MET
Chr 7ADARMET proto-oncogene, receptor tyrosine kinase
Also known as: AUTS9, DA11, DFNB97, HGFR, RCCP2, c-Met
The MET protein is a receptor tyrosine kinase that binds hepatocyte growth factor and regulates cellular proliferation, survival, migration, and morphogenesis during embryonic development and tissue repair. Mutations cause childhood hepatocellular carcinoma, familial renal cell carcinoma, distal arthrogryposis type 11, and autosomal recessive deafness, with both autosomal dominant and recessive inheritance patterns. This gene is highly constrained against loss-of-function mutations, indicating that such variants are likely to be pathogenic when they occur.
Definitive — sufficient evidence for diagnostic panels
3 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
300 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 4 | 0 | 4 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 6 | 124 | 4 | 1 | 135 |
Likely Benign | 3 | 0 | 34 | 99 | 136 |
Benign | 0 | 0 | 3 | 0 | 3 |
Conflicting | — | 22 | |||
| Total | 9 | 124 | 45 | 100 | 300 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MET · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Precise Eating Time to Improve Glycemic Control and Cardiometabolic Health in Prediabetes and Diabetes
RECRUITINGMetformin for People With CFRD on CFTR Modulator Therapy to Improve Ion Channel Function
RECRUITINGResources, Inspiration, Support and Empowerment (RISE) for Black Pregnant Women
ACTIVE NOT RECRUITINGBinimetinib for People With Relapsed/Refractory BRAF Wild Type Hairy Cell Leukemia and Variant
RECRUITINGStudy of Therapeutic Efficacy of Anti-CD19 CAR-T Cells in Refractory Systemic Lupus Erythematosus
ACTIVE NOT RECRUITINGAnti-CD19 CAR-T Cells With Inducible Caspase 9 Safety Switch for B-cell Lymphoma
ACTIVE NOT RECRUITINGSavolitinib for Treating Gastric Cancer and Esophagogastric Junction Adenocarcinoma Patients
ACTIVE NOT RECRUITINGLi-Fraumeni Syndrome/TP53 Biobank
RECRUITINGA Prospective Registry for Patients at High-Risk for Pancreatic Cancer
RECRUITINGA Feasibility Study of Optimal Non-Pharmacological Lifestyle Modifications in People With Type 2 Diabetes
RECRUITINGOpen-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer
ACTIVE NOT RECRUITINGCombination Therapy in Cancers With Mutations in DNA Repair Genes
RECRUITINGExternal Resources
Links to major genomics databases and tools