ACTC1
actin alpha cardiac muscle 1, the group of Actins
Basic information
Region (hg38): 15:34790107-34795589
Previous symbols: [ "ACTC" ]
Links
Phenotypes
GenCC
Source:
- hypertrophic cardiomyopathy 11 (Strong), mode of inheritance: AD
- hypertrophic cardiomyopathy 11 (Strong), mode of inheritance: AD
- familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
- hypertrophic cardiomyopathy 11 (Definitive), mode of inheritance: AD
- hypertrophic cardiomyopathy 11 (Strong), mode of inheritance: AD
- atrial septal defect 5 (Strong), mode of inheritance: AD
- dilated cardiomyopathy 1R (Strong), mode of inheritance: AD
- hypertrophic cardiomyopathy (Definitive), mode of inheritance: AD
- dilated cardiomyopathy (Moderate), mode of inheritance: AD
- arrhythmogenic right ventricular cardiomyopathy (No Known Disease Relationship), mode of inheritance: AD
- arthrogryposis syndrome (Moderate), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cardiomyopathy, dilated, 1R; Cardiomyopathy, familial hypertrophic 11; Atrial septal defect 5 | AD | Cardiovascular | Surveillance (including with electrocardiogram and echocardiogram), preventive measures, and medical management of cardiomyopathies may be helpful to help decrease morbidity and mortality | Cardiovascular | 9563954; 10330430; 10966831; 6267253; 17611253; 18467357; 18506004; 17947298; 20301486; 20301725; 21239446 |
| Different ACTC1-related disorders have been associated with pediatric or adult-onset disease, but surveillance beginning in the pediatric period may be beneficial |
ClinVar
This is a list of variants' phenotypes submitted to
- Hypertrophic_cardiomyopathy_11 (474 variants)
- Dilated_cardiomyopathy_1R (473 variants)
- Atrial_septal_defect_5 (469 variants)
- Cardiovascular_phenotype (169 variants)
- not_provided (165 variants)
- Cardiomyopathy (158 variants)
- Hypertrophic_cardiomyopathy (135 variants)
- not_specified (92 variants)
- ACTC1-related_disorder (25 variants)
- Primary_dilated_cardiomyopathy (7 variants)
- Primary_familial_hypertrophic_cardiomyopathy (6 variants)
- Left_ventricular_noncompaction_cardiomyopathy (5 variants)
- Dilated_Cardiomyopathy,_Dominant (4 variants)
- Familial_restrictive_cardiomyopathy (4 variants)
- Atrial_septal_defect (4 variants)
- Dilated_cardiomyopathy_1A (2 variants)
- Wolff-Parkinson-White_pattern (2 variants)
- Left_ventricular_noncompaction (1 variants)
- Inborn_genetic_diseases (1 variants)
- Left_ventricular_noncompaction_4 (1 variants)
- Left_ventricular_noncompaction_1 (1 variants)
- See_cases (1 variants)
- EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
- Left_ventricular_dilatation (1 variants)
- Arthrogryposis (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACTC1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005159.5. 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 | 207 | 211 | ||||
| missense | 33 | 282 | 321 | |||
| nonsense | 9 | |||||
| start loss | 4 | 4 | ||||
| frameshift | 21 | 22 | ||||
| splice donor/acceptor (+/-2bp) | 8 | |||||
| Total | 4 | 34 | 327 | 209 | 1 |
Highest pathogenic variant AF is 0.00000992939
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ACTC1 | protein_coding | protein_coding | ENST00000290378 | 6 | 8044 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.737 | 0.263 | 125741 | 0 | 7 | 125748 | 0.0000278 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 4.52 | 40 | 235 | 0.170 | 0.0000144 | 2483 |
| Missense in Polyphen | 17 | 102.59 | 0.1657 | 1002 | ||
| Synonymous | 0.0654 | 89 | 89.8 | 0.991 | 0.00000550 | 751 |
| Loss of Function | 2.85 | 2 | 13.1 | 0.152 | 5.61e-7 | 161 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000878 | 0.0000878 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000355 | 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: Cardiomyopathy, dilated 1R (CMD1R) [MIM:613424]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:9563954}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, familial hypertrophic 11 (CMH11) [MIM:612098]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:10330430, ECO:0000269|PubMed:10966831, ECO:0000269|PubMed:14729850, ECO:0000269|PubMed:18403758}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Atrial septal defect 5 (ASD5) [MIM:612794]: A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria. {ECO:0000269|PubMed:17947298}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Cardiac muscle contraction - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Cardiac Progenitor Differentiation;Myometrial Relaxation and Contraction Pathways;Striated Muscle Contraction
(Consensus)
Recessive Scores
- pRec
- 0.907
Intolerance Scores
- loftool
- 0.106
- rvis_EVS
- -0.21
- rvis_percentile_EVS
- 38.28
Haploinsufficiency Scores
- pHI
- 0.768
- hipred
- Y
- hipred_score
- 0.860
- ghis
- 0.540
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.862
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Low | Low | Low |
Mouse Genome Informatics
- Gene name
- Actc1
- 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); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- actc1a
- Affected structure
- myocardium
- Phenotype tag
- abnormal
- Phenotype quality
- decreased length
Gene ontology
- Biological process
- positive regulation of gene expression;actin filament-based movement;muscle filament sliding;skeletal muscle thin filament assembly;actomyosin structure organization;actin-myosin filament sliding;negative regulation of apoptotic process;response to ethanol;cardiac myofibril assembly;cardiac muscle tissue morphogenesis;heart contraction;cardiac muscle contraction;mesenchyme migration
- Cellular component
- extracellular space;cytoplasm;cytosol;actin filament;focal adhesion;membrane;sarcomere;lamellipodium;filopodium;I band;actomyosin, actin portion;cell body;extracellular exosome;blood microparticle;glutamatergic synapse
- Molecular function
- ATP binding;ATPase activity;myosin binding