autosomal dominant nonsyndromic hearing loss 2B

Summary

autosomal dominant nonsyndromic hearing loss 2B (MONDO:0012976) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant nonsyndromic hearing loss 2B
Mondo ID	MONDO:0012976
MeSH	C567214
OMIM	612644
DOID	DOID:0110559
UMLS	C2675236
MedGen	390742
GARD	0018131
Is cancer (heuristic)	no

Also known as: autosomal dominant deafness 2B · autosomal dominant nonsyndromic deafness 2B · autosomal dominant nonsyndromic deafness caused by mutation in GJB3 · autosomal dominant nonsyndromic deafness type 2B · deafness, autosomal dominant 2B · deafness, autosomal dominant 2b · deafness, autosomal dominant type 2B · DFNA2B · GJB3 autosomal dominant nonsyndromic deafness

Data availability: 17 ClinVar variants · 1 GenCC gene-disease record.

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 › autosomal dominant nonsyndromic hearing loss 2B

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 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 37, 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

17 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 6 conflicting classifications of pathogenicity, 2 benign/likely benign, 1 benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
6491	NM_024009.3(GJB3):c.101T>C (p.Leu34Pro)	GJB3	Pathogenic	criteria provided, single submitter
1402757	NM_024009.3(GJB3):c.302G>A (p.Arg101Gln)	GJB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
163536	NM_024009.3(GJB3):c.652_663del (p.Leu218_Asp221del)	GJB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
289016	NM_024009.3(GJB3):c.499G>A (p.Val167Met)	GJB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
6485	NM_024009.3(GJB3):c.547G>A (p.Glu183Lys)	GJB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
6493	NM_024009.3(GJB3):c.580G>A (p.Ala194Thr)	GJB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
876777	NM_024009.3(GJB3):c.316C>T (p.Arg106Cys)	GJB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1310993	NM_024009.3(GJB3):c.670C>T (p.Arg224Ter)	GJB3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3377531	NM_024009.3(GJB3):c.687del (p.Ser230fs)	GJB3	Uncertain significance	criteria provided, single submitter
3381897	NM_024009.3(GJB3):c.350dup (p.Tyr117Ter)	GJB3	Uncertain significance	criteria provided, single submitter
3893124	NM_024009.3(GJB3):c.50C>A (p.Ser17Tyr)	GJB3	Uncertain significance	criteria provided, single submitter
6486	NM_024009.3(GJB3):c.538C>T (p.Arg180Ter)	GJB3	Uncertain significance	criteria provided, multiple submitters, no conflicts
6492	NM_024009.3(GJB3):c.497A>G (p.Asn166Ser)	GJB3	Uncertain significance	criteria provided, single submitter
806107	NM_024009.3(GJB3):c.342del (p.Lys115fs)	GJB3	Uncertain significance	criteria provided, multiple submitters, no conflicts
46084	NM_024009.3(GJB3):c.357C>T (p.Asn119=)	GJB3	Benign	criteria provided, multiple submitters, no conflicts
46085	NM_024009.3(GJB3):c.579C>T (p.Gly193=)	GJB3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
786722	NM_024009.3(GJB3):c.250G>A (p.Val84Ile)	GJB3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · Orphanet: 4 · 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
GJB3	Moderate	Autosomal dominant	autosomal recessive nonsyndromic hearing loss 1A	17

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GJB3	Orphanet:139512	Neuropathy with hearing impairment
GJB3	Orphanet:317	Erythrokeratodermia variabilis
GJB3	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
GJB3	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
GJB3	HGNC:4285	ENSG00000188910	O75712	Gap junction beta-3 protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GJB3	Gap junction beta-3 protein	One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.

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)
GJB3	Other/Unknown	no		Connexin, Connexin31, Connexin_N

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
skin of abdomen	1
skin of leg	1
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GJB3	183	broad	marker	skin of abdomen, skin of leg, upper arm skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GJB3	782

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GJB3	O75712	79.29

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Gap junction assembly	1	292.8×	0.004	GJB3
Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin	1	278.5×	0.004	GJB3

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
placenta development	1	443.5×	0.005	GJB3
cell-cell signaling	1	69.6×	0.014	GJB3

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GJB3	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	GJB3

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)
GJB3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.