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    NIPAL4 NIPA like domain containing 4 [ Homo sapiens (human) ]

    Gene ID: 348938, updated on 5-Mar-2024

    Summary

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    Official Symbol
    NIPAL4provided by HGNC
    Official Full Name
    NIPA like domain containing 4provided by HGNC
    Primary source
    HGNC:HGNC:28018
    See related
    Ensembl:ENSG00000172548 MIM:609383; AllianceGenome:HGNC:28018
    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
    ARCI6; ICHYN; NIPA4; SLC57A6; ICHTHYIN
    Summary
    This gene likely encodes a membrane receptor. Mutations in this gene have been associated with autosomal recessive congenital ichthyosis. [provided by RefSeq, Feb 2010]
    Expression
    Biased expression in skin (RPKM 16.9), esophagus (RPKM 5.1) and 4 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    5q33.3
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (157460213..157474722)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (157979233..157993740)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (156887027..156901730)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene cytoplasmic FMR1 interacting protein 2 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:156789204-156789414 Neighboring gene fibronectin type III domain containing 9 Neighboring gene NIPAL4 divergent transcript Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr5:156817055-156818254 Neighboring gene ribosomal protein L26 pseudogene 18 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16559 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:156905935-156906445 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:156913469-156913969 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:156923503-156924004 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23512 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23513 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23516 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23515 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23514 Neighboring gene ADAM metallopeptidase domain 19 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:156951101-156951600 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23517 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23518 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23519 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23520 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23521 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23522 Neighboring gene Sharpr-MPRA regulatory region 5046 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:157001479-157002008 Neighboring gene uncharacterized LOC124901121 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23524 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16561 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:157004182-157004797 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:157004798-157005414 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:157005415-157006029 Neighboring gene RNA, U6 small nuclear 390, pseudogene

    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. Expanding the clinical phenotype associated with NIPAL4 mutation: Study of a Tunisian consanguineous family with erythrokeratodermia variabilis-Like Autosomal Recessive Congenital Ichthyosis. Charfeddine C, et al. PLoS One, 2021. PMID 34669720, Free PMC Article
    2. Identification of a novel missense mutation in NIPAL4 gene: First 3D model construction predicted its pathogenicity. Laadhar S, et al. Mol Genet Genomic Med, 2020 Mar. PMID 31876100, Free PMC Article
    3. Genetical, clinical, and functional analysis of a large international cohort of patients with autosomal recessive congenital ichthyosis due to mutations in NIPAL4. Ballin N, et al. Hum Mutat, 2019 Dec. PMID 31347739
    4. Cellular and Metabolic Basis for the Ichthyotic Phenotype in NIPAL4 (Ichthyin)-Deficient Canines. Mauldin EA, et al. Am J Pathol, 2018 Jun. PMID 29548991, Free PMC Article
    5. A Japanese Case of Ichthyosiform Erythroderma with a Novel Mutation in NIPAL4/Ichthyin. Kusakabe M, et al. Acta Derm Venereol, 2017 Mar 10. PMID 27868142

    See all (30) 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. Expanding the clinical phenotype associated with NIPAL4 mutation: Study of a Tunisian consanguineous family with erythrokeratodermia variabilis-Like Autosomal Recessive Congenital Ichthyosis.
      Title: Expanding the clinical phenotype associated with NIPAL4 mutation: Study of a Tunisian consanguineous family with erythrokeratodermia variabilis-Like Autosomal Recessive Congenital Ichthyosis.
    3. Variants in NIPAL4 and ALOXE3 cause autosomal recessive congenital ichthyosis in Pakistani families.
      Title: Variants in NIPAL4 and ALOXE3 cause autosomal recessive congenital ichthyosis in Pakistani families.
    4. Identification of a novel missense mutation in NIPAL4 gene: First 3D model construction predicted its pathogenicity.
      Title: Identification of a novel missense mutation in NIPAL4 gene: First 3D model construction predicted its pathogenicity.
    5. Results identified 16 novel mutations in NIPAL4 in a large cohort of families with autosomal recessive congenital ichthyosis (ARCI) and increase the total number of pathogenic mutations to 34.
      Title: Genetical, clinical, and functional analysis of a large international cohort of patients with autosomal recessive congenital ichthyosis due to mutations in NIPAL4.
    6. NIPAL4 mutations are associated with Ichthyotic Phenotype.
      Title: Cellular and Metabolic Basis for the Ichthyotic Phenotype in NIPAL4 (Ichthyin)-Deficient Canines.
    7. Case Report: novel NIPAL4 mutation in Japanese female with ichthyosiform erythroderma.
      Title: A Japanese Case of Ichthyosiform Erythroderma with a Novel Mutation in NIPAL4/Ichthyin.
    8. We have identified a novel NIPAL4 mutation in two patients from Romania with autosomal recessive congenital ichthyosis.
      Title: Novel mutation in NIPAL4 in a Romanian family with autosomal recessive congenital ichthyosis.
    9. FATP4, ichthyin and TGM1 interact in lipid processing essential for maintaining the epidermal barrier function
      Title: Interactions between FATP4 and ichthyin in epidermal lipid processing may provide clues to the pathogenesis of autosomal recessive congenital ichthyosis.
    10. Autosomal recessive congenital ichthyosis patients with NIPAL4 mutations and abnormal ichthyin expression showed increased 12R-LOX and eLOX-3 staining and a colocalization signal of these lipoxygenases that was three times the normal intensity.
      Title: The expression of epidermal lipoxygenases and transglutaminase-1 is perturbed by NIPAL4 mutations: indications of a common metabolic pathway essential for skin barrier homeostasis.
    Submit: New GeneRIF Correction See all GeneRIFs (18)

    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)

    Genotypes

    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 magnesium ion transmembrane transporter activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in magnesium ion transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in magnesium ion transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    magnesium transporter NIPA4
    Names
    NIPA-like protein 4
    non-imprinted in Prader-Willi/Angelman syndrome region protein 4

    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_016626.1 RefSeqGene

      Range
      5195..19704
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001099287.2 → NP_001092757.2  magnesium transporter NIPA4 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC008676
      Consensus CDS
      CCDS47328.2
      UniProtKB/Swiss-Prot
      A8S6F1, A8S6F5, A8S6F8, B4DLF3, Q0D2J8, Q0D2J9, Q0D2K0
      Related
      ENSP00000311687.8, ENST00000311946.8
      Conserved Domains (1) summary
      cl23754
      Location:54 → 348
      EamA; EamA-like transporter family

    2. NM_001172292.2 → NP_001165763.2  magnesium transporter NIPA4 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.
      Source sequence(s)
      AC008676, AK296972
      Consensus CDS
      CCDS54944.1
      Related
      ENSP00000406456.3, ENST00000435489.7

    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_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      157460213..157474722
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011534552.2 → XP_011532854.1  magnesium transporter NIPA4 isoform X1

      See identical proteins and their annotated locations for XP_011532854.1

      Conserved Domains (1) summary
      cl23754
      Location:1 → 245
      EamA; EamA-like transporter family

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      157979233..157993740
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054352513.1 → XP_054208488.1  magnesium transporter NIPA4 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q0D2K0.4 GenPept UniProtKB/Swiss-Prot:Q0D2K0

    Gene LinkOut

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