ACTB
Chr 7ADactin beta
Also known as: BKRNS, BNS, BRWS1, CSMH, DDS1, PS1TP5BP1, THC8
The protein is a major constituent of the contractile apparatus and one of two nonmuscle cytoskeletal actins that are ubiquitously expressed, functioning in cell motility, structure, integrity, and intercellular signaling. Loss-of-function mutations cause autosomal dominant conditions including Baraitser-Winter syndrome 1 (characterized by intellectual disability with distinctive facial features), dystonia-deafness syndrome 1, and thrombocytopenia with dysmorphic features and developmental delay. The gene is highly intolerant to loss-of-function variants, reflecting the essential role of cytoskeletal actin in cellular function.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Extremely missense-constrained (top ~0.01%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
500 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 7 | 19 | 21 | 0 | 47 |
Likely Pathogenic | 8 | 39 | 8 | 0 | 55 |
VUS | 6 | 107 | 17 | 4 | 134 |
Likely Benign | 0 | 0 | 86 | 149 | 235 |
Benign | 0 | 0 | 5 | 1 | 6 |
Conflicting | — | 9 | |||
| Total | 21 | 165 | 137 | 154 | 486 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ACTB · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight
RECRUITINGGenes Associated With Bone Metabolism in the Saliva During Orthodontic Treatment
ACTIVE NOT RECRUITINGClinical Studies of Endometrial Cytology and Cervical Methylation Assays in Endometrial Cancer Screening and Fertility-Preservation Evaluation
NOT YET RECRUITINGCushing's Syndrome Before and After Treatment (CORRECT)
RECRUITINGAir Pollution, Asthma and Circadian Clocks
ACTIVE NOT RECRUITINGOptimization of Cervical Cancer Screening Among Women Living With HIV in Latin American Countries
ACTIVE NOT RECRUITINGImmuno-inflammatory Response of Erdosteine in COPD
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools