PLA2G5

protein-coding

phospholipase A2 group V, the group of Phospholipases

Gene summary

This gene is a member of the secretory phospholipase A2 family. It is located in a tightly-linked cluster of secretory phospholipase A2 genes on chromosome 1. The encoded enzyme catalyzes the hydrolysis of membrane phospholipids to generate lysophospholipids and free fatty acids including arachidonic acid. It preferentially hydrolyzes linoleoyl-containing phosphatidylcholine substrates. Secretion of this enzyme is thought to induce inflammatory responses in neighboring cells. Alternatively spliced transcript variants have been found, but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

MANE transcript

NM_000929.3

Inheritance

ClinVar variants

P:4U:87B:27

Top phenotype

Fleck retina, familial benign

gnomAD constraint

pLI —, LoF o/e 0.85

Max pathogenic AF

—

Genomic locus

chr1:20,028,179-20,091,911

External References & Databases

Ensembl (ENSG00000127472)

Transcript & Mutation Effects

hg38 • Region Span ~63.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial benign flecked retinaLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0009235

Submitter: Ambry Genetics

familial benign flecked retinaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009235

Submitter: Orphanet

familial benign flecked retinaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009235

Submitter: PanelApp Australia

late-adult onset retinitis pigmentosaLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0009984

Submitter: Franklin by Genoox

A index patient was diagnosed with late-onset RP at the age of 88. WES revealed a homozygous PLA2G5 frameshift mutation.

familial benign flecked retinaDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009235

Submitter: G2P

Clinical Genomic Database (CGD)

Fleck retina, familial benignAR

Manifestation: Ophthalmologic

Intervention: General

Rationale: The clinical relevance of the condition is unclear

Refs: 8703867; 17502520; 22137173

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLA2G5 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 128

not specifiedTotal: 32

Familial benign flecked retinaTotal: 6

PLA2G5-related disordersTotal: 2

Late-onset retinal degenerationTotal: 1

Retinal disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000929.3. 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			3 clinvar	21 clinvar	1 clinvar	25
missense		1 clinvar	71 clinvar	5 clinvar		77
nonsense	1 clinvar		6 clinvar			7
start loss			1 clinvar			1
frameshift	1 clinvar		6 clinvar			7
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	2	2	87	26	1	118

Highest pathogenic variant AF is 0.000027259199

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 144 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000929.3	RefSeq	NP_000920.1	4	MANE Select
ENST00000375108.4	Ensembl	ENSP00000364249.3	4	MANE Select
ENST00000894073.1	Ensembl	ENSP00000564132.1	4	Standard
ENST00000894073.2	Ensembl	ENSP00000564132.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ether lipid metabolism - Homo sapiens (human)
Glycerophospholipid metabolism - Homo sapiens (human)
Fat digestion and absorption - Homo sapiens (human)
Vascular smooth muscle contraction - Homo sapiens (human)
alpha-Linolenic acid metabolism - Homo sapiens (human)

Biological Process

phospholipid metabolic process
phosphatidic acid biosynthetic process
platelet activating factor biosynthetic process
positive regulation of phospholipase activity
lipid catabolic process

Molecular Function

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

Cellular Component

extracellular region
Golgi apparatus
plasma membrane
cell surface
perinuclear region of cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375108
Coding exons: 4
Length: 63012
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125745
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.273	82	89.3	0.919	0.00000569	889
Missense (PolyPhen)		24	33.227	0.72231		358
Synonymous	0.969	30	37.5	0.799	0.00000264	263
Loss of Function	0.391	7	8.21	0.853	4.36e-7	81

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: PA2 catalyzes the calcium-dependent hydrolysis of the 2- acyl groups in 3-sn-phosphoglycerides. This isozyme hydrolyzes more efficiently L-alpha-1-palmitoyl-2-oleoyl phosphatidylcholine than L-alpha-1-palmitoyl-2-arachidonyl phosphatidylcholine, L- alpha-1-palmitoyl-2-arachidonyl phosphatidylethanolamine, or L- alpha-1-stearoyl-2-arachidonyl phosphatidylinositol. May be involved in the production of lung surfactant, the remodeling or regulation of cardiac muscle.;
Disease: DISEASE: Fleck retina, familial benign (FRFB) [MIM:228980]: An autosomal recessive condition associated with a distinctive retinal appearance and no apparent visual or electrophysiologic deficits. Affected individuals are asymptomatic, but fundus examination reveals a striking pattern of diffuse, yellow-white, fleck-like lesions extending to the far periphery of the retina but sparing the foveal region. {ECO:0000269|PubMed:22137173}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.588
RVIS EVS: -0.32
RVIS percentile EVS: 31.46

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.171

Gene Damage Prediction

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