Hearing loss, autosomal dominant 37

Summary

Hearing loss, autosomal dominant 37 (MONDO:0032802) is a disease caused by COL11A1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: COL11A1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 84

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hearing loss, autosomal dominant 37
Mondo ID	MONDO:0032802
OMIM	618533
DOID	DOID:0070601
UMLS	C4760307
MedGen	1676950
GARD	0025751
Is cancer (heuristic)	no

Also known as: DEAFNESS, AUTOSOMAL DOMINANT 37 · deafness, autosomal dominant 37 · DFNA37

Data availability: 84 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 dominant disease › autosomal dominant nonsyndromic hearing loss › hearing loss, autosomal dominant 37

Related subtypes (75): autosomal dominant nonsyndromic hearing loss 1, autosomal dominant nonsyndromic hearing loss 2A, autosomal dominant nonsyndromic hearing loss 4A, autosomal dominant nonsyndromic hearing loss 6, autosomal dominant nonsyndromic hearing loss 5, autosomal dominant nonsyndromic hearing loss 10, autosomal dominant nonsyndromic hearing loss 11, autosomal dominant nonsyndromic hearing loss 9, autosomal dominant nonsyndromic hearing loss 7, autosomal dominant nonsyndromic hearing loss 12, autosomal dominant nonsyndromic hearing loss 3A, autosomal dominant nonsyndromic hearing loss 13, autosomal dominant nonsyndromic hearing loss 15, autosomal dominant nonsyndromic hearing loss 17, autosomal dominant nonsyndromic hearing loss 16, autosomal dominant nonsyndromic hearing loss 20, autosomal dominant nonsyndromic hearing loss 23, autosomal dominant nonsyndromic hearing loss 25, autosomal dominant nonsyndromic hearing loss 18, autosomal dominant nonsyndromic hearing loss 24, autosomal dominant nonsyndromic hearing loss 22, autosomal dominant nonsyndromic hearing loss 30, autosomal dominant nonsyndromic hearing loss 36, autosomal dominant nonsyndromic hearing loss 21, autosomal dominant nonsyndromic hearing loss 44, autosomal dominant nonsyndromic hearing loss 48, autosomal dominant nonsyndromic hearing loss 41, autosomal dominant nonsyndromic hearing loss 49, autosomal dominant nonsyndromic hearing loss 43, autosomal dominant nonsyndromic hearing loss 28, autosomal dominant nonsyndromic hearing loss 31, autosomal dominant nonsyndromic hearing loss 47, autosomal dominant auditory neuropathy 1, autosomal dominant nonsyndromic hearing loss 53, autosomal dominant nonsyndromic hearing loss 27, autosomal dominant nonsyndromic hearing loss 59, autosomal dominant nonsyndromic hearing loss 3B, autosomal dominant nonsyndromic hearing loss 2B, autosomal dominant nonsyndromic hearing loss 50, autosomal dominant nonsyndromic hearing loss 51, autosomal dominant nonsyndromic hearing loss 64, autosomal dominant nonsyndromic hearing loss 33, autosomal dominant nonsyndromic hearing loss 4B, autosomal dominant nonsyndromic hearing loss 56, autosomal dominant nonsyndromic hearing loss 54, autosomal dominant nonsyndromic hearing loss 58, autosomal dominant nonsyndromic hearing loss 65, autosomal dominant nonsyndromic hearing loss 67, autosomal dominant nonsyndromic hearing loss 40, autosomal dominant nonsyndromic hearing loss 69, autosomal dominant nonsyndromic hearing loss 68, autosomal dominant nonsyndromic hearing loss 70, autosomal dominant nonsyndromic hearing loss 66, hearing loss, autosomal dominant 74, hearing loss, autosomal dominant 77, hearing loss, autosomal dominant 81, hearing loss, autosomal dominant 82, hearing loss, autosomal dominant 83, hearing loss, autosomal dominant 84, hearing loss, autosomal dominant 80, hearing loss, autosomal dominant 75, hearing loss, autosomal dominant 76, hearing loss, autosomal dominant 71, hearing loss, autosomal dominant 72, hearing loss, autosomal dominant 73, hearing loss, autosomal dominant 34, with or without inflammation, hearing loss, autosomal dominant 78, hearing loss, autosomal dominant 79, hearing loss, autosomal dominant 85, hearing loss, autosomal dominant 86, hearing loss, autosomal dominant 87, hearing loss, autosomal dominant 88, hearing loss, autosomal dominant 89, hearing loss, autosomal dominant 90, autosomal dominant nonsyndromic hearing loss 91

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

84 retrieved; paginated sample, class counts are floors:

24 uncertain significance, 20 conflicting classifications of pathogenicity, 17 benign, 10 likely pathogenic, 5 pathogenic/likely pathogenic, 3 benign/likely benign, 3 pathogenic, 1 likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1175708	NM_001854.4(COL11A1):c.4519-2del	COL11A1	Pathogenic	criteria provided, single submitter
1216773	NM_001854.4(COL11A1):c.2513G>A (p.Gly838Glu)	COL11A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1304338	NM_001854.4(COL11A1):c.2241+5G>T	COL11A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324096	NM_001854.4(COL11A1):c.1245+1G>A	COL11A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1396245	NM_001854.4(COL11A1):c.3168+1G>A	COL11A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
498797	NM_001854.4(COL11A1):c.4547G>T (p.Gly1516Val)	COL11A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
620141	NM_001854.4(COL11A1):c.4084C>T (p.Arg1362Ter)	COL11A1	Pathogenic	criteria provided, multiple submitters, no conflicts
666252	NM_001854.4(COL11A1):c.652-2A>C	COL11A1	Pathogenic	no assertion criteria provided
1172516	NM_001854.4(COL11A1):c.2287G>T (p.Gly763Ter)	COL11A1	Likely pathogenic	criteria provided, single submitter
1174529	NC_000001.10:g.(103388956_103400026)(104094395?)del	COL11A1	Likely pathogenic	criteria provided, single submitter
1179083	NM_001854.4(COL11A1):c.4186G>T (p.Gly1396Cys)	COL11A1	Likely pathogenic	criteria provided, single submitter
1708056	NM_001854.4(COL11A1):c.3600+2T>C	COL11A1	Likely pathogenic	criteria provided, single submitter
3062163	NM_001854.4(COL11A1):c.1473_1475inv (p.Met492Ter)	COL11A1	Likely pathogenic	criteria provided, single submitter
3336601	NM_001854.4(COL11A1):c.4356G>A (p.Lys1452=)	COL11A1	Likely pathogenic	criteria provided, single submitter
424907	NM_001854.4(COL11A1):c.652-1G>C	COL11A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4294470	NM_001854.4(COL11A1):c.1939G>T (p.Glu647Ter)	COL11A1	Likely pathogenic	criteria provided, single submitter
4526648	NM_001854.4(COL11A1):c.1690C>T (p.Arg564Ter)	COL11A1	Likely pathogenic	criteria provided, single submitter
493048	NM_001854.4(COL11A1):c.4302+2T>C	COL11A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1021355	NM_001854.4(COL11A1):c.907G>A (p.Val303Ile)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1038628	NM_001854.4(COL11A1):c.3692G>T (p.Gly1231Val)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1056960	NM_001854.4(COL11A1):c.2231A>G (p.Lys744Arg)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1205360	NM_001854.4(COL11A1):c.2421A>T (p.Arg807Ser)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1206960	NM_001854.4(COL11A1):c.3068C>A (p.Ala1023Glu)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1314615	NM_001854.4(COL11A1):c.565C>T (p.Pro189Ser)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1357917	NM_001854.4(COL11A1):c.2285G>A (p.Arg762Gln)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1418086	NM_001854.4(COL11A1):c.4709T>C (p.Leu1570Pro)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1508766	NM_001854.4(COL11A1):c.5231A>G (p.Tyr1744Cys)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1679801	NM_001854.4(COL11A1):c.1351-1G>A	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1961384	NM_001854.4(COL11A1):c.2203C>G (p.Pro735Ala)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
198474	NM_001854.4(COL11A1):c.965C>T (p.Pro322Leu)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · 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
COL11A1	Strong	Autosomal dominant	hearing loss, autosomal dominant 37	17

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL11A1	Orphanet:2021	Fibrochondrogenesis
COL11A1	Orphanet:440354	Autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome
COL11A1	Orphanet:560	Marshall syndrome
COL11A1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
COL11A1	Orphanet:90654	Stickler syndrome type 2

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COL11A1	HGNC:2186	ENSG00000060718	P12107	Collagen alpha-1(XI) chain	gencc,clinvar
AMY2A	HGNC:477	ENSG00000243480	P04746	Pancreatic alpha-amylase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL11A1	Collagen alpha-1(XI) chain	May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL11A1	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen
AMY2A	Enzyme (other)	yes	3.2.1.1	Alpha_amylase, GH13_cat_dom, A-amylase/branching_C

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	1
periodontal ligament	1
tibia	1
body of pancreas	1
islet of Langerhans	1
pancreas	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL11A1	209	broad	marker	tibia, cartilage tissue, periodontal ligament
AMY2A	125	tissue_specific	marker	body of pancreas, pancreas, islet of Langerhans

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL11A1	2,433
AMY2A	1,844

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AMY2A	P04746	51

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COL11A1	P12107	53.06

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Digestion of dietary carbohydrate	1	475.8×	0.014	AMY2A
Digestion and absorption	1	380.7×	0.014	AMY2A
Digestion	1	285.5×	0.014	AMY2A
MET activates PTK2 signaling	1	190.3×	0.014	COL11A1
Developmental Lineage of Pancreatic Acinar Cells	1	150.3×	0.014	AMY2A
Collagen chain trimerization	1	129.8×	0.014	COL11A1
Developmental Lineage of Pancreatic Ductal Cells	1	114.2×	0.014	COL11A1
Developmental Cell Lineages	1	112.0×	0.014	AMY2A
Assembly of collagen fibrils and other multimeric structures	1	100.2×	0.014	COL11A1
Collagen degradation	1	87.8×	0.014	COL11A1
Collagen biosynthesis and modifying enzymes	1	85.2×	0.014	COL11A1
Non-integrin membrane-ECM interactions	1	77.2×	0.014	COL11A1
Developmental Biology	1	7.2×	0.134	AMY2A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
tendon development	1	2106.5×	0.003	COL11A1
polysaccharide digestion	1	2106.5×	0.003	AMY2A
carbohydrate catabolic process	1	1685.2×	0.003	AMY2A
proteoglycan metabolic process	1	936.2×	0.004	COL11A1
chondrocyte development	1	468.1×	0.005	COL11A1
detection of mechanical stimulus involved in sensory perception of sound	1	468.1×	0.005	COL11A1
cartilage condensation	1	383.0×	0.005	COL11A1
ventricular cardiac muscle tissue morphogenesis	1	351.1×	0.005	COL11A1
endodermal cell differentiation	1	247.8×	0.007	COL11A1
embryonic skeletal system morphogenesis	1	195.9×	0.008	COL11A1
inner ear morphogenesis	1	150.5×	0.009	COL11A1
collagen fibril organization	1	112.3×	0.011	COL11A1
carbohydrate metabolic process	1	68.0×	0.017	AMY2A
sensory perception of sound	1	50.5×	0.021	COL11A1
visual perception	1	39.8×	0.025	COL11A1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
AMY2A	ACARBOSE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AMY2A	1	4
COL11A1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ACARBOSE	4	AMY2A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
AMY2A	20	Binding:15, Functional:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AMY2A	3.2.1.1	alpha-amylase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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)
ACARBOSE	4	AMY2A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	AMY2A
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	1	COL11A1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
COL11A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.