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

Gene ID: 50640, updated on 3-Nov-2024

Summary

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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

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See PNPLA8 in Genome Data Viewer
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_000007.14Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC102724363 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr7:107821713-107822505 Neighboring gene neuronal cell adhesion molecule Neighboring gene ReSE screen-validated silencer GRCh37_chr7:107832147-107832328 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:107850882-107851039 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr7:107851545-107852744 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr7:107886326-107887525 Neighboring gene MPRA-validated peak6682 silencer Neighboring gene RNA, U7 small nuclear 83 pseudogene Neighboring gene Sharpr-MPRA regulatory region 14594 Neighboring gene MPRA-validated peak6683 silencer Neighboring gene MPRA-validated peak6684 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:108164501-108165036 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:108165716-108166676 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26503 Neighboring gene uncharacterized LOC124901722 Neighboring gene ribosomal protein L7 pseudogene 32 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:108209746-108210473 Neighboring gene THAP domain containing 5 Neighboring gene DnaJ heat shock protein family (Hsp40) member B9

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Key regulator PNPLA8 drives phospholipid reprogramming induced proliferation and migration in triple-negative breast cancer. Tan Z, et al. Breast Cancer Res, 2023 Nov 28. PMID 38017485, Free PMC Article
  2. Is calcium-independent phospholipase A2 required for store-operated calcium entry in human platelets? Harper MT, et al. J Thromb Haemost, 2008 Oct. PMID 18680539
  3. Complement-mediated activation of calcium-independent phospholipase A2γ: role of protein kinases and phosphorylation. Elimam H, et al. J Biol Chem, 2013 Feb 8. PMID 23258543, Free PMC Article
  4. Fine mapping for Weaver syndrome in Brown Swiss cattle and the identification of 41 concordant mutations across NRCAM, PNPLA8 and CTTNBP2. McClure M, et al. PLoS One, 2013. PMID 23527149, Free PMC Article
  5. Loss of function variants in human PNPLA8 encoding calcium-independent phospholipase A2 γ recapitulate the mitochondriopathy of the homologous null mouse. Saunders CJ, et al. Hum Mutat, 2015 Mar. PMID 25512002, Free PMC Article

See all (47) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. Observational study of gene-disease association. (HuGE Navigator)
    Title: Schizophrenia: an association study targets phospholipase A2 genes as potential sites of susceptible genes.
  10. iPLA2 activation is not sufficient for SOCE activation. iPLA2 may regulate basal phosphoinositide metabolism
    Title: Is calcium-independent phospholipase A2 required for store-operated calcium entry in human platelets?
Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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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
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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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding NAS
Non-traceable Author Statement
more info
 PubMed 
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 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
NP_001242937.1
NP_001242938.1
NP_001242939.1
NP_001242940.1
NP_056538.1
XP_005250453.1
XP_011514576.1
XP_011514577.1
XP_054214290.1
XP_054214291.1
XP_054214292.1

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

  1. NG_042172.1 RefSeqGene

    Range
    7027..62745
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

    Range
    108470417..108528178 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  2. 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

  3. 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

  1. XR_007060039.1 RNA Sequence

  2. XR_007060036.1 RNA Sequence

  3. XR_007060038.1 RNA Sequence

  4. XR_007060037.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060931.1 Alternate T2T-CHM13v2.0

    Range
    109795069..109852801 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

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

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

RNA

  1. XR_008487622.1 RNA Sequence

  2. XR_008487619.1 RNA Sequence

  3. XR_008487621.1 RNA Sequence

  4. XR_008487620.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9NP80.1 GenPept UniProtKB/Swiss-Prot:Q9NP80

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