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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GMDS
GDP-mannose 4,6-dehydratase
Chromosome 6 · 6p25.3
NCBI Gene: 2762Ensembl: ENSG00000112699.12HGNC: HGNC:4369UniProt: O60547
66PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
GDP-mannose 4,6-dehydratase activityextracellular exosomeidentical protein bindingNADP+ bindingopen-angle glaucomaglaucomaAbnormality of the skeletal systemtype 2 diabetes mellitus
✦AI Summary

GMDS (GDP-mannose 4,6-dehydratase) catalyzes the conversion of GDP-D-mannose to GDP-4-dehydro-6-deoxy-D-mannose, a critical step in fucose biosynthesis 1. This enzyme functions primarily in GDP-L-fucose biosynthetic pathways and is involved in protein glycosylation, particularly fucosylation, which modulates cellular signaling including Notch pathway regulation. GMDS expression is significantly upregulated in lung adenocarcinoma, where it promotes cell proliferation and survival through mechanisms involving the CASP8-CDKN1A axis 2. GMDS knockdown impairs tumor cell growth and induces apoptosis both in vitro and in vivo 2. Beyond cancer, GMDS variants are associated with primary open-angle glaucoma susceptibility, with specific polymorphisms influencing intraocular pressure response to latanoprost treatment 34. Additionally, GMDS gene methylation increases dose-dependently in individuals chr6 exposed to arsenic, suggesting involvement in environmental carcinogenesis 5. The regulatory lncRNA GMDS-AS1 functions as an oncogenic factor, controlling cancer cell behaviors and inflammatory responses through miR-96-5p/caspase-2 signaling 16. GMDS represents a potential biomarker for cancer diagnosis and therapeutic target, with clinical significance for understanding fucosylation-dependent disease pathogenesis.

Sources cited
1
GMDS catalyzes conversion of GDP-mannose to GDP-4-keto-6-deoxymannose in fucosylation pathway; GMDS-AS1 functions as oncogene affecting cancer cell proliferation and migration
PMID: 38591197
2
GMDS is upregulated in lung adenocarcinoma; GMDS knockdown impairs cell proliferation, induces apoptosis and cell cycle arrest; CASP8-CDKN1A axis involved in GMDS-mediated tumorigenesis
PMID: 29843634
3
GMDS identified as novel locus associated with primary open-angle glaucoma through genome-wide association studies
PMID: 28505344
4
GMDS rs9503012 C>T polymorphism associated with intraocular pressure response to latanoprost treatment in POAG patients
PMID: 27862086
5
GMDS gene hypermethylation occurs in dose-dependent manner in chronically arsenic-exposed persons with and without arsenic-induced cancer
PMID: 24255851
6
lncRNA GMDS-AS1 regulates inflammatory responses and apoptosis via miR-96-5p/CASP2 axis in sepsis model
PMID: 34981821
7
GMDS identified as short-lived protein with differential stability across cell lines; HCT116 cells express truncated GMDS with lower stability than full-length form
PMID: 34626566
Disease Associationsⓘ20
open-angle glaucomaOpen Targets
0.49Moderate
glaucomaOpen Targets
0.47Moderate
Abnormality of the skeletal systemOpen Targets
0.46Moderate
type 2 diabetes mellitusOpen Targets
0.38Weak
gastroesophageal reflux diseaseOpen Targets
0.38Weak
coronary artery diseaseOpen Targets
0.36Weak
hemorrhoidOpen Targets
0.35Weak
prostate carcinomaOpen Targets
0.34Weak
ovarian neoplasmOpen Targets
0.33Weak
cardiovascular diseaseOpen Targets
0.32Weak
clear cell renal carcinomaOpen Targets
0.31Weak
esophageal diseaseOpen Targets
0.31Weak
coronary atherosclerosisOpen Targets
0.31Weak
intermediate coronary syndromeOpen Targets
0.31Weak
Myocardial IschemiaOpen Targets
0.30Weak
cervical carcinomaOpen Targets
0.30Weak
deficiency anemiaOpen Targets
0.30Weak
dislocationOpen Targets
0.29Weak
enteritisOpen Targets
0.29Weak
osteoarthritis, kneeOpen Targets
0.28Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
FPGTProtein interaction95%DPM2Protein interaction95%DPM3Protein interaction95%TNKSProtein interaction90%FOXC1Protein interaction89%ALG1Protein interaction87%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
40%
Lung
33%
Brain
27%
Ovary
25%
Heart
24%
Gene Interaction Network
Click a node to explore
GMDSFPGTDPM2DPM3TNKSFOXC1ALG1
PROTEIN STRUCTURE
Preparing viewer…
PDB6GPK · 1.47 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.72LoF Tolerant
pLIⓘ
0.54Intermediate
Observed/Expected LoF0.36 [0.20–0.72]
RankingsWhere GMDS stands among ~20K protein-coding genes
  • #7,069of 20,598
    Most Researched66
  • #5,538of 17,882
    Most Constrained (LOEUF)0.72
Genes detectedGMDS
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Proteome-wide mapping of short-lived proteins in human cells.
PMID: 34626566
Mol Cell · 2021
1.00
2
GMDS knockdown impairs cell proliferation and survival in human lung adenocarcinoma.
PMID: 29843634
BMC Cancer · 2018
0.90
3
The Indispensable Roles of GMDS and GMDS-AS1 in the Advancement of Cancer: Fucosylation, Signal Pathway and Molecular Pathogenesis.
PMID: 38591197
Mini Rev Med Chem · 2024
0.80
4
Genetics of glaucoma.
PMID: 28505344
Hum Mol Genet · 2017
0.70
5
lncRNA GMDS‑AS1 upregulates IL‑6, TNF‑α and IL‑1β, and induces apoptosis in human monocytic THP‑1 cells via miR‑96‑5p/caspase 2 signaling.
PMID: 34981821
Mol Med Rep · 2022
0.60