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GeneE
50 sources retrieved ยท Most recent: April 2026 ยท Index updated 14 days ago
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MET
MET proto-oncogene, receptor tyrosine kinase
Chromosome 7 ยท 7q31.2
NCBI Gene: 4233Ensembl: ENSG00000105976.16HGNC: HGNC:7029UniProt: B4DLF5
1,418PubMed Papers
25Diseases
36Drugs
13Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneKinaseOncogeneReceptor
RESEARCH IMPACT
Highly Studied
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
โœ“ Experimental GO Evidenceโœ“ Swiss-Prot Reviewed
positive regulation of endothelial cell chemotaxiscell surfaceprotein phosphatase bindingidentical protein bindingpapillary renal cell carcinomahereditary papillary renal cell carcinomahepatocellular carcinomanon-small cell lung carcinoma
โœฆAI Summary

MET is a receptor tyrosine kinase that serves as the high-affinity receptor for hepatocyte growth factor (HGF), a critical ligand for normal mammalian development 1. Upon HGF binding, MET activates downstream signaling cascades including MAPK, PI3K/Akt/mTOR, and STAT3 pathways to regulate cell proliferation, migration, morphogenic differentiation, and angiogenesis 2. MET is essential for normal developmental processes such as cell migration, three-dimensional tubular structure organization, liver development, and neuron differentiation. In cancer pathogenesis, MET becomes deregulated through ligand overexpression, receptor overexpression, gene amplification, and activating mutations 3. Aberrant MET signaling drives tumor initiation, proliferation, invasion, and metastasis across multiple cancer types including hepatocellular carcinoma, renal cell carcinoma, non-small cell lung cancer, gastric cancer, and glioblastoma 45. MET overexpression and amplification correlate with poor prognosis, advanced disease, lymph node metastasis, and therapeutic resistance 67. Cancer cells exploit MET's physiological functions to enable invasion and immune evasion within the tumor microenvironment 4. Given these oncogenic roles, MET inhibition has emerged as a validated therapeutic strategy, with multiple inhibitors entering clinical trials for cancer treatment 18.

Sources cited
1
c-MET activation of MAPK, PI3K/Akt/mTOR, STAT3 pathways and modulation of cell proliferation, EMT, morphogenesis, apoptosis, and angiogenesis
PMID: 38503157
2
MET overexpression in cancers; involvement in proliferation, migration, invasion; deregulation through overexpression, amplification, mutations
PMID: 34951962
3
MET as high-affinity HGF receptor; role in cell migration, morphogenic differentiation, tubular structure organization; constitutive phosphorylation in tumors; MET inhibitors block motility and tumorigenicity
PMID: 15922853
4
MET mutations in tumors; HGF/SF overexpression and amplification; signal cascade affecting proliferation, migration, differentiation, survival
PMID: 25987653
5
MET amplification associated with aggressive clinicopathological features including high grade, lymph node metastasis, advanced stage
PMID: 31645095
6
HGF/c-MET pathway in NSCLC tumor microenvironment; roles in tumor cell proliferation, migration, invasion, angiogenesis, immune evasion
PMID: 39201787
7
c-Met expression associated with poor overall survival in gastric cancer; feedback loop between HGF/c-Met and Notch1 signaling in cancer progression
PMID: 29781036
8
HGF/MET pathway deregulation in glioblastoma; MET inhibition as therapeutic target for brain tumors
PMID: 25434379
Disease Associationsโ“˜25
papillary renal cell carcinomaOpen Targets
0.84Strong
hereditary papillary renal cell carcinomaOpen Targets
0.77Strong
hepatocellular carcinomaOpen Targets
0.77Strong
non-small cell lung carcinomaOpen Targets
0.72Strong
renal cell carcinomaOpen Targets
0.72Strong
neoplasmOpen Targets
0.64Moderate
medullary thyroid gland carcinomaOpen Targets
0.58Moderate
listeriosisOpen Targets
0.57Moderate
hereditary neoplastic syndromeOpen Targets
0.53Moderate
Inherited cancer-predisposing syndromeOpen Targets
0.53Moderate
arthrogryposis, distal, IIa 11Open Targets
0.51Moderate
thyroid carcinomaOpen Targets
0.51Moderate
thyroid cancerOpen Targets
0.48Moderate
cancerOpen Targets
0.48Moderate
renal carcinomaOpen Targets
0.48Moderate
kidney neoplasmOpen Targets
0.46Moderate
fibrous dysplasiaOpen Targets
0.46Moderate
osteofibrous dysplasiaOpen Targets
0.46Moderate
pediatric hepatocellular carcinomaOpen Targets
0.45Moderate
lung carcinomaOpen Targets
0.41Moderate
Arthrogryposis, distal, 11UniProt
Deafness, autosomal recessive, 97UniProt
Hepatocellular carcinomaUniProt
Osteofibrous dysplasiaUniProt
Renal cell carcinoma papillaryUniProt
Pathogenic Variants13
NM_000245.4(MET):c.3274G>A (p.Val1092Ile)Pathogenic
Hereditary cancer-predisposing syndrome|Papillary renal cell carcinoma type 1|Renal cell carcinoma
โ˜…โ˜…โ˜†โ˜†2025โ†’ Residue 1092
NM_000245.4(MET):c.3658G>A (p.Val1220Ile)Pathogenic
Papillary renal cell carcinoma type 1|Hereditary cancer-predisposing syndrome|Renal cell carcinoma|not provided
โ˜…โ˜…โ˜†โ˜†2025โ†’ Residue 1220
NM_000245.4(MET):c.3281A>G (p.His1094Arg)Pathogenic
Papillary renal cell carcinoma type 1|not provided|Renal cell carcinoma|Hereditary cancer-predisposing syndrome|MET-related disorder|Autosomal recessive nonsyndromic hearing loss 97;Arthrogryposis, distal, IIa 11;Hepatocellular carcinoma;Osteofibrous dysplasia;Papillary renal cell carcinoma type 1
โ˜…โ˜…โ˜†โ˜†2025โ†’ Residue 1094
NM_000245.4(MET):c.3392T>C (p.Met1131Thr)Pathogenic
Papillary renal cell carcinoma type 1|Hereditary cancer-predisposing syndrome|Renal cell carcinoma|Hereditary papillary renal cell carcinoma
โ˜…โ˜…โ˜†โ˜†2025โ†’ Residue 1131
NM_000245.4(MET):c.3503T>G (p.Phe1168Cys)Likely pathogenic
Renal cell carcinoma
โ˜…โ˜†โ˜†โ˜†2024โ†’ Residue 1168
NM_000245.4(MET):c.3749T>C (p.Met1250Thr)Likely pathogenic
Hereditary cancer-predisposing syndrome|Embryonal rhabdomyosarcoma
โ˜…โ˜†โ˜†โ˜†2024โ†’ Residue 1250
NM_000245.4(MET):c.2521T>G (p.Phe841Val)Pathogenic
Autosomal Recessive Nonsyndromic Hearing Loss and Deafness|Autosomal recessive nonsyndromic hearing loss 97
โ˜…โ˜†โ˜†โ˜†2015โ†’ Residue 841
NM_000245.4(MET):c.3701A>G (p.Tyr1234Cys)Pathogenic
Arthrogryposis, distal, type 1A|Arthrogryposis, distal, IIa 11
โ˜†โ˜†โ˜†โ˜†2024โ†’ Residue 1234
NM_000245.4(MET):c.3750G>A (p.Met1250Ile)Pathogenic
Pediatric hepatocellular carcinoma
โ˜†โ˜†โ˜†โ˜†1999โ†’ Residue 1250
NM_000245.4(MET):c.3731A>G (p.Lys1244Arg)Pathogenic
Pediatric hepatocellular carcinoma
โ˜†โ˜†โ˜†โ˜†1999โ†’ Residue 1244
NM_000245.4(MET):c.3682G>A (p.Asp1228Asn)Pathogenic
Papillary renal cell carcinoma type 1|Embryonal rhabdomyosarcoma
โ˜†โ˜†โ˜†โ˜†1997โ†’ Residue 1228
NM_000245.4(MET):c.3562G>T (p.Val1188Leu)Pathogenic
Papillary renal cell carcinoma type 1
โ˜†โ˜†โ˜†โ˜†1997โ†’ Residue 1188
NM_000245.4(MET):c.2855del (p.Phe952fs)Pathogenic
Colorectal cancer
โ˜†โ˜†โ˜†โ˜†โ†’ Residue 952
View on ClinVar โ†—
Drug Targets36
ALTIRATINIBPhase I
Hepatocyte growth factor receptor inhibitor
AMG-208Phase II
Hepatocyte growth factor receptor inhibitor
AMG-337Phase II
Hepatocyte growth factor receptor inhibitor
clear cell sarcoma
AMIVANTAMABApproved
Epidermal growth factor receptor erbB1 inhibitor
non-small cell lung carcinoma
AMUVATINIBPhase II
Hepatocyte growth factor receptor inhibitor
ARRY-300Phase I
Hepatocyte growth factor receptor inhibitor
BAFISONTAMABPhase I/II
Epidermal growth factor receptor erbB1 inhibitor
neoplasm
BEPERMINOGENE PERPLASMIDPhase III
Hepatocyte growth factor receptor agonist
BMS-777607Phase I/II
Hepatocyte growth factor receptor inhibitor
neoplasm
BMS-817378Phase I
Hepatocyte growth factor receptor inhibitor
neoplasm
BPI-9016Phase I
Tyrosine-protein kinase receptor UFO inhibitor
CABOZANTINIBApproved
Hepatocyte growth factor receptor inhibitor
thyroid cancer
CABOZANTINIB S-MALATEApproved
Hepatocyte growth factor receptor inhibitor
thyroid carcinoma
CAPMATINIBApproved
Hepatocyte growth factor receptor inhibitor
non-small cell lung carcinoma
CAPMATINIB HYDROCHLORIDEApproved
Hepatocyte growth factor receptor inhibitor
non-small cell lung carcinoma
CRIZOTINIBApproved
EML4-ALK inhibitor
non-small cell lung carcinoma
EMD-1204831Phase I
Hepatocyte growth factor receptor inhibitor
EMIBETUZUMABPhase II
Hepatocyte growth factor receptor inhibitor
FORETINIBPhase II
Stem cell growth factor receptor inhibitor
breast cancer
GLESATINIBPhase II
Macrophage-stimulating protein receptor inhibitor
non-small cell lung carcinoma
GOLVATINIBPhase I/II
Hepatocyte growth factor receptor inhibitor
gastric cancer
JNJ-38877605Phase I
Hepatocyte growth factor receptor inhibitor
MERESTINIBPhase II
Hepatocyte growth factor receptor inhibitor
biliary tract cancer
MK-2461Phase I/II
Hepatocyte growth factor receptor inhibitor
Alzheimer disease
MK-8033Phase I
Hepatocyte growth factor receptor inhibitor
ONARTUZUMABPhase III
Hepatocyte growth factor receptor antagonist
non-small cell lung carcinoma
PF-04217903Phase I
Hepatocyte growth factor receptor inhibitor
SAR-125844Phase II
Hepatocyte growth factor receptor inhibitor
SAVOLITINIBPhase III
Hepatocyte growth factor receptor inhibitor
renal cell carcinoma
SGX-523Phase I
Hepatocyte growth factor receptor inhibitor
TELISOTUZUMABPhase I
Hepatocyte growth factor receptor inhibitor
TELISOTUZUMAB VEDOTINPhase III
Hepatocyte growth factor receptor binding agent
non-small cell lung carcinoma
TEPOTINIBApproved
Hepatocyte growth factor receptor inhibitor
non-small cell lung carcinoma
TEPOTINIB HYDROCHLORIDEApproved
Hepatocyte growth factor receptor inhibitor
non-small cell lung carcinoma
TEREVALEFIMPhase III
Hepatocyte growth factor receptor agonist
TIVANTINIBPhase III
Hepatocyte growth factor receptor inhibitor
hepatocellular carcinoma
Related Genes
ANGPT2Protein interaction100%HGFACProtein interaction100%SH3KBP1Protein interaction100%PGFProtein interaction100%SH3GL3Protein interaction100%VEGFCProtein interaction100%
Tissue Expression6 tissues
Liver
100%
Brain
96%
Heart
47%
Lung
29%
Bone Marrow
13%
Ovary
3%
Gene Interaction Network
Click a node to explore
METANGPT2HGFACSH3KBP1PGFSH3GL3VEGFC
PROTEIN STRUCTURE
Preparing viewerโ€ฆ
PDB4R1V ยท 1.20 ร… ยท X-ray
View on RCSB โ†—
Constraintโ“˜
LOEUFโ“˜
0.45Moderately Constrained
pLIโ“˜
1.00Intolerant
Observed/Expected LoF0.35 [0.28โ€“0.45]
RankingsWhere MET stands among ~20K protein-coding genes
  • #92of 20,598
    Most Researched1,418 ยท top 1%
  • #182of 1,025
    FDA-Approved Drug Targets8 ยท top quartile
  • #2,551of 5,498
    Most Pathogenic Variants13
  • #2,468of 17,882
    Most Constrained (LOEUF)0.45 ยท top quartile
Genes detectedMET
Sources retrieved50 papers
Response timeโ€”
๐Ÿ“„ Sources
50โ–ผ
1
c-MET pathway in human malignancies and its targeting by natural compounds for cancer therapy.
PMID: 38503157
Phytomedicine ยท 2024
1.00
2
Roles of MET in human cancer.
PMID: 34951962
Clin Chim Acta ยท 2022
0.90
3
Hepatocyte growth factor and c-Met expression in rat and human liver fibrosis.
PMID: 15287857
Liver Int ยท 2004
0.84
4
MET in glioma: signaling pathways and targeted therapies.
PMID: 31221203
J Exp Clin Cancer Res ยท 2019
0.82
5
c-Met as a target for human cancer and characterization of inhibitors for therapeutic intervention.
PMID: 15922853
Cancer Lett ยท 2005
0.80