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

Gene ID: 2762, updated on 3-Apr-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (1623806..2245605, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (1486810..2109239, complement)
105.20220307 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. 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
  2. Mutation of GDP-mannose-4,6-dehydratase in colorectal cancer metastasis. Nakayama K, et al. PLoS One, 2013. PMID 23922970, Free PMC Article
  3. 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
  4. The FX enzyme is a functional component of lymphocyte activation. Eshel R, et al. Cell Immunol, 2001 Nov 1. PMID 11831876
  5. Disruptions in a cluster of computationally identified enhancers near FOXC1 and GMDS may influence brain development. Haliburton GD, et al. Neurogenetics, 2016 Jan. PMID 26382291, Free PMC Article

See all (59) 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)

Genotypes

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-mannose metabolic process IBA
Inferred from Biological aspect of Ancestor
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
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
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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NEW Try the new Transcript table

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_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
    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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