STAC2
protein-codingSH3 and cysteine rich domain 2
Gene summary
This gene encodes a protein containing an SH3 domain and a zinc finger domain. The encoded protein has been shown to regulate calcium channel inactivation in a human cell line. Reduced expression of this gene has been observed in human heart failure. [provided by RefSeq, May 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.4 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 STAC2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_198993.5. 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 | 1 | 74 | 75 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 1 | 77 | 0 | 0 | 78 |
Highest pathogenic variant AF is 0.000002164699
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_945344.1 | 11 | MANE Select | |
| Ensembl | ENSP00000327509.5 | 11 | MANE Select | |
| RefSeq | NP_001338289.1 | 9 | Standard | |
| Ensembl | ENSP00000463299.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- intracellular signal transduction
- positive regulation of voltage-gated calcium channel activity
- positive regulation of protein localization to plasma membrane
Molecular Function
- protein binding
- metal ion binding
Cellular Component
- cytosol
- extrinsic component of cytoplasmic side of plasma membrane
- sarcolemma
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000333461
- Coding exons
- 11
- Length
- 15337
- Individuals with no LoFs
- 125693
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 55
- Defined
- 125748
- p
- 0.000219
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0999 | 251 | 247 | 1.02 | 0.0000145 | 2645 |
| Missense (PolyPhen) | 77 | 80.286 | 0.95907 | 798 | ||
| Synonymous | -0.242 | 99 | 96.0 | 1.03 | 0.00000531 | 807 |
| Loss of Function | 1.73 | 13 | 21.7 | 0.599 | 0.00000110 | 224 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00050 | 0.00049 | rare |
| Latino/Admixed American | 0.00018 | 0.00017 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00030 | 0.00029 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a redundant role in promoting the expression of calcium channel CACNA1S at the cell membrane, and thereby contributes to increased channel activity. Slows down the inactivation rate of the calcium channel CACNA1C. {ECO:0000250|UniProtKB:Q8R1B0}.;
Recessive Scores
- pRec
- 0.104
Intolerance Scores
- LoFtool
- 0.397
- RVIS EVS
- -0.98
- RVIS percentile EVS
- 8.8
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.164
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |