PIK3R6

Chr 17

phosphoinositide-3-kinase regulatory subunit 6

Also known as: C17orf38, HsT41028, p84 PIKAP, p87(PIKAP), p87PIKAP

NCBI Gene: 146850ENSG00000276231UniProt: Q5UE93

Phosphoinositide 3-kinase gamma is a lipid kinase that produces the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. The kinase is composed of a catalytic subunit and one of several regulatory subunits, and is chiefly activated by G protein-coupled receptors. This gene encodes a regulatory subunit, and is distantly related to the phosphoinositide-3-kinase, regulatory subunit 5 gene which is located adjacent to this gene on chromosome 7. The orthologous protein in the mouse binds to both the catalytic subunit and to G(beta/gamma), and mediates activation of the kinase subunit downstream of G protein-coupled receptors. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

121
ClinVar variants
10
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PIK3R6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 109 VUS of 121 total submissions

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.
1.46LOEUF
pLI 0.000
Z-score -0.68
OE 1.12 (0.87–1.46)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.13Z-score
OE missense 0.98 (0.91–1.06)
437 obs / 444.4 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.1.12 (0.87–1.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.91–1.06)
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.1.02
0≤1.21.6
LoF obs/exp: 40 / 35.6Missense obs/exp: 437 / 444.4Syn Z: -0.24

ClinVar Variant Classifications

121 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
VUS109
Likely Benign2
10
Pathogenic
109
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
0
0
0
VUS
0
106
3
0
109
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total0108130121

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

View in ClinVar →

Protein Context — Lollipop Plot

PIK3R6 · 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
PIK3R6 Promotes Angiogenesis in Hepatocellular carcinoma by Activating STAT3 Signaling Pathway.
Du Y et al.·Altern Ther Health Med
2023
Generation of novel lipid metabolism-based signatures to predict prognosis and immunotherapy response for colorectal adenocarcinoma.
Wang Y et al.·Sci Rep
2024
Review on potential effects of traditional Chinese medicine on glaucoma.
Qi SM et al.·J Ethnopharmacol
2023Review
Multi-omic modeling of antidepressant response implicates dynamic immune and inflammatory changes in individuals who respond to treatment.
Fuh SC et al.·PLoS One
2023Functional
Gene-based association study of rare variants in children of diverse ancestries implicates TNFRSF21 in the development of allergic asthma.
Clay S et al.·J Allergy Clin Immunol
2024
Integrated genomic, transcriptomic, and epigenetic analyses identify a leukotriene synthesis-related M2 macrophage gene signature that predicts prognosis and treatment vulnerability in gliomas.
Ji H et al.·Front Immunol
2022
Phase Ib study of patients with metastatic castrate-resistant prostate cancer treated with different sequencing regimens of atezolizumab and sipuleucel-T.
Dorff T et al.·J Immunother Cancer
2021Clinical trial
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