ACTA2

actin alpha 2, smooth muscle, the group of Actins

Basic information

Region (hg38): 10:88934822-88991339

Links

ENSG00000107796NCBI:59OMIM:102620HGNC:130Uniprot:P62736AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • aortic aneurysm, familial thoracic 6 (Strong), mode of inheritance: AD
  • Moyamoya disease 5 (Strong), mode of inheritance: AD
  • connective tissue disorder (Moderate), mode of inheritance: AD
  • familial thoracic aortic aneurysm and aortic dissection (Supportive), mode of inheritance: AD
  • multisystemic smooth muscle dysfunction syndrome (Supportive), mode of inheritance: Unknown
  • multisystemic smooth muscle dysfunction syndrome (Definitive), mode of inheritance: AD
  • Moyamoya disease 5 (Strong), mode of inheritance: AD
  • multisystemic smooth muscle dysfunction syndrome (Strong), mode of inheritance: AD
  • aortic aneurysm, familial thoracic 6 (Strong), mode of inheritance: AD
  • familial thoracic aortic aneurysm and aortic dissection (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Moyamoya disease 5; Smooth muscle dysfunction syndrome; Aortic aneurysm, familial thoracic 6ADCardiovascularSurveillance for cardiovascular complications (eg, aortic aneurysm), as well as related preventive measures to help control contributory factors may reduce morbidity and mortality by allowing early diagnosis and treatment; There has been a reported increased risk of aortic dissection with minimal aortic dilatation during the pregnancies of affected women, and awareness may allow monitoring and managementCardiovascular; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic17994018; 19409525; 22051261; 22302747; 24243736; 29300374

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACTA2 gene.

  • Aortic_aneurysm,_familial_thoracic_6 (393 variants)
  • Familial_thoracic_aortic_aneurysm_and_aortic_dissection (327 variants)
  • not_provided (153 variants)
  • not_specified (36 variants)
  • Multisystemic_smooth_muscle_dysfunction_syndrome (33 variants)
  • Moyamoya_disease_5 (20 variants)
  • ACTA2-related_disorder (16 variants)
  • Cardiovascular_phenotype (9 variants)
  • Connective_tissue_disorder (6 variants)
  • Familial_aortopathy (4 variants)
  • Moyamoya_disease (3 variants)
  • Isolated_thoracic_aortic_aneurysm (3 variants)
  • Thoracic_aortic_aneurysm_or_dissection (2 variants)
  • Congenital_aneurysm_of_ascending_aorta (1 variants)
  • Arterial_tortuosity (1 variants)
  • Descending_aortic_dissection (1 variants)
  • See_cases (1 variants)
  • alterations_of_great_arteries_and_veins (1 variants)
  • Marfan_syndrome (1 variants)
  • Aneurysm_of_descending_aorta (1 variants)
  • Connective_tissue_dysplasia (1 variants)
  • Aortic_aneurysm,_familial_thoracic_2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACTA2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001613.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
5
clinvar
158
clinvar
163
missense
12
clinvar
36
clinvar
251
clinvar
1
clinvar
300
nonsense
1
clinvar
11
clinvar
12
start loss
2
2
frameshift
2
clinvar
18
clinvar
20
splice donor/acceptor (+/-2bp)
2
clinvar
4
clinvar
7
clinvar
13
Total 14 43 294 159 0

Highest pathogenic variant AF is 0.00000657549

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ACTA2protein_codingprotein_codingENST00000458208 856317
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9300.0698125671061256770.0000239
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense3.20912270.4020.00001412490
Missense in Polyphen1882.0970.21925898
Synonymous1.087284.70.8500.00000541737
Loss of Function3.41217.30.1169.34e-7201

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00002890.0000289
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.00004620.0000462
European (Non-Finnish)0.00003530.0000352
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.;
Disease
DISEASE: Note=ACTA2 mutations predispose patients to a variety of diffuse and diverse vascular diseases, premature onset coronary artery disease (CAD), premature ischemic strokes and Moyamoya disease. {ECO:0000269|PubMed:19409525}.; DISEASE: Aortic aneurysm, familial thoracic 6 (AAT6) [MIM:611788]: A disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. {ECO:0000269|PubMed:17994018, ECO:0000269|PubMed:19409525, ECO:0000269|PubMed:19639654}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Moyamoya disease 5 (MYMY5) [MIM:614042]: A progressive cerebral angiopathy characterized by bilateral intracranial carotid artery stenosis and telangiectatic vessels in the region of the basal ganglia. The abnormal vessels resemble a 'puff of smoke' (moyamoya) on cerebral angiogram. Affected individuals can develop transient ischemic attacks and/or cerebral infarction, and rupture of the collateral vessels can cause intracranial hemorrhage. Hemiplegia of sudden onset and epileptic seizures constitute the prevailing presentation in childhood, while subarachnoid bleeding occurs more frequently in adults. {ECO:0000269|PubMed:20970362}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Multisystemic smooth muscle dysfunction syndrome (MSMDYS) [MIM:613834]: A syndrome characterized by dysfunction of smooth muscle cells throughout the body, leading to aortic and cerebrovascular disease, fixed dilated pupils, hypotonic bladder, malrotation, and hypoperistalsis of the gut and pulmonary hypertension. {ECO:0000269|PubMed:20734336}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Relaxin signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Myometrial Relaxation and Contraction Pathways;Striated Muscle Contraction;Protein alkylation leading to liver fibrosis;Smooth Muscle Contraction;Muscle contraction;EGFR1;PDGFR-beta signaling pathway (Consensus)

Recessive Scores

pRec
0.156

Intolerance Scores

loftool
0.129
rvis_EVS
-0.27
rvis_percentile_EVS
33.97

Haploinsufficiency Scores

pHI
0.767
hipred
Y
hipred_score
0.698
ghis
0.651

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.834

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumLowLow
Primary ImmunodeficiencyMediumLowMedium
CancerMediumLowMedium

Mouse Genome Informatics

Gene name
Acta2
Phenotype
muscle phenotype; vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan);

Zebrafish Information Network

Gene name
acta2
Affected structure
intestine
Phenotype tag
abnormal
Phenotype quality
non-contractile

Gene ontology

Biological process
muscle contraction;regulation of blood pressure;response to virus;positive regulation of gene expression;vascular smooth muscle contraction;positive regulation of transcription, DNA-templated;glomerular mesangial cell development;mesenchyme migration
Cellular component
extracellular space;cytoplasm;cytosol;actin cytoskeleton;lamellipodium;filopodium;smooth muscle contractile fiber;protein-containing complex;cell body;extracellular exosome
Molecular function
ATP binding;protein kinase binding