PLCL1

Chr 2

phospholipase C like 1 (inactive)

Also known as: PLCE, PLCL, PLDL1, PPP1R127, PRIP

NCBI Gene: 5334ENSG00000115896UniProt: Q15111

Predicted to enable GABA receptor binding activity and phosphatidylinositol-4,5-bisphosphate phospholipase C activity. Predicted to be involved in several processes, including gamma-aminobutyric acid signaling pathway; negative regulation of cold-induced thermogenesis; and phosphatidylinositol-mediated signaling. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

179
ClinVar variants
38
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— PLCL1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
38 Pathogenic / Likely Pathogenic· 135 VUS of 179 total submissions

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.
0.48LOEUF
pLI 0.012
Z-score 4.09
OE 0.29 (0.18–0.48)
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.
1.86Z-score
OE missense 0.78 (0.72–0.84)
437 obs / 561.2 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.0.29 (0.18–0.48)
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 (0.72–0.84)
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.1.06
0≤1.21.6
LoF obs/exp: 11 / 38.3Missense obs/exp: 437 / 561.2Syn Z: -0.70

ClinVar Variant Classifications

179 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic1
VUS135
Likely Benign3
Benign2
Conflicting1
37
Pathogenic
1
Likely Pathogenic
135
VUS
3
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
37
0
37
Likely Pathogenic
0
0
1
0
1
VUS
0
131
3
1
135
Likely Benign
0
1
1
1
3
Benign
0
0
0
2
2
Conflicting
—1
Total0132424179

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

View in ClinVar →

Protein Context — Lollipop Plot

PLCL1 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
PLCL1 suppresses tumour progression by regulating AMPK/mTOR-mediated autophagy in renal cell carcinoma.
Pan Z et al.·Aging (Albany NY)
2023
The juvenile idiopathic inflammatory myopathies: pathogenesis, clinical and autoantibody phenotypes, and outcomes.
Rider LG et al.·J Intern Med
2016Review
A novel necroptosis-related gene index for predicting prognosis and a cold tumor immune microenvironment in stomach adenocarcinoma.
Khan M et al.·Front Immunol
2022Review
A multilevel study on the genetic relationship between schizophrenia and inflammatory bowel disease.
Li C et al.·Hum Immunol
2025
Telomere-related gene risk model for prognosis and drug treatment efficiency prediction in kidney cancer.
Li SC et al.·Front Immunol
2022Functional
Machine learning model in multi-omics perspective demystifies the prognostic significance of crotonylation heterogeneity in clear cell renal cell carcinoma.
Dai H et al.·BMC Urol
2025Functional
Identification of new susceptibility loci associated with rheumatoid arthritis.
Leng RX et al.·Ann Rheum Dis
2020
Gamma-Aminobutyric Acid Type A Receptor Subunit Pi is a potential chemoresistance regulator in colorectal cancer.
Wang T et al.·Mol Biol Rep
2023
Genetic loci associated with prevalent and incident myocardial infarction and coronary heart disease in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium.
Hahn J et al.·PLoS One
2020Cohort
The CC2D2B is a novel genetic modifier of the clinical phenotype in patients with hereditary angioedema due to C1 inhibitor deficiency.
Rupar N et al.·Gene
2024Cohort
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools