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    PNPLA1 patatin like phospholipase domain containing 1 [ Homo sapiens (human) ]

    Gene ID: 285848, updated on 3-Apr-2024

    Summary

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    Official Symbol
    PNPLA1provided by HGNC
    Official Full Name
    patatin like phospholipase domain containing 1provided by HGNC
    Primary source
    HGNC:HGNC:21246
    See related
    Ensembl:ENSG00000180316 MIM:612121; AllianceGenome:HGNC:21246
    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
    ARCI10; dJ50J22.1
    Summary
    The protein encoded by this gene belongs to the patatin-like phospholipase (PNPLA) family, which is characterized by the presence of a highly conserved patatin domain. PNPLA family members have diverse lipolytic and acyltransferase activities, and are key elements in lipid metabolism. While other members of this family have been well characterized, the function of this gene remained an enigma. However, recent studies show that this gene is expressed in the skin epidermal keratinocytes, and has a role in glycerophospholipid metabolism in the cutaneous barrier. Consistent with these observations, mutations in this gene are associated with ichthyosis in human (autosomal recessive congenital ichthyoses, ARCI) and dog. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]
    Expression
    Biased expression in skin (RPKM 6.2), kidney (RPKM 1.5) and 2 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    6p21.31
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (36243168..36313955)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (36059864..36134277)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (36210945..36281732)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:36098441-36099044 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17107 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17109 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24420 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:36106471-36106971 Neighboring gene mitogen-activated protein kinase 13 Neighboring gene BRPF3 antisense RNA 1 Neighboring gene MPRA-validated peak5782 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17110 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24421 Neighboring gene bromodomain and PHD finger containing 3 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:36203227-36203772 Neighboring gene Sharpr-MPRA regulatory region 10771 Neighboring gene uncharacterized LOC105375036 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17111 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:36235945-36236531 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:36253718-36253903 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:36269917-36270417 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24422 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24423 Neighboring gene BCL2 interacting protein 5 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24424 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24425 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:36343773-36344272 Neighboring gene ETS variant transcription factor 7 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:36354517-36355340 Neighboring gene ETV7 and PTX1 antisense RNA 1

    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. Impaired production of skin barrier lipid acylceramides and abnormal localization of PNPLA1 due to ichthyosis-causing mutations in PNPLA1. Nohara T, et al. J Dermatol Sci, 2022 Aug. PMID 35970721
    2. Homozygous variant p.Ser427Pro in PNPLA1 is a preventive factor from atopic dermatitis. Watanabe N, et al. J Dermatol Sci, 2020 Jan. PMID 31864761
    3. Targeted regions sequencing identified four novel PNPLA1 mutations in two Chinese families with autosomal recessive congenital ichthyosis. Li L, et al. Mol Genet Genomic Med, 2020 Feb. PMID 31833240, Free PMC Article
    4. Novel and Recurrent PNPLA1 Mutations in Spanish Patients with Autosomal Recessive Congenital Ichthyosis; Evidence of a Founder Effect. Esperón-Moldes U, et al. Acta Derm Venereol, 2019 Sep 1. PMID 31120544
    5. Impairment of lipophagy by PNPLA1 mutations causes lipid droplet accumulation in primary fibroblasts of Autosomal Recessive Congenital Ichthyosis patients. Onal G, et al. J Dermatol Sci, 2019 Jan. PMID 30655104

    See all (33) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Expanding the molecular and clinical spectrum of autosomal recessive congenital ichthyosis caused by pathogenic variants in NIPAL4 and PNPLA1 and evaluation of novel therapeutic interventions.
      Title: Expanding the molecular and clinical spectrum of autosomal recessive congenital ichthyosis caused by pathogenic variants in NIPAL4 and PNPLA1 and evaluation of novel therapeutic interventions.
    2. Impaired production of skin barrier lipid acylceramides and abnormal localization of PNPLA1 due to ichthyosis-causing mutations in PNPLA1.
      Title: Impaired production of skin barrier lipid acylceramides and abnormal localization of PNPLA1 due to ichthyosis-causing mutations in PNPLA1.
    3. Targeted regions sequencing identified four novel PNPLA1 mutations in two Chinese families with autosomal recessive congenital ichthyosis.
      Title: Targeted regions sequencing identified four novel PNPLA1 mutations in two Chinese families with autosomal recessive congenital ichthyosis.
    4. Homozygous variant p.Ser427Pro in PNPLA1 is a preventive factor from atopic dermatitis.
      Title: Homozygous variant p.Ser427Pro in PNPLA1 is a preventive factor from atopic dermatitis.
    5. PNPLA1 c.417_418delinsTC mutation has founder effects in the Spanish patients with autosomal recessive congenital ichthyosis.
      Title: Novel and Recurrent PNPLA1 Mutations in Spanish Patients with Autosomal Recessive Congenital Ichthyosis; Evidence of a Founder Effect.
    6. PNPLA1 mutations caused disturbances in both autophagosome formation and fusion of autophagosomes with lysosomes. Results indicate a possible role for PNPLA1 protein in lipid droplets regulation via lipophagy-mediated degradation.
      Title: Impairment of lipophagy by PNPLA1 mutations causes lipid droplet accumulation in primary fibroblasts of Autosomal Recessive Congenital Ichthyosis patients.
    7. Prospective observation of additional patients will allow to confirm that a cyclic scaling course is a distinctive manifestation in a subset of PNPLA1-associated autosomal recessive congenital ichthyosis
      Title: Novel PNPLA1 mutations in two Italian siblings with autosomal recessive congenital ichthyosis.
    8. The results here report on three patients with mutations in the ichthyosis-related gene, PNPLA1, involved in lipid metabolism, presenting with erythrokeratoderma.
      Title: Erythrokeratoderma: a manifestation associated with multiple types of ichthyoses with different gene defects.
    9. 16 PNPLA1 mutations are known in autosomal recessive congenital ichthyosis.
      Title: [PNPLA1 mutations in autosomal recessive congenital ichtyosis].
    10. Study results suggest that ABHD5 functions to retain triglyceride, the substrate of PNPLA1, in the endoplasmic reticulum, the site of acylceramide production, and to present TG to PNPLA1. These findings reveal the molecular mechanism by which ABHD5 mutations cause ichthyosis symptoms in Chanarin-Dorfman syndrome.
      Title: Molecular mechanism of the ichthyosis pathology of Chanarin-Dorfman syndrome: Stimulation of PNPLA1-catalyzed ω-O-acylceramide production by ABHD5.
    Submit: New GeneRIF Correction See all GeneRIFs (26)

    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
    Autosomal recessive congenital ichthyosis 10
    MedGen: C3554355 OMIM: 615024 GeneReviews: Not available
    		Compare labs

    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

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ38755, MGC119319, MGC119320, MGC119321

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables acyltransferase activity, transferring groups other than amino-acyl groups IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables omega-hydroxyceramide transacylase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables structural constituent of skin epidermis IC
    Inferred by Curator
    more info
    		 PubMed 
    enables triglyceride lipase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in ceramide biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in lipid homeostasis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in omega-hydroxyceramide biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in triglyceride catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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
    		  

    General protein information

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    Preferred Names
    omega-hydroxyceramide transacylase
    Names
    patatin-like phospholipase domain-containing protein 1
    NP_001139188.1
    NP_001139189.2
    NP_001361552.1
    NP_775947.2
    XP_011512822.1
    XP_016866268.1
    XP_047274634.1
    XP_054211212.1
    XP_054211213.1
    XP_054211214.1

    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_032813.2 RefSeqGene

      Range
      31894..75789
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001145716.2 → NP_001139188.1  omega-hydroxyceramide transacylase isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame acceptor splice site at an internal coding exon compared to variant 1, which results in a longer isoform (2), containing an internal protein segment not found in isoform 1. Isoform 2, like isoform 1, lacks the N-terminal catalytic patatin domain, and thought unlikely to function as a lipolytic enzyme (PMID:16799181).
      Source sequence(s)
      AK096074, BC103905, BC103906
      Consensus CDS
      CCDS47416.1
      UniProtKB/TrEMBL
      A0A0C4DG24
      Related
      ENSP00000321116.5, ENST00000312917.9
      Conserved Domains (1) summary
      cl11396
      Location:1 → 302
      Patatin_and_cPLA2; Patatins and Phospholipases

    2. NM_001145717.1 → NP_001139189.2  omega-hydroxyceramide transacylase isoform 3

      See identical proteins and their annotated locations for NP_001139189.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) contains an alternate 5' terminal exon compared to variant 1, resulting in translation initiation from an in-frame upstream start codon, and a longer isoform (3) with a distinct N-terminus compared to isoform 1. Isoform 3 contains the N-terminal catalytic patatin domain, that is conserved in other mammalian orthologs (mouse, rat, cow), and essential for lipase activity (PMIDS:16799181, 22246504).
      Source sequence(s)
      AK096074, AM182887, FJ457781
      Consensus CDS
      CCDS54997.1
      UniProtKB/Swiss-Prot
      A3RMU3, J3JS20, Q2A6N1, Q3SY95, Q3SY96, Q5R3L2, Q8N8W4
      UniProtKB/TrEMBL
      A0A0C4DG24, B8XXQ3
      Related
      ENSP00000378072.2, ENST00000394571.3
      Conserved Domains (1) summary
      cd07219
      Location:2 → 388
      Pat_PNPLA1; Patatin-like phospholipase domain containing protein 1

    3. NM_001374623.1 → NP_001361552.1  omega-hydroxyceramide transacylase isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) represents the longest transcript and encodes the longest isoform (4).
      Source sequence(s)
      Z84484
      Consensus CDS
      CCDS93903.1
      UniProtKB/TrEMBL
      A0A0C4DG24, A0A1B0GW56
      Related
      ENSP00000490785.2, ENST00000636260.2
      Conserved Domains (2) summary
      cd07219
      Location:2 → 388
      Pat_PNPLA1; Patatin-like phospholipase domain containing protein 1
      PHA03378
      Location:325 → 476
      PHA03378; EBNA-3B; Provisional

    4. NM_173676.2 → NP_775947.2  omega-hydroxyceramide transacylase isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the shortest isoform (1), which lacks the N-terminal catalytic patatin domain, and thought unlikely to function as a lipolytic enzyme (PMID:16799181).
      Source sequence(s)
      AK096074, BC103906, BC103907
      Consensus CDS
      CCDS34438.1
      UniProtKB/TrEMBL
      A0A0C4DG24
      Related
      ENSP00000373367.3, ENST00000388715.7
      Conserved Domains (1) summary
      cl11396
      Location:1 → 293
      Patatin_and_cPLA2; Patatins and Phospholipases

    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_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      36243168..36313955
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011514520.3 → XP_011512822.1  omega-hydroxyceramide transacylase isoform X2

      See identical proteins and their annotated locations for XP_011512822.1

      UniProtKB/TrEMBL
      A0A0C4DG24
      Conserved Domains (1) summary
      cl11396
      Location:1 → 293
      Patatin_and_cPLA2; Patatins and Phospholipases

    2. XM_047418678.1 → XP_047274634.1  omega-hydroxyceramide transacylase isoform X1

    3. XM_017010779.2 → XP_016866268.1  omega-hydroxyceramide transacylase isoform X3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      36059864..36134277
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054355238.1 → XP_054211213.1  omega-hydroxyceramide transacylase isoform X2

    2. XM_054355237.1 → XP_054211212.1  omega-hydroxyceramide transacylase isoform X1

    3. XM_054355239.1 → XP_054211214.1  omega-hydroxyceramide transacylase isoform X3

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001039725.1: Suppressed sequence

      Description
      NM_001039725.1: This RefSeq was permanently suppressed because currently there is not sufficient data to support this transcript.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8N8W4.3 GenPept UniProtKB/Swiss-Prot:Q8N8W4

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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