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    GMDS GDP-mannose 4,6-dehydratase [ Homo sapiens (human) ]

    Gene ID: 2762, updated on 27-Nov-2024

    Summary

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    Official Symbol
    GMDSprovided by HGNC
    Official Full Name
    GDP-mannose 4,6-dehydrataseprovided by HGNC
    Primary source
    HGNC:HGNC:4369
    See related
    Ensembl:ENSG00000112699 MIM:602884; AllianceGenome:HGNC:4369
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    GMD; SDR3E1
    Summary
    GDP-mannose 4,6-dehydratase (GMD; EC 4.2.1.47) catalyzes the conversion of GDP-mannose to GDP-4-keto-6-deoxymannose, the first step in the synthesis of GDP-fucose from GDP-mannose, using NADP+ as a cofactor. The second and third steps of the pathway are catalyzed by a single enzyme, GDP-keto-6-deoxymannose 3,5-epimerase, 4-reductase, designated FX in humans (MIM 137020).[supplied by OMIM, Aug 2009]
    Expression
    Broad expression in colon (RPKM 6.8), stomach (RPKM 6.6) and 23 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See GMDS in Genome Data Viewer
    Location:
    6p25.3
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (1623806..2245605, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (1486810..2109239, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (1624041..2245839, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:1606326-1606826 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:1606827-1607327 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr6:1607685-1608194 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16824 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23864 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:1613862-1614479 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:1614480-1615096 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:1618844-1619706 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23865 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:1629302-1630229 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:1630230-1631156 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:1633959-1634459 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:1636810-1637341 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:1644131-1645078 Neighboring gene uncharacterized LOC107986514 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23866 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23867 Neighboring gene FOXC1 upstream transcript Neighboring gene forkhead box C1 Neighboring gene NANOG hESC enhancer GRCh37_chr6:1729872-1730373 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23868 Neighboring gene uncharacterized LOC124901239 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23869 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23870 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:1873801-1874302 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:1874303-1874803 Neighboring gene NANOG hESC enhancer GRCh37_chr6:1919859-1920404 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16825 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr6:1952649-1953848 Neighboring gene MPRA-validated peak5622 silencer Neighboring gene NANOG hESC enhancer GRCh37_chr6:2117206-2117756 Neighboring gene Sharpr-MPRA regulatory region 5333 Neighboring gene NANOG hESC enhancer GRCh37_chr6:2222412-2223029 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23871 Neighboring gene Sharpr-MPRA regulatory region 10202 Neighboring gene uncharacterized LOC107986512 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:2245481-2245981 Neighboring gene GMDS divergent transcript Neighboring gene high mobility group nucleosomal binding domain 2 pseudogene 28 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:2423149-2423723 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr6:2434059-2435258 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16827 Neighboring gene long intergenic non-protein coding RNA 1600 Neighboring gene long intergenic non-protein coding RNA 2521

    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. The FX enzyme is a functional component of lymphocyte activation. Eshel R, et al. Cell Immunol, 2001 Nov 1. PMID 11831876
    2. GDP-mannose-4,6-dehydratase (GMDS) deficiency renders colon cancer cells resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor- and CD95-mediated apoptosis by inhibiting complex II formation. Moriwaki K, et al. J Biol Chem, 2011 Dec 16. PMID 22027835, Free PMC Article
    3. Mutation of GDP-mannose-4,6-dehydratase in colorectal cancer metastasis. Nakayama K, et al. PLoS One, 2013. PMID 23922970, Free PMC Article
    4. GMDS knockdown impairs cell proliferation and survival in human lung adenocarcinoma. Wei X, et al. BMC Cancer, 2018 May 29. PMID 29843634, Free PMC Article
    5. FX enzyme and GDP-L-Fuc transporter expression in colorectal cancer. Villar-Portela S, et al. Histopathology, 2013 Aug. PMID 23730929

    See all (63) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. we present an analysis of the sequence and structural features governing TNKS interactions with two model binding partners: the PARylated partner telomeric repeat-binding factor 1 (TRF1) and the non-PARylated partner GDP-mannose 4,6-dehydratase (GMD).
      Title: Structural and functional analysis of parameters governing tankyrase-1 interaction with telomeric repeat-binding factor 1 and GDP-mannose 4,6-dehydratase.
    2. Study findings suggest that GMDS upregulation is critical for cell proliferation and survival in human lung adenocarcinoma and might serve as a potential biomarker for lung adenocarcinoma diagnosis and treatment.
      Title: GMDS knockdown impairs cell proliferation and survival in human lung adenocarcinoma.
    3. Disruptions of enhancers near FOXC1 and GMDS may influence brain development.
      Title: Disruptions in a cluster of computationally identified enhancers near FOXC1 and GMDS may influence brain development.
    4. Data indicate three loci associated with primary open-angle glaucoma (POAG) were located upstream of ATP binding cassette transporter 1 (ABCA1), within actin filament associated protein 1 (AFAP1) and within GDP-mannose 46-dehydratase (GMDS).
      Title: Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma.
    5. These data demonstrate involvement of GMDS mutation in the progression of colorectal cancer.
      Title: Mutation of GDP-mannose-4,6-dehydratase in colorectal cancer metastasis.
    6. Fx enzyme and GDP-L-Fuc Tr overexpression in the tumur tissue of colorectal cancer (CRC) patients suggests that GDP-L-Fuc transport to the Golgi apparatus may be an important factor associated with increased alpha(1,6)fucosylation in CRC.
      Title: FX enzyme and GDP-L-Fuc transporter expression in colorectal cancer.
    7. GMD inhibits tankyrase 1 poly(ADP-ribose) polymerase activity in vitro, dependent on the GMD tankyrase 1 binding motif. In vivo, depletion of GMD led to degradation of tankyrase 1, dependent on the catalytic PARP activity of tankyrase 1.
      Title: GDP-mannose-4,6-dehydratase is a cytosolic partner of tankyrase 1 that inhibits its poly(ADP-ribose) polymerase activity.
    8. Results indicate that GMDS regulates the formation of secondary complex II from the primary DISC independent of direct fucosylation of death receptors.
      Title: GDP-mannose-4,6-dehydratase (GMDS) deficiency renders colon cancer cells resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor- and CD95-mediated apoptosis by inhibiting complex II formation.
    9. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    10. Observational study of gene-disease association. (HuGE Navigator)
      Title: New genetic associations detected in a host response study to hepatitis B vaccine.
    Submit: New GeneRIF Correction See all GeneRIFs (12)

    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

    EBI GWAS Catalog

    Description
    Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma.
    EBI GWAS Catalog
    Discovery and replication of dopamine-related gene effects on caudate volume in young and elderly populations (N=1198) using genome-wide search.
    EBI GWAS Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    EBI GWAS Catalog
    Polymorphic markers associated with severe oxaliplatin-induced, chronic peripheral neuropathy in colon cancer patients.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of GDP-mannose 4,6-dehydratase (GMDS) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

    Go to the HIV-1, Human Interaction Database

    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 GDP-mannose 4,6-dehydratase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables GDP-mannose 4,6-dehydratase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables GDP-mannose 4,6-dehydratase activity IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    enables GDP-mannose 4,6-dehydratase activity TAS
    Traceable Author Statement
    more info
    		  
    enables NADP+ binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in 'de novo' GDP-L-fucose biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in 'de novo' GDP-L-fucose biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in 'de novo' GDP-L-fucose biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in GDP-L-fucose biosynthetic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in GDP-mannose metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in GDP-mannose metabolic process IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in Notch signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm IC
    Inferred by Curator
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 

    General protein information

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    Preferred Names
    GDP-mannose 4,6 dehydratase
    Names
    GDP-D-mannose dehydratase
    short chain dehydrogenase/reductase family 3E, member 1
    NP_001240775.1
    NP_001491.1
    XP_006715129.1
    XP_011512802.1
    XP_011512804.1
    XP_011512805.1
    XP_011512807.1
    XP_011512808.1
    XP_011512809.1
    XP_016866241.1
    XP_047274611.1
    XP_054211164.1
    XP_054211165.1
    XP_054211166.1
    XP_054211167.1
    XP_054211168.1
    XP_054211169.1
    XP_054211170.1
    XP_054211171.1

    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.

    mRNA and Protein(s)

    1. NM_001253846.2 → NP_001240775.1  GDP-mannose 4,6 dehydratase isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) is shorter and has a distinct N-terminus, compared to isoform 1.
      Source sequence(s)
      AF040260
      Consensus CDS
      CCDS58994.1
      UniProtKB/TrEMBL
      B2R9X3
      Related
      ENSP00000436726.1, ENST00000530927.5
      Conserved Domains (2) summary
      TIGR01472
      Location:5 → 336
      gmd; GDP-mannose 4,6-dehydratase
      pfam16363
      Location:4 → 328
      GDP_Man_Dehyd; GDP-mannose 4,6 dehydratase

    2. NM_001500.4 → NP_001491.1  GDP-mannose 4,6 dehydratase isoform 1

      See identical proteins and their annotated locations for NP_001491.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AF042377, BM665440, BQ923510
      Consensus CDS
      CCDS4474.1
      UniProtKB/Swiss-Prot
      E9PI88, O60547, O75357, Q5T954, Q6FH09, Q9UGZ3, Q9UJK9
      UniProtKB/TrEMBL
      B2R9X3
      Related
      ENSP00000370194.4, ENST00000380815.5
      Conserved Domains (1) summary
      TIGR01472
      Location:24 → 366
      gmd; GDP-mannose 4,6-dehydratase

    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_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      1623806..2245605 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011514500.2 → XP_011512802.1  GDP-mannose 4,6 dehydratase isoform X1

      UniProtKB/TrEMBL
      B2R9X3
      Conserved Domains (2) summary
      TIGR01472
      Location:4 → 336
      gmd; GDP-mannose 4,6-dehydratase
      pfam16363
      Location:5 → 328
      GDP_Man_Dehyd; GDP-mannose 4,6 dehydratase

    2. XM_017010752.2 → XP_016866241.1  GDP-mannose 4,6 dehydratase isoform X4

    3. XM_011514502.4 → XP_011512804.1  GDP-mannose 4,6 dehydratase isoform X3

      UniProtKB/TrEMBL
      B2R9X3
      Conserved Domains (2) summary
      pfam16363
      Location:27 → 329
      GDP_Man_Dehyd; GDP-mannose 4,6 dehydratase
      cl21454
      Location:24 → 329
      NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

    4. XM_047418655.1 → XP_047274611.1  GDP-mannose 4,6 dehydratase isoform X2

    5. XM_011514507.3 → XP_011512809.1  GDP-mannose 4,6 dehydratase isoform X8

      Conserved Domains (2) summary
      pfam16363
      Location:27 → 216
      GDP_Man_Dehyd; GDP-mannose 4,6 dehydratase
      cl21454
      Location:24 → 215
      NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

    6. XM_006715066.4 → XP_006715129.1  GDP-mannose 4,6 dehydratase isoform X9

      Conserved Domains (2) summary
      pfam01370
      Location:26 → 257
      Epimerase; NAD dependent epimerase/dehydratase family
      cl21454
      Location:24 → 257
      NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

    7. XM_011514506.3 → XP_011512808.1  GDP-mannose 4,6 dehydratase isoform X7

      Conserved Domains (2) summary
      pfam16363
      Location:27 → 217
      GDP_Man_Dehyd; GDP-mannose 4,6 dehydratase
      cl21454
      Location:24 → 214
      NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

    8. XM_011514505.3 → XP_011512807.1  GDP-mannose 4,6 dehydratase isoform X6

      Conserved Domains (2) summary
      pfam16363
      Location:27 → 217
      GDP_Man_Dehyd; GDP-mannose 4,6 dehydratase
      cl21454
      Location:24 → 214
      NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

    9. XM_011514503.4 → XP_011512805.1  GDP-mannose 4,6 dehydratase isoform X5

      Conserved Domains (2) summary
      pfam16363
      Location:27 → 217
      GDP_Man_Dehyd; GDP-mannose 4,6 dehydratase
      cl21454
      Location:24 → 214
      NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

    RNA

    1. XR_007059239.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      1486810..2109239 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054355189.1 → XP_054211164.1  GDP-mannose 4,6 dehydratase isoform X1

    2. XM_054355192.1 → XP_054211167.1  GDP-mannose 4,6 dehydratase isoform X4

    3. XM_054355191.1 → XP_054211166.1  GDP-mannose 4,6 dehydratase isoform X3

    4. XM_054355190.1 → XP_054211165.1  GDP-mannose 4,6 dehydratase isoform X2

    5. XM_054355196.1 → XP_054211171.1  GDP-mannose 4,6 dehydratase isoform X8

    6. XM_054355193.1 → XP_054211168.1  GDP-mannose 4,6 dehydratase isoform X5

    7. XM_054355195.1 → XP_054211170.1  GDP-mannose 4,6 dehydratase isoform X7

    8. XM_054355194.1 → XP_054211169.1  GDP-mannose 4,6 dehydratase isoform X6

    RNA

    1. XR_008487300.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O60547.1 GenPept UniProtKB/Swiss-Prot:O60547

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