ACTA2
actin alpha 2, smooth muscle, the group of Actins
Basic information
Region (hg38): 10:88934822-88991339
Links
Phenotypes
GenCC
Source:
- 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:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Moyamoya disease 5; Smooth muscle dysfunction syndrome; Aortic aneurysm, familial thoracic 6 | AD | Cardiovascular | Surveillance 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 management | Cardiovascular; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic | 17994018; 19409525; 22051261; 22302747; 24243736; 29300374 |
ClinVar
This is a list of variants' phenotypes submitted to
- 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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 158 | 163 | ||||
| missense | 12 | 36 | 251 | 300 | ||
| nonsense | 11 | 12 | ||||
| start loss | 2 | 2 | ||||
| frameshift | 18 | 20 | ||||
| splice donor/acceptor (+/-2bp) | 13 | |||||
| Total | 14 | 43 | 294 | 159 | 0 |
Highest pathogenic variant AF is 0.00000657549
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ACTA2 | protein_coding | protein_coding | ENST00000458208 | 8 | 56317 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.930 | 0.0698 | 125671 | 0 | 6 | 125677 | 0.0000239 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.20 | 91 | 227 | 0.402 | 0.0000141 | 2490 |
| Missense in Polyphen | 18 | 82.097 | 0.21925 | 898 | ||
| Synonymous | 1.08 | 72 | 84.7 | 0.850 | 0.00000541 | 737 |
| Loss of Function | 3.41 | 2 | 17.3 | 0.116 | 9.34e-7 | 201 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.0000353 | 0.0000352 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Low | Medium |
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