SKAP2

Chr 7

src kinase associated phosphoprotein 2

Also known as: PRAP, RA70, SAPS, SCAP2, SKAP-HOM, SKAP55R

NCBI Gene: 8935ENSG00000005020UniProt: O75563

The protein encoded by this gene shares homology with Src kinase-associated phosphoprotein 1, and is a substrate of Src family kinases. It is an adaptor protein that is thought to play an essential role in the Src signaling pathway, and in regulating proper activation of the immune system. This protein contains an amino terminal coiled-coil domain for self-dimerization, a plecskstrin homology (PH) domain required for interactions with lipids at the membrane, and a Src homology (SH3) domain at the carboxy terminus. Some reports indicate that this protein inhibits actin polymerization through interactions with actin assembly factors, and might negatively regulate the invasiveness of tumors by modulating actin assembly. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2015]

73
ClinVar variants
31
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SKAP2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 37 VUS of 73 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.67LOEUF
pLI 0.001
Z-score 2.76
OE 0.38 (0.23–0.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.30Z-score
OE missense 0.73 (0.63–0.84)
133 obs / 182.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.38 (0.23–0.67)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.63–0.84)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.08
0≤1.21.6
LoF obs/exp: 9 / 23.4Missense obs/exp: 133 / 182.3Syn Z: -0.46

ClinVar Variant Classifications

73 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic4
VUS37
Likely Benign2
Benign3
27
Pathogenic
4
Likely Pathogenic
37
VUS
2
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
0
4
0
4
VUS
0
33
4
0
37
Likely Benign
0
2
0
0
2
Benign
0
2
0
1
3
Total03735173

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SKAP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Targeting SKAP2 restores sperm motility and morphology through modulating mitochondrial organization and cytoskeletal remodeling.
Gan S et al.·Signal Transduct Target Ther
2025Functional
Diabetes With Multiple Autoimmune and Inflammatory Conditions Linked to an Activating SKAP2 Mutation.
Rutsch N et al.·Diabetes Care
2021
Predictors of the Initiation of Islet Autoimmunity and Progression to Multiple Autoantibodies and Clinical Diabetes: The TEDDY Study.
Krischer JP et al.·Diabetes Care
2022
Comprehensive transcriptomic analysis and machine learning reveal unique gene expression profiles in patients with immune-mediated necrotizing myopathy.
Liu H et al.·J Gene Med
2024Cohort
Clinical features, epidemiology, autoantibody status, HLA haplotypes and genetic mechanisms of type 1 diabetes mellitus among children in Qatar.
Haris B et al.·Sci Rep
2021Functional
Brain matters: unveiling the distinct contributions of region, age, and sex to glia diversity and CNS function.
Seeker LA et al.·Acta Neuropathol Commun
2023
HOXA genes cluster: clinical implications of the smallest deletion.
Pezzani L et al.·Ital J Pediatr
2015Case report
2D-DIGE-based proteomic analysis of intracoronary versus peripheral arterial blood platelets from acute myocardial infarction patients: Upregulation of platelet activation biomarkers at the culprit site.
Vélez P et al.·Proteomics Clin Appl
2016Cohort
Bioinformatic analysis of brucellosis and construction of a diagnostic model based on key genes.
Wang X et al.·Sci Rep
2025Functional
Pleomorphic Parotid Adenoma in a Child Affected with Cri du Chat Syndrome: Clinical, Cytogenetic, and Molecular Analysis.
Danesino C et al.·Int J Mol Sci
2024Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools