SKAP1
protein-codingsrc kinase associated phosphoprotein 1, the group of Pleckstrin homology domain containing|MicroRNA protein coding host genes
Gene summary
This gene encodes a T cell adaptor protein, a class of intracellular molecules with modular domains capable of recruiting additional proteins but that exhibit no intrinsic enzymatic activity. The encoded protein contains a unique N-terminal region followed by a PH domain and C-terminal SH3 domain. Along with the adhesion and degranulation-promoting adaptor protein, the encoded protein plays a critical role in inside-out signaling by coupling T-cell antigen receptor stimulation to the activation of integrins. [provided by RefSeq, Jul 2008]
- SCAP1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~296.8 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 SKAP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003726.4. 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 | 1 | ||||
| missense | 45 | 3 | 48 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 49 | 3 | 0 | 52 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003717.3 | 12 | MANE Select | |
| Ensembl | ENSP00000338171.6 | 12 | MANE Select | |
| RefSeq | NP_001068567.1 | 12 | Standard | |
| Ensembl | ENSP00000464198.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Rap1 signaling pathway - Homo sapiens (human)
- T-Cell antigen Receptor (TCR) Signaling Pathway
- TCR
Biological Process
- microtubule cytoskeleton organization
- positive regulation of cell-matrix adhesion
- adaptive immune response
- positive regulation of adaptive immune response
- positive regulation of signal transduction
Molecular Function
- SH3/SH2 adaptor activity
- protein binding
- SH3 domain binding
- protein kinase binding
- protein phosphatase binding
Cellular Component
- ruffle
- immunological synapse
- nucleus
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000336915
- Coding exons
- 12
- Length
- 296836
- Individuals with no LoFs
- 125725
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 21
- Defined
- 125746
- p
- 0.0000835
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.786 | 160 | 191 | 0.840 | 0.00000990 | 2377 |
| Missense (PolyPhen) | 42 | 60.1 | 0.69884 | 774 | ||
| Synonymous | 1.05 | 56 | 67.0 | 0.836 | 0.00000346 | 621 |
| Loss of Function | 2.04 | 15 | 26.3 | 0.571 | 0.00000145 | 300 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000096 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Positively regulates T-cell receptor signaling by enhancing the MAP kinase pathway. Required for optimal conjugation between T-cells and antigen-presenting cells by promoting the clustering of integrin ITGAL on the surface of T-cells. May be involved in high affinity immunoglobulin epsilon receptor signaling in mast cells. {ECO:0000269|PubMed:10856234, ECO:0000269|PubMed:11909961, ECO:0000269|PubMed:12652296, ECO:0000269|PubMed:15939789, ECO:0000269|PubMed:16980616}.;
Recessive Scores
- pRec
- 0.106
Intolerance Scores
- LoFtool
- 0.783
- RVIS EVS
- 0.17
- RVIS percentile EVS
- 65.76
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.969
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |