neoplasms Pik3r1 anogenital venereal wart Mapk8 anti-basement membrane glomerulonephritis Mapk8 , Rapgef1 anxiety disorder Mapt Arenaviridae infectious disease Mapk8 arteriosclerosis Vldlr astigmatism Grin2b astroblastoma Pik3r1 Ataxia Grin2b , Mapt , Reln atherosclerosis Akt1 atopic dermatitis Mapk8 atrial fibrillation Mapt attention deficit hyperactivity disorder Cdk5r1 , Grin2b autism spectrum disorder Gria1 , Grin2b , Map1b , Pafah1b3 , Reln autistic disorder Crkl , Dab1 , Gria1 , Grin2a , Grin2b , Reln , Vldlr autosomal dominant intellectual developmental disorder Grin2b autosomal dominant intellectual developmental disorder 21 Grin2a autosomal dominant intellectual developmental disorder 45 Pafah1b3 autosomal dominant intellectual developmental disorder 6 Grin2b Autosomal Dominant Intellectual Developmental Disorder 67 Gria1 Autosomal Dominant Nonsyndromic Deafness 83 Map1b autosomal recessive intellectual developmental disorder 76 Gria1 autosomal recessive polycystic kidney disease Akt1 , Pik3ca , Src B-Cell Chronic Lymphocytic Leukemia Cbl B-lymphoblastic leukemia/lymphoma with hyperdiploidy Cbl bacterial pneumonia Mapk8 Bannayan-Riley-Ruvalcaba syndrome Pik3ca Bardet-Biedl syndrome Map3k11 basal cell carcinoma Pik3ca benign epilepsy with centrotemporal spikes Grin2a , Reln bipolar disorder Akt1 , Grin2a , Grin2b , Gsk3b , Reln bone osteosarcoma Akt1 brain disease Cdk5r1 Brain Hypoxia-Ischemia Cdk5r1 , Grin2a , Grin2b , Mapt Brain Injuries Akt1 , Gsk3b , Map1b brain ischemia Akt1 , Cdk5 , Mapk8 , Mapt , Src Brain Neoplasms Pik3ca , Pik3r1 breast adenocarcinoma Akt1 , Pik3ca breast angiosarcoma Pik3ca breast cancer Akt1 , Map2k7 , Mapt , Pik3ca Breast Cancer, Familial Akt1 , Pik3ca breast carcinoma Pik3ca Breast Neoplasms Akt1 , Crkl , Gsk3b , Map2k7 , Pik3ca , Pik3r1 , Src bronchopulmonary dysplasia Itga3 Burkitt lymphoma Pik3r1 Burns Fyn , Gsk3b Calcification of Aortic Valve Akt1 calcinosis Itgb1 candidiasis Mapk8 cannabis abuse Akt1 Carcinogenesis Akt1 , Pafah1b1 carcinoma Pik3r1 cardiac arrest Akt1 Cardiomegaly Akt1 , Gsk3b , Itga3 , Mapk8 , Src , Vldlr cardiomyopathy Akt1 , Itgb1 , Mapt Cardiovascular Abnormalities Pik3ca Carotid Artery Injuries Cbl Carpenter Syndrome 2 Pafah1b3 Catalepsy Fyn CD3epsilon deficiency Cbl , Pafah1b2 Central Nervous System Viral Diseases Gria1 , Grin2a cerebellar ataxia, mental retardation and dysequlibrium syndrome Vldlr Cerebellar Ataxia, Mental Retardation, and Dysequilibrium Syndrome 1 Vldlr cerebellar hypoplasia Vldlr Cerebral Cavernous Malformation 4 Pik3ca cerebral palsy Grin2b Charcot-Marie-Tooth disease axonal type 2O Akt1 Charcot-Marie-Tooth disease type 1C Grin2a Charcot-Marie-Tooth disease type 2 Arhgef2 Chromosome 11, Partial Trisomy 11q Cbl , Pafah1b2 chromosome 15q11.2 deletion syndrome Pafah1b1 chromosome 22q11.2 deletion syndrome, distal Crkl chromosome 22q11.2 microduplication syndrome Crkl chromosome 9p deletion syndrome Vldlr chronic mucocutaneous candidiasis Mapk8 chronic myeloid leukemia Akt1 , Crkl chronic obstructive pulmonary disease Grin2b , Mapk8 CLAPO Syndrome Pik3ca Classical Lissencephalies and Subcortical Band Heterotopias Pafah1b1 CLOVES syndrome Pik3ca , Pik3r1 cocaine abuse Gria1 cocaine dependence Gria1 Cocaine-Related Disorders Cdk5 , Gria1 Cockayne syndrome B Mapk8 cognitive disorder Cdk5r1 , Gria1 , Grin2a , Grin2b , Gsk3b , Mapt Cognitive Dysfunction Mapt colitis Src colon adenocarcinoma Map2k7 , Pik3ca , Src colon cancer Akt1 , Gsk3b , Map2k7 , Src colon carcinoma Akt1 , Crkl , Pik3ca , Src Colonic Neoplasms Gsk3b , Mapk8 , Pik3r1 , Src colorectal adenocarcinoma Gsk3b , Mapk8 colorectal adenoma Mapk8 colorectal cancer Akt1 , Cbl , Grin2a , Pik3ca , Pik3r1 , Src colorectal carcinoma Pik3ca , Src Colorectal Neoplasms Akt1 , Grin2a , Pik3ca , Pik3r1 , Src complex cortical dysplasia with other brain malformations Pik3ca congenital diaphragmatic hernia Cbl congenital disorder of glycosylation Ij Cbl congenital hypoplastic anemia Pafah1b3 congenital myasthenic syndrome 13 Cbl congestive heart failure Cbl , Gsk3b , Itgb1 , Map2k7 Contrast-Induced Nephropathy Mapk8 coronary artery disease Akt1 , Lrp8 COVID-19 Cdk5 Cowden syndrome Pik3ca Cowden syndrome 5 Pik3ca Cowden syndrome 6 Akt1 craniosynostosis Pafah1b3 Craniosynostosis Syndrome, Autosomal Recessive Grin2b Creutzfeldt-Jakob disease Mapt cryptorchidism Cbl Currarino syndrome Pik3ca cutaneous Paget's disease Pik3ca degenerative disc disease Gsk3b dementia Lrp8 , Lrpap1 , Mapt , Vldlr dengue disease Mapk8 depressive disorder Cdk5 , Cdk5r1 , Gsk3b , Reln developmental and epileptic encephalopathy 27 Grin2b developmental coordination disorder Pafah1b1 Developmental Disabilities Cbl , Grin2a , Grin2b , Map1b , Pik3ca Developmental Disease Grin2b Diabetic Cardiomyopathies Akt1 , Pik3ca diabetic encephalopathy Gsk3b Diabetic Nephropathies Gsk3b diabetic retinopathy Akt1 Diamond-Blackfan anemia Pafah1b3 diaphragmatic eventration Pik3ca diffuse large B-cell lymphoma Pik3ca DiGeorge syndrome Crkl dilated cardiomyopathy Gsk3b , Itgb1 Dilated Cardiomyopathy with Left Ventricular Noncompaction Cbl disease of cellular proliferation Pik3ca , Pik3r1 , Src Disease Progression Pik3ca Down syndrome Pik3ca , Reln Drug-Induced Dyskinesia Gsk3b , Mapt ductal carcinoma in situ Src Dwarfism Cbl , Pafah1b2 dystonia Grin2b Eczema Itga3 egg allergy Grin2b Ehlers-Danlos syndrome classic type 1 Rapgef1 Ellis-Van Creveld syndrome Lrpap1 endometrial adenocarcinoma Pik3r1 endometrial cancer Pik3r1 endometrial carcinoma Gsk3b , Pik3ca , Pik3r1 Endometrial Neoplasms Gsk3b , Pik3ca Endometrioid Carcinomas Akt1 endometriosis Itgb1 , Mapk8 Endotoxemia Akt1 , Mapk8 epidermal nevus Pik3ca epilepsy Akt1 , Crkl , Gria1 , Grin2a , Grin2b , Map1b , Mapt , Reln Episodic Ataxia Type 9 Grin2a , Grin2b esophageal atresia Itgb1 esophageal cancer Akt1 , Pik3ca esophageal carcinoma Map2k7 , Pik3ca esophagus adenocarcinoma Pik3ca esophagus squamous cell carcinoma Akt1 essential tremor Mapt estrogen-receptor positive breast cancer Pik3ca Experimental Arthritis Akt1 , Cbl , Gsk3b Experimental Autoimmune Encephalomyelitis Mapt Experimental Colitis Akt1 Experimental Diabetes Mellitus Akt1 , Grin2b , Itga3 , Itgb1 , Mapt , Pik3r1 , Vldlr Experimental Leukemia Cbl Experimental Liver Cirrhosis Fyn , Itgb1 , Reln Experimental Mammary Neoplasms Akt1 , Gsk3b , Map2k7 , Pik3r1 extrahepatic cholestasis Mapk8 Facial Asymmetry Pik3ca familial adenomatous polyposis Akt1 familial adenomatous polyposis 1 Gria1 familial hemophagocytic lymphohistiocytosis 5 Map2k7 familial hyperlipidemia Vldlr familial multiple nevi flammei Pik3ca familial temporal lobe epilepsy 1 Grin2a , Reln familial temporal lobe epilepsy 7 Reln fetal alcohol spectrum disorder Grin2b Fetal Growth Retardation Gria1 , Grin2a , Grin2b Fibrosis Akt1 , Map2k7 focal epilepsy Grin2a , Src Focal Epilepsy with Speech Disorder and with or without Mental Retardation Grin2a focal segmental glomerulosclerosis Vldlr focal segmental glomerulosclerosis 5 Akt1 frontotemporal dementia Mapt GABA aminotransferase deficiency Grin2a gallbladder cancer Pik3ca gallbladder carcinoma Pik3ca gastric adenocarcinoma Akt1 , Pik3ca gastroesophageal reflux disease Itga3 Gastrointestinal Neoplasms Pik3ca gastrointestinal stromal tumor Arhgef2 Generalized Epilepsy Grin2a , Grin2b genetic disease Akt1 , Cbl , Gria1 , Grin2a , Grin2b , Itga3 , Lrp8 , Map1b , Mapt , Pafah1b1 , Pik3ca , Pik3r1 , Reln , Vldlr glioblastoma Akt1 , Pik3ca , Pik3r1 Gliosis Itgb1 , Mapt glomerulonephritis Itga3 , Itgb1 glucose intolerance Pik3r1 glycogen storage disease II Pik3ca glycogen storage disease V Map3k11 Growth Disorders Cbl , Pik3ca head and neck cancer Pik3ca Head and Neck Neoplasms Pik3ca head and neck squamous cell carcinoma Akt1 , Pik3ca Hearing Loss, Cisplatin-Induced Gsk3b Hearing Loss, Noise-Induced Src heart disease Gsk3b Helicobacter Infections Mapk8 hematologic cancer Cbl Hematologic Neoplasms Cbl Hemimegalencephaly Pik3ca hepatic encephalopathy Gria1 hepatitis Mapk8 hepatocellular carcinoma Akt1 , Cbl , Mapk8 , Mapt , Pafah1b1 , Pik3ca , Pik3r1 , Src Hepatomegaly Akt1 Hereditary Neoplastic Syndromes Akt1 , Gria1 , Pik3ca heroin dependence Gria1 , Grin2a high grade glioma Map3k11 , Pik3ca Hirschsprung's disease Itgb1 HIV Encephalitis Cdk5 Huntington's disease Grin2a , Grin2b hydrocephalus Itgb1 Hyperalgesia Gria1 , Grin2a , Grin2b , Itga3 , Itgb1 , Mapk8 Hypercholesterolemia Vldlr hyperglycemia Cbl hyperhomocysteinemia Gria1 , Grin2a , Grin2b Hyperkinesis Gria1 Hyperoxaluria Rap1a Hyperplasia Akt1 , Pik3ca Hypertelorism Pik3ca hypertension Akt1 , Gsk3b , Mapk8 , Pik3r1 , Src Hypertriglyceridemia Akt1 , Vldlr hypoglycemia Grin2b , Pik3r1 Hypotension Gria1 , Grin2b hypothyroidism Cdk5r1 , Map1b , Reln Hypoxia Grin2b immunodeficiency 17 Cbl , Pafah1b2 immunodeficiency 18 Cbl , Pafah1b2 immunodeficiency 19 Cbl , Pafah1b2 immunodeficiency 36 Pik3r1 immunodeficiency 42 Arhgef2 impotence Akt1 in situ carcinoma Akt1 Infectious Ectromelia Mapk8 Inflammation Akt1 , Cdk5 inflammatory bowel disease 28 Cbl , Pafah1b2 influenza A Mapk8 Insulin Resistance Pik3r1 INTELLECTUAL DEVELOPMENTAL DISORDER WITH PERSISTENCE OF FETAL HEMOGLOBIN Pafah1b3 intellectual disability Crkl , Gria1 , Grin2a , Grin2b , Map3k11 , Mapt , Pafah1b1 , Pafah1b2 , Reln , Vldlr intermediate coronary syndrome Akt1 interstitial lung disease 2 Akt1 Intervertebral Disc Displacement Akt1 Intestinal Neoplasms Gsk3b , Mapk8 invasive ductal carcinoma Akt1 , Crkl Iron Overload Mapt isolated microphthalmia 5 Cbl , Pafah1b2 Junctional Epidermolysis Bullosa 7, with Interstitial Lung Disease and Nephrotic Syndrome Itga3 juvenile myelomonocytic leukemia Cbl keratoacanthoma Pik3ca Kidney Neoplasms Akt1 Kidney Reperfusion Injury Src Klippel-Trenaunay syndrome Pik3ca Koolen de Vries syndrome Mapt Kuhnt-Junius degeneration Mapk8 Landau-Kleffner syndrome Grin2a , Grin2b Language Development Disorders Grin2a larynx cancer Map2k7 late onset Parkinson's disease Mapt learning disability Gria1 , Mapt , Pafah1b1 lethal congenital glycogen storage disease of heart Cdk5 lissencephaly Pafah1b1 , Reln lissencephaly 1 Pafah1b1 lissencephaly 7 with cerebellar hypoplasia Cdk5 liver cancer Pik3ca liver cirrhosis Reln Liver Metastasis Map2k7 , Src Liver Reperfusion Injury Gsk3b , Mapk8 long QT syndrome Cdk5 long QT syndrome 10 Cbl lung adenocarcinoma Akt1 , Map2k7 , Pik3ca , Pik3r1 , Src lung cancer Pik3ca lung carcinoma Crkl , Map2k7 , Pik3ca lung metastasis Src Lung Neoplasms Akt1 , Map2k7 , Pik3ca lung non-small cell carcinoma Akt1 , Cbl , Itgb1 , Map2k7 , Pik3ca lung oat cell carcinoma Akt1 , Pik3ca lung small cell carcinoma Akt1 , Itgb1 , Pik3ca , Pik3r1 lung squamous cell carcinoma Akt1 , Map2k7 , Pik3ca , Src Lymphatic Metastasis Cbl , Itgb1 , Pik3ca , Src lymphoma Pafah1b2 lymphopenia Cbl Macrocephaly Map1b , Pik3ca Macrocephaly Mesodermal Hamartoma Spectrum Akt1 major depressive disorder Reln male infertility Cbl malignant astrocytoma Akt1 malignant ovarian germ cell neoplasm Cbl mantle cell lymphoma Gsk3b maple syrup urine disease Pafah1b3 medulloblastoma Pik3ca megacolon Crkl , Mapk8 Megalencephaly - Cutis Marmorata Telangiectatica Congenita Pik3ca , Pik3r1 Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome Pik3ca Megalodactyly Pik3ca melanoma Akt1 , Grin2a , Pik3ca , Pik3r1 membranous glomerulonephritis Lrpap1 Memory Disorders Akt1 , Mapt Meningeal Neoplasms Akt1 meningioma Akt1 mesangial proliferative glomerulonephritis Rapgef1 metabolic dysfunction-associated steatotic liver disease Mapk8 , Vldlr Metabolic Syndrome Lrpap1 MHC class II deficiency Arhgef2 , Grin2a microcephaly Arhgef2 , Cbl , Grin2a , Vldlr middle cerebral artery infarction Cdk5 , Gsk3b , Mapt , Reln Miller-Dieker lissencephaly syndrome Pafah1b1 Monoclonal B-Cell Lymphocytosis Rapgef1 morphine dependence Gria1 , Grin2a morphine withdrawal syndrome Gria1 Mouth Neoplasms Pik3ca mucolipidosis type IV Map2k7 Multiple Abnormalities Gsk3b multiple myeloma Cbl , Pik3ca multiple system atrophy Mapt Multiple System Atrophy (MSA) with Orthostatic Hypotension Mapt muscular atrophy Akt1 , Gsk3b myelofibrosis Src myeloid neoplasm Cbl myocardial infarction Akt1 , Gsk3b , Itga3 , Itgb1 , Lrp8 , Lrpap1 , Mapk8 Myocardial Reperfusion Injury Akt1 , Cbl , Gsk3b , Mapk8 , Rap1a myoepithelioma Arhgef2 Myopia 23, Autosomal Recessive Lrpap1 Nasopharyngeal Neoplasms Pik3ca nasopharynx carcinoma Grin2a , Src Nematode Infections Pik3r1 Neointima Akt1 neonatal abstinence syndrome Grin2a Neoplasm Invasiveness Itgb1 , Src Neoplasm Metastasis Itgb1 , Pik3ca , Src Neoplastic Cell Transformation Gsk3b , Mapk8 nephronophthisis 15 Pafah1b2 nephrotic syndrome Itga3 , Nck2 , Vldlr Nerve Degeneration Cdk5r1 , Lrp8 Nervous System Malformations Pafah1b1 , Reln , Vldlr Nervous System Trauma Grin2b neural tube defect Itgb1 Neuralgia Cdk5 , Grin2a , Src neuroblastoma Map2k7 , Pik3ca neurodegenerative disease Mapt NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, ARTHROGRYPOSIS, AND STRUCTURAL BRAIN ANOMALIES Grin2a , Pafah1b1 , Pik3ca neurodevelopmental disorder with midbrain and hindbrain malformations Arhgef2 Neurodevelopmental Disorders Cbl , Crkl , Gria1 , Grin2a , Grin2b , Map1b , Pik3r1 neuronal ceroid lipofuscinosis 6A Gsk3b nicotine dependence Grin2b non-Hodgkin lymphoma Pik3ca non-syndromic intellectual disability Gria1 Noonan Like Syndrome Cbl Noonan syndrome Cbl Noonan syndrome 1 Cbl Noonan syndrome 8 Arhgef2 , Pik3ca Noonan Syndrome-Like Disorder with or without Juvenile Myelomonocytic Leukemia Cbl Norman-Roberts syndrome Reln obesity Akt1 , Mapt , Pik3r1 , Vldlr Olfaction Disorders Gria1 opioid abuse Grin2a , Grin2b oral squamous cell carcinoma Gsk3b osteoarthritis Pik3r1 Osteoarthritis, Experimental Lrpap1 Osteoarthritis, Hip Mapt osteogenesis imperfecta type 1 Itga3 osteosarcoma Akt1 , Cbl ovarian cancer Akt1 , Crkl , Pik3ca ovarian germ cell cancer Cbl Ovarian Neoplasms Akt1 , Gsk3b , Map2k7 , Pik3ca , Pik3r1 ovarian serous cystadenocarcinoma Pik3ca Oxygen-Induced Retinopathy Mapk8 Pain Akt1 pancreatic acinar cell adenocarcinoma Src pancreatic adenocarcinoma Mapk8 , Pik3ca pancreatic cancer Akt1 pancreatic ductal adenocarcinoma Mapk8 pancreatic intraductal papillary-mucinous neoplasm Akt1 papillary renal cell carcinoma Pik3ca paraplegia Akt1 Paraproteinemias Pik3ca parathyroid carcinoma Arhgef2 Parkinson's disease Akt1 , Gsk3b , Mapt Parkinsonism Mapk8 , Mapt , Src Penile Neoplasms Pik3ca Penoscrotal Transposition Itga3 Peripheral Nerve Injuries Cbl peripheral T-cell lymphoma Fyn peritonitis Gsk3b periventricular nodular heterotopia Map1b Periventricular Nodular Heterotopia 9 Map1b Peters anomaly Dab1 phenylketonuria Grin2b phimosis Itga3 Pick's disease Mapt placental insufficiency Grin2a , Grin2b plasma cell neoplasm Pik3ca pleomorphic xanthoastrocytoma Reln Poisoning Gsk3b polycystic kidney disease Pik3ca portal hypertension Pik3r1 post-traumatic stress disorder Grin2a pre-malignant neoplasm Akt1 , Map2k7 , Mapk8 Premature Aging Mapt primary coenzyme Q10 deficiency 7 Rapgef1 primary immunodeficiency disease Crkl , Pik3r1 primary ovarian insufficiency Fyn progressive supranuclear palsy Mapt Progressive Supranuclear Palsy Atypical Mapt prostate adenocarcinoma Akt1 , Pik3ca prostate cancer Akt1 , Lrpap1 , Map2k7 , Mapt , Pik3ca , Pik3r1 , Src prostate carcinoma Crkl prostate carcinoma in situ Map2k7 Prostatic Neoplasms Akt1 , Gsk3b , Map2k7 , Pik3ca , Pik3r1 proteinuria Nck2 Proteus syndrome Akt1 Pseudomonas Infections Mapk8 Psychomotor Agitation Mapt PTEN hamartoma tumor syndrome Pik3ca pulmonary fibrosis Fyn pulmonary tuberculosis Akt1 pyridoxine-dependent epilepsy Grin2a RASopathy Cbl , Pafah1b2 rectal benign neoplasm Mapk8 , Pik3ca Recurrent Infections, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations Map3k11 renal cell carcinoma Akt1 , Pik3ca , Pik3r1 Renal Cell Carcinoma 1 Pik3ca Reperfusion Injury Akt1 , Gria1 , Grin2a , Grin2b , Mapk8 , Pik3r1 , Src respiratory failure Itga3 , Mapt retinitis pigmentosa Grin2b rhabdomyosarcoma Cbl rheumatoid arthritis Pik3r1 Right Ventricular Hypertrophy Akt1 rosette-forming glioneuronal tumor Pik3ca Sacroiliac Arthritis Reln sarcoma Pik3ca schizoaffective disorder Gria1 schizophrenia Akt1 , Cbl , Crkl , Fyn , Grin2a , Grin2b , Gsk3b , Lrp8 , Map2k7 , Mapk8 , Pafah1b1 , Pafah1b3 , Reln sciatic neuropathy Grin2b , Gsk3b seborrheic keratosis Pik3ca semantic dementia Mapt sensorineural hearing loss Src Sepsis Fyn , Grin2a , Gsk3b , Mapk8 Septic Peritonitis Pik3r1 severe congenital neutropenia 3 Arhgef2 severe congenital neutropenia 5 Arhgef2 sexual health disorder Gria1 SHORT syndrome Pik3r1 Shy-Drager Syndrome Mapt skin cancer Crkl skin disease Fyn skin melanoma Akt1 , Pik3ca , Pik3r1 Skin Neoplasms Akt1 skin squamous cell carcinoma Fyn Sleep Deprivation Grin2b Smith-Kingsmore Syndrome Pik3r1 spastic ataxia Dab1 speech disorder Grin2a Spinal Cord Injuries Akt1 , Map1b , Mapt Spinal Cord Reperfusion Injury Cdk5 , Cdk5r1 spinocerebellar ataxia type 37 Dab1 Splenomegaly Mapt Sporadic Creutzfeldt-Jakob Disease Mapt Sporadic Papillary Renal Cell Carcinoma Pik3ca squamous cell carcinoma Akt1 , Itgb1 , Pik3ca Staphylococcal Pneumonia Akt1 status epilepticus Dab1 , Gria1 , Grin2a , Gsk3b , Reln , Src steatotic liver disease Akt1 , Mapk8 stomach cancer Map2k7 , Pik3ca , Src Stomach Neoplasms Fyn , Mapk8 , Pik3ca Stroke Akt1 , Cbl , Mapk8 , Pik3ca , Src Subarachnoid Hemorrhage Gsk3b subcortical band heterotopia Pafah1b1 substance-induced psychosis Akt1 substance-related disorder Gsk3b syndromic intellectual disability Mapt T-cell non-Hodgkin lymphoma Akt1 Tachycardia Gsk3b tauopathy Cdk5 , Gsk3b , Mapt temporal lobe epilepsy Fyn , Grin2b , Mapt , Reln Thrombocytopenia 6 Src thrombosis Lrp8 Thyroid Neoplasms Akt1 , Pik3ca Tinnitus Grin2a transient cerebral ischemia Cbl , Cdk5 , Grin2a , Grin2b transitional cell carcinoma Akt1 , Pik3ca Trauma and Stressor Related Disorders Src traumatic brain injury Gria1 , Itgb1 , Mapt trichodontoosseous syndrome Itga3 trigeminal neuralgia Cdk5 , Cdk5r1 , Mapk8 type 1 diabetes mellitus Cbl type 2 diabetes mellitus Akt1 , Gsk3b , Mapk8 , Pik3r1 , Src ureteral obstruction Akt1 urinary bladder cancer Akt1 , Gsk3b , Map2k7 , Pik3ca , Src uterine cancer Pik3ca , Pik3r1 uterine carcinosarcoma Pik3ca , Pik3r1 Uterine Cervical Neoplasms Akt1 , Pik3ca vascular dementia Cdk5 , Grin2a , Grin2b , Gsk3b , Mapt Vascular Malformations Pik3ca , Pik3r1 vasculitis Cbl velocardiofacial syndrome Crkl Ventilator-Induced Lung Injury Akt1 Ventricular Dysfunction, Left Pik3ca visual epilepsy Gria1 , Map1b , Pafah1b1 vitiligo Pik3r1 vulva cancer Akt1 Weight Gain Mapt , Pik3ca Weight Loss Mapt Williams-Beuren syndrome Src withdrawal disorder Gria1 , Grin2a , Grin2b X-linked agammaglobulinemia Pik3r1
