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 glut... See more...

Aliases for GSS Gene

Aliases for GSS Gene

  • Glutathione Synthetase 2 3 4 5
  • Glutathione Synthase 3 4
  • GSH Synthetase 3 4
  • EC 6.3.2.3 4 52
  • GSH-S 3 4
  • HEL-S-64p 3
  • HEL-S-88n 3
  • GSHS 3

External Ids for GSS Gene

Previous GeneCards Identifiers for GSS Gene

  • GC20M033274
  • GC20M034184
  • GC20M034232
  • GC20M034233
  • GC20M032980
  • GC20M033517
  • GC20M030294

Summaries for GSS Gene

Entrez Gene Summary for GSS Gene

  • 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]

GeneCards Summary for GSS Gene

GSS (Glutathione Synthetase) is a Protein Coding gene. Diseases associated with GSS include Glutathione Synthetase Deficiency and Glutathione Synthetase Deficiency Of Erythrocytes, Hemolytic Anemia Due To. Among its related pathways are Metabolism and Amino Acid metabolism. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and peptide binding.

Additional gene information for GSS Gene

No data available for CIViC Summary , UniProtKB/Swiss-Prot Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GSS Gene

Genomics for GSS Gene

GeneHancer (GH) Regulatory Elements for GSS Gene

Promoters and enhancers for GSS Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH20J034954 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 500.7 +0.1 82 2.7 ZNF217 CTCF TCF12 NRF1 USF1 POLR2G NCOR1 GTF2E2 PHF8 TEAD4 MYH7B GSS lnc-MYH7B-3 NCOA6 RPL36P4 RBM39 ERGIC3 ENSG00000272945 RBM12 PROCR
GH20J034921 Enhancer 1.1 Ensembl ENCODE dbSUPER 11.5 +33.6 33555 2.5 TCF12 JUND FOS EP300 TEAD1 SREBF2 FOXA2 DEK CEBPB ZNF316 PIGU GSS MIR499A EDEM2 MMP24OS NCOA6 piR-59804-013 MYH7B ACSS2
GH20J034925 Enhancer 0.8 Ensembl ENCODE dbSUPER 11.8 +28.7 28697 3.1 RBM22 JUN RCOR1 JUND SUPT5H TCF7L2 POLR2A SCRT2 PIGU GSS MIR499A NCOA6 MMP24 PROCR piR-59804-013 MYH7B ACSS2
GH20J034036 Enhancer 1.3 Ensembl ENCODE dbSUPER 4.8 +903.1 903126 37 CTCF SIN3A ZNF300 USF1 TEAD4 ZNF10 ZIC2 REST TCF7 RELA RALY MAP1LC3A AHCY GSS MYH7B MIR4755 lnc-ASIP-1
GH20J034890 Enhancer 1.2 Ensembl ENCODE dbSUPER 4.5 +64.8 64827 5.2 PHB2 FOS AFF1 USF2 MYC EP300 CTBP1 RBM25 LEF1 NCOR1 CPNE1 RBM39 RBM12 PIGU NCOA6 TRPC4AP RPL36P4 ERGIC3 RALY MAP1LC3A
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GSS on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GSS

Top Transcription factor binding sites by QIAGEN in the GSS gene promoter:
  • AML1a
  • Arnt
  • HNF-4alpha1
  • Ik-3
  • PPAR-alpha
  • STAT3
  • USF-1

Genomic Locations for GSS Gene

Genomic Locations for GSS Gene
chr20:34,928,432-34,956,027
(GRCh38/hg38)
Size:
27,596 bases
Orientation:
Minus strand
chr20:33,516,236-33,543,620
(GRCh37/hg19)
Size:
27,385 bases
Orientation:
Minus strand

Genomic View for GSS Gene

Genes around GSS on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GSS Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GSS Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GSS Gene

Proteins for GSS Gene

  • Protein details for GSS Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P48637-GSHB_HUMAN
    Recommended name:
    Glutathione synthetase
    Protein Accession:
    P48637
    Secondary Accessions:
    • B2R697
    • B6F210
    • E1P5P9
    • Q4TTD9

    Protein attributes for GSS Gene

    Size:
    474 amino acids
    Molecular mass:
    52385 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Homodimer.
    Miscellaneous:
    • [Isoform 2]: Detected in colon, kidney, lung, liver, placenta, peripheral blood and uterus, but not in heart, skeletal muscle and spleen.

    Three dimensional structures from OCA and Proteopedia for GSS Gene

    Alternative splice isoforms for GSS Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GSS Gene

Selected DME Specific Peptides for GSS Gene

P48637:
  • LPGQPEAVARLRATFAGLYSLD
  • ALKQIEINT
  • KILSNNPSKGLA
  • DGGVAAGVAVLDNPY
  • KPQREGGGNN
  • QCISELGIFGVYVR
  • TLVMNKHVGHLLRTKA
  • AVVYFRDGYMP
  • VLLIAQEKERNIFDQRA
  • NCLLRPGSPA
  • DRALAEGVLLR
  • ASFGGLASRTPAVH

Post-translational modifications for GSS Gene

  • Ubiquitination at Lys12, Lys112, and Lys400
  • Modification sites at PhosphoSitePlus

Domains & Families for GSS Gene

Gene Families for GSS Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • FDA approved drug targets
  • Plasma proteins
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for GSS Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ50601, highly similar to Glutathione synthetase (EC 6.3.2.3) (B7Z514_HUMAN)
  • Glutathione synthase (GSHB_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P48637

UniProtKB/Swiss-Prot:

GSHB_HUMAN :
  • Belongs to the eukaryotic GSH synthase family.
Family:
  • Belongs to the eukaryotic GSH synthase family.
genes like me logo Genes that share domains with GSS: view

Function for GSS Gene

Molecular function for GSS Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + glycine + L-gamma-glutamyl-L-cysteine = ADP + glutathione + H(+) + phosphate; Xref=Rhea:RHEA:13557, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57305, ChEBI:CHEBI:57925, ChEBI:CHEBI:58173, ChEBI:CHEBI:456216; EC=6.3.2.3;.
GENATLAS Biochemistry:
glutathione synthetase,52.4kDa

Enzyme Numbers (IUBMB) for GSS Gene

Phenotypes From GWAS Catalog for GSS Gene

Gene Ontology (GO) - Molecular Function for GSS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000287 magnesium ion binding IDA 10369661
GO:0004363 glutathione synthase activity TAS,IBA 21873635
GO:0005515 protein binding IPI 21044950
GO:0005524 ATP binding IDA 10369661
GO:0016594 glycine binding IEA --
genes like me logo Genes that share ontologies with GSS: view
genes like me logo Genes that share phenotypes with GSS: view

Human Phenotype Ontology for GSS Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for GSS Gene

MGI Knock Outs for GSS:
  • Gss Gss<tm1Wink>

Animal Model Products

  • Taconic Biosciences Mouse Models for GSS

CRISPR Products

Clone Products

No data available for Transcription Factor Targets and HOMER Transcription for GSS Gene

Localization for GSS Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GSS gene
Compartment Confidence
cytosol 4
nucleus 3
plasma membrane 2
extracellular 2
mitochondrion 2
peroxisome 2
cytoskeleton 1
endoplasmic reticulum 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for GSS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
GO:0070062 extracellular exosome HDA 19056867
genes like me logo Genes that share ontologies with GSS: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for GSS Gene

Pathways & Interactions for GSS Gene

genes like me logo Genes that share pathways with GSS: view

Pathways by source for GSS Gene

UniProtKB/Swiss-Prot P48637-GSHB_HUMAN

  • Pathway: Sulfur metabolism; glutathione biosynthesis; glutathione from L-cysteine and L-glutamate: step 2/2.

Gene Ontology (GO) - Biological Process for GSS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006520 cellular amino acid metabolic process TAS 8896573
GO:0006750 glutathione biosynthetic process TAS --
GO:0006979 response to oxidative stress TAS 465367
GO:0007399 nervous system development TAS 8896573
GO:0007568 aging IEA --
genes like me logo Genes that share ontologies with GSS: view

No data available for SIGNOR curated interactions for GSS Gene

Drugs & Compounds for GSS Gene

(20) Drugs for GSS Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Cysteine Approved Nutra Target 289
Glutathione Approved, Investigational Nutra Target 0
Glycine Approved, Vet_approved Nutra Full agonist, Agonist, Target 369
Acetylcysteine Approved, Investigational Pharma Target, stimulator Antioxidant;mucolytic agent 409
Copper Approved, Investigational Pharma Target 236

(21) Additional Compounds for GSS Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor 58-64-0
Phosphate
  • [po(OH)3]
  • Acide phosphorique
  • Acidum phosphoricum
  • H3PO4
  • Orthophosphoric acid
14066-19-4, 14265-44-2
Phosphite
  • [P(OH)3]
  • H3PO3
  • P(OH)3
  • Phosphite
  • Phosphorige saeure
14901-63-4
genes like me logo Genes that share compounds with GSS: view

Transcripts for GSS Gene

mRNA/cDNA for GSS Gene

3 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
28 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for GSS Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4a · 4b · 4c · 4d ^ 5a · 5b · 5c · 5d · 5e ^ 6a · 6b ^ 7 ^ 8a · 8b · 8c ^ 9 ^ 10 ^ 11 ^ 12a · 12b ^ 13a ·
SP1: - - - - - -
SP2: - -
SP3: - -
SP4:
SP5: -
SP6: -
SP7: - - -
SP8: - - -
SP9:
SP10:
SP11:

ExUns: 13b · 13c ^ 14 ^ 15a · 15b · 15c
SP1: - -
SP2:
SP3: - - -
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11: -

Relevant External Links for GSS Gene

GeneLoc Exon Structure for
GSS

Expression for GSS Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GSS Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for GSS Gene



Protein tissue co-expression partners for GSS Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GSS

SOURCE GeneReport for Unigene cluster for GSS Gene:

Hs.82327

Evidence on tissue expression from TISSUES for GSS Gene

  • Nervous system(4.9)
  • Liver(4.7)
  • Lung(4.7)
  • Kidney(4.6)
  • Intestine(4.4)
  • Eye(2.7)
  • Blood(2.6)
  • Skin(2.6)
  • Heart(2)
  • Stomach(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for GSS Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • cardiovascular
  • immune
  • nervous
  • skeletal muscle
  • urinary
Regions:
Head and neck:
  • brain
  • cerebellum
  • eye
  • head
Abdomen:
  • kidney
Limb:
  • lower limb
  • upper limb
General:
  • blood
  • red blood cell
  • spinal cord
  • white blood cell
genes like me logo Genes that share expression patterns with GSS: view

No data available for mRNA differential expression in normal tissues , Protein differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for GSS Gene

Orthologs for GSS Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for GSS Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PRNP 31
  • 100 (a)
OneToOne
GSS 30
  • 99.65 (n)
dog
(Canis familiaris)
Mammalia GSS 31 30
  • 92.19 (n)
OneToOne
cow
(Bos Taurus)
Mammalia GSS 31 30
  • 90.08 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Gss 17 31 30
  • 88.33 (n)
rat
(Rattus norvegicus)
Mammalia Gss 30
  • 87.9 (n)
oppossum
(Monodelphis domestica)
Mammalia GSS 31
  • 83 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia GSS 31
  • 59 (a)
OneToOne
chicken
(Gallus gallus)
Aves GSS 31 30
  • 70.32 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia GSS 31
  • 69 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia gss 30
  • 65.33 (n)
zebrafish
(Danio rerio)
Actinopterygii gss 31 30
  • 62.77 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta GS 31 30
  • 53.38 (n)
OneToMany
CG32495 31
  • 35 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000534 30
  • 53.33 (n)
worm
(Caenorhabditis elegans)
Secernentea gss-1 31 30
  • 47.2 (n)
OneToOne
M176.2 32
  • 39 (a)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0F07557g 30
  • 46.84 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ACR284C 30
  • 46.49 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GSH2 31 30
  • 45.42 (n)
OneToOne
thale cress
(Arabidopsis thaliana)
eudicotyledons GSH2 30
  • 50.44 (n)
rice
(Oryza sativa)
Liliopsida Os11g0642800 30
  • 50.04 (n)
bread mold
(Neurospora crassa)
Ascomycetes NCU06191 30
  • 50.36 (n)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes gsa1 30
  • 46.38 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3374 31
  • 43 (a)
OneToOne
Species where no ortholog for GSS was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for GSS Gene

ENSEMBL:
Gene Tree for GSS (if available)
TreeFam:
Gene Tree for GSS (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GSS: view image

Paralogs for GSS Gene

No data available for Paralogs for GSS Gene

Variants for GSS Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GSS Gene

SNP ID Clinical significance and condition Chr 20 pos Variation AA Info Type
650657 Uncertain Significance: Gluthathione synthetase deficiency 34,931,393(-) C/T MISSENSE_VARIANT
653428 Uncertain Significance: Gluthathione synthetase deficiency 34,937,001(-) G/C MISSENSE_VARIANT
668330 Likely Benign: not provided 34,931,935(-) G/A INTRON_VARIANT
680913 Likely Benign: not provided 34,929,387(-) C/G INTRON_VARIANT
698137 Likely Benign: not provided 34,931,995(-) G/A MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for GSS Gene

Structural Variations from Database of Genomic Variants (DGV) for GSS Gene

Variant ID Type Subtype PubMed ID
nsv1055447 CNV loss 25217958
nsv833962 CNV loss 17160897

Variation tolerance for GSS Gene

Residual Variation Intolerance Score: 61.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.76; 33.33% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GSS Gene

Human Gene Mutation Database (HGMD)
GSS
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GSS

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GSS Gene

Disorders for GSS Gene

MalaCards: The human disease database

(7) MalaCards diseases for GSS Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search GSS in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

GSHB_HUMAN
  • Glutathione synthetase deficiency (GSS deficiency) [MIM:266130]: Severe form characterized by an increased rate of hemolysis and defective function of the central nervous system. {ECO:0000269 PubMed:27581854, ECO:0000269 PubMed:8896573, ECO:0000269 PubMed:9215686}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Glutathione synthetase deficiency of erythrocytes (GLUSYNDE) [MIM:231900]: Mild form causing hemolytic anemia. Note=The disease is caused by mutations affecting the gene represented in this entry.

Genatlas disease for GSS Gene

pyroglutamicaciduria,including a severe form characterized by acute metabolic acidosis from the neonatal period,hemolytic anemia progressive encephalopathy and 5-oxyprolinuria. A milder form is restricted to erythrocyctes

Additional Disease Information for GSS

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with GSS: view

Publications for GSS Gene

  1. Molecular basis of glutathione synthetase deficiency and a rare gene permutation event. (PMID: 10369661) Polekhina G … Parker MW (The EMBO journal 1999) 3 4 23 54
  2. Mutations in the glutathione synthetase gene cause 5-oxoprolinuria. (PMID: 8896573) Shi ZZ … Lieberman MW (Nature genetics 1996) 3 4 23 54
  3. The gene encoding human glutathione synthetase (GSS) maps to the long arm of chromosome 20 at band 11.2. (PMID: 8825653) Webb GC … Board PG (Genomics 1995) 2 3 23 54
  4. Sequencing and expression of a cDNA for human glutathione synthetase. (PMID: 7646467) Gali RR … Board PG (The Biochemical journal 1995) 3 4 23 54
  5. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41 54

Products for GSS Gene

  • Signalway ELISA kits for GSS
  • Signalway Proteins for GSS

Sources for GSS Gene