PLCXD2

Chr 3

phosphatidylinositol specific phospholipase C X domain containing 2

Also known as: PLCXD-2

NCBI Gene: 257068 ENSG00000240891 UniProt: Q0VAA5 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable phosphoric diester hydrolase activity. Predicted to be involved in lipid catabolic process and signal transduction. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

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

37 VUS of 44 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 OE?0.90 (0.57–1.45)

0≤0.351.4

Missense OE?0.93 (0.82–1.06)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 12 / 13.3Missense obs/exp: 163 / 175.6Syn Z: 0.63

This gene — mechanism propensity

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

44 submitted variants in ClinVar

ClinVar

Classification Summary

VUS37

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	25	12	37
Likely Benign	1	3	4
Benign	0	0	0
Total	26	15	41

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap PLCXD2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →