Autosomal recessive nonsyndromic hearing loss 53

Summary

Autosomal recessive nonsyndromic hearing loss 53 (MONDO:0012333) is a disease caused by COL11A2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: COL11A2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 84

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive nonsyndromic hearing loss 53
Mondo ID	MONDO:0012333
MeSH	C566453
OMIM	609706
DOID	DOID:0110509
UMLS	C1864746
MedGen	400602
GARD	0022616
Is cancer (heuristic)	no

Also known as: autosomal recessive deafness 53 · autosomal recessive nonsyndromic deafness 53 · autosomal recessive nonsyndromic deafness caused by mutation in COL11A2 · autosomal recessive nonsyndromic deafness type 53 · COL11A2 autosomal recessive nonsyndromic deafness · deafness, autosomal recessive 53 · deafness, autosomal recessive type 53 · DFNB53

Data availability: 84 ClinVar variants · 3 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 disease › hearing loss, autosomal recessive › autosomal recessive nonsyndromic hearing loss 53

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 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, autosomal recessive nonsyndromic hearing loss 97, 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

84 retrieved; paginated sample, class counts are floors:

26 conflicting classifications of pathogenicity, 15 benign, 14 uncertain significance, 12 likely pathogenic, 8 pathogenic, 5 pathogenic/likely pathogenic, 3 likely benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
160366	NM_080680.3(COL11A2):c.109G>T (p.Ala37Ser)	COL11A2	Pathogenic	criteria provided, single submitter
17128	NM_080680.3(COL11A2):c.3991C>T (p.Arg1331Ter)	COL11A2	Pathogenic	criteria provided, multiple submitters, no conflicts
218349	NM_080680.3(COL11A2):c.2662C>A (p.Pro888Thr)	COL11A2	Pathogenic	no assertion criteria provided
2757004	NM_080680.3(COL11A2):c.3329dup (p.Gly1111fs)	COL11A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2913625	NM_080680.3(COL11A2):c.4798C>T (p.Arg1600Ter)	COL11A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3017031	NM_080680.3(COL11A2):c.1297C>T (p.Arg433Ter)	COL11A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3601055	NM_080680.3(COL11A2):c.3512_3528+1del	COL11A2	Pathogenic	criteria provided, single submitter
3601057	NM_080680.3(COL11A2):c.3636+1G>A	COL11A2	Pathogenic	criteria provided, single submitter
3601060	NM_080680.3(COL11A2):c.4483-1G>C	COL11A2	Pathogenic	criteria provided, single submitter
4072339	NM_080680.3(COL11A2):c.840T>A (p.Tyr280Ter)	COL11A2	Pathogenic	criteria provided, single submitter
4072340	NM_080680.3(COL11A2):c.1573C>T (p.Gln525Ter)	COL11A2	Pathogenic	criteria provided, single submitter
423882	NM_080680.3(COL11A2):c.3058C>T (p.Arg1020Ter)	COL11A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
813821	NM_080680.3(COL11A2):c.3385G>A (p.Gly1129Arg)	COL11A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1687174	NM_080680.3(COL11A2):c.4294G>T (p.Gly1432Ter)	COL11A2	Likely pathogenic	criteria provided, single submitter
3593490	NM_080680.3(COL11A2):c.4081A>T (p.Lys1361Ter)	COL11A2	Likely pathogenic	criteria provided, single submitter
3593492	NM_080680.3(COL11A2):c.3746G>A (p.Gly1249Glu)	COL11A2	Likely pathogenic	criteria provided, single submitter
3593493	NM_080680.3(COL11A2):c.2734_2736+14del	COL11A2	Likely pathogenic	criteria provided, single submitter
3593494	NM_080680.3(COL11A2):c.2589dup (p.Ser864fs)	COL11A2	Likely pathogenic	criteria provided, single submitter
3593495	NM_080680.3(COL11A2):c.2567G>A (p.Gly856Glu)	COL11A2	Likely pathogenic	criteria provided, single submitter
3593497	NM_080680.3(COL11A2):c.2062G>A (p.Gly688Arg)	COL11A2	Likely pathogenic	criteria provided, single submitter
3593499	NM_080680.3(COL11A2):c.129_132dup (p.Asp45delinsProTer)	COL11A2	Likely pathogenic	criteria provided, single submitter
3601058	NM_080680.3(COL11A2):c.4339G>C (p.Gly1447Arg)	COL11A2	Likely pathogenic	criteria provided, single submitter
3601061	NM_080680.3(COL11A2):c.4553G>C (p.Gly1518Ala)	COL11A2	Likely pathogenic	criteria provided, single submitter
634526	NM_080680.3(COL11A2):c.2754del (p.Gly919fs)	COL11A2	Likely pathogenic	criteria provided, single submitter
813820	NM_080680.3(COL11A2):c.968dup (p.Ala324fs)	COL11A2	Likely pathogenic	criteria provided, single submitter
1129450	NM_080680.3(COL11A2):c.2220G>T (p.Glu740Asp)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1200125	NM_080680.3(COL11A2):c.973G>A (p.Asp325Asn)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1213287	NM_080680.3(COL11A2):c.1999G>A (p.Gly667Ser)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1375471	NM_080680.3(COL11A2):c.1399G>A (p.Val467Met)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1398032	NM_080680.3(COL11A2):c.2179G>A (p.Gly727Arg)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 20 · 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
COL11A2	Definitive	Autosomal dominant	autosomal dominant nonsyndromic hearing loss 13	20

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL11A2	Orphanet:1427	Autosomal recessive otospondylomegaepiphyseal dysplasia
COL11A2	Orphanet:166100	Autosomal dominant otospondylomegaepiphyseal dysplasia
COL11A2	Orphanet:2021	Fibrochondrogenesis
COL11A2	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
COL11A2	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
COL11A2	HGNC:2187	ENSG00000204248	P13942	Collagen alpha-2(XI) chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL11A2	Collagen alpha-2(XI) chain	May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL11A2	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen

Expression context

Cohort genes with no expression data: 0.

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
adenohypophysis	1
male germ line stem cell (sensu Vertebrata) in testis	1
pituitary gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL11A2	134	broad	yes	pituitary gland, male germ line stem cell (sensu Vertebrata) in testis, adenohypophysis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL11A2	1,583

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COL11A2	P13942	50.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
MET activates PTK2 signaling	1	380.7×	0.006	COL11A2
Collagen chain trimerization	1	259.6×	0.006	COL11A2
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.006	COL11A2
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.006	COL11A2
Collagen degradation	1	175.7×	0.006	COL11A2
Collagen biosynthesis and modifying enzymes	1	170.4×	0.006	COL11A2
Non-integrin membrane-ECM interactions	1	154.3×	0.006	COL11A2

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
soft palate development	1	3370.4×	0.002	COL11A2
cartilage development	1	251.5×	0.007	COL11A2
roof of mouth development	1	247.8×	0.007	COL11A2
collagen fibril organization	1	224.7×	0.007	COL11A2
skeletal system development	1	125.8×	0.010	COL11A2
sensory perception of sound	1	100.9×	0.010	COL11A2

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COL11A2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	COL11A2

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)
COL11A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.