Autosomal recessive nonsyndromic hearing loss 97

disease
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Also known as autosomal recessive deafness 97autosomal recessive nonsyndromic deafness 97autosomal recessive nonsyndromic deafness caused by mutation in METautosomal recessive nonsyndromic deafness type 97deafness, autosomal recessive 97deafness, autosomal recessive type 97DFNB97MET autosomal recessive nonsyndromic deafness

Summary

Autosomal recessive nonsyndromic hearing loss 97 (MONDO:0014739) is a disease caused by MET (GenCC Strong), with 1 cohort gene.

At a glance

  • Causal gene: MET (GenCC Strong)
  • Cohort genes: 1
  • ClinVar variants: 267

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameautosomal recessive nonsyndromic hearing loss 97
Mondo IDMONDO:0014739
OMIM616705
DOIDDOID:0110539
UMLSC4084709
MedGen899875
GARD0022655
Is cancer (heuristic)no

Also known as: autosomal recessive deafness 97 · autosomal recessive nonsyndromic deafness 97 · autosomal recessive nonsyndromic deafness caused by mutation in MET · autosomal recessive nonsyndromic deafness type 97 · deafness, autosomal recessive 97 · deafness, autosomal recessive type 97 · DFNB97 · MET autosomal recessive nonsyndromic deafness

Data availability: 267 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive diseasehearing loss, autosomal recessiveautosomal recessive nonsyndromic hearing loss 97

Related subtypes (101): autosomal recessive nonsyndromic hearing loss 5, autosomal recessive nonsyndromic hearing loss 1A, autosomal recessive nonsyndromic hearing loss 2, autosomal recessive nonsyndromic hearing loss 3, autosomal recessive nonsyndromic hearing loss 4, autosomal recessive nonsyndromic hearing loss 6, autosomal recessive nonsyndromic hearing loss 7, autosomal recessive nonsyndromic hearing loss 9, autosomal recessive nonsyndromic hearing loss 8, autosomal recessive nonsyndromic hearing loss 12, autosomal recessive nonsyndromic hearing loss 15, autosomal recessive nonsyndromic hearing loss 18A, autosomal recessive nonsyndromic hearing loss 17, autosomal recessive nonsyndromic hearing loss 13, autosomal recessive nonsyndromic hearing loss 21, autosomal recessive nonsyndromic hearing loss 14, autosomal recessive nonsyndromic hearing loss 16, autosomal recessive nonsyndromic hearing loss 20, autosomal recessive nonsyndromic hearing loss 26, autosomal recessive nonsyndromic hearing loss 27, autosomal recessive nonsyndromic hearing loss 22, autosomal recessive nonsyndromic hearing loss 31, autosomal recessive nonsyndromic hearing loss 30, autosomal recessive nonsyndromic hearing loss 33, autosomal recessive nonsyndromic hearing loss 37, autosomal recessive nonsyndromic hearing loss 38, autosomal recessive nonsyndromic hearing loss 40, autosomal recessive nonsyndromic hearing loss 39, autosomal recessive nonsyndromic hearing loss 35, autosomal recessive nonsyndromic hearing loss 32, autosomal recessive nonsyndromic hearing loss 36, autosomal recessive nonsyndromic hearing loss 48, autosomal recessive nonsyndromic hearing loss 23, autosomal recessive nonsyndromic hearing loss 42, autosomal recessive nonsyndromic hearing loss 46, autosomal recessive nonsyndromic hearing loss 53, autosomal recessive nonsyndromic hearing loss 28, autosomal recessive nonsyndromic hearing loss 51, autosomal recessive nonsyndromic hearing loss 47, autosomal recessive nonsyndromic hearing loss 55, autosomal recessive nonsyndromic hearing loss 62, autosomal recessive nonsyndromic hearing loss 49, autosomal recessive nonsyndromic hearing loss 44, autosomal recessive nonsyndromic hearing loss 66, autosomal recessive nonsyndromic hearing loss 59, autosomal recessive nonsyndromic hearing loss 65, autosomal recessive nonsyndromic hearing loss 67, autosomal recessive nonsyndromic hearing loss 68, autosomal recessive nonsyndromic hearing loss 24, autosomal recessive nonsyndromic hearing loss 63, autosomal recessive nonsyndromic hearing loss 45, autosomal recessive nonsyndromic hearing loss 1B, autosomal recessive nonsyndromic hearing loss 71, autosomal recessive nonsyndromic hearing loss 77, autosomal recessive nonsyndromic hearing loss 25, autosomal recessive nonsyndromic hearing loss 79, autosomal recessive nonsyndromic hearing loss 84A, autosomal recessive nonsyndromic hearing loss 85, autosomal recessive nonsyndromic hearing loss 91, autosomal recessive nonsyndromic hearing loss 83, autosomal recessive nonsyndromic hearing loss 74, autosomal recessive nonsyndromic hearing loss 61, autosomal recessive nonsyndromic hearing loss 89, autosomal recessive nonsyndromic hearing loss 29, autosomal recessive nonsyndromic hearing loss 96, autosomal recessive nonsyndromic hearing loss 86, autosomal recessive nonsyndromic hearing loss 98, autosomal recessive nonsyndromic hearing loss 93, autosomal recessive nonsyndromic hearing loss 70, autosomal recessive nonsyndromic hearing loss 84B, autosomal recessive nonsyndromic hearing loss 18B, autosomal recessive nonsyndromic hearing loss 88, autosomal recessive nonsyndromic hearing loss 76, autosomal recessive nonsyndromic hearing loss 101, autosomal recessive nonsyndromic hearing loss 102, autosomal recessive nonsyndromic hearing loss 103, autosomal recessive nonsyndromic hearing loss 104, hearing loss, autosomal recessive 111, hearing loss, autosomal recessive 118, with cochlear aplasia, hearing loss, autosomal recessive 119, hearing loss, autosomal recessive 117, hearing loss, autosomal recessive 112, hearing loss, autosomal recessive 113, hearing loss, autosomal recessive 100, hearing loss, autosomal recessive 94, hearing loss, autosomal recessive 114, hearing loss, autosomal recessive 115, hearing loss, autosomal recessive 99, hearing loss, autosomal recessive 106, hearing loss, autosomal recessive 107, hearing loss, autosomal recessive 108, hearing loss, autosomal recessive 57, hearing loss, autosomal recessive 109, hearing loss, autosomal recessive 116, hearing loss, autosomal recessive 110, hearing loss, autosomal recessive 120, hearing loss, autosomal recessive 121, hearing loss, autosomal recessive 122, hearing loss, autosomal recessive 123, autosomal recessive nonsyndromic hearing loss 124, hearing loss, autosomal recessive 125

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

267 retrieved; paginated sample, class counts are floors:

130 uncertain significance, 124 conflicting classifications of pathogenicity, 6 benign, 5 benign/likely benign, 1 pathogenic/likely pathogenic, 1 pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
13887NM_000245.4(MET):c.3281A>G (p.His1094Arg)METPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
183686NM_000245.4(MET):c.2521T>G (p.Phe841Val)METPathogeniccriteria provided, single submitter
1021858NM_000245.4(MET):c.3403A>T (p.Ser1135Cys)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1320342NM_000245.4(MET):c.617T>C (p.Phe206Ser)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
132694NM_000245.4(MET):c.1039G>A (p.Ala347Thr)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
134654NM_000245.4(MET):c.1771C>T (p.Arg591Trp)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
135966NM_000245.4(MET):c.3218C>T (p.Pro1073Leu)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
135968NM_000245.4(MET):c.4007G>A (p.Arg1336Gln)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
135974NM_000245.4(MET):c.65G>T (p.Ser22Ile)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
135975NM_000245.4(MET):c.689C>T (p.Thr230Met)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1388673NM_000245.4(MET):c.2588A>G (p.Asn863Ser)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
142059NM_000245.4(MET):c.406G>A (p.Val136Ile)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
142060NM_000245.4(MET):c.2543T>C (p.Val848Ala)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1429037NM_000245.4(MET):c.1347C>A (p.Asp449Glu)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1438566NM_000245.4(MET):c.2555T>C (p.Met852Thr)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1447271NM_000245.4(MET):c.229G>A (p.Asp77Asn)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1505421NM_000245.4(MET):c.2662C>G (p.His888Asp)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
167292NM_000245.4(MET):c.901A>G (p.Thr301Ala)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1692567NM_000245.4(MET):c.62G>A (p.Arg21Lys)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1734426NM_000245.4(MET):c.3682G>T (p.Asp1228Tyr)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1776377NM_000245.4(MET):c.1610A>G (p.Gln537Arg)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1784380NM_000245.4(MET):c.200C>A (p.Thr67Asn)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
184358NM_000245.4(MET):c.1669A>G (p.Thr557Ala)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
184359NM_000245.4(MET):c.146A>G (p.Glu49Gly)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
185464NM_000245.4(MET):c.2278A>G (p.Ile760Val)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
185606NM_000245.4(MET):c.1081G>T (p.Ala361Ser)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
186678NM_000245.4(MET):c.2825C>T (p.Ser942Leu)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
187360NM_000245.4(MET):c.2455G>A (p.Ala819Thr)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
188112NM_000245.4(MET):c.40C>T (p.Leu14Phe)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
188184NM_000245.4(MET):c.2909G>A (p.Arg970His)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

GeneClassificationInheritanceDiseaseRecords
METStrongAutosomal recessiveautosomal recessive nonsyndromic hearing loss 9714

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
METOrphanet:319298Papillary renal cell carcinoma
METOrphanet:33402Pediatric hepatocellular carcinoma
METOrphanet:47044Hereditary papillary renal cell carcinoma
METOrphanet:488265Osteofibrous dysplasia
METOrphanet:90636Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
METHGNC:7029ENSG00000105976P08581Hepatocyte growth factor receptorgencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
METHepatocyte growth factor receptorReceptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

FamilyGenesFoldFDR
Kinase127.7×0.036

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
METKinaseyes2.7.10.1Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Semap_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)1
unknown0

Top tissues across cohort

TissueCohort genes
cartilage tissue1
germinal epithelium of ovary1
pigmented layer of retina1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
MET270ubiquitousmarkerpigmented layer of retina, germinal epithelium of ovary, cartilage tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
MET5,823

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
METP08581130

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 44. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Drug-mediated inhibition of MET activation15710.0×0.004MET
MET activates STAT313806.7×0.004MET
MET activates PTPN1112284.0×0.004MET
MET interacts with TNS proteins12284.0×0.004MET
MET Receptor Activation11903.3×0.004MET
MET activates PI3K/AKT signaling11903.3×0.004MET
Sema4D mediated inhibition of cell attachment and migration11427.5×0.004MET
MET receptor recycling11142.0×0.004MET
MET activates RAS signaling11038.2×0.004MET
MET activates RAP1 and RAC111038.2×0.004MET
Listeria monocytogenes entry into host cells11038.2×0.004MET
InlB-mediated entry of Listeria monocytogenes into host cell1761.3×0.005MET
Sema4D in semaphorin signaling1671.8×0.005MET
MET promotes cell motility1601.0×0.005MET
MECP2 regulates neuronal receptors and channels1601.0×0.005MET
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation1571.0×0.005MET
Negative regulation of MET activity1519.1×0.005MET
Semaphorin interactions1393.8×0.006MET
MET activates PTK2 signaling1380.7×0.006MET
PI3K/AKT Signaling in Cancer1368.4×0.006MET
Bacterial Infection Pathways1335.9×0.006MET
Signaling by MET1317.2×0.006MET
Transcriptional Regulation by MECP21317.2×0.006MET
Negative regulation of the PI3K/AKT network1278.5×0.007MET
MITF-M-dependent gene expression1181.3×0.010MET
MAPK1/MAPK3 signaling1131.3×0.013MET
Constitutive Signaling by Aberrant PI3K in Cancer1126.9×0.013MET
MITF-M-regulated melanocyte development1114.2×0.014MET
MAPK family signaling cascades1102.9×0.015MET
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling196.8×0.015MET

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
negative regulation of hydrogen peroxide-mediated programmed cell death14213.0×0.003MET
hepatocyte growth factor receptor signaling pathway12106.5×0.003MET
endothelial cell morphogenesis11053.2×0.003MET
positive regulation of endothelial cell chemotaxis1991.3×0.003MET
positive chemotaxis1802.5×0.003MET
branching morphogenesis of an epithelial tube1732.7×0.003MET
pancreas development1674.1×0.003MET
excitatory postsynaptic potential1443.5×0.004MET
semaphorin-plexin signaling pathway1401.2×0.004MET
negative regulation of autophagy1259.3×0.006MET
liver development1221.7×0.006MET
cell surface receptor protein tyrosine kinase signaling pathway1173.7×0.007MET
neuron differentiation1100.3×0.012MET
cell surface receptor signaling pathway164.1×0.017MET
positive regulation of transcription by RNA polymerase II114.9×0.067MET

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

SymbolExample approved molecule
METAFATINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
MET954

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
AFATINIB4MET
FEDRATINIB4MET
TIVOZANIB4MET
AXITINIB4MET
SORAFENIB4MET
NERATINIB4MET
INFIGRATINIB PHOSPHATE4MET
INFIGRATINIB4MET
PALBOCICLIB4MET
ENTRECTINIB4MET
DABRAFENIB4MET
CABOZANTINIB S-MALATE4MET
AFATINIB DIMALEATE4MET
CABOZANTINIB4MET
CERITINIB4MET
VANDETANIB4MET
BOSUTINIB4MET
CAPMATINIB4MET
TEPOTINIB4MET
BRIGATINIB4MET
ENSARTINIB4MET
PAZOPANIB4MET
NINTEDANIB4MET
SUNITINIB4MET
ERLOTINIB4MET
CRIZOTINIB4MET
MIDOSTAURIN4MET
GEFITINIB4MET
LINSITINIB3MET
RIGOSERTIB3MET

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

SymbolAssaysType breakdown
MET2,015Binding:2005, Functional:6, ADMET:4

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
MET2.7.10.1receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

SymbolChEMBL assays
MET2,015

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

CompoundMax phaseCohort target (bioactivity)
AFATINIB4MET
FEDRATINIB4MET
TIVOZANIB4MET
AXITINIB4MET
SORAFENIB4MET
NERATINIB4MET
INFIGRATINIB PHOSPHATE4MET
INFIGRATINIB4MET
PALBOCICLIB4MET
ENTRECTINIB4MET
DABRAFENIB4MET
CABOZANTINIB S-MALATE4MET
AFATINIB DIMALEATE4MET
CABOZANTINIB4MET
CERITINIB4MET
VANDETANIB4MET
BOSUTINIB4MET
CAPMATINIB4MET
TEPOTINIB4MET
BRIGATINIB4MET
ENSARTINIB4MET
PAZOPANIB4MET
NINTEDANIB4MET
SUNITINIB4MET
ERLOTINIB4MET
CRIZOTINIB4MET
MIDOSTAURIN4MET
GEFITINIB4MET
LINSITINIB3MET
RIGOSERTIB3MET

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1MET
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

  • Cohort genes: MET