PIK3R1

Chr 5ARAD

phosphoinositide-3-kinase regulatory subunit 1

Also known as: AGM7, GRB1, IMD36, p85, p85-ALPHA, p85alpha

NCBI Gene: 5295ENSG00000145675UniProt: P27986OMIM: 171833

Phosphatidylinositol 3-kinase phosphorylates the inositol ring of phosphatidylinositol at the 3-prime position. The enzyme comprises a 110 kD catalytic subunit and a regulatory subunit of either 85, 55, or 50 kD. This gene encodes the 85 kD regulatory subunit. Phosphatidylinositol 3-kinase plays an important role in the metabolic actions of insulin, and a mutation in this gene has been associated with insulin resistance. Alternative splicing of this gene results in four transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Agammaglobulinemia 7, autosomal recessiveMIM #615214
AR
Immunodeficiency 36MIM #616005
AD
SHORT syndromeMIM #269880
AD

Clinical highlights

Gene-disease validity (ClinGen)
agammaglobulinemia 7, autosomal recessive · ARLimitednot for standalone diagnostic reporting2 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
4
Active trials
343
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.23
LOEUF· LoF intol.
LOF
Mechanism· G2P
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GeneReview available — PIK3R1
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.23LOEUF
pLI 1.000
Z-score 5.61
OE 0.11 (0.06–0.23)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.72Z-score
OE missense 0.62 (0.55–0.69)
245 obs / 397.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.11 (0.06–0.23)
0≤0.351.4
Missense OE?0.62 (0.55–0.69)
0≤0.61.4
Synonymous OE?0.84
0≤1.21.6
LoF obs/exp: 5 / 46.1Missense obs/exp: 245 / 397.7Syn Z: 1.56

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

PIK3R1 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients