CAPZA1
protein-codingcapping actin protein of muscle Z-line subunit alpha 1, the group of Dynactin subunits
Gene summary
CAPZA1 is a member of the F-actin capping protein alpha subunit family. This gene encodes the alpha subunit of the barbed-end actin binding protein. The protein regulates growth of the actin filament by capping the barbed end of growing actin filaments. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~51.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CAPZA1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006135.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 38 | 1 | 39 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 45 | 1 | 0 | 46 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006126.1 | 10 | MANE Select | |
| Ensembl | ENSP00000263168.3 | 10 | MANE Select | |
| Ensembl | ENSP00000574685.1 | 10 | Standard | |
| Ensembl | ENSP00000574686.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
- Vesicle-mediated transport
- Membrane Trafficking
- Factors involved in megakaryocyte development and platelet production
Biological Process
- endoplasmic reticulum to Golgi vesicle-mediated transport
- blood coagulation
- antigen processing and presentation of exogenous peptide antigen via MHC class II
- actin cytoskeleton organization
- cell junction assembly
Molecular Function
- actin binding
- protein binding
- cadherin binding
- actin filament binding
Cellular Component
- extracellular region
- cytosol
- cytoskeleton
- F-actin capping protein complex
- actin cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000263168
- Coding exons
- 10
- Length
- 52447
- Individuals with no LoFs
- 125694
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125697
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.30 | 113 | 159 | 0.710 | 0.00000840 | 1910 |
| Missense (PolyPhen) | 16 | 40.122 | 0.39879 | 517 | ||
| Synonymous | 0.806 | 46 | 53.5 | 0.860 | 0.00000274 | 491 |
| Loss of Function | 3.42 | 2 | 17.4 | 0.115 | 7.35e-7 | 219 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000063 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000019 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments. May play a role in the formation of epithelial cell junctions. {ECO:0000269|PubMed:22891260}.;
Recessive Scores
- pRec
- 0.176
Intolerance Scores
- LoFtool
- 0.0503
- RVIS EVS
- 0.35
- RVIS percentile EVS
- 74.18
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.937
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |