GCLC glutamate-cysteine ligase catalytic subunit [Homo sapiens (human)] - Gene

Summary

Official Symbol: GCLCprovided by HGNC
Official Full Name: glutamate-cysteine ligase catalytic subunitprovided by HGNC
Primary source: HGNC:HGNC:4311
See related: Ensembl:ENSG00000001084 MIM:606857; AllianceGenome:HGNC:4311
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: GCL; GCS; GLCL; GLCLC; CNSHA7
Summary: 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]
Expression: Ubiquitous expression in liver (RPKM 39.8), urinary bladder (RPKM 19.1) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6p12.1

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (53497341..53545101, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (53337262..53388129, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (53362139..53409899, complement)

Chromosome 6 - NC_000006.12 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: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

SNORA56-mediated pseudouridylation of 28 S rRNA inhibits ferroptosis and promotes colorectal cancer proliferation by enhancing GCLC translation.
Title: SNORA56-mediated pseudouridylation of 28 S rRNA inhibits ferroptosis and promotes colorectal cancer proliferation by enhancing GCLC translation.
H1N1 influenza virus infection through NRF2-KEAP1-GCLC pathway induces ferroptosis in nasal mucosal epithelial cells.
Title: H1N1 influenza virus infection through NRF2-KEAP1-GCLC pathway induces ferroptosis in nasal mucosal epithelial cells.
Glutamate-cysteine ligase catalytic and its modifier function as novel immunotargets in gastric adenocarcinoma.
Title: Glutamate-cysteine ligase catalytic and its modifier function as novel immunotargets in gastric adenocarcinoma.
Ferroptosis-Related Gene GCLC Is a Novel Prognostic Molecular and Correlates with Immune Infiltrates in Lung Adenocarcinoma.
Title: Ferroptosis-Related Gene GCLC Is a Novel Prognostic Molecular and Correlates with Immune Infiltrates in Lung Adenocarcinoma.
Genetic variation at the catalytic subunit of glutamate cysteine ligase contributes to the susceptibility to sporadic colorectal cancer: a pilot study.
Title: Genetic variation at the catalytic subunit of glutamate cysteine ligase contributes to the susceptibility to sporadic colorectal cancer: a pilot study.
Association of Polymorphisms of Glutamate Cysteine Ligase Genes GCLC C-129 T and GCLM C-588 T with Risk of Polycystic Ovary Syndrome in Chinese Women.
Title: Association of Polymorphisms of Glutamate Cysteine Ligase Genes GCLC C-129 T and GCLM C-588 T with Risk of Polycystic Ovary Syndrome in Chinese Women.
Non-canonical Glutamate-Cysteine Ligase Activity Protects against Ferroptosis.
Title: Non-canonical Glutamate-Cysteine Ligase Activity Protects against Ferroptosis.
Genetic variants in glutamate cysteine ligase confer protection against type 2 diabetes.
Title: Genetic variants in glutamate cysteine ligase confer protection against type 2 diabetes.
Genetic susceptibility analysis of GCLC rs17883901 polymorphism to preeclampsia in Chinese Han women.
Title: Genetic susceptibility analysis of GCLC rs17883901 polymorphism to preeclampsia in Chinese Han women.
Results provide evidence that the functional SNPs rs17883901 in GCLC and rs713041 in GPX4 modulate the risk for diabetic retinopathy in the studied population of type 1 diabetes individuals, widening the spectrum of candidate genes for this complication.
Title: Allelic variations in genes belonging to glutathione system increase proliferative retinopathy risk in type 1 diabetes individuals.

Submit: New GeneRIF Correction See all GeneRIFs (86)

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
Gamma-glutamylcysteine synthetase deficiency MedGen: C1856603 OMIM: 230450 GeneReviews: Not available	not available
Myocardial infarction, susceptibility to MedGen: C1832662 OMIM: 608446 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH68488 (e-PCR)
- UniSTS:72993

G67294 (e-PCR)
- UniSTS:186428

G67293 (e-PCR)
- UniSTS:186429

D6S385 (e-PCR)
- UniSTS:65341

G67295 (e-PCR)
- UniSTS:186430

D6S2060 (e-PCR)
- UniSTS:79692

STS-M90656 (e-PCR)
- UniSTS:38741

RH45278 (e-PCR)
- UniSTS:29825

D11S3114 (e-PCR)
- UniSTS:152207

SHGC-132802 (e-PCR)
- UniSTS:170899

SHGC-81565 (e-PCR)
- UniSTS:103323

RH36336 (e-PCR)
- UniSTS:22943

Gclc (e-PCR), detects polymorphism
- UniSTS:256937

RH102364 (e-PCR)
- UniSTS:96698

STS-N29549 (e-PCR)
- UniSTS:68555

SHGC-53188 (e-PCR)
- UniSTS:78314

D6S1623 (e-PCR)
- UniSTS:18933

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ADP binding	IDA Inferred from Direct Assay more info	PubMed
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables glutamate binding	IDA Inferred from Direct Assay more info	PubMed
enables glutamate-cysteine ligase activity	IBA Inferred from Biological aspect of Ancestor more info
enables glutamate-cysteine ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables glutamate-cysteine ligase activity	IMP Inferred from Mutant Phenotype 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-containing complex binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in L-ascorbic acid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in blood vessel diameter maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell redox homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to fibroblast growth factor stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to follicle-stimulating hormone stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to glucose stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to hepatocyte growth factor stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to insulin stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to mechanical stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to thyroxine stimulus	IEA Inferred from Electronic Annotation more info
involved_in cysteine metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in glutamate metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in glutathione biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in glutathione biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in glutathione biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in glutathione biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of extrinsic apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of hepatic stellate cell activation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of protein ubiquitination	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IEA Inferred from Electronic Annotation more info
involved_in regulation of mitochondrial depolarization	IEA Inferred from Electronic Annotation more info
involved_in response to activity	IEA Inferred from Electronic Annotation more info
involved_in response to arsenic-containing substance	IEA Inferred from Electronic Annotation more info
involved_in response to cadmium ion	IEA Inferred from Electronic Annotation more info
involved_in response to heat	IDA Inferred from Direct Assay more info	PubMed
involved_in response to hormone	IDA Inferred from Direct Assay more info	PubMed
involved_in response to human chorionic gonadotropin	IEA Inferred from Electronic Annotation more info
involved_in response to interleukin-1	IEA Inferred from Electronic Annotation more info
involved_in response to nitrosative stress	IEA Inferred from Electronic Annotation more info
involved_in response to nutrient	IEA Inferred from Electronic Annotation more info
involved_in response to oxidative stress	IDA Inferred from Direct Assay more info	PubMed
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytosol	TAS Traceable Author Statement more info
part_of glutamate-cysteine ligase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of glutamate-cysteine ligase complex	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: glutamate--cysteine ligase catalytic subunit

Names: GCS heavy chain; gamma-ECS; gamma-glutamylcysteine synthetase

NP_001184044.1

EC 6.3.2.2

NP_001489.1

EC 6.3.2.2

XP_054211163.1

EC 6.3.2.2

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_012071.2 RefSeqGene

Range

5029..52789

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1166

mRNA and Protein(s)

NM_001197115.2 → NP_001184044.1 glutamate--cysteine ligase catalytic subunit isoform b

See identical proteins and their annotated locations for NP_001184044.1

Status: REVIEWED

Description

Transcript Variant: This variant (2, also referred to as delta4) lacks an in-frame exon in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform b), compared to isoform a.

Source sequence(s)

AB262176, AB516284, AK313480, AL531593, BC039894, BI550814

Consensus CDS

CCDS75471.1

UniProtKB/TrEMBL

A0A2R8YEL6, E1CEI4, H0Y9I7

Related

ENSP00000424211.2, ENST00000513939.6

Conserved Domains (1) summary

pfam03074
Location:198 → 570

GCS; Glutamate-cysteine ligase
NM_001498.4 → NP_001489.1 glutamate--cysteine ligase catalytic subunit isoform a

See identical proteins and their annotated locations for NP_001489.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).

Source sequence(s)

AB262176, AK313480, AL531593, BC039894, BI550814

Consensus CDS

CCDS4952.1

UniProtKB/Swiss-Prot

P48506, Q14399

UniProtKB/TrEMBL

A0A2R8YEL6, Q14TF0

Related

ENSP00000497574.1, ENST00000650454.1

Conserved Domains (2) summary

pfam03074
Location:236 → 608

GCS; Glutamate-cysteine ligase

cl28253
Location:22 → 76

RpsA; Ribosomal protein S1 [Translation, ribosomal structure and biogenesis]

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

53497341..53545101 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060930.1 Alternate T2T-CHM13v2.0

Range

53337262..53388129 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054355188.1 → XP_054211163.1 glutamate--cysteine ligase catalytic subunit isoform X1

UniProtKB/Swiss-Prot

P48506, Q14399

UniProtKB/TrEMBL

Q14TF0