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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
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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

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