PIK3R5

Chr 17AR

phosphoinositide-3-kinase regulatory subunit 5

NCBI Gene: 23533ENSG00000141506UniProt: Q8WYR1

Regulatory subunit of the PI3K gamma complex. Required for recruitment of the catalytic subunit to the plasma membrane via interaction with beta-gamma G protein dimers. Required for G protein-mediated activation of PIK3CG (By similarity)

Primary Disease Associations & Inheritance

Ataxia-oculomotor apraxia 3MIM #615217
AR
12
ClinVar variants
3
Pathogenic / LP
0.30
pLI score
0
Active trials
Clinical Summary— PIK3R5
🧬
Gene-Disease Validity (ClinGen)
ataxia with oculomotor apraxia type 3 · ARDisputed

Disputed — evidence questions this relationship

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
3 Pathogenic / Likely Pathogenic· 1 VUS of 12 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.39LOEUF
pLI 0.300
Z-score 4.70
OE 0.23 (0.14–0.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
2.86Z-score
OE missense 0.65 (0.60–0.71)
352 obs / 538.8 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.0.23 (0.14–0.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.60–0.71)
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.0.88
0≤1.21.6
LoF obs/exp: 10 / 43.4Missense obs/exp: 352 / 538.8Syn Z: 1.49

ClinVar Variant Classifications

12 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3
VUS1
Likely Benign1
Benign5
Conflicting2
3
Pathogenic
1
VUS
1
Likely Benign
5
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
3
0
3
Likely Pathogenic
0
0
0
0
0
VUS
0
1
0
0
1
Likely Benign
0
0
1
0
1
Benign
0
0
0
5
5
Conflicting
—2
Total014512

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

View in ClinVar →

Protein Context — Lollipop Plot

PIK3R5 · 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

Ataxia-oculomotor apraxia 3

MIM #615217

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Targeting a lineage-specific PI3Kɣ-Akt signaling module in acute myeloid leukemia using a heterobifunctional degrader molecule.
Kelly LM et al.·Nat Cancer
2024Functional
GWAS of multiple neuropathology endophenotypes identifies new risk loci and provides insights into the genetic risk of dementia.
Shade LMP et al.·Nat Genet
2024
Identification of PIK3R5 as a hub in septic myocardial injury and the cardioprotective effects of Psoralidin.
Wang X et al.·Phytomedicine
2024
Clinical and Genetic Characterization of Brazilian Patients with Ataxia and Oculomotor Apraxia.
da Costa SCG et al.·Mov Disord
2022Cohort
Phosphoinositide 3'-Kinase γ Facilitates Polyomavirus Infection.
Clark P et al.·Viruses
2020
miR-210-5p promotes epithelial-mesenchymal transition by inhibiting PIK3R5 thereby activating oncogenic autophagy in osteosarcoma cells.
Liu W et al.·Cell Death Dis
2020
A missense mutation in PIK3R5 gene in a family with ataxia and oculomotor apraxia.
Al Tassan N et al.·Hum Mutat
2012Case report
Generation of novel lipid metabolism-based signatures to predict prognosis and immunotherapy response for colorectal adenocarcinoma.
Wang Y et al.·Sci Rep
2024
PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors.
Quintanilha JCF et al.·Pharmacogenomics J
2022
HCP5, as the sponge of miR-1291, facilitates AML cell proliferation and restrains apoptosis via increasing PIK3R5 expression.
Liu Y et al.·Hum Genomics
2021
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