TISIDB

Summary
Symbol	GMDS
Name	GDP-mannose 4,6-dehydratase
Aliases	GMD; SDR3E1; short chain dehydrogenase/reductase family 3E, member 1; GDP-D-mannose dehydratase; GDP-mannose ......
Chromosomal Location	6p25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	-
Domain	PF16363 GDP-mannose 4
Function	Catalyzes the conversion of GDP-D-mannose to GDP-4-dehydro-6-deoxy-D-mannose.

> Gene Ontology [ TOP ]
Biological Process	GO:0007219 Notch signaling pathway GO:0009225 nucleotide-sugar metabolic process GO:0009226 nucleotide-sugar biosynthetic process GO:0019673 GDP-mannose metabolic process GO:0042350 GDP-L-fucose biosynthetic process GO:0042351 'de novo' GDP-L-fucose biosynthetic process GO:0046368 GDP-L-fucose metabolic process
Molecular Function	GO:0008446 GDP-mannose 4,6-dehydratase activity GO:0016829 lyase activity GO:0016835 carbon-oxygen lyase activity GO:0016836 hydro-lyase activity GO:0048037 cofactor binding GO:0050661 NADP binding GO:0050662 coenzyme binding GO:0070401 NADP+ binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00051 Fructose and mannose metabolism hsa00520 Amino sugar and nucleotide sugar metabolism hsa01100 Metabolic pathways
Reactome	R-HSA-446203: Asparagine N-linked glycosylation R-HSA-446193: Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein R-HSA-6787639: GDP-fucose biosynthesis R-HSA-392499: Metabolism of proteins R-HSA-597592: Post-translational protein modification R-HSA-446219: Synthesis of substrates in N-glycan biosythesis

Summary
Symbol	GMDS
Name	GDP-mannose 4,6-dehydratase
Aliases	GMD; SDR3E1; short chain dehydrogenase/reductase family 3E, member 1; GDP-D-mannose dehydratase; GDP-mannose ......
Chromosomal Location	6p25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between GMDS and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between GMDS and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
19361506	Colon carcinoma	Promote immunity (NK cell function)	When mock and GMDS-rescued cells were transplanted into athymic mice, tumor growth and metastasis of the GMDS-rescued cells were dramatically suppressed through NK cell-mediated tumor surveillance.
22027835	Colon Carcinoma	Promote immunity	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. DR4, but not DR5, was found to be fucosylated; however, GMDS deficiency inhibited both DR4- and DR5-mediated apoptosis despite the absence of fucosylation on DR5. In addition, GMDS deficiency also inhibited CD95-mediated apoptosis but not the intrinsic apoptosis pathway induced by anti-cancer drugs. Binding of TRAIL and CD95 ligand to their cognate receptors primarily leads to formation of a complex comprising the receptor, FADD, and caspase-8, referred to as the death-inducing signaling complex (DISC). GMDS deficiency did not affect formation of the primary DISC or recruitment to and activation of caspase-8 on the DISC. However, formation of secondary FADD-dependent complex II, comprising caspase-8 and cFLIP, was significantly inhibited by GMDS deficiency.

Summary
Symbol	GMDS
Name	GDP-mannose 4,6-dehydratase
Aliases	GMD; SDR3E1; short chain dehydrogenase/reductase family 3E, member 1; GDP-D-mannose dehydratase; GDP-mannose ......
Chromosomal Location	6p25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of GMDS in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	GMDS
Name	GDP-mannose 4,6-dehydratase
Aliases	GMD; SDR3E1; short chain dehydrogenase/reductase family 3E, member 1; GDP-D-mannose dehydratase; GDP-mannose ......
Chromosomal Location	6p25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of GMDS in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.182	0.52
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.121	0.95
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.398	0.793
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.241	0.505
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.259	0.864
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.221	0.91
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.132	0.69
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.002	0.998
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.203	0.883
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.269	0.843
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	-0.353	0.858
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.118	0.134

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of GMDS in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	0	9.5	0.492
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	GMDS
Name	GDP-mannose 4,6-dehydratase
Aliases	GMD; SDR3E1; short chain dehydrogenase/reductase family 3E, member 1; GDP-D-mannose dehydratase; GDP-mannose ......
Chromosomal Location	6p25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of GMDS. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	GMDS
Name	GDP-mannose 4,6-dehydratase
Aliases	GMD; SDR3E1; short chain dehydrogenase/reductase family 3E, member 1; GDP-D-mannose dehydratase; GDP-mannose ......
Chromosomal Location	6p25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of GMDS. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by GMDS. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	GMDS
Name	GDP-mannose 4,6-dehydratase
Aliases	GMD; SDR3E1; short chain dehydrogenase/reductase family 3E, member 1; GDP-D-mannose dehydratase; GDP-mannose ......
Chromosomal Location	6p25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of GMDS. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	GMDS
Name	GDP-mannose 4,6-dehydratase
Aliases	GMD; SDR3E1; short chain dehydrogenase/reductase family 3E, member 1; GDP-D-mannose dehydratase; GDP-mannose ......
Chromosomal Location	6p25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of GMDS expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	GMDS
Name	GDP-mannose 4,6-dehydratase
Aliases	GMD; SDR3E1; short chain dehydrogenase/reductase family 3E, member 1; GDP-D-mannose dehydratase; GDP-mannose ......
Chromosomal Location	6p25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between GMDS and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	GMDS
Name	GDP-mannose 4,6-dehydratase
Aliases	GMD; SDR3E1; short chain dehydrogenase/reductase family 3E, member 1; GDP-D-mannose dehydratase; GDP-mannose ......
Chromosomal Location	6p25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting GMDS collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting GMDS.

ID	Name	Drug Type	Targets	#Targets
DB02547	Guanosine-5'-Diphosphate-Rhamnose	Small Molecule	GMDS	1
DB04315	Guanosine-5'-Diphosphate	Small Molecule	ADSSL1, ARF1, ARF4, ARF6, ARL1, ARL3, ARL5A, ARL5B, CDC42, EEF1A1, ......	36

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