PNPLA8 patatin like phospholipase domain containing 8 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PNPLA8provided by HGNC
Official Full Name: patatin like phospholipase domain containing 8provided by HGNC
Primary source: HGNC:HGNC:28900
See related: Ensembl:ENSG00000135241 MIM:612123; AllianceGenome:HGNC:28900
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MMLA; IPLA2G; IPLA2-2; iPLA2gamma; PNPLA-gamma
Summary: This gene encodes a member of the patatin-like phospholipase domain containing protein family. Members of this family are phospholipases which catalyze the cleavage of fatty acids from membrane phospholipids. The product of this gene is a calcium-independent phospholipase. Mutations in this gene have been associated with mitochondrial myopathy with lactic acidosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2015]
Expression: Ubiquitous expression in bone marrow (RPKM 15.3), adrenal (RPKM 14.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 7q31.1

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (108470417..108528178, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (109795069..109852801, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (108110861..108168622, complement)

Chromosome 7 - NC_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Biallelic null variants in PNPLA8 cause microcephaly by reducing the number of basal radial glia.
Title: Biallelic null variants in PNPLA8 cause microcephaly by reducing the number of basal radial glia.
Key regulator PNPLA8 drives phospholipid reprogramming induced proliferation and migration in triple-negative breast cancer.
Title: Key regulator PNPLA8 drives phospholipid reprogramming induced proliferation and migration in triple-negative breast cancer.
12-LOX catalyzes the oxidation of 2-arachidonoyl-lysolipids in platelets generating eicosanoid-lysolipids that are attenuated by iPLA2gamma knockout.
Title: 12-LOX catalyzes the oxidation of 2-arachidonoyl-lysolipids in platelets generating eicosanoid-lysolipids that are attenuated by iPLA(2)γ knockout.
we report two unrelated individuals with variable but similar clinical features of microcephaly, severe global developmental delay, spasticity, lactic acidosis, and progressive cerebellar atrophy with biallelic loss-of-function variants in PNPLA8.
Title: A neurodegenerative mitochondrial disease phenotype due to biallelic loss-of-function variants in PNPLA8 encoding calcium-independent phospholipase A2γ.
Stable isotope kinetics revealed that in non-failing human hearts, cPLA2zeta metabolically channels arachidonic acid into EETs, whereas in failing hearts, increased iPLA2gamma activity channels AA into toxic HETEs. These results mechanistically identify the sequelae of pathological remodeling of human mitochondrial phospholipases in failing myocardium.
Title: Heart failure-induced activation of phospholipase iPLA(2)γ generates hydroxyeicosatetraenoic acids opening the mitochondrial permeability transition pore.
iPLA2gamma plays an important role in in vivo Thromboxane A2 production accompanied by thrombus formation.
Title: Group VIB calcium-independent phospholipase A2 (iPLA2γ) regulates platelet activation, hemostasis and thrombosis in mice.
iPLA2gamma plays a cardioprotective role during the acute stage of Chagas' disease.
Title: The absence of myocardial calcium-independent phospholipase A2γ results in impaired prostaglandin E2 production and decreased survival in mice with acute Trypanosoma cruzi infection.
Thus, complement-mediated activation of iPLA(2)gamma is mediated via ERK and p38 pathways, and phosphorylation of Ser-511 and/or Ser-515 plays a key role in the catalytic activity and signaling of iPLA(2)gamma.
Title: Complement-mediated activation of calcium-independent phospholipase A2γ: role of protein kinases and phosphorylation.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Observational study of gene-disease association. (HuGE Navigator)
Title: Schizophrenia: an association study targets phospholipase A2 genes as potential sites of susceptible genes.

Submit: New GeneRIF Correction See all GeneRIFs (12)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Mitochondrial myopathy-lactic acidosis-deafness syndrome MedGen: C1855033 OMIM: 251950 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Large-scale genome-wide association study of Asian population reveals genetic factors in FRMD4A and other loci influencing smoking initiation and nicotine dependence. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:1317478 (e-PCR)
- UniSTS:47361

STS-N66001 (e-PCR)
- UniSTS:51917

RH48733 (e-PCR)
- UniSTS:35032

D5S1597E (e-PCR)
- UniSTS:151019

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	NAS Non-traceable Author Statement more info	PubMed
enables calcium-dependent phospholipase A2 activity	IEA Inferred from Electronic Annotation more info
enables calcium-independent phospholipase A2 activity	IBA Inferred from Biological aspect of Ancestor more info
enables calcium-independent phospholipase A2 activity	IDA Inferred from Direct Assay more info	PubMed
enables calcium-independent phospholipase A2 activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables lysophospholipase activity	IEA Inferred from Electronic Annotation more info
enables phospholipase A1 activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in arachidonate metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in arachidonate metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in arachidonate secretion	IDA Inferred from Direct Assay more info	PubMed
involved_in cardiolipin metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in fatty acid metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in intracellular signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in linoleic acid metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in lipid homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in phosphatidylcholine catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in phosphatidylethanolamine catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in prostaglandin biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cellular response to oxidative stress	IEA Inferred from Electronic Annotation more info
involved_in triglyceride homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial membrane	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	HTP more info	PubMed
located_in mitochondrion	ISS Inferred from Sequence or Structural Similarity more info
located_in peroxisomal membrane	IDA Inferred from Direct Assay more info	PubMed
located_in peroxisome	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: calcium-independent phospholipase A2-gamma

Names: intracellular membrane-associated calcium-independent phospholipase A2 gamma; membrane-associated calcium-independent phospholipase A2 gamma

NP_001242936.1

EC 3.1.1.5

NP_001242937.1

EC 3.1.1.5

NP_001242938.1

EC 3.1.1.5

NP_001242939.1

EC 3.1.1.5

NP_001242940.1

EC 3.1.1.5

NP_056538.1

EC 3.1.1.5

XP_005250453.1

EC 3.1.1.5

XP_011514576.1

EC 3.1.1.5

XP_011514577.1

EC 3.1.1.5

XP_054214290.1

EC 3.1.1.5

XP_054214291.1

EC 3.1.1.5

XP_054214292.1

EC 3.1.1.5

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_042172.1 RefSeqGene

Range

7027..62745

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001256007.3 → NP_001242936.1 calcium-independent phospholipase A2-gamma isoform 1

See identical proteins and their annotated locations for NP_001242936.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein (isoform 1).

Source sequence(s)

AC005058, AL834147, BC032999, DW410822

Consensus CDS

CCDS34733.1

UniProtKB/Swiss-Prot

A4D0S1, C9JZI4, O95035, Q8N3I3, Q9H7T5, Q9NP80, Q9NR17, Q9NUN2, Q9NZ79

UniProtKB/TrEMBL

A8K6U0

Related

ENSP00000257694.8, ENST00000257694.13

Conserved Domains (1) summary

cd07211
Location:435 → 741

Pat_PNPLA8; Patatin-like phospholipase domain containing protein 8
NM_001256008.3 → NP_001242937.1 calcium-independent phospholipase A2-gamma isoform 1

See identical proteins and their annotated locations for NP_001242937.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein (isoform 1).

Source sequence(s)

AC005058, AL834147, BC032999, DW410822

Consensus CDS

CCDS34733.1

UniProtKB/Swiss-Prot

A4D0S1, C9JZI4, O95035, Q8N3I3, Q9H7T5, Q9NP80, Q9NR17, Q9NUN2, Q9NZ79

UniProtKB/TrEMBL

A8K6U0

Related

ENSP00000406779.1, ENST00000436062.5

Conserved Domains (1) summary

cd07211
Location:435 → 741

Pat_PNPLA8; Patatin-like phospholipase domain containing protein 8
NM_001256009.3 → NP_001242938.1 calcium-independent phospholipase A2-gamma isoform 2

See identical proteins and their annotated locations for NP_001242938.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR and uses an alternate in-frame splice site in the 3' coding region compared to variant 1. The resulting protein (isoform 2) is shorter compared to isoform 1.

Source sequence(s)

AC005058, AL834147, BC032999, DW410822

Consensus CDS

CCDS59508.1

UniProtKB/TrEMBL

A8K6U0

Related

ENSP00000394988.2, ENST00000426128.6

Conserved Domains (1) summary

cd07211
Location:435 → 679

Pat_PNPLA8; Patatin-like phospholipase domain containing protein 8
NM_001256010.3 → NP_001242939.1 calcium-independent phospholipase A2-gamma isoform 3

See identical proteins and their annotated locations for NP_001242939.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR and coding region and uses a downstream start codon compared to variant 1. The resulting protein (isoform 3) has a shorter N-terminus compared to isoform 1. Variants 5 and 6 encode the same protein.

Source sequence(s)

AC005058, AL834147, BC032999, DW410822

Consensus CDS

CCDS59075.1

UniProtKB/TrEMBL

A0A0C4DG51

Related

ENSP00000387789.1, ENST00000453144.5

Conserved Domains (1) summary

cd07211
Location:335 → 641

Pat_PNPLA8; Patatin-like phospholipase domain containing protein 8
NM_001256011.3 → NP_001242940.1 calcium-independent phospholipase A2-gamma isoform 3

See identical proteins and their annotated locations for NP_001242940.1

Status: REVIEWED

Description

Transcript Variant: This variant (6) differs in the 5' UTR and coding region and uses a downstream start codon compared to variant 1. The resulting protein (isoform 3) has a shorter N-terminus compared to isoform 1. Variants 5 and 6 encode the same protein.

Source sequence(s)

AC005058, AK024335, AL834147, BC032999, DW410822, N57453

Consensus CDS

CCDS59075.1

UniProtKB/TrEMBL

A0A0C4DG51

Related

ENSP00000402274.1, ENST00000453085.1

Conserved Domains (1) summary

cd07211
Location:335 → 641

Pat_PNPLA8; Patatin-like phospholipase domain containing protein 8
NM_015723.5 → NP_056538.1 calcium-independent phospholipase A2-gamma isoform 1

See identical proteins and their annotated locations for NP_056538.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2 and 3 encode the same protein (isoform 1).

Source sequence(s)

AC005058, AL834147, BC032999, DW410822

Consensus CDS

CCDS34733.1

UniProtKB/Swiss-Prot

A4D0S1, C9JZI4, O95035, Q8N3I3, Q9H7T5, Q9NP80, Q9NR17, Q9NUN2, Q9NZ79

UniProtKB/TrEMBL

A8K6U0

Related

ENSP00000410804.1, ENST00000422087.5

Conserved Domains (1) summary

cd07211
Location:435 → 741

Pat_PNPLA8; Patatin-like phospholipase domain containing protein 8

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000007.14 Reference GRCh38.p14 Primary Assembly

Range

108470417..108528178 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011516275.4 → XP_011514577.1 calcium-independent phospholipase A2-gamma isoform X2

UniProtKB/TrEMBL

A8K6U0

Conserved Domains (1) summary

cd07211
Location:463 → 707

Pat_PNPLA8; Patatin-like phospholipase domain containing protein 8
XM_011516274.4 → XP_011514576.1 calcium-independent phospholipase A2-gamma isoform X1

See identical proteins and their annotated locations for XP_011514576.1

UniProtKB/TrEMBL

A8K6U0

Conserved Domains (1) summary

cd07211
Location:463 → 769

Pat_PNPLA8; Patatin-like phospholipase domain containing protein 8
XM_005250396.6 → XP_005250453.1 calcium-independent phospholipase A2-gamma isoform X3

See identical proteins and their annotated locations for XP_005250453.1

UniProtKB/TrEMBL

A8K6U0

Conserved Domains (1) summary

cd07211
Location:435 → 679

Pat_PNPLA8; Patatin-like phospholipase domain containing protein 8

RNA

XR_007060039.1 RNA Sequence
XR_007060036.1 RNA Sequence
XR_007060038.1 RNA Sequence
XR_007060037.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060931.1 Alternate T2T-CHM13v2.0

Range

109795069..109852801 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054358316.1 → XP_054214291.1 calcium-independent phospholipase A2-gamma isoform X2

UniProtKB/TrEMBL

A8K6U0
XM_054358315.1 → XP_054214290.1 calcium-independent phospholipase A2-gamma isoform X1

UniProtKB/TrEMBL

A8K6U0
XM_054358317.1 → XP_054214292.1 calcium-independent phospholipase A2-gamma isoform X3

UniProtKB/TrEMBL

A8K6U0