PIK3R5

Chr 17AR

phosphoinositide-3-kinase regulatory subunit 5

Also known as: F730038I15Rik, FOAP-2, P101-PI3K, p101

The PIK3R5 protein is the 101 kD regulatory subunit of phosphoinositide 3-kinase gamma that recruits the catalytic subunit to the plasma membrane through interaction with G protein beta-gamma dimers, enabling G protein-mediated signaling pathways involved in cell growth and survival. Mutations cause ataxia-oculomotor apraxia 3, which follows autosomal recessive inheritance and primarily affects cerebellar and oculomotor systems. The gene is highly constrained against loss-of-function variation (LOEUF 0.391), indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.391 OMIM phenotype
Clinical SummaryPIK3R5
🧬
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
10 unique Pathogenic / Likely Pathogenic· 124 VUS of 215 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.39LOEUF
pLI 0.300
Z-score 4.70
OE 0.23 (0.140.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.86Z-score
OE missense 0.65 (0.600.71)
352 obs / 538.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.23 (0.140.39)
00.351.4
Missense OE0.65 (0.600.71)
00.61.4
Synonymous OE0.88
01.21.6
LoF obs/exp: 10 / 43.4Missense obs/exp: 352 / 538.8Syn Z: 1.49

ClinVar Variant Classifications

215 submitted variants in ClinVar

Classification Summary

Pathogenic10
VUS124
Likely Benign25
Benign18
Conflicting4
10
Pathogenic
124
VUS
25
Likely Benign
18
Benign
4
Conflicting

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
120
4
0
124
Likely Benign
0
6
3
16
25
Benign
0
2
7
9
18
Conflicting
4
Total01282425181

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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