PLA2G4C

protein-coding

phospholipase A2 group IVC, the group of Phospholipases

Gene summary

This gene encodes a protein which is a member of the phospholipase A2 enzyme family which hydrolyzes glycerophospholipids to produce free fatty acids and lysophospholipids, both of which serve as precursors in the production of signaling molecules. The encoded protein has been shown to be a calcium-independent and membrane bound enzyme. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2009]

MANE transcript

NM_003706.3

Inheritance

—

ClinVar variants

U:108B:9

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr19:48,047,843-48,110,817

External References & Databases

Ensembl (ENSG00000105499)

Transcript & Mutation Effects

hg38 • Region Span ~63.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLA2G4C variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 103

not providedTotal: 4

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003706.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar		2 clinvar	4
missense			102 clinvar	5 clinvar	2 clinvar	109
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	108	5	4	117

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 68 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003706.3	RefSeq	NP_003697.2	16	MANE Select
ENST00000599921.6	Ensembl	ENSP00000469473.1	16	MANE Select
NM_001159322.2	RefSeq	NP_001152794.1	17	Standard
NM_001159323.2	RefSeq	NP_001152795.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
Platelet activation - Homo sapiens (human)
Oxytocin signaling pathway - Homo sapiens (human)
Fc epsilon RI signaling pathway - Homo sapiens (human)
Ether lipid metabolism - Homo sapiens (human)

Biological Process

phospholipid metabolic process
inflammatory response
parturition
arachidonic acid metabolic process
intracellular signal transduction

Molecular Function

lysophospholipase activity
phospholipase A2 activity
calcium ion binding
phospholipid binding
calcium-dependent phospholipid binding

Cellular Component

nuclear envelope
nucleoplasm
cytoplasm
endoplasmic reticulum membrane
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000599111
Coding exons: 17
Length: 62975
Individuals with no LoFs: 125612
Homozygous LoFs: 0
Heterozygous LoFs: 136
Defined: 125748
p: 0.000541

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.174	300	309	0.972	0.0000167	3571
Missense (PolyPhen)		85	84.54	1.0054		1008
Synonymous	-1.00	140	126	1.11	0.00000763	1062
Loss of Function	1.53	25	34.7	0.720	0.00000181	379

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0039	0.0039	notable
Latino/Admixed American	0.00040	0.00040	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00065	0.00065	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00030	0.00030	rare
South Asian	0.00013	0.00013	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has a preference for arachidonic acid at the sn-2 position of phosphatidylcholine as compared with palmitic acid. {ECO:0000269|PubMed:10085124, ECO:0000269|PubMed:9705332}.;

Recessive Scores

pRec: 0.0690

Intolerance Scores

LoFtool: 0.938
RVIS EVS: 2.45
RVIS percentile EVS: 98.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.910

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium