PLCXD2

Chr 3

phosphatidylinositol specific phospholipase C X domain containing 2

Also known as: PLCXD-2

NCBI Gene: 257068ENSG00000240891UniProt: Q0VAA5OMIM: 617015

The protein catalyzes the hydrolysis of inositol from phosphatidylinositol and may hydrolyze multi-phosphorylated derivatives like PIP2 to generate second messengers IP3 and DAG for cell signaling. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy. The gene shows very low constraint against loss-of-function variants (pLI near 0), consistent with a recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.45
Clinical Summary— PLCXD2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 38 VUS of 61 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.45LOEUF
pLI 0.000
Z-score 0.34
OE 0.90 (0.57–1.45)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.34Z-score
OE missense 0.93 (0.82–1.06)
163 obs / 175.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.90 (0.57–1.45)
0≤0.351.4
Missense OE0.93 (0.82–1.06)
0≤0.61.4
Synonymous OE0.91
0≤1.21.6
LoF obs/exp: 12 / 13.3Missense obs/exp: 163 / 175.6Syn Z: 0.63
DN
0.6454th %ile
GOF
0.5759th %ile
LOF
0.3260th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

61 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
VUS38
Likely Benign4
16
Pathogenic
38
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
0
0
0
VUS
0
25
13
0
38
Likely Benign
0
1
3
0
4
Benign
0
0
0
0
0
Total02632058

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

View in ClinVar →

Protein Context — Lollipop Plot

PLCXD2 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

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