SCATTER FACTOR/HEPATOCYTE GROWTH FACTOR SIGNALING PATHWAY (PW:0000578)
Description
Scatter factor/hepatocyte growth factor (Sf/Hgf) signaling pathway is a central regulator of invasive growth, a complex multi-step program required for embryonic and organ development as well as wound healing in adult cells but also characteristic of cancer progression. Met - the receptor for Hgf has first been identified in the 1980s as on oncogene. Both the ligand and the receptor are heterodimers that result from the processing of precursor molecules. Binding of Hgf leads to receptor autophosphorylation of tyrosine residues within the activation loop of the kinase domain and of two C-terminal located tyrosines that are essential for the interaction of receptor with adapters such as Grb2 and Gab1 or with downstream signaling molecules. Gab1 - a member of the Gab family of adapters that couple signaling via many receptors to their downstream effectors - appears to be the only Gab member to interact with Met and the main adapter protein for the pathway. Interestingly, it is in response to Hgf and not other growth factors that Gab1 experiences prolonged phosphorylation. Receptor phosphorylated Gab1 can recruit a number of other proteins; several, including the p85alpha regulatory subunit of PI3K (Pik3r1), Plcg1 or Shc1 can also be recruited by the activated receptor. Gab1 can interact with Grb2 raising the possibility that Gab1 is recruited to the receptor either directly or indirectly. Activated Gab1 also recruits Ptpn11 (known as Shp2); Ptpn11 or Grb2-Sos via Ras can activate the Raf/Mek/Erk MAPK signaling pathway. Pik3r1 recruitment directly by Met or indirectly through Gab1 triggers the PI3K-Akt pathway and the survival response. Hgf signaling can also transduce to members of Ras superfamily such as Rap1 via Gab1-dependent activation of Crkl adapter. Phosphorylation of a serine residue within the juxtamembrane domain of the receptor downregulates the kinase activity; within the same domain, a tyrosine residue is recognized by Cbl ubiquitin ligase. Ubiquitination of the receptor leads to its endocytosis and degradation. Overexpression or mutations in ligand and/or receptor resulting in deregulated signaling have been linked to numerous forms of cancers including bladder, breast, colorectal, kidney, lung, ovarian and prostate as well as melanoma and brain tumors.
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Pathway Diagram:
Genes in Pathway:
G
Cbl Cbl proto-oncogene
ISO RGD
PMID:18175071 RGD:2299174
NCBI chr 8:53,384,656...53,468,067
G
Crkl CRK like proto-oncogene, adaptor protein
ISO RGD
PMID:14685170 RGD:1642762
NCBI chr11:97,033,033...97,067,457
G
Gab1 GRB2-associated binding protein 1
ISO RGD
PMID:18175071 PMID:14685170 RGD:2299174 , RGD:1642762
NCBI chr19:44,035,693...44,143,617
G
Grb2 growth factor receptor bound protein 2
ISO RGD
PMID:18175071 PMID:14685170 RGD:2299174 , RGD:1642762
NCBI chr10:101,380,354...101,448,138
G
Hgf hepatocyte growth factor
ISO RGD
PMID:18175071 PMID:14685170 RGD:2299174 , RGD:1642762
NCBI chr 4:19,628,902...19,700,467
G
Met MET proto-oncogene, receptor tyrosine kinase
ISO IMP RGD
PMID:14685170 PMID:17065554 PMID:18175071 RGD:1642762 , RGD:2317513 , RGD:2299174
NCBI chr 4:46,756,823...46,864,041
G
Pik3r1 phosphoinositide-3-kinase regulatory subunit 1
ISO RGD
PMID:14685170 PMID:18175071 RGD:1642762 , RGD:2299174
NCBI chr 2:34,612,946...34,697,660
G
Plcg1 phospholipase C, gamma 1
ISO RGD
PMID:14685170 PMID:18175071 RGD:1642762 , RGD:2299174
NCBI chr 3:169,805,299...169,836,040
G
Ptpn11 protein tyrosine phosphatase, non-receptor type 11
ISO RGD
PMID:14685170 PMID:18175071 RGD:1642762 , RGD:2299174
NCBI chr12:41,026,079...41,085,577
G
Shc1 SHC adaptor protein 1
ISO RGD
PMID:14685170 PMID:18175071 RGD:1642762 , RGD:2299174
NCBI chr 2:177,135,649...177,147,257
G
Src SRC proto-oncogene, non-receptor tyrosine kinase
ISO RGD
PMID:14685170 PMID:18175071 RGD:1642762 , RGD:2299174
NCBI chr 3:166,511,616...166,559,463
G
Met MET proto-oncogene, receptor tyrosine kinase
ISO RGD
PMID:19506583 PMID:20519133 PMID:20951313 PMID:21277552 RGD:5490965 , RGD:5133241 , RGD:5133242 , RGD:5133243
NCBI chr 4:46,756,823...46,864,041
Pathway Gene Annotations
Disease Annotations Associated with Genes in the scatter factor/hepatocyte growth factor signaling pathway
Cbl acute myeloid leukemia , B-Cell Chronic Lymphocytic Leukemia , B-lymphoblastic leukemia/lymphoma with hyperdiploidy , Carotid Artery Injuries , CD3epsilon deficiency , chromosome 11 partial duplication syndrome , 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 , Familial Atrial Fibrillation 14 , genetic disease , Growth Disorders , Hematologic Neoplasms , hepatocellular carcinoma , Hereditary Neoplastic Syndromes , 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 , transient cerebral ischemia , type 1 diabetes mellitus , vasculitis 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 Gab1 autosomal recessive nonsyndromic deafness 26 , Experimental Liver Cirrhosis , Helicobacter Infections , polycystic ovary syndrome Grb2 breast cancer , endometrial carcinoma , prostate adenocarcinoma , prostate cancer Hgf Acute Liver Failure , acute myeloid leukemia , adult-onset Still's disease , angle-closure glaucoma , arteriosclerosis , atrial fibrillation , autism spectrum disorder , autosomal recessive nonsyndromic deafness 39 , Barrett's esophagus , biliary tract benign neoplasm , bilirubin metabolic disorder , brain infarction , breast cancer , cardiomyopathy , carotid artery disease , central nervous system disease , CHARGE syndrome , cholangiocarcinoma , cholesteatoma , Choroidal Neovascularization , Chronic Hepatitis , Copper-Overload Cirrhosis , coronary artery disease , COVID-19 , dermatomyositis , diabetes mellitus , Diabetic Nephropathies , diabetic neuropathy , diabetic retinopathy , epilepsy , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , Experimental Liver Neoplasms , Experimental Melanoma , Experimental Neoplasms , Facial Nerve Injuries , Gallbladder Neoplasms , graft-versus-host disease , Hearing Loss , hepatocellular carcinoma , high grade glioma , hypertension , interstitial lung disease , inverted papilloma , keratoconus , Lentigo , limb ischemia , liver cirrhosis , Liver Injury , Liver Neoplasms , localized scleroderma , malignant astrocytoma , malignant mesothelioma , meningioma , Metabolic Syndrome , myocardial infarction , Myocardial Ischemia , myopia , myositis , Nasal Polyps , Neoplasm Invasiveness , Neoplasm Metastasis , neovascular inflammatory vitreoretinopathy , Nerve Sheath Neoplasms , neuroblastoma , obesity , Optic Nerve Injuries , Pain , pancreatic cancer , pancreatitis , Parkinson's disease , Penetrating Wounds , pleomorphic xanthoastrocytoma , polymyositis , Polyomavirus Infections , pulmonary fibrosis , Reperfusion Injury , Retina Reperfusion Injury , retinal degeneration , Retinal Neovascularization , retinitis pigmentosa , retinopathy of prematurity , rheumatoid arthritis , Rhinosinusitis , schizophrenia , sciatic neuropathy , Skin Neoplasms , Spinal Cord Injuries , squamous cell carcinoma , Stroke , systemic scleroderma , thrombosis , tongue squamous cell carcinoma , vascular disease , vitiligo , Wounds and Injuries Met acute kidney failure , Acute Liver Failure , acute myeloid leukemia , adenocarcinoma , Animal Disease Models , Animal Hepatitis , arteriosclerosis , autism spectrum disorder , autistic disorder , autosomal recessive nonsyndromic deafness 97 , Bile Duct Neoplasms , breast cancer , breast carcinoma , Carcinogenesis , carcinoma , Cardiomegaly , childhood hepatocellular carcinoma , cholangiocarcinoma , Chronic Hepatitis , cognitive disorder , colorectal cancer , Colorectal Neoplasms , congenital diaphragmatic hernia , congenital disorder of glycosylation Ii , Copper-Overload Cirrhosis , cystic fibrosis , Cystic, Mucinous, and Serous Neoplasms , distal arthrogryposis type 1 , Distal Arthrogryposis Type 11 , distal arthrogryposis type 1A , Endometrial Neoplasms , Esophageal Neoplasms , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , Experimental Liver Neoplasms , Gallbladder Neoplasms , gastrinoma , gestational diabetes , Gilles de la Tourette syndrome , glioblastoma , hepatoblastoma , hepatocellular carcinoma , Hepatomegaly , Hereditary Neoplastic Syndromes , high grade glioma , Hodgkin's lymphoma , Hypertriglyceridemia , intellectual disability , invasive ductal carcinoma , Kidney Neoplasms , large cell carcinoma , liver benign neoplasm , lung carcinoma , Lung Neoplasms , lung non-small cell carcinoma , lung squamous cell carcinoma , Lymphatic Metastasis , lymphedema , malignant astrocytoma , malignant mesothelioma , melanoma , metabolic dysfunction-associated steatotic liver disease , multiple myeloma , Nasal Polyps , Neoplasm Invasiveness , Neoplasm Metastasis , Nerve Sheath Neoplasms , neuroblastoma , nonsyndromic deafness , oral squamous cell carcinoma , Osteofibrous Dysplasia , osteosarcoma , ovarian cancer , Ovarian Neoplasms , pancreatic cancer , pancreatic ductal carcinoma , pancreatitis , papillary renal cell carcinoma , periodontitis , pleomorphic xanthoastrocytoma , primary biliary cholangitis , prostate carcinoma , Prostatic Neoplasms , renal cell carcinoma , Renal Cell Carcinoma 1 , Reperfusion Injury , sarcoma , schizophrenia , sinusitis , Spinal Cord Injuries , squamous cell carcinoma , steatotic liver disease , Stomach Neoplasms , tongue squamous cell carcinoma Pik3r1 agammaglobulinemia 7 , Alzheimer's disease , Animal Mammary Neoplasms , astroblastoma , Breast Neoplasms , Burkitt lymphoma , carcinoma , CLOVES syndrome , Colonic Neoplasms , colorectal cancer , endometrial adenocarcinoma , endometrial cancer , endometrial carcinoma , Experimental Diabetes Mellitus , Experimental Mammary Neoplasms , genetic disease , glucose intolerance , hepatocellular carcinoma , hypertension , hypoglycemia , immunodeficiency 14 , immunodeficiency 36 , Insulin Resistance , lung adenocarcinoma , lung small cell carcinoma , Megalencephaly - Cutis Marmorata Telangiectatica Congenita , 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 , Smith-Kingsmore Syndrome , type 2 diabetes mellitus , Vascular Malformations , vitiligo , X-linked agammaglobulinemia Plcg1 acute myocardial infarction , adult T-cell leukemia/lymphoma , Alzheimer's disease , angiosarcoma , breast cancer , breast carcinoma , colon cancer , colorectal cancer , Experimental Diabetes Mellitus , familial adenomatous polyposis , focal epilepsy , hepatocellular carcinoma , hereditary breast ovarian cancer syndrome , IMMUNE DYSREGULATION, AUTOIMMUNITY, AND AUTOINFLAMMATION , laryngeal squamous cell carcinoma , lung adenocarcinoma , lung cancer , lung non-small cell carcinoma , Memory Disorders , oral squamous cell carcinoma , polycystic kidney disease , primary cutaneous T-cell non-Hodgkin lymphoma , Sezary's disease Ptpn11 acute myeloid leukemia , acute promyelocytic leukemia , adenocarcinoma , anogenital venereal wart , aortic valve stenosis , arrhythmogenic right ventricular cardiomyopathy , atrial heart septal defect 1 , atrophic gastritis , autism spectrum disorder , Cafe-au-Lait Spots , cancer , cardiofaciocutaneous syndrome , cardiomyopathy , Cardiovascular Abnormalities , Carotid Artery Injuries , cervical cancer , chondroma , Costello syndrome , craniosynostosis , Developmental Disabilities , dilated cardiomyopathy , disease of metabolism , Duane retraction syndrome , Dwarfism , embryonal rhabdomyosarcoma , Experimental Leukemia , Failure to Thrive , Fetal Growth Retardation , Funnel Chest , genetic disease , glaucoma , Haemophilus Infections , Helicobacter Infections , hemorrhagic disease , hepatocellular adenoma , hereditary multiple exostoses , Hereditary Neoplastic Syndromes , high grade glioma , Hydrops Fetalis , hypertrophic cardiomyopathy , idiopathic scoliosis , influenza , intellectual disability , juvenile myelomonocytic leukemia , learning disability , Leber congenital amaurosis , leukemia , long QT syndrome , long QT syndrome 1 , lung squamous cell carcinoma , lymphoma , malignant astrocytoma , metachondromatosis , microcephaly , myeloid leukemia associated with Down Syndrome , neuroblastoma , Neurodevelopmental Disorders , neurofibroma , neurofibromatosis-Noonan syndrome , Noonan Like Syndrome , Noonan syndrome , Noonan syndrome 1 , Noonan syndrome 3 , Noonan syndrome with multiple lentigines , Noonan syndrome with multiple lentigines 1 , Noonan Syndrome-Like Disorder with or without Juvenile Myelomonocytic Leukemia , Ollier disease , Osteochondroma , patent ductus arteriosus , patent foramen ovale , ptosis , RASopathy , Right Ventricular Hypertrophy , Romano-Ward Syndrome , scoliosis , spermatogenic failure 57 , squamous cell carcinoma , Staphylococcal Pneumonia , stomach cancer , strabismus , T-cell acute lymphoblastic leukemia , tetralogy of Fallot , thrombocytopenia , tricuspid valve insufficiency , Ventricular Premature Complexes , Ventricular Tachycardia , Werner syndrome 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 Src Aicardi-Goutieres Syndrome 5 , autosomal recessive polycystic kidney disease , brain ischemia , Breast Neoplasms , Cardiomegaly , Chronic Cerebral Hypoperfusion , colitis , colon adenocarcinoma , colon cancer , colon carcinoma , Colonic Neoplasms , colorectal cancer , colorectal carcinoma , Colorectal Neoplasms , congenital disorder of glycosylation , ductal carcinoma in situ , focal epilepsy , Hearing Loss, Noise-Induced , hepatocellular carcinoma , Hyperalgesia , hypertension , Kidney Reperfusion Injury , lesion of sciatic nerve , Liver Metastasis , lung adenocarcinoma , lung metastasis , lung squamous cell carcinoma , Lymphatic Metastasis , morphine withdrawal syndrome , 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
acute kidney failure Met Acute Liver Failure Hgf , Met acute myeloid leukemia Cbl , Hgf , Met , Ptpn11 acute myocardial infarction Plcg1 acute promyelocytic leukemia Ptpn11 adenocarcinoma Met , Ptpn11 adult T-cell leukemia/lymphoma Plcg1 adult-onset Still's disease Hgf agammaglobulinemia 7 Pik3r1 Aicardi-Goutieres Syndrome 5 Src Albuminuria Shc1 Alzheimer's disease Pik3r1 , Plcg1 , Shc1 amyotrophic lateral sclerosis type 1 Shc1 angiosarcoma Plcg1 angle-closure glaucoma Hgf Animal Disease Models Met Animal Hepatitis Met Animal Mammary Neoplasms Pik3r1 anogenital venereal wart Ptpn11 aortic valve stenosis Ptpn11 arrhythmogenic right ventricular cardiomyopathy Ptpn11 arteriosclerosis Hgf , Met astroblastoma Pik3r1 atrial fibrillation Hgf atrial heart septal defect 1 Ptpn11 atrophic gastritis Ptpn11 autism spectrum disorder Hgf , Met , Ptpn11 autistic disorder Crkl , Met autosomal recessive nonsyndromic deafness 26 Gab1 autosomal recessive nonsyndromic deafness 39 Hgf autosomal recessive nonsyndromic deafness 97 Met autosomal recessive polycystic kidney disease Src B-Cell Chronic Lymphocytic Leukemia Cbl B-lymphoblastic leukemia/lymphoma with hyperdiploidy Cbl Barrett's esophagus Hgf Bile Duct Neoplasms Met biliary tract benign neoplasm Hgf bilirubin metabolic disorder Hgf brain infarction Hgf brain ischemia Src breast cancer Grb2 , Hgf , Met , Plcg1 breast carcinoma Met , Plcg1 Breast Neoplasms Crkl , Pik3r1 , Shc1 , Src Burkitt lymphoma Pik3r1 Cafe-au-Lait Spots Ptpn11 cancer Ptpn11 Carcinogenesis Met carcinoma Met , Pik3r1 cardiofaciocutaneous syndrome Ptpn11 Cardiomegaly Met , Shc1 , Src cardiomyopathy Hgf , Ptpn11 Cardiovascular Abnormalities Ptpn11 carotid artery disease Hgf Carotid Artery Injuries Cbl , Ptpn11 CD3epsilon deficiency Cbl central nervous system disease Hgf cervical cancer Ptpn11 Charcot-Marie-Tooth disease type 2 Shc1 CHARGE syndrome Hgf Chemical and Drug Induced Liver Injury Shc1 childhood hepatocellular carcinoma Met cholangiocarcinoma Hgf , Met cholesteatoma Hgf chondroma Ptpn11 Choroidal Neovascularization Hgf chromosome 11 partial duplication syndrome Cbl chromosome 22q11.2 deletion syndrome, distal Crkl chromosome 22q11.2 microduplication syndrome Crkl Chronic Cerebral Hypoperfusion Src Chronic Hepatitis Hgf , Met , Shc1 chronic myeloid leukemia Crkl CLOVES syndrome Pik3r1 cognitive disorder Met colitis Src colon adenocarcinoma Src colon cancer Plcg1 , Src colon carcinoma Crkl , Src Colonic Neoplasms Pik3r1 , Src colorectal cancer Cbl , Met , Pik3r1 , Plcg1 , Src colorectal carcinoma Src Colorectal Neoplasms Met , Src congenital diaphragmatic hernia Cbl , Met congenital disorder of glycosylation Src congenital disorder of glycosylation Ii Met congenital disorder of glycosylation Ij Cbl congenital myasthenic syndrome 13 Cbl congestive heart failure Cbl Copper-Overload Cirrhosis Hgf , Met coronary artery disease Hgf Costello syndrome Ptpn11 COVID-19 Hgf craniosynostosis Ptpn11 cryptorchidism Cbl cystic fibrosis Met Cystic, Mucinous, and Serous Neoplasms Met dermatomyositis Hgf Developmental Disabilities Cbl , Ptpn11 diabetes mellitus Hgf Diabetic Nephropathies Hgf diabetic neuropathy Hgf diabetic retinopathy Hgf DiGeorge syndrome Crkl dilated cardiomyopathy Ptpn11 Dilated Cardiomyopathy with Left Ventricular Noncompaction Cbl disease of metabolism Ptpn11 distal arthrogryposis type 1 Met Distal Arthrogryposis Type 11 Met distal arthrogryposis type 1A Met Duane retraction syndrome Ptpn11 ductal carcinoma in situ Src Dwarfism Cbl , Ptpn11 embryonal rhabdomyosarcoma Ptpn11 endometrial adenocarcinoma Pik3r1 endometrial cancer Pik3r1 endometrial carcinoma Grb2 , Pik3r1 Endometrial Neoplasms Met epilepsy Crkl , Hgf Esophageal Neoplasms Met Experimental Arthritis Cbl Experimental Diabetes Mellitus Hgf , Met , Pik3r1 , Plcg1 Experimental Leukemia Cbl , Ptpn11 Experimental Liver Cirrhosis Gab1 , Hgf , Met Experimental Liver Neoplasms Hgf , Met Experimental Mammary Neoplasms Pik3r1 Experimental Melanoma Hgf Experimental Neoplasms Hgf Facial Nerve Injuries Hgf Failure to Thrive Ptpn11 familial adenomatous polyposis Plcg1 Familial Atrial Fibrillation 14 Cbl familial hyperlipidemia Shc1 Fetal Growth Retardation Ptpn11 focal epilepsy Plcg1 , Src Funnel Chest Ptpn11 Gallbladder Neoplasms Hgf , Met gastrinoma Met gastrointestinal stromal tumor Shc1 genetic disease Cbl , Pik3r1 , Ptpn11 gestational diabetes Met Gilles de la Tourette syndrome Met glaucoma Ptpn11 glioblastoma Met glomerulosclerosis Shc1 glucose intolerance Pik3r1 graft-versus-host disease Hgf Growth Disorders Cbl Haemophilus Infections Ptpn11 Hearing Loss Hgf Hearing Loss, Noise-Induced Src Helicobacter Infections Gab1 , Ptpn11 Hematologic Neoplasms Cbl hemorrhagic disease Ptpn11 hepatoblastoma Met hepatocellular adenoma Ptpn11 hepatocellular carcinoma Cbl , Hgf , Met , Pik3r1 , Plcg1 , Shc1 , Src Hepatomegaly Met hereditary breast ovarian cancer syndrome Plcg1 hereditary multiple exostoses Ptpn11 Hereditary Neoplastic Syndromes Cbl , Met , Ptpn11 high grade glioma Hgf , Met , Ptpn11 Hodgkin's lymphoma Met Hydrops Fetalis Ptpn11 Hyperalgesia Src hyperglycemia Cbl , Shc1 hypertension Hgf , Pik3r1 , Src Hypertensive Nephropathy Shc1 Hypertriglyceridemia Met hypertrophic cardiomyopathy Ptpn11 hypoglycemia Pik3r1 idiopathic scoliosis Ptpn11 IMMUNE DYSREGULATION, AUTOIMMUNITY, AND AUTOINFLAMMATION Plcg1 immunodeficiency 14 Pik3r1 immunodeficiency 17 Cbl immunodeficiency 18 Cbl immunodeficiency 19 Cbl immunodeficiency 36 Pik3r1 immunodeficiency 42 Shc1 inflammatory bowel disease 28 Cbl influenza Ptpn11 Insulin Resistance Pik3r1 , Shc1 intellectual disability Crkl , Met , Ptpn11 interstitial lung disease Hgf invasive ductal carcinoma Crkl , Met inverted papilloma Hgf isolated microphthalmia 5 Cbl juvenile myelomonocytic leukemia Cbl , Ptpn11 keratoconus Hgf Kidney Neoplasms Met Kidney Reperfusion Injury Src large cell carcinoma Met laryngeal squamous cell carcinoma Plcg1 learning disability Ptpn11 Leber congenital amaurosis Ptpn11 Left Ventricular Hypertrophy Shc1 Lentigo Hgf lesion of sciatic nerve Src leukemia Ptpn11 limb ischemia Hgf liver benign neoplasm Met liver cirrhosis Hgf , Shc1 Liver Injury Hgf Liver Metastasis Src Liver Neoplasms Hgf localized scleroderma Hgf long QT syndrome Ptpn11 long QT syndrome 1 Ptpn11 long QT syndrome 10 Cbl lung adenocarcinoma Pik3r1 , Plcg1 , Src lung cancer Plcg1 lung carcinoma Crkl , Met lung metastasis Src Lung Neoplasms Met lung non-small cell carcinoma Cbl , Met , Plcg1 lung small cell carcinoma Pik3r1 lung squamous cell carcinoma Met , Ptpn11 , Src Lymphatic Metastasis Cbl , Met , Src lymphedema Met lymphoma Ptpn11 lymphopenia Cbl male infertility Cbl malignant astrocytoma Hgf , Met , Ptpn11 malignant mesothelioma Hgf , Met malignant ovarian germ cell neoplasm Cbl megacolon Crkl Megalencephaly - Cutis Marmorata Telangiectatica Congenita Pik3r1 melanoma Met Memory Disorders Plcg1 meningioma Hgf metabolic dysfunction-associated steatotic liver disease Met Metabolic Syndrome Hgf metachondromatosis Ptpn11 MHC class II deficiency Shc1 microcephaly Cbl , Ptpn11 morphine withdrawal syndrome Src multiple myeloma Cbl , Met myelofibrosis Src myeloid leukemia associated with Down Syndrome Ptpn11 myeloid neoplasm Cbl myocardial infarction Hgf Myocardial Ischemia Hgf Myocardial Reperfusion Injury Cbl myopia Hgf myositis Hgf Nasal Polyps Hgf , Met nasopharynx carcinoma Src Nematode Infections Pik3r1 Neoplasm Invasiveness Hgf , Met , Src Neoplasm Metastasis Hgf , Met , Src neovascular inflammatory vitreoretinopathy Hgf Nerve Sheath Neoplasms Hgf , Met Neuralgia Src neuroblastoma Hgf , Met , Ptpn11 Neurodevelopmental Disorders Cbl , Crkl , Pik3r1 , Ptpn11 neurofibroma Ptpn11 neurofibromatosis-Noonan syndrome Ptpn11 nonsyndromic deafness Met Noonan Like Syndrome Cbl , Ptpn11 Noonan syndrome Cbl , Ptpn11 Noonan syndrome 1 Cbl , Ptpn11 Noonan syndrome 3 Ptpn11 Noonan syndrome with multiple lentigines Ptpn11 Noonan syndrome with multiple lentigines 1 Ptpn11 Noonan Syndrome-Like Disorder with or without Juvenile Myelomonocytic Leukemia Cbl , Ptpn11 obesity Hgf , Pik3r1 Ollier disease Ptpn11 Optic Nerve Injuries Hgf oral squamous cell carcinoma Met , Plcg1 osteoarthritis Pik3r1 Osteochondroma Ptpn11 Osteofibrous Dysplasia Met osteosarcoma Cbl , Met ovarian cancer Crkl , Met ovarian germ cell cancer Cbl Ovarian Neoplasms Met , Pik3r1 Pain Hgf pancreatic acinar cell adenocarcinoma Src pancreatic cancer Hgf , Met pancreatic ductal carcinoma Met pancreatitis Hgf , Met papillary renal cell carcinoma Met parathyroid carcinoma Shc1 Parkinson's disease Hgf Parkinsonism Src patent ductus arteriosus Ptpn11 patent foramen ovale Ptpn11 Penetrating Wounds Hgf periodontitis Met Peripheral Nerve Injuries Cbl pleomorphic xanthoastrocytoma Hgf , Met polycystic kidney disease Plcg1 polycystic ovary syndrome Gab1 polymyositis Hgf Polyomavirus Infections Hgf portal hypertension Pik3r1 primary biliary cholangitis Met primary cutaneous T-cell non-Hodgkin lymphoma Plcg1 primary immunodeficiency disease Crkl , Pik3r1 prostate adenocarcinoma Grb2 prostate cancer Grb2 , Pik3r1 , Src prostate carcinoma Crkl , Met Prostatic Neoplasms Met , Pik3r1 ptosis Ptpn11 pulmonary fibrosis Hgf RASopathy Cbl , Ptpn11 renal cell carcinoma Met , Pik3r1 Renal Cell Carcinoma 1 Met Reperfusion Injury Hgf , Met , Pik3r1 , Src Retina Reperfusion Injury Hgf retinal degeneration Hgf Retinal Neovascularization Hgf retinitis pigmentosa Hgf retinopathy of prematurity Hgf rhabdomyosarcoma Cbl rheumatoid arthritis Hgf , Pik3r1 Rhinosinusitis Hgf Right Ventricular Hypertrophy Ptpn11 Romano-Ward Syndrome Ptpn11 sarcoma Met schizophrenia Cbl , Crkl , Hgf , Met sciatic neuropathy Hgf scoliosis Ptpn11 sensorineural hearing loss Src Septic Peritonitis Pik3r1 severe congenital neutropenia 3 Shc1 severe congenital neutropenia 5 Shc1 Sezary's disease Plcg1 SHORT syndrome Pik3r1 sinusitis Met skin cancer Crkl Skin Neoplasms Hgf Smith-Kingsmore Syndrome Pik3r1 spermatogenic failure 57 Ptpn11 Spinal Cord Injuries Hgf , Met squamous cell carcinoma Hgf , Met , Ptpn11 Staphylococcal Pneumonia Ptpn11 status epilepticus Src steatotic liver disease Met , Shc1 stomach cancer Ptpn11 , Src Stomach Neoplasms Met strabismus Ptpn11 Stroke Hgf , Src systemic scleroderma Hgf T-cell acute lymphoblastic leukemia Ptpn11 tetralogy of Fallot Ptpn11 thrombocytopenia Ptpn11 Thrombocytopenia 6 Src thrombosis Hgf tongue squamous cell carcinoma Hgf , Met transient cerebral ischemia Cbl Trauma and Stressor Related Disorders Src tricuspid valve insufficiency Ptpn11 type 1 diabetes mellitus Cbl type 2 diabetes mellitus Pik3r1 , Src urinary bladder cancer Src vascular disease Hgf Vascular Malformations Pik3r1 vasculitis Cbl velocardiofacial syndrome Crkl Ventricular Premature Complexes Ptpn11 Ventricular Tachycardia Ptpn11 vitiligo Hgf , Pik3r1 Werner syndrome Ptpn11 Williams-Beuren syndrome Src Wounds and Injuries Hgf X-linked agammaglobulinemia Pik3r1
