PLA2G10

Chr 16

phospholipase A2 group X

Also known as: GXPLA2, GXSPLA2, SPLA2, sPLA2-X

The protein is a secretory calcium-dependent phospholipase A2 that hydrolyzes phospholipids to release fatty acids and lysophospholipids, playing key roles in lipid metabolism, inflammation, gut epithelial function, and antimicrobial defense. Mutations cause autosomal recessive benign recurrent intrahepatic cholestasis type 2, a liver disorder characterized by episodic cholestasis with pruritus and jaundice. The gene shows tolerance to loss-of-function variation, consistent with the recessive inheritance pattern of associated disease.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.93
Clinical SummaryPLA2G10
Population Constraint (gnomAD)
Low constraint (pLI 0.07) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
25 unique Pathogenic / Likely Pathogenic· 20 VUS of 49 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.93LOEUF
pLI 0.070
Z-score -0.68
OE 2.05 (0.341.93)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.03Z-score
OE missense 1.02 (0.741.42)
25 obs / 24.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE2.05 (0.341.93)
00.351.4
Missense OE1.02 (0.741.42)
00.61.4
Synonymous OE0.76
01.21.6
LoF obs/exp: 1 / 0.5Missense obs/exp: 25 / 24.6Syn Z: 0.66
DN
0.6550th %ile
GOF
0.7127th %ile
LOF
0.2289th %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

49 submitted variants in ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic5
VUS20
Likely Benign3
20
Pathogenic
5
Likely Pathogenic
20
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
5
0
5
VUS
0
7
13
0
20
Likely Benign
0
1
1
1
3
Benign
0
0
0
0
0
Total0839148

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

View in ClinVar →

Protein Context — Lollipop Plot

PLA2G10 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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