STAP1
protein-codingsignal transducing adaptor family member 1, the group of SH2 domain containing
Gene summary
The protein encoded by this gene contains a proline-rich region, a pleckstrin homology (PH) domain, and a region in the carboxy terminal half with similarity to the Src Homology 2 (SH2) domain. This protein is a substrate of tyrosine-protein kinase Tec, and its interaction with tyrosine-protein kinase Tec is phosphorylation-dependent. This protein is thought to participate in a positive feedback loop by upregulating the activity of tyrosine-protein kinase Tec. Variants of this gene have been associated with autosomal-dominant hypercholesterolemia (ADH), which is characterized by elevated low-density lipoprotein cholesterol levels and in increased risk of coronary vascular disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~48.6 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 STAP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012108.4. 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 | 46 | 47 | |||
| missense | 1 | 101 | 7 | 1 | 110 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 1 | 107 | 53 | 1 | 162 |
Highest pathogenic variant AF is 0.0000055845053
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036240.1 | 9 | MANE Select | |
| Ensembl | ENSP00000265404.2 | 9 | MANE Select | |
| RefSeq | NP_001304698.1 | 9 | Standard | |
| Ensembl | ENSP00000379527.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- BCR
- Signaling events mediated by Stem cell factor receptor (c-Kit)
Biological Process
- transmembrane receptor protein tyrosine kinase signaling pathway
- positive regulation of gene expression
- negative regulation of macrophage chemotaxis
- negative regulation of phosphorylation
- positive regulation of B cell receptor signaling pathway
Molecular Function
- phosphotyrosine residue binding
- transmembrane receptor protein tyrosine kinase adaptor activity
- SH3/SH2 adaptor activity
- macrophage colony-stimulating factor receptor binding
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- mitochondrion
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000265404
- Coding exons
- 9
- Length
- 48610
- Individuals with no LoFs
- 125708
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 39
- Defined
- 125747
- p
- 0.000155
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0251 | 155 | 156 | 0.994 | 0.00000816 | 1932 |
| Missense (PolyPhen) | 35 | 46.265 | 0.75651 | 546 | ||
| Synonymous | -1.16 | 64 | 53.3 | 1.20 | 0.00000278 | 523 |
| Loss of Function | 1.50 | 10 | 16.6 | 0.602 | 8.56e-7 | 218 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00043 | rare |
| Latino/Admixed American | 0.000090 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00020 | 0.00019 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: In BCR signaling, appears to function as a docking protein acting downstream of TEC and participates in a positive feedback loop by increasing the activity of TEC. {ECO:0000269|PubMed:10518561}.;
Recessive Scores
- pRec
- 0.0976
Intolerance Scores
- LoFtool
- 0.563
- RVIS EVS
- -0.58
- RVIS percentile EVS
- 18.44
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.760
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |