PLCH2

Chr 1

phospholipase C eta 2

Also known as: PLC-L4, PLC-eta2, PLCL4, PLCeta2

NCBI Gene: 9651ENSG00000149527UniProt: O75038

Phospholipase C eta 2 cleaves PtdIns(4,5)P2 to generate the second messengers diacylglycerol and inositol 1,4,5-trisphosphate, and may be important for formation and maintenance of neuronal networks in the postnatal brain. Mutations cause neurodevelopmental disorders with autosomal recessive inheritance. The gene shows no constraint against loss-of-function variants in the general population.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
131
P/LP submissions
0%
P/LP missense
0.96
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— PLCH2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
124 unique Pathogenic / Likely Pathogenic· 272 VUS of 471 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
0.96LOEUF
pLI 0.000
Z-score 1.80
OE 0.72 (0.55–0.96)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.23Z-score
OE missense 0.87 (0.81–0.93)
615 obs / 707.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.72 (0.55–0.96)
0≤0.351.4
Missense OE0.87 (0.81–0.93)
0≤0.61.4
Synonymous OE1.11
0≤1.21.6
LoF obs/exp: 35 / 48.6Missense obs/exp: 615 / 707.3Syn Z: -1.50
DN
0.6746th %ile
GOF
0.72top 25%
LOF
0.4430th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

471 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic121
Likely Pathogenic3
VUS272
Likely Benign34
Benign16
121
Pathogenic
3
Likely Pathogenic
272
VUS
34
Likely Benign
16
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
121
0
121
Likely Pathogenic
0
0
3
0
3
VUS
0
254
18
0
272
Likely Benign
0
20
4
10
34
Benign
1
3
4
8
16
Total127715018446

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

View in ClinVar →

Protein Context — Lollipop Plot

PLCH2 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
High-Throughput Sequencing Reveals That Rotundine Inhibits Colorectal Cancer by Regulating Prognosis-Related Genes
Huang L et al.·J Pers Med
2023
Associations of selenium exposure with blood lipids: Exploring mediating DNA methylation sites in general Chinese urban non-smokers.
Nie X et al.·Sci Total Environ
2023
Deciphering the causal association and underlying transcriptional mechanisms between telomere length and abdominal aortic aneurysm.
Zhang J et al.·Front Immunol
2024Functional
Sperm DNA methylation mediates the association of male age on reproductive outcomes among couples undergoing infertility treatment
Oluwayiose OA et al.·Sci Rep
2021
Elucidating the Molecular Basis of Thermal Stress Response in Juvenile Turbot (Scophthalmus maximus) via an Integrative Transcriptome-Metabolome Approach.
Chen X et al.·Biology (Basel)
2025
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

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