PLA2G4B

protein-coding

phospholipase A2 group IVB, the group of C2 domain containing phospholipases|Phospholipases

Gene summary

This gene encodes a member of the cytosolic phospholipase A2 protein family. Phospholipase A2 enzymes hydrolyze the sn-2 bond of phospholipids, releasing lysophospholipids and fatty acids. This enzyme may be associated with mitochondria and early endosomes. Most tissues also express read-through transcripts from the upstream gene into this gene, some of which may encode fusion proteins combining the N-terminus of the upstream gene including its JmjC domain with the almost complete coding region of this gene, including the C2 and cytoplasmic phospholipase A2 domains. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001114633.2

Inheritance

—

ClinVar variants

U:76B:36

Top phenotype

JMJD7-PLA2G4B-related disorder

gnomAD constraint

pLI —, LoF o/e 1.07

Max pathogenic AF

—

Genomic locus

chr15:41,837,775-41,848,147

External References & Databases

Ensembl (ENSG00000243708)

NCBI Gene (100137049)

Transcript & Mutation Effects

hg38 • Region Span ~10.4 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 PLA2G4B variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 79

JMJD7-PLA2G4B-related disorderTotal: 28

PLA2G4B-related disorderTotal: 7

not providedTotal: 6

Neurodevelopmental disorderTotal: 1

Autism spectrum disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001114633.2. 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				13 clinvar	6 clinvar	19
missense			74 clinvar	12 clinvar	5 clinvar	91
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	76	25	11	112

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001114633.2	RefSeq	NP_001108105.1	20	MANE Select
ENST00000458483.4	Ensembl	ENSP00000416610.1	20	MANE Select
ENST00000452633.5	Ensembl	ENSP00000396045.1	20	Standard
ENST00000569354.1	Ensembl	ENSP00000456919.1	2	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)
Fc gamma R-mediated phagocytosis - Homo sapiens (human)

Biological Process

phospholipid metabolic process
phosphatidic acid biosynthetic process
inflammatory response
parturition
arachidonic acid metabolic process

Molecular Function

lysophospholipase activity
phospholipase A2 activity
calcium ion binding
calcium-dependent phospholipid binding
phospholipase A1 activity

Cellular Component

extracellular region
cytoplasm
mitochondrial inner membrane
cytosol
early endosome membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000542534
Coding exons: 25
Length: 20063
Individuals with no LoFs: 125344
Homozygous LoFs: 0
Heterozygous LoFs: 404
Defined: 125748
p: 0.00161

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.99	744	606	1.23	0.0000377	6479
Missense (PolyPhen)		242	206.03	1.1746		2291
Synonymous	-2.79	322	264	1.22	0.0000171	2069
Loss of Function	-0.453	59	55.4	1.07	0.00000246	613

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0048	0.0046	notable
Latino/Admixed American	0.0017	0.0017	notable
Ashkenazi Jewish	0.00031	0.00030	rare
East Asian	0.0024	0.0023	notable
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.0010	0.00098	notable
South Asian	0.0034	0.0033	notable
Other	0.0015	0.0015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Calcium-dependent phospholipase A2 that selectively hydrolyzes glycerophospholipids in the sn-2 position with a preference for arachidonoyl phospholipids. Has a much weaker activity than PLA2G4A. Isoform 3 has calcium-dependent activity against palmitoyl-arachidonyl-phosphatidylethanolamine and low level lysophospholipase activity but no activity against phosphatidylcholine. Isoform 5 does have activity against phosphatidylcholine. {ECO:0000269|PubMed:10085124, ECO:0000269|PubMed:10358058, ECO:0000269|PubMed:16617059}.;

Recessive Scores

pRec: 0.103

Intolerance Scores

RVIS EVS: 0.06
RVIS percentile EVS: 58.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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