GSS glutathione synthetase [Homo sapiens (human)] - Gene

Summary

Official Symbol: GSSprovided by HGNC
Official Full Name: glutathione synthetaseprovided by HGNC
Primary source: HGNC:HGNC:4624
See related: Ensembl:ENSG00000100983 MIM:601002; AllianceGenome:HGNC:4624
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GSHS; CNSHA6; HEL-S-64p; HEL-S-88n
Summary: Glutathione is important for a variety of biological functions, including protection of cells from oxidative damage by free radicals, detoxification of xenobiotics, and membrane transport. The protein encoded by this gene functions as a homodimer to catalyze the second step of glutathione biosynthesis, which is the ATP-dependent conversion of gamma-L-glutamyl-L-cysteine to glutathione. Defects in this gene are a cause of glutathione synthetase deficiency. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in kidney (RPKM 14.9), colon (RPKM 13.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 20q11.22

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	20	NC_000020.11 (34928432..34956027, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	20	NC_060944.1 (36649086..36676682, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	20	NC_000020.10 (33516235..33543830, complement)

Chromosome 20 - NC_000020.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Salivary IL-6, MMP-8 and GSS mRNA levels in combination with urine test analysis could be useful diagnostic tool for the very distributed disorder of pyelonephritis in childhood.
Title: Association of mRNA Levels of IL6, MMP-8, GSS in Saliva and Pyelonephritis in Children.
Data suggest that the potential of clusterin and glutathione synthetase (GSH-S) as platelet biomarkers for early detection of colorectal cancer (CRC) could improve existing screening modalities in clinical application.
Title: Protein levels of clusterin and glutathione synthetase in platelets allow for early detection of colorectal cancer.
Mutation in Glutathione Synthase gene is associated with chronic metabolic acidosis in glutathione synthetase deficiency.
Title: Clinical findings and effect of sodium hydrogen carbonate in patients with glutathione synthetase deficiency.
Four SNPs (rs7265992, rs6060124, rs7260770, and rs4911455) in GSS were significantly associated with bladder cancer recurrence after transurethral resection and BCG treatment.
Title: Genetic Variations in Glutathione Pathway Genes Predict Cancer Recurrence in Patients Treated with Transurethral Resection and Bacillus Calmette-Guerin Instillation for Non-muscle Invasive Bladder Cancer.
In this study, clinical, biochemical, and genetic aspects of five Chinese 5-oxoprolinuria patients with OPLAH or GSS gene mutations were investigated.
Title: Five Chinese patients with 5-oxoprolinuria due to glutathione synthetase and 5-oxoprolinase deficiencies.
GCLC and GSS were expressed at higher levels in colon cancer tissue, as compared with normal mucosa.
Title: Involvement of glutathione and glutathione metabolizing enzymes in human colorectal cancer cell lines and tissues.
Studied the role of protein-protein interactions in the structural stability, activity and allostery of enzymes using the obligate homodimer human glutathione synthetase as an ideal model.
Title: The role of strong electrostatic interactions at the dimer interface of human glutathione synthetase.
Its depletion causes protein oxidization in ATL cells.
Title: Carnosol, rosemary ingredient, induces apoptosis in adult T-cell leukemia/lymphoma cells via glutathione depletion: proteomic approach using fluorescent two-dimensional differential gel electrophoresis.
The findings indicate that Asp458 is essential for hGS catalysis and that it impacts the allostery of hGS.
Title: Aspartate 458 of human glutathione synthetase is important for cooperativity and active site structure.
These results imply that residues V44 and V45 are integral to the stability of human glutathione synthetase.
Title: Valine 44 and valine 45 of human glutathione synthetase are key for subunit stability and negative cooperativity.

Submit: New GeneRIF Correction See all GeneRIFs (24)

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

Associated conditions

Description	Tests
Glutathione synthetase deficiency with 5-oxoprolinuria MedGen: C0398746 OMIM: 266130 GeneReviews: Not available	Compare labs
Glutathione synthetase deficiency without 5-oxoprolinuria MedGen: C1856399 OMIM: 231900 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome wide association study for plasma levels of natural anticoagulant inhibitors and protein C anticoagulant pathway: the MARTHA project. EBI GWAS Catalog EBI GWAS CatalogPubMed

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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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Exposure to HIV-1 clade B Tat protein has a greater inhibition of GSS, GPx1, SOD1, and CAT expression compared with exposure to clade C Tat protein in monocyte-derived immature dendritic cells	PubMed
	tat	HIV-1 Tat causes a greater than 50% decrease in intracellular reduced glutathione (GSH), leading to the extracellular appearance of acidic FGF-1, an effect that is partially mediated through modulation of GSH biosynthetic enzymes	PubMed

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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

MARC_11817-11818:1029268323:1 (e-PCR)
- UniSTS:267270

A006I18 (e-PCR)
- UniSTS:63689

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables glutathione binding	IBA Inferred from Biological aspect of Ancestor more info
enables glutathione binding	IDA Inferred from Direct Assay more info	PubMed
enables glutathione synthase activity	IBA Inferred from Biological aspect of Ancestor more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables magnesium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in amino acid metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in glutathione biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in nervous system development	TAS Traceable Author Statement more info	PubMed
involved_in response to cadmium ion	IEA Inferred from Electronic Annotation more info
involved_in response to oxidative stress	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed

General protein information

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Preferred Names: glutathione synthetase

Names: GSH synthetase; GSH-S; glutathione synthase

NP_000169.1

EC 6.3.2.3

NP_001309423.1

EC 6.3.2.3

NP_001309424.1

EC 6.3.2.3

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.

Genomic

NG_008848.2 RefSeqGene

Range

5222..32596

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1168

mRNA and Protein(s)

NM_000178.4 → NP_000169.1 glutathione synthetase

See identical proteins and their annotated locations for NP_000169.1

Status: REVIEWED

Source sequence(s)

AL133324, AU076581, BC007927

Consensus CDS

CCDS13245.1

UniProtKB/Swiss-Prot

B2R697, B6F210, E1P5P9, P48637, Q4TTD9

UniProtKB/TrEMBL

A0A2R8Y430, V9HWJ1

Related

ENSP00000498303.1, ENST00000651619.1

Conserved Domains (1) summary

cd00228
Location:6 → 474

eu-GS; Eukaryotic Glutathione Synthetase (eu-GS); catalyses the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. Belongs to the ATP-grasp superfamily.
NM_001322494.1 → NP_001309423.1 glutathione synthetase

Status: REVIEWED

Source sequence(s)

BC007927, DC328543

Consensus CDS

CCDS13245.1

UniProtKB/Swiss-Prot

B2R697, B6F210, E1P5P9, P48637, Q4TTD9

UniProtKB/TrEMBL

A0A2R8Y430, V9HWJ1

Related

ENSP00000493903.1, ENST00000643188.1

Conserved Domains (1) summary

cd00228
Location:6 → 474

eu-GS; Eukaryotic Glutathione Synthetase (eu-GS); catalyses the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. Belongs to the ATP-grasp superfamily.
NM_001322495.1 → NP_001309424.1 glutathione synthetase

Status: REVIEWED

Source sequence(s)

AL133324, BC007927

Consensus CDS

CCDS13245.1

UniProtKB/Swiss-Prot

B2R697, B6F210, E1P5P9, P48637, Q4TTD9

UniProtKB/TrEMBL

A0A2R8Y430, V9HWJ1

Related

ENSP00000495750.1, ENST00000644793.1

Conserved Domains (1) summary

cd00228
Location:6 → 474

eu-GS; Eukaryotic Glutathione Synthetase (eu-GS); catalyses the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. Belongs to the ATP-grasp superfamily.