PIK3CG

Chr 7AR

phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma

Also known as: IMD97, PI3CG, PI3K, PI3Kgamma, PIK3, p110gamma, p120-PI3K

NCBI Gene: 5294ENSG00000105851UniProt: P48736

Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids and are involved in the immune response. The protein encoded by this gene is a class I catalytic subunit of PI3K. Like other class I catalytic subunits (p110-alpha p110-beta, and p110-delta), the encoded protein binds a p85 regulatory subunit to form PI3K. This gene is located in a commonly deleted segment of chromosome 7 previously identified in myeloid leukemias. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2015]

Primary Disease Associations & Inheritance

Immunodeficiency 97 with autoinflammationMIM #619802
AR
169
ClinVar variants
23
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— PIK3CG
🧬
Gene-Disease Validity (ClinGen)
immunodeficiency 97 with autoinflammation · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 106 VUS of 169 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
0.59LOEUF
pLI 0.000
Z-score 3.72
OE 0.40 (0.28–0.59)
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.
1.97Z-score
OE missense 0.78 (0.73–0.84)
514 obs / 655.8 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.0.40 (0.28–0.59)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.73–0.84)
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.0.99
0≤1.21.6
LoF obs/exp: 18 / 44.9Missense obs/exp: 514 / 655.8Syn Z: 0.11

ClinVar Variant Classifications

169 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic1
VUS106
Likely Benign29
Benign10
Conflicting1
22
Pathogenic
1
Likely Pathogenic
106
VUS
29
Likely Benign
10
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
3
18
0
22
Likely Pathogenic
0
0
1
0
1
VUS
2
99
5
0
106
Likely Benign
0
11
2
16
29
Benign
0
0
3
7
10
Conflicting
—1
Total31132923169

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

View in ClinVar →

Protein Context — Lollipop Plot

PIK3CG · 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

Immunodeficiency 97 with autoinflammation

MIM #619802

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
Targeting PI3Kγ in cancer.
Mognol GP et al.·Trends Cancer
2025Review
PI3K inhibitors: Efficacy in diverse cancer forms.
Kianfar E et al.·Cancer Treat Res Commun
2025Review
A common variant in PIK3CG gene associated with the prognosis of heart failure.
Hu D et al.·J Cell Mol Med
2024
Whole exome sequencing for identifying rare genetic variants related to idiopathic granulomatous mastitis.
Ozer L et al.·Clin Rheumatol
2025
Generation of novel lipid metabolism-based signatures to predict prognosis and immunotherapy response for colorectal adenocarcinoma.
Wang Y et al.·Sci Rep
2024
Integrated analysis of DNA methylation and transcriptome profiles to identify oxidative stress-related placenta-specific molecules for preeclampsia.
Xu Y et al.·J Obstet Gynaecol Res
2025
Spatial transcriptomics uncovers lipid metabolic dysregulation driving immune-stroma crosstalk in Sjögren's Disease.
Li S et al.·EBioMedicine
2026
Molecular Diversity of Embryonic-Type Neuroectodermal Tumors Arising From Testicular Germ Cell Tumors.
Zong Y et al.·Mod Pathol
2025
There is no gene for CVID - novel monogenetic causes for primary antibody deficiency.
Ramirez NJ et al.·Curr Opin Immunol
2021Review
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
Slow-Flow Vascular MalformationFast-Flow Vascular MalformationVascular Malformations

A Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations

RECRUITING
NCT05983159Phase PHASE2Murdoch Childrens Research InstituteStarted 2024-09-13
AlpelisibMirdametinib

External Resources

Links to major genomics databases and tools