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    PNPLA4 patatin like phospholipase domain containing 4 [ Homo sapiens (human) ]

    Gene ID: 8228, updated on 10-Dec-2024

    Summary

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    Official Symbol
    PNPLA4provided by HGNC
    Official Full Name
    patatin like phospholipase domain containing 4provided by HGNC
    Primary source
    HGNC:HGNC:24887
    See related
    Ensembl:ENSG00000006757 MIM:300102; AllianceGenome:HGNC:24887
    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
    GS2; DXS1283E; iPLA2eta
    Summary
    This gene encodes a member of the patatin-like family of phospholipases. The encoded enzyme has both triacylglycerol lipase and transacylase activities and may be involved in adipocyte triglyceride homeostasis. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome Y. [provided by RefSeq, Feb 2010]
    Expression
    Ubiquitous expression in kidney (RPKM 9.2), thyroid (RPKM 8.6) and 25 other tissues See more
    Orthologs
    all
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    Genomic context

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    See PNPLA4 in Genome Data Viewer
    Location:
    Xp22.31
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (7898247..7927724, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (7451884..7481358, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (7866288..7895765, complement)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124905241 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chrX:7682068-7682794 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chrX:7682795-7683521 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chrX:7889540-7890739 Neighboring gene Sharpr-MPRA regulatory region 9499 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29394 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29396 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29395 Neighboring gene uncharacterized LOC107985675 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29393 Neighboring gene variable charge X-linked Neighboring gene Sharpr-MPRA regulatory region 2843 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:8073020-8073627 Neighboring gene S232-VCX2 recombination region Neighboring gene microRNA 651 Neighboring gene variable charge X-linked 2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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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    Related articles in PubMed

    1. GS2 as a retinol transacylase and as a catalytic dyad independent regulator of retinylester accretion. Gao JG, et al. Mol Genet Metab, 2009 Apr. PMID 19181555
    2. Isolation of a new gene GS2 (DXS1283E) from a CpG island between STS and KAL1 on Xp22.3. Lee WC, et al. Genomics, 1994 Jul 15. PMID 7806223
    3. Association of copy number variation in X chromosome-linked PNPLA4 with heterotaxy and congenital heart disease. Gao H, et al. Chin Med J (Engl), 2024 Aug 5. PMID 38973237
    4. A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies. Kohda M, et al. PLoS Genet, 2016 Jan. PMID 26741492, Free PMC Article
    5. Identification of a novel keratinocyte retinyl ester hydrolase as a transacylase and lipase. Gao J, et al. J Invest Dermatol, 2005 Jun. PMID 15955102

    See all (25) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Association of copy number variation in X chromosome-linked PNPLA4 with heterotaxy and congenital heart disease.
      Title: Association of copy number variation in X chromosome-linked PNPLA4 with heterotaxy and congenital heart disease.
    2. These results strongly suggest that PNPLA9, -6 and -4 play a key role in GPL turnover and homeostasis in human cells. A hypothetical model suggesting how these enzymes could recognize the relative concentration of the different GPLs is proposed
      Title: The PNPLA-family phospholipases involved in glycerophospholipid homeostasis of HeLa cells.
    3. No association between genetic variants in PNPLA4 genes and childhood and adolescent obesity
      Title: Genetic variance in the adiponutrin gene family and childhood obesity.
    4. GS2 promotes RE accumulation and may do so either as a catalyst or as a regulatory protein that enhances retinylesters formation catalyzed by other acyl transferases.
      Title: GS2 as a retinol transacylase and as a catalytic dyad independent regulator of retinylester accretion.
    5. Observational study of gene-disease association. (HuGE Navigator)
      Title: Genetic variance in the adiponutrin gene family and childhood obesity.
    6. we report the identity of an inhibitor, TIP47, which prevents retinylester hydrolysis catalyzed by GS2 lipase and hormone-sensitive lipase
      Title: Molecular screening for GS2 lipase regulators: inhibition of keratinocyte retinylester hydrolysis by TIP47.
    7. iPLA2epsilon (adiponutrin), iPLA2zeta (TTS-2.2), and iPLA2eta (GS2) are three novel TAG lipases/acylglycerol transacylases that likely participate in TAG hydrolysis and the acyl-CoA independent transacylation of acylglycerols
      Title: Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities.
    8. The GS2 gene (PNPLA4) encodes a keratinocyte retinyl ester hydrolase. The protein also catalyzes fatty acyl CoA-dependent and -independent retinol esterification, using triolein as substrate and generates diacylglyceride and free fatty acid.
      Title: Identification of a novel keratinocyte retinyl ester hydrolase as a transacylase and lipase.
    Submit: New GeneRIF Correction

    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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 acylglycerol O-acyltransferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables all-trans-retinyl-palmitate hydrolase, all-trans-retinol forming activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables calcium-dependent phospholipase A2 activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables calcium-independent phospholipase A2 activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables diolein transacylation activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables mono-olein transacylation activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables phospholipase A2 activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables retinyl-palmitate esterase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables triacylglycerol lipase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables triacylglycerol lipase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables triacylglycerol lipase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in lipid homeostasis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in retinol metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in triglyceride catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in triglyceride catabolic process TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    is_active_in lipid droplet IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    patatin-like phospholipase domain-containing protein 4
    Names
    IPLA2 eta
    calcium independent phospholipases A2 eta
    calcium-independent phospholipase A2-eta
    NP_001135861.1
    NP_001166143.1
    NP_004641.1

    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_016624.1 RefSeqGene

      Range
      5327..34493
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001142389.2 → NP_001135861.1  patatin-like phospholipase domain-containing protein 4 isoform 1

      See identical proteins and their annotated locations for NP_001135861.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Variants 1 and 2 encode the same isoform (1).
      Source sequence(s)
      AC005296, BM850121, U03886
      Consensus CDS
      CCDS14129.1
      UniProtKB/Swiss-Prot
      A8K1H3, B4E362, P41247, Q8WW83
      Related
      ENSP00000415245.1, ENST00000444736.5
      Conserved Domains (1) summary
      cd07222
      Location:5 → 250
      Pat_PNPLA4; Patatin-like phospholipase domain containing protein 4

    2. NM_001172672.2 → NP_001166143.1  patatin-like phospholipase domain-containing protein 4 isoform 2

      See identical proteins and their annotated locations for NP_001166143.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AC005296, AK304586, U03886
      Consensus CDS
      CCDS55368.1
      UniProtKB/Swiss-Prot
      P41247
      Related
      ENSP00000443157.1, ENST00000537427.5
      Conserved Domains (1) summary
      cl11396
      Location:1 → 163
      Patatin_and_cPLA2; Patatins and Phospholipases

    3. NM_004650.3 → NP_004641.1  patatin-like phospholipase domain-containing protein 4 isoform 1

      See identical proteins and their annotated locations for NP_004641.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1). Variants 1 and 2 encode the same isoform (1).
      Source sequence(s)
      AC005296, DB468796, U03886
      Consensus CDS
      CCDS14129.1
      UniProtKB/Swiss-Prot
      A8K1H3, B4E362, P41247, Q8WW83
      Related
      ENSP00000370430.4, ENST00000381042.9
      Conserved Domains (1) summary
      cd07222
      Location:5 → 250
      Pat_PNPLA4; Patatin-like phospholipase domain containing protein 4

    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_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      7898247..7927724 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      7451884..7481358 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P41247.3 GenPept UniProtKB/Swiss-Prot:P41247

    Gene LinkOut

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