Autosomal dominant nonsyndromic hearing loss 20

Summary

Autosomal dominant nonsyndromic hearing loss 20 (MONDO:0011480) is a disease caused by ACTG1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ACTG1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 485

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant nonsyndromic hearing loss 20
Mondo ID	MONDO:0011480
MeSH	C565754
OMIM	604717
DOID	DOID:0110550
UMLS	C1858172
MedGen	346852
GARD	0018111
Is cancer (heuristic)	no

Also known as: ACTG1 autosomal dominant nonsyndromic deafness · autosomal dominant deafness 20 · autosomal dominant nonsyndromic deafness 20 · autosomal dominant nonsyndromic deafness caused by mutation in ACTG1 · autosomal dominant nonsyndromic deafness type 20 · deafness, autosomal dominant 20 · deafness, autosomal dominant 20/26 · deafness, autosomal dominant type 20 · DFNA20 · DFNA26

Data availability: 485 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 › autosomal dominant nonsyndromic hearing loss 20

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 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 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

485 retrieved; paginated sample, class counts are floors:

265 likely benign, 95 uncertain significance, 37 conflicting classifications of pathogenicity, 37 benign/likely benign, 23 benign, 12 likely pathogenic, 8 pathogenic/likely pathogenic, 7 pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1483014	NM_001614.5(ACTG1):c.1013C>G (p.Ser338Trp)	ACTG1	Pathogenic	criteria provided, single submitter
18316	NM_001614.5(ACTG1):c.353A>T (p.Lys118Met)	ACTG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
18317	NM_001614.5(ACTG1):c.994C>G (p.Pro332Ala)	ACTG1	Pathogenic	criteria provided, single submitter
18318	NM_001614.5(ACTG1):c.791C>T (p.Pro264Leu)	ACTG1	Pathogenic	criteria provided, multiple submitters, no conflicts
18320	NM_001614.5(ACTG1):c.1109T>C (p.Val370Ala)	ACTG1	Pathogenic	no assertion criteria provided
18321	NM_001614.5(ACTG1):c.354G>C (p.Lys118Asn)	ACTG1	Pathogenic	no assertion criteria provided
18322	NM_001614.5(ACTG1):c.721G>A (p.Glu241Lys)	ACTG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2444245	NM_001614.5(ACTG1):c.151G>A (p.Asp51Asn)	ACTG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
29587	NM_001614.5(ACTG1):c.404C>T (p.Ala135Val)	ACTG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
29589	NM_001614.5(ACTG1):c.760C>T (p.Arg254Trp)	ACTG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
29590	NM_001614.5(ACTG1):c.766C>T (p.Arg256Trp)	ACTG1	Pathogenic	criteria provided, single submitter
505063	NM_001614.5(ACTG1):c.548G>A (p.Arg183Gln)	ACTG1	Pathogenic	criteria provided, multiple submitters, no conflicts
517300	NM_001614.5(ACTG1):c.617G>A (p.Arg206Gln)	ACTG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
807364	NM_001614.5(ACTG1):c.94C>T (p.Pro32Ser)	ACTG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
808333	NM_001614.5(ACTG1):c.547C>T (p.Arg183Trp)	ACTG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1174523	NM_001614.5(ACTG1):c.440G>A (p.Arg147His)	ACTG1	Likely pathogenic	criteria provided, single submitter
1526065	NM_001614.5(ACTG1):c.848T>C (p.Met283Thr)	ACTG1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1685234	NM_001614.5(ACTG1):c.434C>T (p.Ser145Phe)	ACTG1	Likely pathogenic	criteria provided, single submitter
18315	NM_001614.5(ACTG1):c.266C>T (p.Thr89Ile)	ACTG1	Likely pathogenic	criteria provided, single submitter
1994494	NM_001614.5(ACTG1):c.431C>T (p.Ala144Val)	ACTG1	Likely pathogenic	criteria provided, single submitter
2003119	NM_001614.5(ACTG1):c.188G>C (p.Gly63Ala)	ACTG1	Likely pathogenic	criteria provided, single submitter
2951653	NM_001614.5(ACTG1):c.714_716del (p.Lys238_Ser239delinsAsn)	ACTG1	Likely pathogenic	criteria provided, single submitter
3601143	NM_001614.5(ACTG1):c.494T>A (p.Ile165Asn)	ACTG1	Likely pathogenic	criteria provided, single submitter
3751495	NM_001614.5(ACTG1):c.442A>G (p.Thr148Ala)	ACTG1	Likely pathogenic	criteria provided, single submitter
473006	NM_001614.5(ACTG1):c.457A>G (p.Met153Val)	ACTG1	Likely pathogenic	criteria provided, single submitter
803470	NM_001614.5(ACTG1):c.608C>T (p.Thr203Met)	ACTG1	Likely pathogenic	criteria provided, single submitter
978237	NM_001614.5(ACTG1):c.493A>G (p.Ile165Val)	ACTG1	Likely pathogenic	criteria provided, single submitter
1174527	NM_001614.5(ACTG1):c.826G>A (p.Glu276Lys)	ACTG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1175712	NM_001614.5(ACTG1):c.830C>T (p.Thr277Ile)	ACTG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1188717	NM_001614.5(ACTG1):c.124-9C>T	ACTG1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · 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
ACTG1	Definitive	Autosomal dominant	nonsyndromic genetic hearing loss	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ACTG1	Orphanet:2995	Baraitser-Winter cerebrofrontofacial syndrome
ACTG1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
ACTG1	Orphanet:98942	Coloboma of choroid and retina
ACTG1	Orphanet:98944	Coloboma of iris

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
ACTG1	HGNC:144	ENSG00000184009	P63261	Actin, cytoplasmic 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ACTG1	Actin, cytoplasmic 2	Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

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)
ACTG1	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS

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
amniotic fluid	1
ileal mucosa	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ACTG1	288	ubiquitous	marker	ileal mucosa, ventricular zone, amniotic fluid

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ACTG1	1,017

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ACTG1	P63261	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 69. 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
Formation of annular gap junctions	1	1038.2×	0.010	ACTG1
GBP-mediated host defense	1	1038.2×	0.010	ACTG1
Gap junction degradation	1	951.7×	0.010	ACTG1
Regulation of CDH1 Function	1	951.7×	0.010	ACTG1
RHOBTB GTPase Cycle	1	815.7×	0.010	ACTG1
Cell-extracellular matrix interactions	1	671.8×	0.010	ACTG1
Gap junction trafficking and regulation	1	475.8×	0.010	ACTG1
Gap junction trafficking	1	475.8×	0.010	ACTG1
RHOBTB2 GTPase cycle	1	475.8×	0.010	ACTG1
Signaling by RAS mutants	1	423.0×	0.010	ACTG1
Interaction between L1 and Ankyrins	1	368.4×	0.010	ACTG1
RHO GTPases activate IQGAPs	1	346.1×	0.010	ACTG1
Parasite infection	1	346.1×	0.010	ACTG1
Leishmania phagocytosis	1	346.1×	0.010	ACTG1
RHO GTPases Activate WASPs and WAVEs	1	317.2×	0.010	ACTG1
Signaling by high-kinase activity BRAF mutants	1	317.2×	0.010	ACTG1
Sensory processing of sound	1	308.6×	0.010	ACTG1
Formation of the dystrophin-glycoprotein complex (DGC)	1	308.6×	0.010	ACTG1
MAP2K and MAPK activation	1	285.5×	0.010	ACTG1
Fcgamma receptor (FCGR) dependent phagocytosis	1	278.5×	0.010	ACTG1
Signaling by RAF1 mutants	1	278.5×	0.010	ACTG1
EPHB-mediated forward signaling	1	265.6×	0.010	ACTG1
Signaling by moderate kinase activity BRAF mutants	1	253.8×	0.010	ACTG1
Paradoxical activation of RAF signaling by kinase inactive BRAF	1	253.8×	0.010	ACTG1
Signaling downstream of RAS mutants	1	253.8×	0.010	ACTG1
Adherens junctions interactions	1	248.3×	0.010	ACTG1
Cell-cell junction organization	1	248.3×	0.010	ACTG1
Oncogenic MAPK signaling	1	248.3×	0.010	ACTG1
Recycling pathway of L1	1	223.9×	0.010	ACTG1
Signaling by VEGF	1	219.6×	0.010	ACTG1

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
morphogenesis of a polarized epithelium	1	4213.0×	0.002	ACTG1
regulation of transepithelial transport	1	4213.0×	0.002	ACTG1
protein localization to bicellular tight junction	1	2808.7×	0.002	ACTG1
tight junction assembly	1	2407.4×	0.002	ACTG1
regulation of stress fiber assembly	1	991.3×	0.003	ACTG1
regulation of synaptic vesicle endocytosis	1	887.0×	0.003	ACTG1
regulation of focal adhesion assembly	1	601.9×	0.004	ACTG1
positive regulation of wound healing	1	526.6×	0.004	ACTG1
maintenance of blood-brain barrier	1	481.5×	0.004	ACTG1
cell motility	1	401.2×	0.004	ACTG1
sarcomere organization	1	383.0×	0.004	ACTG1
platelet aggregation	1	337.0×	0.004	ACTG1
cellular response to type II interferon	1	208.1×	0.006	ACTG1
axonogenesis	1	160.5×	0.008	ACTG1
angiogenesis	1	62.4×	0.017	ACTG1
positive regulation of cell migration	1	61.7×	0.017	ACTG1
positive regulation of gene expression	1	38.7×	0.026	ACTG1

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
ACTG1	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	ACTG1

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)
ACTG1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.