PLA2G10

Chr 16

phospholipase A2 group X

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

NCBI Gene: 8399 ENSG00000069764 UniProt: O15496

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.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the phospholipase A2 family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature enzyme. This calcium-dependent enzyme hydrolyzes glycerophospholipids to produce free fatty acids and lysophospholipids. In one example, this enzyme catalyzes the release of arachidonic acid from cell membrane phospholipids, thus playing a role in the production of various inflammatory lipid mediators, such as prostaglandins. The encoded protein may promote the survival of breast cancer cells through its role in lipid metabolism. [provided by RefSeq, Nov 2015]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.93

Clinical Summary— PLA2G10

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Population Constraint (gnomAD)

Low constraint (pLI 0.07) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

7 VUS of 9 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.93LOEUF

pLI 0.070

Z-score -0.68

OE 2.05 (0.34–1.93)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.03Z-score

OE missense 1.02 (0.74–1.42)

25 obs / 24.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?2.05 (0.34–1.93)

0≤0.351.4

Missense OE?1.02 (0.74–1.42)

0≤0.61.4

Synonymous OE?0.76

0≤1.21.6

LoF obs/exp: 1 / 0.5Missense obs/exp: 25 / 24.6Syn Z: 0.66

This gene — mechanism propensity

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

9 submitted variants in ClinVar

ClinVar

Classification Summary

VUS7

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	7	0	7
Likely Benign	1	1	2
Benign	0	0	0
Total	8	1	9

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

View in ClinVar →

25 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap PLA2G10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →