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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 6.3.2.2 4 56
  • 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

  • GLCLC
  • 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 Gamma-Glutamylcysteine Synthetase Deficiency, Hemolytic Anemia Due To and Myocardial Infarction. Among its related pathways are Aryl Hydrocarbon Receptor and Glutathione metabolism. Gene Ontology (GO) annotations related to this gene include protein heterodimerization activity and coenzyme binding.

Gene Wiki entry for GCLC Gene

Additional gene information 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

GeneHancer (GH) Regulatory Elements for GCLC Gene

Promoters and enhancers for GCLC 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
GH06I053543 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 550.2 +72.3 72280 3.4 PKNOX1 CLOCK FOXA2 MLX ZFP64 ARID4B NEUROD1 SIN3A DMAP1 ZNF2 GCLC GC06P053583 GC06M053483
GH06I053614 Enhancer 1.4 Ensembl ENCODE dbSUPER 550.8 +1.1 1130 3.5 FOXA2 ARNT MLX ARID4B SIN3A DMAP1 YY1 SLC30A9 FOS NFYC LOC101927136 GCLC LINC01564 GC06P053583
GH06I053511 Enhancer 0.9 ENCODE dbSUPER 11.4 +103.3 103314 3.4 CTCF FOXA2 TAF1 MAX ZNF644 RAD21 YY1 TEAD3 HNF4G MIXL1 GCLC LINC01564 LOC105375095 GC06M053483 GC06P053583
GH06I053547 Promoter/Enhancer 2.1 FANTOM5 Ensembl ENCODE dbSUPER 4.3 +68.8 68767 2 CLOCK MLX ZFP64 DMAP1 YY1 SLC30A9 ZNF213 E2F8 ZNF143 SP3 GCLC GC06P053583 GC06M053483
GH06I053650 Enhancer 1.4 Ensembl ENCODE dbSUPER 6.3 -34.7 -34705 2.3 PKNOX1 CLOCK MLX ZFP64 ARID4B SIN3A DMAP1 ZNF2 ZBTB7B YY1 GCLC KLHL31 GSTA4 LINC01564
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around GCLC on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the GCLC gene promoter:

Genomic Locations for GCLC Gene

Genomic Locations for GCLC Gene
chr6:53,497,341-53,616,970
(GRCh38/hg38)
Size:
119,630 bases
Orientation:
Minus strand
chr6:53,362,139-53,481,768
(GRCh37/hg19)

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:
    P48506-GSH1_HUMAN
    Recommended name:
    Glutamate--cysteine ligase catalytic subunit
    Protein Accession:
    P48506
    Secondary Accessions:
    • Q14399

    Protein attributes for GCLC Gene

    Size:
    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

P48506:
  • DHFENIQSTNWQTMRFKPPPPNS
  • CLQVTFQA
  • ISASVDDRT
  • MIEGTPG
  • GIDHLLAQHVAHLFIRD
  • KSRYDSIDSY
  • ALSAASP
  • INVPIFKD

Post-translational modifications for GCLC Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for GCLC Gene

Gene Families for GCLC Gene

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

Protein Domains for GCLC Gene

Graphical View of Domain Structure for InterPro Entry

P48506

UniProtKB/Swiss-Prot:

GSH1_HUMAN :
  • Belongs to the glutamate--cysteine ligase type 3 family.
Family:
  • Belongs to the glutamate--cysteine ligase type 3 family.
genes like me logo Genes that share domains with GCLC: view

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

Phenotypes From GWAS Catalog for GCLC Gene

Gene Ontology (GO) - Molecular Function for GCLC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000287 magnesium ion binding IDA 24639
GO:0003824 catalytic activity IEA --
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

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

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

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nucleoli (2)
  • Nucleus (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for GCLC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol IEA,TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0017109 glutamate-cysteine ligase complex IEA,IBA --
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 TAS,IEA --
GO:0006979 response to oxidative stress IDA,IEA 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

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Glutamic Acid Approved Nutra Full agonist, Agonist, Target 251
L-Cysteine Approved Nutra Target 0
Vitamin E Approved, Vet_approved Nutra Enzyme, inducer 434,438
Sulfamethoxazole Approved Pharma 169
Famotidine Approved Pharma Histamine H2-receptor antagonist 64

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
Phosphate
  • NFB Orthophosphate
  • O-Phosphoric acid
  • Ortho-phosphate
  • Orthophosphate (PO43-)
  • Orthophosphate(3-)
14265-44-2
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

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
GCLC
ECgene alternative splicing isoforms for
GCLC

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:

GCLC

SOURCE GeneReport for Unigene cluster for GCLC Gene:

Hs.654465

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)
  • Adrenal gland(2)
  • Blood(2)

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

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

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
chimpanzee
(Pan troglodytes)
Mammalia GCLC 34 33
  • 99.9 (n)
OneToOne
dog
(Canis familiaris)
Mammalia GCLC 34 33
  • 92.99 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia GCLC 34
  • 90 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia GCLC 34
  • 90 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Gclc 33
  • 88.91 (n)
mouse
(Mus musculus)
Mammalia Gclc 16 34 33
  • 88.57 (n)
cow
(Bos Taurus)
Mammalia GCLC 34 33
  • 86.12 (n)
OneToOne
chicken
(Gallus gallus)
Aves GCLC 34 33
  • 80.11 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia GCLC 34
  • 88 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia gclc 33
  • 75.88 (n)
Str.15467 33
African clawed frog
(Xenopus laevis)
Amphibia Xl.3837 33
zebrafish
(Danio rerio)
Actinopterygii gclc 34 33
  • 74 (n)
OneToOne
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8363 33
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP001512 33
  • 58.22 (n)
fruit fly
(Drosophila melanogaster)
Insecta Gclc 35 33 34
  • 57.92 (n)
worm
(Caenorhabditis elegans)
Secernentea gcs-1 34 33
  • 56.88 (n)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GSH1 33 34 36
  • 53.51 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0F14058g 33
  • 53.3 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AFR086C 33
  • 51.85 (n)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes gcs1 33
  • 55.4 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.10402 34
  • 55 (a)
OneToMany
-- 34
  • 49 (a)
OneToMany
-- 34
  • 47 (a)
OneToMany
bread mold
(Neurospora crassa)
Ascomycetes NCU01157 33
  • 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

ENSEMBL:
Gene Tree for GCLC (if available)
TreeFam:
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 Variation AA Info Type
rs121907946 pathogenic, Gamma-glutamylcysteine synthetase deficiency, hemolytic anemia due to, Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency (HAGGSD) [MIM:230450] 53,507,001(-) T/A/C coding_sequence_variant, missense_variant
rs760031222 Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency (HAGGSD) [MIM:230450] 53,520,845(-) G/A 5_prime_UTR_variant, coding_sequence_variant, missense_variant
VAR_015403 Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency (HAGGSD) [MIM:230450] p.Pro158Leu
rs17883901 benign, not specified 53,545,239(-) G/A/T upstream_transcript_variant
rs3830798 benign, not specified 53,544,654(-) CCTCCTCCTCCTCCTCCTCCTCC/CCTCCTCCTCCTCC/CCTCCTCCTCCTCCTCC/CCTCCTCCTCCTCCTCCTCC/CCTCCTCCTCCTCCTCCTCCTCCTCC/CCTCCTCCTCCTCCTCCTCCTCCTCCTCC/CCTCCTCCTCCTCCTCCTCCTCCTCCTCCTCC 5_prime_UTR_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)

Additional Variant Information for GCLC Gene

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

SNP Genotyping and Copy Number Assay Products

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: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
gamma-glutamylcysteine synthetase deficiency, hemolytic anemia due to
  • hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency
myocardial infarction
  • myocardial infarction, susceptibility to
hemolytic anemia
  • anemia hemolytic
ancylostomiasis
  • 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

UniProtKB/Swiss-Prot

GSH1_HUMAN
  • 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.

Additional Disease Information for GCLC

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 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 JJ … Mulcahy RT (Biochemical and biophysical research communications 1992) 2 3 4 22 58
  2. Association of polymorphisms of glutamate-cystein ligase and microsomal triglyceride transfer protein genes in non-alcoholic fatty liver disease. (PMID: 19817962) Oliveira CP … Corrêa-Giannella ML (Journal of gastroenterology and hepatology 2010) 3 22 44 58
  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 JR (Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2009) 3 22 44 58
  4. Genetic background of lead and mercury metabolism in a group of medical students in Austria. (PMID: 19515364) Gundacker C … Gencik M (Environmental research 2009) 3 22 44 58
  5. Lung function loss, smoking, vitamin C intake, and polymorphisms of the glutamate-cysteine ligase genes. (PMID: 18420959) Siedlinski M … Boezen HM (American journal of respiratory and critical care medicine 2008) 3 22 44 58

Products for GCLC Gene

Sources for GCLC Gene

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