arthrogryposis, distal, IIa 11

Summary

arthrogryposis, distal, IIa 11 (MONDO:0031045) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 57

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	arthrogryposis, distal, IIa 11
Mondo ID	MONDO:0031045
OMIM	620019
UMLS	C5774205
MedGen	1823978
GARD	0025683
Is cancer (heuristic)	no

Also known as: arthrogryposis, distal, IIa 11 · DA11

Data availability: 57 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 › distal arthrogryposis › arthrogryposis, distal, IIa 11

Related subtypes (22): arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome, arthrogryposis-like hand anomaly-sensorineural deafness syndrome, Gordon syndrome, congenital contractural arachnodactyly, arthrogryposis, distal, type 2E, trismus-pseudocamptodactyly syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, Freeman-Sheldon syndrome, Sheldon-hall syndrome, Ehlers-Danlos syndrome, musculocontractural type, arthrogryposis-severe scoliosis syndrome, distal arthrogryposis type 5D, autism spectrum disorder - epilepsy - arthrogryposis syndrome, arthrogryposis, distal, with impaired proprioception and touch, digitotalar dysmorphism, distal arthrogryposis type 10, distal arthrogryposis Moore weaver type, arthrogryposis, distal, type 1C, arthrogryposis-ectodermal dysplasia-other anomalies syndrome, ACTC1-related distal arthrogryposis with congenital heart disease, arthrogryposis, distal, type 2B4, arthrogryposis, distal, type 12

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

57 retrieved; paginated sample, class counts are floors:

25 conflicting classifications of pathogenicity, 24 uncertain significance, 5 benign/likely benign, 1 pathogenic/likely pathogenic, 1 pathogenic; risk factor, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
13887	NM_000245.4(MET):c.3281A>G (p.His1094Arg)	MET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
446117	NM_000245.4(MET):c.3701A>G (p.Tyr1234Cys)	MET	Pathogenic; risk factor	no assertion criteria provided
1021858	NM_000245.4(MET):c.3403A>T (p.Ser1135Cys)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1320342	NM_000245.4(MET):c.617T>C (p.Phe206Ser)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135966	NM_000245.4(MET):c.3218C>T (p.Pro1073Leu)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
142059	NM_000245.4(MET):c.406G>A (p.Val136Ile)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
184358	NM_000245.4(MET):c.1669A>G (p.Thr557Ala)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
186678	NM_000245.4(MET):c.2825C>T (p.Ser942Leu)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
188364	NM_000245.4(MET):c.1132G>A (p.Val378Ile)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
216513	NM_000245.4(MET):c.632T>G (p.Leu211Trp)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
220057	NM_000245.4(MET):c.4145G>A (p.Arg1382Gln)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
246627	NM_000245.4(MET):c.1853C>T (p.Thr618Met)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
411906	NM_000245.4(MET):c.4150G>A (p.Ala1384Thr)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
41623	NM_000245.4(MET):c.2908C>T (p.Arg970Cys)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
41624	NM_000245.4(MET):c.2975C>T (p.Thr992Ile)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
41627	NM_000245.4(MET):c.504G>T (p.Glu168Asp)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
41630	NM_000245.4(MET):c.967A>G (p.Ser323Gly)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
480824	NM_000245.4(MET):c.803C>T (p.Thr268Ile)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
524884	NM_000245.4(MET):c.850A>G (p.Ile284Val)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
524894	NM_000245.4(MET):c.306C>G (p.Ser102Arg)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
572844	NM_000245.4(MET):c.1291A>G (p.Met431Val)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
584708	NM_000245.4(MET):c.569A>G (p.Asp190Gly)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
584713	NM_000245.4(MET):c.1640G>A (p.Arg547Gln)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
647594	NM_000245.4(MET):c.800A>G (p.Glu267Gly)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
665074	NM_000245.4(MET):c.4118A>G (p.Asp1373Gly)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
665399	NM_000245.4(MET):c.1414C>T (p.Pro472Ser)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
848962	NM_000245.4(MET):c.1450C>T (p.His484Tyr)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
134650	NM_000245.4(MET):c.3973G>A (p.Glu1325Lys)	MET	Uncertain significance	criteria provided, multiple submitters, no conflicts
135961	NM_000245.4(MET):c.1510G>T (p.Val504Phe)	MET	Uncertain significance	criteria provided, multiple submitters, no conflicts
1461779	NM_000245.4(MET):c.73G>T (p.Glu25Ter)	MET	Uncertain significance	criteria provided, multiple submitters, no conflicts

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.

Gene	Classification	Inheritance	Disease	Records
MET	Limited	Autosomal dominant	arthrogryposis, distal, IIa 11	14

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MET	Orphanet:319298	Papillary renal cell carcinoma
MET	Orphanet:33402	Pediatric hepatocellular carcinoma
MET	Orphanet:47044	Hereditary papillary renal cell carcinoma
MET	Orphanet:488265	Osteofibrous dysplasia
MET	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MET	HGNC:7029	ENSG00000105976	P08581	Hepatocyte growth factor receptor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MET	Hepatocyte growth factor receptor	Receptor 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.

Family	Genes	Fold	FDR
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MET	Kinase	yes	2.7.10.1	Prot_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)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	1
germinal epithelium of ovary	1
pigmented layer of retina	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MET	270	ubiquitous	marker	pigmented layer of retina, germinal epithelium of ovary, cartilage tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MET	5,823

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MET	P08581	130

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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Drug-mediated inhibition of MET activation	1	5710.0×	0.004	MET
MET activates STAT3	1	3806.7×	0.004	MET
MET activates PTPN11	1	2284.0×	0.004	MET
MET interacts with TNS proteins	1	2284.0×	0.004	MET
MET Receptor Activation	1	1903.3×	0.004	MET
MET activates PI3K/AKT signaling	1	1903.3×	0.004	MET
Sema4D mediated inhibition of cell attachment and migration	1	1427.5×	0.004	MET
MET receptor recycling	1	1142.0×	0.004	MET
MET activates RAS signaling	1	1038.2×	0.004	MET
MET activates RAP1 and RAC1	1	1038.2×	0.004	MET
Listeria monocytogenes entry into host cells	1	1038.2×	0.004	MET
InlB-mediated entry of Listeria monocytogenes into host cell	1	761.3×	0.005	MET
Sema4D in semaphorin signaling	1	671.8×	0.005	MET
MET promotes cell motility	1	601.0×	0.005	MET
MECP2 regulates neuronal receptors and channels	1	601.0×	0.005	MET
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	1	571.0×	0.005	MET
Negative regulation of MET activity	1	519.1×	0.005	MET
Semaphorin interactions	1	393.8×	0.006	MET
MET activates PTK2 signaling	1	380.7×	0.006	MET
PI3K/AKT Signaling in Cancer	1	368.4×	0.006	MET
Bacterial Infection Pathways	1	335.9×	0.006	MET
Signaling by MET	1	317.2×	0.006	MET
Transcriptional Regulation by MECP2	1	317.2×	0.006	MET
Negative regulation of the PI3K/AKT network	1	278.5×	0.007	MET
MITF-M-dependent gene expression	1	181.3×	0.010	MET
MAPK1/MAPK3 signaling	1	131.3×	0.013	MET
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.013	MET
MITF-M-regulated melanocyte development	1	114.2×	0.014	MET
MAPK family signaling cascades	1	102.9×	0.015	MET
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.015	MET

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 term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of hydrogen peroxide-mediated programmed cell death	1	4213.0×	0.003	MET
hepatocyte growth factor receptor signaling pathway	1	2106.5×	0.003	MET
endothelial cell morphogenesis	1	1053.2×	0.003	MET
positive regulation of endothelial cell chemotaxis	1	991.3×	0.003	MET
positive chemotaxis	1	802.5×	0.003	MET
branching morphogenesis of an epithelial tube	1	732.7×	0.003	MET
pancreas development	1	674.1×	0.003	MET
excitatory postsynaptic potential	1	443.5×	0.004	MET
semaphorin-plexin signaling pathway	1	401.2×	0.004	MET
negative regulation of autophagy	1	259.3×	0.006	MET
liver development	1	221.7×	0.006	MET
cell surface receptor protein tyrosine kinase signaling pathway	1	173.7×	0.007	MET
neuron differentiation	1	100.3×	0.012	MET
cell surface receptor signaling pathway	1	64.1×	0.017	MET
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	MET

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.

Symbol	Example approved molecule
MET	AFATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MET	95	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AFATINIB	4	MET
FEDRATINIB	4	MET
TIVOZANIB	4	MET
AXITINIB	4	MET
SORAFENIB	4	MET
NERATINIB	4	MET
INFIGRATINIB PHOSPHATE	4	MET
INFIGRATINIB	4	MET
PALBOCICLIB	4	MET
ENTRECTINIB	4	MET
DABRAFENIB	4	MET
CABOZANTINIB S-MALATE	4	MET
AFATINIB DIMALEATE	4	MET
CABOZANTINIB	4	MET
CERITINIB	4	MET
VANDETANIB	4	MET
BOSUTINIB	4	MET
CAPMATINIB	4	MET
TEPOTINIB	4	MET
BRIGATINIB	4	MET
ENSARTINIB	4	MET
PAZOPANIB	4	MET
NINTEDANIB	4	MET
SUNITINIB	4	MET
ERLOTINIB	4	MET
CRIZOTINIB	4	MET
MIDOSTAURIN	4	MET
GEFITINIB	4	MET
LINSITINIB	3	MET
RIGOSERTIB	3	MET

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
MET	2,015	Binding:2005, Functional:6, ADMET:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MET	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
MET	2,015

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.

Compound	Max phase	Cohort target (bioactivity)
AFATINIB	4	MET
FEDRATINIB	4	MET
TIVOZANIB	4	MET
AXITINIB	4	MET
SORAFENIB	4	MET
NERATINIB	4	MET
INFIGRATINIB PHOSPHATE	4	MET
INFIGRATINIB	4	MET
PALBOCICLIB	4	MET
ENTRECTINIB	4	MET
DABRAFENIB	4	MET
CABOZANTINIB S-MALATE	4	MET
AFATINIB DIMALEATE	4	MET
CABOZANTINIB	4	MET
CERITINIB	4	MET
VANDETANIB	4	MET
BOSUTINIB	4	MET
CAPMATINIB	4	MET
TEPOTINIB	4	MET
BRIGATINIB	4	MET
ENSARTINIB	4	MET
PAZOPANIB	4	MET
NINTEDANIB	4	MET
SUNITINIB	4	MET
ERLOTINIB	4	MET
CRIZOTINIB	4	MET
MIDOSTAURIN	4	MET
GEFITINIB	4	MET
LINSITINIB	3	MET
RIGOSERTIB	3	MET

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MET
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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.