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Aliases for GCLC Gene

Aliases for GCLC Gene

  • Glutamate-Cysteine Ligase Catalytic Subunit 2 3 5
  • Gamma-Glutamylcysteine Synthetase 3 4
  • GCS Heavy Chain 3 4
  • EC 4 61
  • Gamma-ECS 3 4
  • GLCLC 3 4
  • GLCL 3 4
  • Glutamate-Cysteine Ligase, Catalytic Subunit 2
  • Glutamate--Cysteine Ligase Catalytic Subunit 3
  • GCL 3
  • GCS 3

External Ids for GCLC Gene

Previous HGNC Symbols for GCLC Gene

  • GLCL

Previous GeneCards Identifiers for GCLC Gene

  • GC06M053365
  • GC06M053408
  • GC06M053409
  • GC06M053470
  • GC06M053193

Summaries for GCLC Gene

Entrez Gene Summary for GCLC Gene

  • Glutamate-cysteine ligase, also known as gamma-glutamylcysteine synthetase is the first rate-limiting enzyme of glutathione synthesis. The enzyme consists of two subunits, a heavy catalytic subunit and a light regulatory subunit. This locus encodes the catalytic subunit, while the regulatory subunit is derived from a different gene located on chromosome 1p22-p21. Mutations at this locus have been associated with hemolytic anemia due to deficiency of gamma-glutamylcysteine synthetase and susceptibility to myocardial infarction.[provided by RefSeq, Oct 2010]

GeneCards Summary for GCLC Gene

GCLC (Glutamate-Cysteine Ligase Catalytic Subunit) is a Protein Coding gene. Diseases associated with GCLC include Hemolytic Anemia Due To Gamma-Glutamylcysteine Synthetase Deficiency and Myocardial Infarction. Among its related pathways are Photodynamic therapy-induced NFE2L2 (NRF2) survival signaling and Glutathione metabolism. GO annotations related to this gene include protein heterodimerization activity and coenzyme binding.

Gene Wiki entry for GCLC Gene

No data available for CIViC summary , UniProtKB/Swiss-Prot , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for GCLC Gene

Genomics for GCLC Gene

Regulatory Elements for GCLC Gene

Enhancers for GCLC Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH06G053646 1.3 Ensembl ENCODE dbSUPER 8.8 -30.7 -30672 1.3 ELF3 SOX13 ZBTB40 KAT2B TEAD3 RFXANK GATAD1 ZSCAN29 IKZF2 GATAD2A GCLC LINC01564 KLHL31
GH06G053511 1 ENCODE dbSUPER 11.4 +103.3 103315 3.4 CTCF FOXA2 TAF1 MAX ZNF644 THRB RAD21 KAT2B YY1 TEAD3 GCLC LINC01564 LOC105375095 GC06M053483 GC06P053583
GH06G053650 1.6 Ensembl ENCODE dbSUPER 6.3 -34.7 -34705 2.3 PKNOX1 FOXA2 MLX ZFP64 ARID4B SIN3A DMAP1 ZNF2 ZBTB7B YY1 GCLC KLHL31 GSTA4 LINC01564
GH06G053679 1.5 Ensembl ENCODE dbSUPER 5.5 -62.8 -62766 0.5 CREB3L1 AGO1 ARID4B SIN3A GLI4 DMAP1 ZNF48 ZNF2 ZNF143 ZNF263 KLHL31 GCLC ENSG00000227885
GH06G053517 0.7 FANTOM5 11.6 +99.8 99797 0.2 ZNF362 JUN CEBPG ZNF384 RARA TEAD3 CEBPA FOS GCLC LINC01564 GC06M053483 GC06P053583
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around GCLC on UCSC Golden Path with GeneCards custom track

Genomic Location for GCLC Gene

53,497,341 bp from pter
53,616,970 bp from pter
119,630 bases
Minus strand

Genomic View for GCLC Gene

Genes around GCLC on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for GCLC Gene

Proteins for GCLC Gene

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

    Protein Symbol:
    Recommended name:
    Glutamate--cysteine ligase catalytic subunit
    Protein Accession:
    Secondary Accessions:
    • Q14399

    Protein attributes for GCLC Gene

    637 amino acids
    Molecular mass:
    72766 Da
    Quaternary structure:
    • Heterodimer of a catalytic heavy chain and a regulatory light chain.

neXtProt entry for GCLC Gene

Selected DME Specific Peptides for GCLC Gene


Post-translational modifications for GCLC Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for GCLC Gene

Protein Domains for GCLC Gene

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the glutamate--cysteine ligase type 3 family.
  • Belongs to the glutamate--cysteine ligase type 3 family.
genes like me logo Genes that share domains with GCLC: view

No data available for Gene Families for GCLC Gene

Function for GCLC Gene

Molecular function for GCLC Gene

UniProtKB/Swiss-Prot CatalyticActivity:
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine.
UniProtKB/Swiss-Prot EnzymeRegulation:
Feedback inhibition by glutathione.

Enzyme Numbers (IUBMB) for GCLC Gene

Gene Ontology (GO) - Molecular Function for GCLC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0000287 magnesium ion binding IDA 24639
GO:0004357 glutamate-cysteine ligase activity IEA,IMP 16183645
GO:0005524 ATP binding IEA --
GO:0016595 glutamate binding IDA 9841880
genes like me logo Genes that share ontologies with GCLC: view
genes like me logo Genes that share phenotypes with GCLC: view

Human Phenotype Ontology for GCLC Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for GCLC Gene

MGI Knock Outs for GCLC:

Animal Model Products

Inhibitory RNA Products

Clone Products

  • Applied Biological Materials Clones for GCLC

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

Localization for GCLC Gene

Subcellular locations from

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 GCLC gene
Compartment Confidence
cytosol 5
mitochondrion 3
nucleus 3
extracellular 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for GCLC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0017109 glutamate-cysteine ligase complex IEA --
genes like me logo Genes that share ontologies with GCLC: view

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

Pathways & Interactions for GCLC Gene

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

UniProtKB/Swiss-Prot P48506-GSH1_HUMAN

  • Pathway: Sulfur metabolism; glutathione biosynthesis; glutathione from L-cysteine and L-glutamate: step 1/2.

Gene Ontology (GO) - Biological Process for GCLC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006534 cysteine metabolic process IDA 2294991
GO:0006536 glutamate metabolic process IDA 2294991
GO:0006749 glutathione metabolic process IEA --
GO:0006750 glutathione biosynthetic process IEA,TAS --
GO:0006979 response to oxidative stress IDA 10395918
genes like me logo Genes that share ontologies with GCLC: view

No data available for SIGNOR curated interactions for GCLC Gene

Drugs & Compounds for GCLC Gene

(15) Drugs for GCLC Gene - From: DrugBank, PharmGKB, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
L-Cysteine Approved Nutra Target 0
Vitamin E Approved, Vet_approved Nutra Enzyme, inducer 414,411
Sulfamethoxazole Approved Pharma 161
Famotidine Approved Pharma Histamine H2-receptor antagonist 61
Phosphoric acid Approved Pharma 0

(9) Additional Compounds for GCLC Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
  • NFB Orthophosphate
  • O-Phosphoric acid
  • Ortho-phosphate
  • Orthophosphate (PO43-)
  • Orthophosphate(3-)
genes like me logo Genes that share compounds with GCLC: view

Transcripts for GCLC Gene

Unigene Clusters for GCLC Gene

Glutamate-cysteine ligase, catalytic subunit:
Representative Sequences:

Inhibitory RNA Products

Clone Products

  • Applied Biological Materials Clones for GCLC

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

ExUns: 1 ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6a · 6b ^ 7a · 7b ^ 8a · 8b ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13a · 13b ^ 14 ^ 15a · 15b ^ 16 ^ 17
SP1: - - - - - - -
SP2: - -
SP3: -
SP4: -
SP5: -
SP6: - - - - - - -
SP7: -
SP8: -

Relevant External Links for GCLC Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for GCLC Gene

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

Protein differential expression in normal tissues from HIPED for GCLC Gene

This gene is overexpressed in Lymph node (9.9) and Spleen (6.3).

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

Protein tissue co-expression partners for GCLC Gene

NURSA nuclear receptor signaling pathways regulating expression of GCLC Gene:


SOURCE GeneReport for Unigene cluster for GCLC Gene:


Evidence on tissue expression from TISSUES for GCLC Gene

  • Nervous system(4.9)
  • Liver(4.6)
  • Lung(2.7)
  • Kidney(2.2)
  • Heart(2.1)
  • Blood(2)

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

Germ Layers:
  • ectoderm
  • mesoderm
  • cardiovascular
  • nervous
  • skeletal muscle
Head and neck:
  • brain
  • cerebellum
  • head
  • blood
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
genes like me logo Genes that share expression patterns with GCLC: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for GCLC Gene

Orthologs for GCLC Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for GCLC Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia GCLC 34 35
  • 99.9 (n)
(Canis familiaris)
Mammalia GCLC 34 35
  • 92.99 (n)
(Monodelphis domestica)
Mammalia GCLC 35
  • 90 (a)
(Ornithorhynchus anatinus)
Mammalia GCLC 35
  • 90 (a)
(Rattus norvegicus)
Mammalia Gclc 34
  • 88.91 (n)
(Mus musculus)
Mammalia Gclc 34 16 35
  • 88.57 (n)
(Bos Taurus)
Mammalia GCLC 34 35
  • 86.12 (n)
(Gallus gallus)
Aves GCLC 34 35
  • 80.11 (n)
(Anolis carolinensis)
Reptilia GCLC 35
  • 88 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia gclc 34
  • 75.88 (n)
Str.15467 34
African clawed frog
(Xenopus laevis)
Amphibia Xl.3837 34
(Danio rerio)
Actinopterygii gclc 34 35
  • 74 (n)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8363 34
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP001512 34
  • 58.22 (n)
fruit fly
(Drosophila melanogaster)
Insecta Gclc 36 34 35
  • 57.92 (n)
(Caenorhabditis elegans)
Secernentea gcs-1 34 35
  • 56.88 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GSH1 34 35 37
  • 53.51 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0F14058g 34
  • 53.3 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AFR086C 34
  • 51.85 (n)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes gcs1 34
  • 55.4 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.10402 35
  • 55 (a)
-- 35
  • 49 (a)
-- 35
  • 47 (a)
bread mold
(Neurospora crassa)
Ascomycetes NCU01157 34
  • 53.58 (n)
Species where no ortholog for GCLC was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • rice (Oryza sativa)
  • 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)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for GCLC Gene

Gene Tree for GCLC (if available)
Gene Tree for GCLC (if available)

Paralogs for GCLC Gene

No data available for Paralogs for GCLC Gene

Variants for GCLC Gene

Sequence variations from dbSNP and Humsavar for GCLC Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type
rs121907946 Pathogenic, Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency (HAGGSD) [MIM:230450] 53,507,001(-) CCAGC(A/T)TGTTG downstream-variant-500B, reference, missense
rs760031222 Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency (HAGGSD) [MIM:230450] 53,520,845(+) CCGGC(A/G)TTTTC reference, missense, utr-variant-5-prime
VAR_015403 Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency (HAGGSD) [MIM:230450]
rs1000005683 -- 53,504,152(+) AGCAA(C/T)ATAGT intron-variant
rs1000032438 -- 53,535,605(+) ACTTA(C/T)ATCCA intron-variant

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

Variant ID Type Subtype PubMed ID
esv2763940 CNV gain+loss 21179565

Variation tolerance for GCLC Gene

Residual Variation Intolerance Score: 25.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.08; 38.00% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for GCLC Gene

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

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

Disorders for GCLC Gene

MalaCards: The human disease database

(5) MalaCards diseases for GCLC Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency
  • gamma-glutamylcysteine synthetase deficiency, hemolytic anemia due to
myocardial infarction
  • myocardial infarction, protection against
hemolytic anemia
  • anemia hemolytic
  • ancylostoma duodenale infection
diabetic encephalopathy
- elite association - COSMIC cancer census association via MalaCards
Search GCLC in MalaCards View complete list of genes associated with diseases


  • Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency (HAGGSD) [MIM:230450]: A disease characterized by hemolytic anemia, glutathione deficiency, myopathy, late-onset spinocerebellar degeneration, and peripheral neuropathy. {ECO:0000269 PubMed:10515893, ECO:0000269 PubMed:10733484, ECO:0000269 PubMed:12663448}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for GCLC

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

No data available for Genatlas for GCLC Gene

Publications for GCLC Gene

  1. Cloning and nucleotide sequence of a full-length cDNA for human liver gamma-glutamylcysteine synthetase. (PMID: 1350904) Gipp J.J. … Mulcahy R.T. (Biochem. Biophys. Res. Commun. 1992) 2 3 4 22 64
  2. Association of polymorphisms of glutamate-cystein ligase and microsomal triglyceride transfer protein genes in non-alcoholic fatty liver disease. (PMID: 19817962) Oliveira C.P. … CorrA-a-Giannella M.L. (J. Gastroenterol. Hepatol. 2010) 3 22 46 64
  3. Evaluation of glutathione metabolic genes on outcomes in advanced non-small cell lung cancer patients after initial treatment with platinum-based chemotherapy: an NCCTG-97-24-51 based study. (PMID: 19347979) Yang P. … Jett J.R. (J Thorac Oncol 2009) 3 22 46 64
  4. Genetic background of lead and mercury metabolism in a group of medical students in Austria. (PMID: 19515364) Gundacker C. … Gencik M. (Environ. Res. 2009) 3 22 46 64
  5. Lung function loss, smoking, vitamin C intake, and polymorphisms of the glutamate-cysteine ligase genes. (PMID: 18420959) Siedlinski M. … Boezen H.M. (Am. J. Respir. Crit. Care Med. 2008) 3 22 46 64

Products for GCLC Gene

Sources for GCLC Gene

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