ACTG1

Chr 17AD

actin gamma 1

Also known as: ACT, ACTG, DFNA20, DFNA26, HEL-176

NCBI Gene: 71ENSG00000184009UniProt: P63261

Actins are highly conserved proteins that are involved in various types of cell motility and in maintenance of the cytoskeleton. Three main groups of actin isoforms have been identified in vertebrate animals: alpha, beta, and gamma. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins co-exist in most cell types as components of the cytoskeleton and as mediators of internal cell motility. Actin gamma 1, encoded by this gene, is a cytoplasmic actin found in all cell types. Mutations in this gene are associated with DFNA20/26, a subtype of autosomal dominant non-syndromic sensorineural progressive hearing loss and also with Baraitser-Winter syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

Primary Disease Associations & Inheritance

Baraitser-Winter syndrome 2MIM #614583
AD
Deafness, autosomal dominant 20/26MIM #604717
AD
584
ClinVar variants
45
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ACTG1
🧬
Gene-Disease Validity (ClinGen)
Baraitser-winter syndrome 2 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
45 Pathogenic / Likely Pathogenic· 162 VUS of 584 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.86LOEUF
pLI 0.005
Z-score 1.95
OE 0.43 (0.24–0.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.16Z-score
OE missense 0.37 (0.30–0.45)
72 obs / 196.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.43 (0.24–0.86)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.37 (0.30–0.45)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.3.73
0≤1.21.6
LoF obs/exp: 6 / 13.8Missense obs/exp: 72 / 196.7Syn Z: -18.97

ClinVar Variant Classifications

584 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic29
VUS162
Likely Benign327
Benign18
Conflicting32
16
Pathogenic
29
Likely Pathogenic
162
VUS
327
Likely Benign
18
Benign
32
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
6
10
0
16
Likely Pathogenic
0
26
3
0
29
VUS
9
119
25
9
162
Likely Benign
0
1
101
225
327
Benign
0
0
14
4
18
Conflicting
—32
Total9152153238584

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ACTG1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ACTG1-related Baraitser-Winter syndrome

definitive
ADGain Of FunctionAltered Gene Product Structure
Dev. DisordersEyeEar
G2P ↗
missense variantinframe deletioninframe insertion

ACTG1-related isolated ocular coloboma

limited
ADUndeterminedAltered Gene Product Structure
Eye
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
ACTIN, GAMMA-1; ACTG1
MIM #102560 · *

Baraitser-Winter syndrome 2

MIM #614583

Molecular basis of disorder known

Autosomal dominant

Deafness, autosomal dominant 20/26

MIM #604717

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — ACTG1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Baraitser-Winter cerebrofrontofacial syndrome.
Yates TM et al.·Clin Genet
2017Review
Molecular genotype-phenotype correlation in ACTB- and ACTG1-related non-muscle actinopathies.
Di Donato N et al.·Am J Hum Genet
2026
Genetic etiology of non-syndromic hearing loss in Europe.
Del Castillo I et al.·Hum Genet
2022Review
De Novo ACTG1 Variant Expands the Phenotype and Genotype of Partial Deafness and Baraitser-Winter Syndrome.
Dawidziuk M et al.·Int J Mol Sci
2022Case report
Bioinformatic identification and experiment validation revealed that ACTG1 is a promising prognostic signature and therapeutic target for sepsis.
Yao H et al.·J Leukoc Biol
2023
Mendelian non-syndromic and syndromic hearing loss genes contribute to presbycusis.
Cornejo-Sanchez DM et al.·Eur J Hum Genet
2025
A likely pathogenic ACTG1 variant in a child showing partial phenotypic overlap with Baraitser-Winter syndrome.
Graziani L et al.·Am J Med Genet A
2023Case report
Inherited deficiency of DIAPH1 identifies a DNA double strand break repair pathway regulated by γ-actin.
Woodward BL et al.·Nat Commun
2025
Update on the ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome.
Di Donato N et al.·Am J Med Genet A
2016
Cochleo-vestibular phenotype in patients with pathogenic variations in the ACTG1 gene.
González-Aguado R et al.·Acta Otorrinolaringol Esp (Engl Ed)
2025Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools