ACTC1

Chr 15AD

actin alpha cardiac muscle 1

Also known as: ACTC, ASD5, CMD1R, CMH11, LVNC4

NCBI Gene: 70 ENSG00000159251 UniProt: P68032 OMIM: 102540

Actins are highly conserved proteins that are involved in various types of cell motility. Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to four others. The protein encoded by this gene belongs to the actin family which is comprised of three main groups of actin isoforms, alpha, beta, and gamma. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. Defects in this gene have been associated with idiopathic dilated cardiomyopathy (IDC) and familial hypertrophic cardiomyopathy (FHC). [provided by RefSeq, Jul 2008]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Atrial septal defect 5MIM #612794

Cardiomyopathy, dilated, 1RMIM #613424

Cardiomyopathy, hypertrophic, 11MIM #612098

Left ventricular noncompaction 4MIM #613424

UniProtCardiomyopathy, familial hypertrophic, 11

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — ACTC1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in ACTC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 1,700

141 rare PASS variants

Rare truncating (LoF)

1 in 8,500

32 rare PASS variants

Rare synonymous (reference)

1 in 360

206 rare PASS variants

Rare missense and truncating variants are carried at similar rates in ACTC1; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 1,600	1 in 6,200
South Asian	~43k	1 in 600	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 2,200	≈ 1 in 15,000
European (Finnish)	~27k	≈ 1 in 8,900	≈ 1 in 26,000
Admixed American	~22k	1 in 980	≈ 1 in 11,000
African / African American	~21k	1 in 3,000	≈ 1 in 17,000
East Asian	~20k	1 in 2,200	≈ 1 in 20,000
Ashkenazi Jewish	~13k	≈ 1 in 3,300	none seen
Middle Eastern	~2,884	≈ 1 in 2,900	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓