PIK3R6

Chr 17

phosphoinositide-3-kinase regulatory subunit 6

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

NCBI Gene: 146850 ENSG00000276231 UniProt: Q5UE93 OMIM: 611462

The PIK3R6 protein is a regulatory subunit of PI3K gamma, a lipid kinase that produces phosphatidylinositol 3,4,5-trisphosphate and mediates signaling downstream of G protein-coupled receptors. Mutations in PIK3R6 cause autosomal recessive immunodeficiency with recurrent infections, growth retardation, and neurodevelopmental delays. The gene shows very low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected patients.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOEUF 1.46

Clinical Summary— PIK3R6

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

106 VUS of 130 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.13Z-score

OE missense 0.98 (0.91–1.06)

437 obs / 444.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.12 (0.87–1.46)

0≤0.351.4

Missense OE?0.98 (0.91–1.06)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 40 / 35.6Missense obs/exp: 437 / 444.4Syn Z: -0.24

ClinVar Variant Classifications

130 submitted variants in ClinVar

ClinVar

Classification Summary

VUS106

Likely Benign2

106

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	106	106
Likely Benign	2	2
Benign	0	0
Total	108	108

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap PIK3R6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →