PIK3C2G

Chr 12

phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma

Also known as: PI3K-C2-gamma, PI3K-C2GAMMA

The protein generates phosphatidylinositol 3-phosphate and phosphatidylinositol 3,4-bisphosphate that function as second messengers in cellular signaling pathways. Mutations cause autosomal recessive neurodevelopmental disorder with hypotonia, seizures, and brain atrophy, typically presenting in infancy. The gene shows very low constraint against loss-of-function variants, consistent with recessive inheritance requiring biallelic mutations for disease manifestation.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
7
Pubs (1 yr)
53
P/LP submissions
12%
P/LP missense
1.14
LOEUF
Mechanism
Clinical SummaryPIK3C2G
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
52 unique Pathogenic / Likely Pathogenic· 248 VUS of 340 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.14LOEUF
pLI 0.000
Z-score 0.60
OE 0.92 (0.751.14)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.97Z-score
OE missense 1.10 (1.041.17)
757 obs / 685.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.92 (0.751.14)
00.351.4
Missense OE1.10 (1.041.17)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 63 / 68.4Missense obs/exp: 757 / 685.3Syn Z: -0.18

ClinVar Variant Classifications

340 submitted variants in ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic6
VUS248
Likely Benign22
Benign3
46
Pathogenic
6
Likely Pathogenic
248
VUS
22
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
4
39
0
46
Likely Pathogenic
2
2
2
0
6
VUS
2
232
12
2
248
Likely Benign
1
11
5
5
22
Benign
0
2
1
0
3
Total8251597325

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

View in ClinVar →

Protein Context — Lollipop Plot

PIK3C2G · protein map & ClinVar variants

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

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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