ACTA2

Chr 10AD

actin alpha 2, smooth muscle

Also known as: ACTSA, SMDYS

This gene encodes one of six different actin proteins. Actins are highly conserved proteins that are involved in cell motility, structure, integrity, and intercellular signaling. The encoded protein is a smooth muscle actin that is involved in vascular contractility and blood pressure homeostasis. Mutations in this gene cause a variety of vascular diseases, such as thoracic aortic disease, coronary artery disease, stroke, and Moyamoya disease, as well as multisystemic smooth muscle dysfunction syndrome. [provided by RefSeq, Sep 2017]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Aortic aneurysm, familial thoracic 6MIM #611788
AD
Moyamoya disease 5MIM #614042
Smooth muscle dysfunction syndromeMIM #613834
AD

Clinical highlights

Gene-disease validity (ClinGen)
multisystemic smooth muscle dysfunction syndrome · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.
7
Active trials
Pubs (1 yr)
P/LP submissions
P/LP missense
0.36
LOEUF
LOF
Mechanism· predicted
📖
GeneReview available — ACTA2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint?
0.36LOEUF
pLI 0.930
Z-score 3.41
OE 0.12 (0.050.36)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
3.20Z-score
OE missense 0.40 (0.340.48)
91 obs / 226.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.12 (0.050.36)
00.351.4
Missense OE?0.40 (0.340.48)
00.61.4
Synonymous OE?0.85
01.21.6
LoF obs/exp: 2 / 17.3Missense obs/exp: 91 / 226.5Syn Z: 1.08

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ACTA2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Rare DisordersUndiagnosed DisordersDisorders of Unknown Prevalence

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

RECRUITING
NCT01793168Sanford HealthStarted 2010-07
HIV-1-infection

DORAvirine Versus DOlutegravir Based Antiretroviral Regimens in Treatment-naïve People Living With HIV-1 Infection

RECRUITING
NCT06203132Phase PHASE3ANRS, Emerging Infectious DiseasesStarted 2025-01-27
Doravirine + tenofovir DF + lamivudineDolutegravir + tenofovir DF + lamivudine or emtricitabine
Metastatic Colorectal CancerMetastatic Cancer to Liver

FAPI Molecular Imaging for Diagnosis of the CMS4 Unfavorable Colorectal Cancer Subtype

RECRUITING
NCT06191120Phase NAUMC UtrechtStarted 2024-08-05
[18F]-ALF-FAPI-74 PET/CT scan
AIDS-Related Kaposi SarcomaSkin Kaposi Sarcoma

Nirogacestat in Patients With Kaposi Sarcoma

NOT YET RECRUITING
NCT07539454Phase PHASE2AIDS Malignancy ConsortiumStarted 2026-09-17
Biospecimen CollectionChest RadiographyComputed Tomography
Chronic Kidney DiseasesMAFLD

Pathogenesis of Chronic Kidney Disease Associated With Metabolic Dysfunction- Associated Fatty Liver Disease (MAFLD) and Treatment Response of Oral Semaglutide.

NOT YET RECRUITING
NCT07391267Phase NAInstitute of Liver and Biliary Sciences, IndiaStarted 2026-02-01
Semaglutide Oral TabletPlaceboStandard medical treatment
Multisystemic Smooth Muscle Dysfunction Syndrome

A Single Patient Study of Sapropterin for Multisystem Smooth Muscle Dysfunction Syndrome

NOT YET RECRUITING
NCT07574034Phase NAGregor AndelfingerStarted 2026-06-01
Kuvan (Sapropterine)
Cirrhosis, Liver

EGCG for Hepatocellular Carcinoma Chemoprevention

RECRUITING
NCT06015022Phase PHASE2University of Texas Southwestern Medical CenterStarted 2024-09-01
Epigallocatechin gallate (EGCG)Placebo