TISIDB

Summary
Symbol	GSS
Name	glutathione synthetase
Aliases	GSHS; HEL-S-64p; HEL-S-88n; GSH synthetase; GSH-S; epididymis secretory sperm binding protein Li 64p; epidid ......
Chromosomal Location	20q11.2
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	PF03917 Eukaryotic glutathione synthase PF03199 Eukaryotic glutathione synthase
Function	-

> Gene Ontology [ TOP ]
Biological Process	GO:0001101 response to acid chemical GO:0006520 cellular amino acid metabolic process GO:0006575 cellular modified amino acid metabolic process GO:0006749 glutathione metabolic process GO:0006750 glutathione biosynthetic process GO:0006790 sulfur compound metabolic process GO:0006979 response to oxidative stress GO:0007568 aging GO:0009410 response to xenobiotic stimulus GO:0009991 response to extracellular stimulus GO:0010035 response to inorganic substance GO:0010038 response to metal ion GO:0019184 nonribosomal peptide biosynthetic process GO:0031667 response to nutrient levels GO:0034612 response to tumor necrosis factor GO:0042398 cellular modified amino acid biosynthetic process GO:0043200 response to amino acid GO:0044272 sulfur compound biosynthetic process GO:0046686 response to cadmium ion
Molecular Function	GO:0000287 magnesium ion binding GO:0004363 glutathione synthase activity GO:0016594 glycine binding GO:0016597 amino acid binding GO:0016874 ligase activity GO:0016879 ligase activity, forming carbon-nitrogen bonds GO:0016881 acid-amino acid ligase activity GO:0031406 carboxylic acid binding GO:0033218 amide binding GO:0042277 peptide binding GO:0043168 anion binding GO:0043295 glutathione binding GO:0072341 modified amino acid binding GO:1900750 oligopeptide binding GO:1901681 sulfur compound binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00270 Cysteine and methionine metabolism hsa00480 Glutathione metabolism hsa01100 Metabolic pathways
Reactome	R-HSA-211859: Biological oxidations R-HSA-156590: Glutathione conjugation R-HSA-174403: Glutathione synthesis and recycling R-HSA-1430728: Metabolism R-HSA-156580: Phase II conjugation

Summary
Symbol	GSS
Name	glutathione synthetase
Aliases	GSHS; HEL-S-64p; HEL-S-88n; GSH synthetase; GSH-S; epididymis secretory sperm binding protein Li 64p; epidid ......
Chromosomal Location	20q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between GSS 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 [ TOP ]
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Summary
Symbol	GSS
Name	glutathione synthetase
Aliases	GSHS; HEL-S-64p; HEL-S-88n; GSH synthetase; GSH-S; epididymis secretory sperm binding protein Li 64p; epidid ......
Chromosomal Location	20q11.2
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 GSS 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	logFC: -2.79; FDR: 0.04170	Resistant to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	logFC: -2.74; FDR: 0.04110	Resistant to T cell-mediated killing
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	GSS
Name	glutathione synthetase
Aliases	GSHS; HEL-S-64p; HEL-S-88n; GSH synthetase; GSH-S; epididymis secretory sperm binding protein Li 64p; epidid ......
Chromosomal Location	20q11.2
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 GSS 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	-0.035	0.892
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.119	0.96
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.142	0.932
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.231	0.45
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.086	0.96
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.419	0.854
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.266	0.475
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.325	0.834
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.208	0.904
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.097	0.957
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	-0.028	0.991
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.098	0.159

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of GSS 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	2.7	-2.7	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	3.4	-3.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	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	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	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	GSS
Name	glutathione synthetase
Aliases	GSHS; HEL-S-64p; HEL-S-88n; GSH synthetase; GSH-S; epididymis secretory sperm binding protein Li 64p; epidid ......
Chromosomal Location	20q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of GSS. 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	GSS
Name	glutathione synthetase
Aliases	GSHS; HEL-S-64p; HEL-S-88n; GSH synthetase; GSH-S; epididymis secretory sperm binding protein Li 64p; epidid ......
Chromosomal Location	20q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of GSS. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by GSS. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	GSS
Name	glutathione synthetase
Aliases	GSHS; HEL-S-64p; HEL-S-88n; GSH synthetase; GSH-S; epididymis secretory sperm binding protein Li 64p; epidid ......
Chromosomal Location	20q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of GSS. 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	GSS
Name	glutathione synthetase
Aliases	GSHS; HEL-S-64p; HEL-S-88n; GSH synthetase; GSH-S; epididymis secretory sperm binding protein Li 64p; epidid ......
Chromosomal Location	20q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of GSS expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	GSS
Name	glutathione synthetase
Aliases	GSHS; HEL-S-64p; HEL-S-88n; GSH synthetase; GSH-S; epididymis secretory sperm binding protein Li 64p; epidid ......
Chromosomal Location	20q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between GSS and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	GSS
Name	glutathione synthetase
Aliases	GSHS; HEL-S-64p; HEL-S-88n; GSH synthetase; GSH-S; epididymis secretory sperm binding protein Li 64p; epidid ......
Chromosomal Location	20q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting GSS collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting GSS.

ID	Name	Drug Type	Targets	#Targets
DB00143	Glutathione	Small Molecule	AKR1B1, CYP3A4, ESD, GGT1, GLO1, GLRX, GLRX2, GPX1, GPX2, GPX3, GP ......	41
DB00145	Glycine	Small Molecule	AGXT, AGXT2, ALAS1, ALAS2, BAAT, GARS, GATM, GCAT, GCSH, GLDC, GLR ......	30
DB00151	L-Cysteine	Small Molecule	CARS, CARS2, CBS, CDO1, CSAD, CTH, GCLC, GCLM, GOT1, GSS, MGMT, NF ......	13
DB03408	gamma-Glutamylcysteine	Small Molecule	GSS	1
DB04395	Phosphoaminophosphonic Acid-Adenylate Ester	Small Molecule	ACTA1, CCT3, CFTR, CSNK2A1, DAPK1, DTYMK, EPHA2, EPHB2, GALK1, GSK ......	26
DB06151	Acetylcysteine	Small Molecule	ACY1, CHUK, GRIN1, GRIN2A, GRIN2B, GRIN2D, GRIN3A, GSS, IKBKB, SLC ......	10
DB09130	Copper	Small Molecule	A1BG, ACTG1, ACTN1, ACY1, AFM, AGT, AHCY, AHSG, AKR1A1, ANXA4, ANX ......	141

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