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    GNPTAB N-acetylglucosamine-1-phosphate transferase subunits alpha and beta [ Homo sapiens (human) ]

    Gene ID: 79158, updated on 27-Nov-2024

    Summary

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    Official Symbol
    GNPTABprovided by HGNC
    Official Full Name
    N-acetylglucosamine-1-phosphate transferase subunits alpha and betaprovided by HGNC
    Primary source
    HGNC:HGNC:29670
    See related
    Ensembl:ENSG00000111670 MIM:607840; AllianceGenome:HGNC:29670
    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
    ICD; GNPTA
    Summary
    This gene encodes two of three subunit types of the membrane-bound enzyme N-acetylglucosamine-1-phosphotransferase, a heterohexameric complex composed of two alpha, two beta, and two gamma subunits. The encoded protein is proteolytically cleaved at the Lys928-Asp929 bond to yield mature alpha and beta polypeptides while the gamma subunits are the product of a distinct gene (GeneID 84572). In the Golgi apparatus, the heterohexameric complex catalyzes the first step in the synthesis of mannose 6-phosphate recognition markers on certain oligosaccharides of newly synthesized lysosomal enzymes. These recognition markers are essential for appropriate trafficking of lysosomal enzymes. Mutations in this gene have been associated with both mucolipidosis II and mucolipidosis IIIA.[provided by RefSeq, May 2010]
    Expression
    Ubiquitous expression in colon (RPKM 16.4), lung (RPKM 13.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See GNPTAB in Genome Data Viewer
    Location:
    12q23.2
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (101745499..101830959, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (101706726..101792185, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (102139277..102224737, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene choline phosphotransferase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6865 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6866 Neighboring gene uncharacterized LOC124902997 Neighboring gene synaptonemal complex protein 3 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_22731 Neighboring gene RNA, U6 small nuclear 101, pseudogene Neighboring gene ST13, Hsp70 interacting protein pseudogene 22 Neighboring gene RNA, 5S ribosomal pseudogene 368 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:102181608-102181804 Neighboring gene small nucleolar RNA U13 Neighboring gene RNA, U6 small nuclear 172, pseudogene Neighboring gene Sharpr-MPRA regulatory region 5955 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4771 Neighboring gene RNA, 5S ribosomal pseudogene 369 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:102248561-102249060 Neighboring gene CRISPRi-validated cis-regulatory element chr12.3153 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6867 Neighboring gene RNA, U6 small nuclear 1183, 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. A novel intermediate mucolipidosis II/IIIαβ caused by GNPTAB mutation in the cytosolic N-terminal domain. Leroy JG, et al. Eur J Hum Genet, 2014 May. PMID 24045841, Free PMC Article
    2. GNPTAB missense mutations cause loss of GlcNAc-1-phosphotransferase activity in mucolipidosis type II through distinct mechanisms. Ludwig NF, et al. Int J Biochem Cell Biol, 2017 Nov. PMID 28918368
    3. Missense mutation in the N-acetylglucosamine-1-phosphotransferase gene (GNPTA) in a patient with mucolipidosis II induces changes in the size and cellular distribution of GNPTG. Tiede S, et al. Hum Mutat, 2006 Aug. PMID 16835905
    4. Mucolipidosis II: a single causal mutation in the N-acetylglucosamine-1-phosphotransferase gene (GNPTAB) in a French Canadian founder population. Plante M, et al. Clin Genet, 2008 Mar. PMID 18190596
    5. Solving a case of allelic dropout in the GNPTAB gene: implications in the molecular diagnosis of mucolipidosis type III alpha/beta. Coutinho MF, et al. J Pediatr Endocrinol Metab, 2016 Oct 1. PMID 27710913

    See all (79) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Pathogenic variants in GNPTAB and GNPTG encoding distinct subunits of GlcNAc-1-phosphotransferase differentially impact bone resorption in patients with mucolipidosis type II and III.
      Title: Pathogenic variants in GNPTAB and GNPTG encoding distinct subunits of GlcNAc-1-phosphotransferase differentially impact bone resorption in patients with mucolipidosis type II and III.
    2. Disease-causing missense mutations within the N-terminal transmembrane domain of GlcNAc-1-phosphotransferase impair endoplasmic reticulum translocation or Golgi retention.
      Title: Disease-causing missense mutations within the N-terminal transmembrane domain of GlcNAc-1-phosphotransferase impair endoplasmic reticulum translocation or Golgi retention.
    3. Identification and characterization of 30 novel pathogenic variations in 69 unrelated Indian patients with Mucolipidosis Type II and Type III.
      Title: Identification and characterization of 30 novel pathogenic variations in 69 unrelated Indian patients with Mucolipidosis Type II and Type III.
    4. Combined in vitro and in silico analyses of missense mutations in GNPTAB provide new insights into the molecular bases of mucolipidosis II and III alpha/beta.
      Title: Combined in vitro and in silico analyses of missense mutations in GNPTAB provide new insights into the molecular bases of mucolipidosis II and III alpha/beta.
    5. Do Genes Associated with Dyslexia of Chinese Characters Evolve Neutrally?
      Title: Do Genes Associated with Dyslexia of Chinese Characters Evolve Neutrally?
    6. Structures of Bacterial MraY and Human GPT Provide Insights into Rational Antibiotic Design.
      Title: Structures of Bacterial MraY and Human GPT Provide Insights into Rational Antibiotic Design.
    7. We evaluated 51 stuttering individuals with a mutation in either the GNPTAB, GNPTG, NAGPA, or AP4E1 gene. Mutation carriers achieved significantly less resolution in PSI following therapy, with PSI scores showing significantly less improvement in individuals who carry a mutation (p = 0.0157, RR = 1.75, OR = 2.92) while the group difference in DWS between carriers and non-carriers was statistically not significant.
      Title: Genetic factors and therapy outcomes in persistent developmental stuttering.
    8. These data suggest that vocalization defects in mice carrying human stuttering mutations in Gnptab derive from abnormalities in astrocytes, particularly in the corpus callosum, and provide support for hypotheses that focus on deficits in interhemispheric communication in stuttering.
      Title: Human GNPTAB stuttering mutations engineered into mice cause vocalization deficits and astrocyte pathology in the corpus callosum.
    9. Data provide an overview on 258 mutations in GNPTAB including 58 novel ones. Comprehensive functional studies of GNPTAB missense mutations did not only gain insights into the composition and function of the GlcNAc-1-phosphotransferase, but also helped to define genotype-phenotype correlations to predict the clinical outcome in patients with mucolipidosis.
      Title: The lysosomal storage disorders mucolipidosis type II, type III alpha/beta, and type III gamma: Update on GNPTAB and GNPTG mutations.
    10. Study identifies GNPTAB as a host factor for Ebola virus (EBOV) infection. This requirement is confirmed in primary cells from mucolipidosis II and mucolipidosis III patients with defective GNPTAB variants. An inhibitor of the SKI-1/S1P protease required for GNPTAB activity blocks EBOV infection, suggesting that targeting GNPTAB may be a strategy for a host-targeted antiviral therapy for EBOV.
      Title: A genome-wide CRISPR screen identifies N-acetylglucosamine-1-phosphate transferase as a potential antiviral target for Ebola virus.
    Submit: New GeneRIF Correction See all GeneRIFs (45)

    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
    Mucolipidosis type II
    MedGen: C2673377 OMIM: 252500 GeneReviews: GNPTAB-Related Disorders
    		Compare labs
    Pseudo-Hurler polydystrophy
    MedGen: C0033788 OMIM: 252600 GeneReviews: GNPTAB-Related Disorders
    		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)

    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

    Clone Names

    • MGC4170, KIAA1208, DKFZp762B226

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables calcium ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in N-glycan processing to lysosome IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in N-glycan processing to lysosome IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in carbohydrate phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in lysosome organization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in secretion of lysosomal enzymes IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in Golgi apparatus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in Golgi membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    N-acetylglucosamine-1-phosphotransferase subunits alpha/beta
    Names
    GlcNAc phosphotransferase
    N-acetylglucosamine-1-phosphate transferase alpha and beta subunits
    UDP-N-acetylglucosamine-1-phosphotransferase subunits alpha/beta
    UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosamine
    glcNAc-1-phosphotransferase subunits alpha/beta
    glucosamine (UDP-N-acetyl)-lysosomal-enzyme N-acetylglucosamine phosphotransferase
    stealth protein GNPTAB
    NP_077288.2
    XP_006719656.1
    XP_011537033.1
    XP_054229177.1
    XP_054229178.1

    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_021243.1 RefSeqGene

      Range
      4909..90369
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_024312.5 → NP_077288.2  N-acetylglucosamine-1-phosphotransferase subunits alpha/beta precursor

      See identical proteins and their annotated locations for NP_077288.2

      Status: REVIEWED

      Source sequence(s)
      AC063950, AM085438, BP276948
      Consensus CDS
      CCDS9088.1
      UniProtKB/Swiss-Prot
      A2RRQ9, Q3T906, Q3ZQK2, Q6IPW5, Q86TQ2, Q96N13, Q9ULL2
      Related
      ENSP00000299314.7, ENST00000299314.12
      Conserved Domains (6) summary
      pfam00066
      Location:435 → 469
      Notch; LNR domain
      pfam06464
      Location:699 → 814
      DMAP_binding; DMAP1-binding Domain
      pfam11380
      Location:322 → 429
      Stealth_CR2; Stealth protein CR2, conserved region 2
      pfam17101
      Location:73 → 101
      Stealth_CR1; Stealth protein CR1, conserved region 1
      pfam17102
      Location:955 → 1003
      Stealth_CR3; Stealth protein CR3, conserved region 3
      pfam17103
      Location:1138 → 1194
      Stealth_CR4; Stealth protein CR4, conserved region 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_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      101745499..101830959 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011538731.3 → XP_011537033.1  N-acetylglucosamine-1-phosphotransferase subunits alpha/beta isoform X1

      Conserved Domains (6) summary
      pfam00066
      Location:408 → 442
      Notch; LNR domain
      pfam06464
      Location:672 → 787
      DMAP_binding; DMAP1-binding Domain
      pfam11380
      Location:295 → 402
      Stealth_CR2; Stealth protein CR2, conserved region 2
      pfam17101
      Location:46 → 74
      Stealth_CR1; Stealth protein CR1, conserved region 1
      pfam17102
      Location:928 → 976
      Stealth_CR3; Stealth protein CR3, conserved region 3
      pfam17103
      Location:1111 → 1167
      Stealth_CR4; Stealth protein CR4, conserved region 4

    2. XM_006719593.4 → XP_006719656.1  N-acetylglucosamine-1-phosphotransferase subunits alpha/beta isoform X2

      Conserved Domains (5) summary
      pfam00066
      Location:435 → 469
      Notch; LNR domain
      pfam06464
      Location:699 → 814
      DMAP_binding; DMAP1-binding Domain
      pfam11380
      Location:322 → 429
      Stealth_CR2; Stealth protein CR2, conserved region 2
      pfam17101
      Location:73 → 101
      Stealth_CR1; Stealth protein CR1, conserved region 1
      pfam17102
      Location:955 → 1003
      Stealth_CR3; Stealth protein CR3, conserved region 3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      101706726..101792185 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054373202.1 → XP_054229177.1  N-acetylglucosamine-1-phosphotransferase subunits alpha/beta isoform X1

    2. XM_054373203.1 → XP_054229178.1  N-acetylglucosamine-1-phosphotransferase subunits alpha/beta isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q3T906.1 GenPept UniProtKB/Swiss-Prot:Q3T906

    Gene LinkOut

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

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