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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SKAP1
src kinase associated phosphoprotein 1
Chromosome 17 · 17q21.32
NCBI Gene: 8631Ensembl: ENSG00000141293.18HGNC: HGNC:15605UniProt: Q86WV1
48PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingT cell receptor signaling pathwaypositive regulation of leukocyte cell-cell adhesioncytoplasmAbnormality of the skeletal systemovarian carcinomaovarian serous carcinomageneralised epilepsy
✦AI Summary

SKAP1 (src kinase associated phosphoprotein 1) is a cytosolic adapter protein that primarily functions in T cell receptor (TCR) signaling and immune cell adhesion. In normal immune function, SKAP1 positively regulates TCR-mediated signaling by enhancing the MAP kinase pathway and promoting LFA-1 integrin clustering on T cell surfaces, facilitating optimal adhesion between T cells and antigen-presenting cells 1. However, emerging evidence reveals unexpected roles in cancer pathogenesis. SKAP1 expression is significantly elevated in multiple cancers including colorectal, gastric, and pancreatic neuroendocrine tumors, where high levels independently predict poor survival 234. In colorectal cancer, SKAP1 expressed by tumor cells—rather than immune cells—promotes growth through the NFATc1/CXCL8 axis, enhancing neutrophil extracellular trap formation that impairs antitumor immunity 2. In gastric cancer, SKAP1 activates JAK1/PI3K/AKT signaling to promote cell proliferation and invasion while predicting poor immunotherapy response 3. A competing endogenous RNA network regulates SKAP1 via miR-218-5p in colorectal cancer 5. Conversely, genetic studies indicate decreased SKAP1 expression in blood increases endometrial cancer risk, suggesting context-dependent effects on immune surveillance 6. SKAP1 additionally emerges as a plasma biomarker associated with Alzheimer's disease severity 7. These findings position SKAP1 as a multifunctional molecule with divergent roles in immune regulation and cancer biology.

Sources cited
1
SKAP1 is a cytosolic adapter protein that positively regulates TCR/CD3-mediated signaling, promotes LFA-1 integrin clustering, and enhances T cell-APC interaction
PMID: 34295339
2
SKAP1 expression in colon cancer cells promotes tumor growth via the NFATc1/CXCL8 axis by enhancing neutrophil extracellular trap formation; high SKAP1 levels predict poor colon cancer survival
PMID: 39269257
3
SKAP1 is upregulated in gastric cancer, promotes cell proliferation, migration and invasion through JAK1/PI3K/AKT signaling, and predicts poor immunotherapy outcomes
PMID: 37511629
4
SKAP1 upregulation in colorectal cancer is regulated by THUMPD3-AS1 competing for miR-218-5p binding; SKAP1 knockdown inhibits CRC cell proliferation, migration and invasion
PMID: 35538197
5
SKAP1 levels are positively associated with tumor progression and metastasis in pancreatic neuroendocrine tumors through integrin activation pathways
PMID: 40007573
6
Decreased SKAP1 expression in blood is associated with increased endometrial cancer risk, suggesting SKAP1 impacts T cell immune responses and tumor immunosurveillance
PMID: 36908940
7
SKAP1 is identified as a plasma protein biomarker associated with Alzheimer's disease severity in multi-omics analysis
PMID: 39358810
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.40Moderate
ovarian carcinomaOpen Targets
0.39Weak
ovarian serous carcinomaOpen Targets
0.31Weak
generalised epilepsyOpen Targets
0.30Weak
irritable bowel syndromeOpen Targets
0.28Weak
inflammatory bowel diseaseOpen Targets
0.28Weak
blepharitisOpen Targets
0.27Weak
malignant epithelial tumor of ovaryOpen Targets
0.26Weak
eye inflammationOpen Targets
0.26Weak
high grade ovarian serous adenocarcinomaOpen Targets
0.25Weak
SnoringOpen Targets
0.24Weak
adolescent idiopathic scoliosisOpen Targets
0.21Weak
diabetes mellitusOpen Targets
0.19Weak
prostate carcinomaOpen Targets
0.18Weak
ovarian cancerOpen Targets
0.18Weak
hypertensionOpen Targets
0.18Weak
Abruptio PlacentaeOpen Targets
0.16Weak
endometriosisOpen Targets
0.15Weak
atrial fibrillationOpen Targets
0.13Weak
cervix erosionOpen Targets
0.13Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PLCG1Protein interaction100%GRB2Protein interaction100%ZAP70Protein interaction100%FYB1Protein interaction99%FYNProtein interaction99%LCKProtein interaction99%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
91%
Lung
25%
Brain
13%
Heart
6%
Ovary
2%
Gene Interaction Network
Click a node to explore
SKAP1PLCG1GRB2ZAP70FYB1FYNLCK
PROTEIN STRUCTURE
Preparing viewer…
PDB1U5D · 1.70 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.11LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.75 [0.52–1.11]
RankingsWhere SKAP1 stands among ~20K protein-coding genes
  • #9,132of 20,598
    Most Researched48
  • #11,431of 17,882
    Most Constrained (LOEUF)1.11
Genes detectedSKAP1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
SKAP1 Expression in Cancer Cells Enhances Colon Tumor Growth and Impairs Cytotoxic Immunity by Promoting Neutrophil Extracellular Trap Formation via the NFATc1/CXCL8 Axis.
PMID: 39269257
Adv Sci (Weinh) · 2024
1.00
2
Multi-omics analysis reveals the key factors involved in the severity of the Alzheimer's disease.
PMID: 39358810
Alzheimers Res Ther · 2024
0.90
3
SKAP1 Is a Novel Biomarker and Therapeutic Target for Gastric Cancer: Evidence from Expression, Functional, and Bioinformatic Analyses.
PMID: 37511629
Int J Mol Sci · 2023
0.80
4
The Multiple Roles of the Cytosolic Adapter Proteins ADAP, SKAP1 and SKAP2 for TCR/CD3 -Mediated Signaling Events.
PMID: 34295339
Front Immunol · 2021
0.70
5
THUMPD3-AS1 facilitates cell growth and aggressiveness by the miR-218-5p/SKAP1 axis in colorectal cancer.
PMID: 35538197
Cell Biochem Biophys · 2022
0.60