PIK3AP1

Chr 10

phosphoinositide-3-kinase adaptor protein 1

Also known as: BCAP

NCBI Gene: 118788ENSG00000155629UniProt: Q6ZUJ8

Predicted to enable phosphatidylinositol 3-kinase regulatory subunit binding activity and signaling receptor binding activity. Predicted to be involved in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; regulation of inflammatory response; and regulation of innate immune response. Predicted to be located in membrane. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

300
ClinVar variants
9
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PIK3AP1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 158 VUS of 300 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.12LOEUF
pLI 1.000
Z-score 5.64
OE 0.03 (0.01–0.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
2.26Z-score
OE missense 0.71 (0.65–0.78)
346 obs / 486.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.03 (0.01–0.12)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.65–0.78)
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.0.86
0≤1.21.6
LoF obs/exp: 1 / 39.0Missense obs/exp: 346 / 486.0Syn Z: 1.54

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
VUS158
Likely Benign122
Benign7
Conflicting4
9
Pathogenic
158
VUS
122
Likely Benign
7
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
0
0
0
VUS
3
143
11
1
158
Likely Benign
0
3
46
73
122
Benign
0
1
3
3
7
Conflicting
—4
Total31476977300

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

View in ClinVar →

Protein Context — Lollipop Plot

PIK3AP1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
DNA-dependent protein kinase regulates lysosomal AMP-dependent protein kinase activation and autophagy.
Puustinen P et al.·Autophagy
2020
PAGE-based transfer learning from single-cell to bulk sequencing enhances model generalization for sepsis diagnosis.
Jin N et al.·Brief Bioinform
2024Functional
Abnormal methylation of PIK3AP1 was involved in regulating the immune inflammatory response of GES-1 cells induced by Helicobacter pylori.
Zhang A et al.·Biochem Biophys Res Commun
2020
Molecular Subtypes of Balanopreputial and Urethral Male Genital Lichen Sclerosus: Distinct Transcriptomic and Clinicopathological Profiles.
Xiu X et al.·Lab Invest
2025
S1PR4 ablation reduces tumor growth and improves chemotherapy via CD8+ T cell expansion.
Olesch C et al.·J Clin Invest
2020
Prediction of a competing endogenous RNA co-expression network as a prognostic marker in glioblastoma.
Peng Q et al.·J Cell Mol Med
2020
New insights into the genetic predisposition of brucellosis and its effect on the gut and vaginal microbiota in goats.
Sallam AM et al.·Sci Rep
2023
Targeting periodontal inflammatory microenvironment to ameliorate periodontitis: A nitrogen ions implantation technique.
Liu Z et al.·Int Immunopharmacol
2026
Elucidating sleep disorders: a comprehensive bioinformatics analysis of functional gene sets and hub genes.
Lin J et al.·Front Immunol
2024Functional
Composite likelihood-based meta-analysis of breast cancer association studies.
Politopoulos I et al.·J Hum Genet
2011Meta-analysis
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Cancer-associated fibroblasts-derived exosome PIK3AP1 promotes the malignant progression and immune escape of prostate cancer cells.
Li T et al.·Pathol Res Pract
2025
PI3K-Akt pathway-independent PIK3AP1 identified as a replication inhibitor of the African swine fever virus based on iTRAQ proteomic analysis.
Yang B et al.·Virus Res
2023🔓 Open Access
MiR-1246 regulates the PI3K/AKT signaling pathway by targeting PIK3AP1 and inhibits thyroid cancer cell proliferation and tumor growth.
Li J et al.·Mol Cell Biochem
2022🔓 Open Access
Overexpression of long non-coding RNA WT1-AS or silencing of PIK3AP1 are inhibitory to cervical cancer progression.
Tong W et al.·Cell Cycle
2021
BRG1 regulates lipid metabolism in hepatocellular carcinoma through the PIK3AP1/PI3K/AKT pathway by mediating GLMP expression.
Liu G et al.·Dig Liver Dis
2022
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