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

    Gene ID: 50640, updated on 3-Apr-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_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (108470417..108528178, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (109795069..109852801, complement)
    105.20220307 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
    • 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. A neurodegenerative mitochondrial disease phenotype due to biallelic loss-of-function variants in PNPLA8 encoding calcium-independent phospholipase A2γ. Shukla A, et al. Am J Med Genet A, 2018 May. PMID 29681094, Free PMC Article
    2. Heart failure-induced activation of phospholipase iPLA(2)γ generates hydroxyeicosatetraenoic acids opening the mitochondrial permeability transition pore. Moon SH, et al. J Biol Chem, 2018 Jan 5. PMID 29158256, Free PMC Article
    3. 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
    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. 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

    See all (44) 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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    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

    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 phosphatidyl phospholipase B 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 arachidonic acid metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in arachidonic acid metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in arachidonic acid 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 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_2023_10

    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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