Gene Details | GeDiPNet - Complete Gene Info, Disease Associations & Pathways

Gene Gene information from NCBI Gene database. Gene SNPs miRNA Transcription factors Gene ontology Other IDs Protein Pathways Associated diseases
Entrez ID	2729
Gene name	Glutamate-cysteine ligase catalytic subunit
Gene symbol	GCLC
Synonyms (NCBI Gene)	CNSHA7GCLGCSGLCLGLCLC
Chromosome	6
Chromosome location	6p12.1
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 ca

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SNP ID	Visualize variation	Clinical significance	Consequence
rs1554152412	A>T	Likely-pathogenic	Missense variant, 5 prime UTR variant, coding sequence variant, intron variant

168

Show/Hide all (168)

miRTarBase ID	miRNA	Experiments	Reference
MIRT021012	hsa-miR-155-5p	Proteomics	18668040
MIRT440579	ebv-miR-BART7-3p	HITS-CLIP	22473208
MIRT440579	ebv-miR-BART7-3p	HITS-CLIP	22473208
MIRT727590	hsa-miR-30a-5p	HITS-CLIP	22473208
MIRT727589	hsa-miR-30b-5p	HITS-CLIP	22473208
MIRT727588	hsa-miR-30c-5p	HITS-CLIP	22473208
MIRT727586	hsa-miR-30d-5p	HITS-CLIP	22473208
MIRT727587	hsa-miR-30e-5p	HITS-CLIP	22473208
MIRT1014731	hsa-miR-1206	CLIP-seq
MIRT1014732	hsa-miR-1236	CLIP-seq
MIRT1014733	hsa-miR-1272	CLIP-seq
MIRT1014734	hsa-miR-1283	CLIP-seq
MIRT1014735	hsa-miR-1297	CLIP-seq
MIRT1014736	hsa-miR-1323	CLIP-seq
MIRT1014737	hsa-miR-137	CLIP-seq
MIRT1014738	hsa-miR-15a	CLIP-seq
MIRT1014739	hsa-miR-15b	CLIP-seq
MIRT1014740	hsa-miR-16	CLIP-seq
MIRT1014741	hsa-miR-190	CLIP-seq
MIRT1014742	hsa-miR-190b	CLIP-seq
MIRT1014743	hsa-miR-195	CLIP-seq
MIRT1014744	hsa-miR-2053	CLIP-seq
MIRT1014745	hsa-miR-216b	CLIP-seq
MIRT1014746	hsa-miR-25	CLIP-seq
MIRT1014747	hsa-miR-26a	CLIP-seq
MIRT1014748	hsa-miR-26b	CLIP-seq
MIRT1014749	hsa-miR-3120-3p	CLIP-seq
MIRT1014750	hsa-miR-3156-5p	CLIP-seq
MIRT1014751	hsa-miR-32	CLIP-seq
MIRT1014752	hsa-miR-338-5p	CLIP-seq
MIRT1014753	hsa-miR-363	CLIP-seq
MIRT1014754	hsa-miR-367	CLIP-seq
MIRT1014755	hsa-miR-3942-3p	CLIP-seq
MIRT1014756	hsa-miR-3976	CLIP-seq
MIRT1014757	hsa-miR-424	CLIP-seq
MIRT1014758	hsa-miR-4260	CLIP-seq
MIRT1014759	hsa-miR-4275	CLIP-seq
MIRT1014760	hsa-miR-433	CLIP-seq
MIRT1014761	hsa-miR-4453	CLIP-seq
MIRT1014762	hsa-miR-4465	CLIP-seq
MIRT1014763	hsa-miR-4477a	CLIP-seq
MIRT1014764	hsa-miR-4538	CLIP-seq
MIRT1014765	hsa-miR-4632	CLIP-seq
MIRT1014766	hsa-miR-4676-5p	CLIP-seq
MIRT1014767	hsa-miR-4760-5p	CLIP-seq
MIRT1014768	hsa-miR-4761-5p	CLIP-seq
MIRT1014769	hsa-miR-4797-5p	CLIP-seq
MIRT1014770	hsa-miR-486-3p	CLIP-seq
MIRT1014771	hsa-miR-497	CLIP-seq
MIRT1014772	hsa-miR-520a-5p	CLIP-seq
MIRT1014773	hsa-miR-525-5p	CLIP-seq
MIRT1014774	hsa-miR-548a-3p	CLIP-seq
MIRT1014775	hsa-miR-548c-3p	CLIP-seq
MIRT1014776	hsa-miR-548e	CLIP-seq
MIRT1014777	hsa-miR-548f	CLIP-seq
MIRT1014778	hsa-miR-548g	CLIP-seq
MIRT1014779	hsa-miR-548o	CLIP-seq
MIRT1014780	hsa-miR-569	CLIP-seq
MIRT1014781	hsa-miR-575	CLIP-seq
MIRT1014782	hsa-miR-580	CLIP-seq
MIRT1014783	hsa-miR-646	CLIP-seq
MIRT1014784	hsa-miR-92a	CLIP-seq
MIRT1014785	hsa-miR-92b	CLIP-seq
MIRT1014786	hsa-miR-122	CLIP-seq
MIRT1014732	hsa-miR-1236	CLIP-seq
MIRT1014787	hsa-miR-1246	CLIP-seq
MIRT1014788	hsa-miR-1257	CLIP-seq
MIRT1014789	hsa-miR-127-5p	CLIP-seq
MIRT1014735	hsa-miR-1297	CLIP-seq
MIRT1014790	hsa-miR-1303	CLIP-seq
MIRT1014791	hsa-miR-135a	CLIP-seq
MIRT1014792	hsa-miR-135b	CLIP-seq
MIRT1014737	hsa-miR-137	CLIP-seq
MIRT1014745	hsa-miR-216b	CLIP-seq
MIRT1014746	hsa-miR-25	CLIP-seq
MIRT1014747	hsa-miR-26a	CLIP-seq
MIRT1014748	hsa-miR-26b	CLIP-seq
MIRT1014793	hsa-miR-3119	CLIP-seq
MIRT1014794	hsa-miR-3125	CLIP-seq
MIRT1014751	hsa-miR-32	CLIP-seq
MIRT1014753	hsa-miR-363	CLIP-seq
MIRT1014795	hsa-miR-3668	CLIP-seq
MIRT1014754	hsa-miR-367	CLIP-seq
MIRT1014796	hsa-miR-3916	CLIP-seq
MIRT1014755	hsa-miR-3942-3p	CLIP-seq
MIRT1014759	hsa-miR-4275	CLIP-seq
MIRT1014797	hsa-miR-4320	CLIP-seq
MIRT1014762	hsa-miR-4465	CLIP-seq
MIRT1014798	hsa-miR-4635	CLIP-seq
MIRT1014799	hsa-miR-4790-3p	CLIP-seq
MIRT1014783	hsa-miR-646	CLIP-seq
MIRT1014800	hsa-miR-877	CLIP-seq
MIRT1014784	hsa-miR-92a	CLIP-seq
MIRT1014785	hsa-miR-92b	CLIP-seq
MIRT2000453	hsa-miR-1238	CLIP-seq
MIRT2000454	hsa-miR-140-3p	CLIP-seq
MIRT2000455	hsa-miR-3137	CLIP-seq
MIRT2000456	hsa-miR-3622b-5p	CLIP-seq
MIRT1014760	hsa-miR-433	CLIP-seq
MIRT1014766	hsa-miR-4676-5p	CLIP-seq
MIRT1014772	hsa-miR-520a-5p	CLIP-seq
MIRT1014773	hsa-miR-525-5p	CLIP-seq
MIRT1014781	hsa-miR-575	CLIP-seq
MIRT2000457	hsa-miR-586	CLIP-seq
MIRT2233962	hsa-miR-101	CLIP-seq
MIRT1014731	hsa-miR-1206	CLIP-seq
MIRT1014732	hsa-miR-1236	CLIP-seq
MIRT1014787	hsa-miR-1246	CLIP-seq
MIRT1014733	hsa-miR-1272	CLIP-seq
MIRT2233963	hsa-miR-1279	CLIP-seq
MIRT1014734	hsa-miR-1283	CLIP-seq
MIRT1014735	hsa-miR-1297	CLIP-seq
MIRT1014736	hsa-miR-1323	CLIP-seq
MIRT2233964	hsa-miR-133a	CLIP-seq
MIRT2233965	hsa-miR-133b	CLIP-seq
MIRT1014737	hsa-miR-137	CLIP-seq
MIRT1014738	hsa-miR-15a	CLIP-seq
MIRT1014739	hsa-miR-15b	CLIP-seq
MIRT1014740	hsa-miR-16	CLIP-seq
MIRT1014743	hsa-miR-195	CLIP-seq
MIRT1014745	hsa-miR-216b	CLIP-seq
MIRT1014746	hsa-miR-25	CLIP-seq
MIRT1014747	hsa-miR-26a	CLIP-seq
MIRT1014748	hsa-miR-26b	CLIP-seq
MIRT2233966	hsa-miR-3064-5p	CLIP-seq
MIRT1014749	hsa-miR-3120-3p	CLIP-seq
MIRT2233967	hsa-miR-3168	CLIP-seq
MIRT1014751	hsa-miR-32	CLIP-seq
MIRT2233968	hsa-miR-329	CLIP-seq
MIRT1014752	hsa-miR-338-5p	CLIP-seq
MIRT2233969	hsa-miR-362-3p	CLIP-seq
MIRT1014753	hsa-miR-363	CLIP-seq
MIRT1014754	hsa-miR-367	CLIP-seq
MIRT2233970	hsa-miR-3941	CLIP-seq
MIRT1014757	hsa-miR-424	CLIP-seq
MIRT2233971	hsa-miR-4277	CLIP-seq
MIRT2233972	hsa-miR-4282	CLIP-seq
MIRT1014797	hsa-miR-4320	CLIP-seq
MIRT1014760	hsa-miR-433	CLIP-seq
MIRT1014762	hsa-miR-4465	CLIP-seq
MIRT2233973	hsa-miR-4492	CLIP-seq
MIRT2233974	hsa-miR-4498	CLIP-seq
MIRT2233975	hsa-miR-4506	CLIP-seq
MIRT2233976	hsa-miR-4645-3p	CLIP-seq
MIRT2233977	hsa-miR-4666-5p	CLIP-seq
MIRT1014766	hsa-miR-4676-5p	CLIP-seq
MIRT2233978	hsa-miR-4789-5p	CLIP-seq
MIRT1014769	hsa-miR-4797-5p	CLIP-seq
MIRT1014771	hsa-miR-497	CLIP-seq
MIRT2233979	hsa-miR-520d-5p	CLIP-seq
MIRT2233980	hsa-miR-524-5p	CLIP-seq
MIRT1014774	hsa-miR-548a-3p	CLIP-seq
MIRT1014775	hsa-miR-548c-3p	CLIP-seq
MIRT1014776	hsa-miR-548e	CLIP-seq
MIRT1014777	hsa-miR-548f	CLIP-seq
MIRT1014779	hsa-miR-548o	CLIP-seq
MIRT2233981	hsa-miR-568	CLIP-seq
MIRT1014781	hsa-miR-575	CLIP-seq
MIRT2233982	hsa-miR-579	CLIP-seq
MIRT2233983	hsa-miR-582-5p	CLIP-seq
MIRT2233984	hsa-miR-602	CLIP-seq
MIRT2233985	hsa-miR-603	CLIP-seq
MIRT1014783	hsa-miR-646	CLIP-seq
MIRT2233986	hsa-miR-656	CLIP-seq
MIRT2233987	hsa-miR-762	CLIP-seq
MIRT1014784	hsa-miR-92a	CLIP-seq
MIRT1014785	hsa-miR-92b	CLIP-seq
MIRT2233988	hsa-miR-95	CLIP-seq

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Transcription factor	Regulation	Reference
FOSL1	Unknown	16054171
JUN	Unknown	11233143;11912197;16054171
JUND	Unknown	16054171
MAF	Unknown	16054171
MTF1	Activation	15378601
NFE2	Unknown	16054171
NFE2L2	Repression	22459801
NFE2L2	Unknown	16054171
NFKB1	Unknown	11233143
RELA	Unknown	11233143
SP1	Activation	15342415;18245173

Show/Hide all (59)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0000287	Function	Magnesium ion binding	IDA	24639
GO:0003824	Function	Catalytic activity	IEA
GO:0004357	Function	Glutamate-cysteine ligase activity	IBA
GO:0004357	Function	Glutamate-cysteine ligase activity	IDA	8104187, 9675072, 11972604
GO:0004357	Function	Glutamate-cysteine ligase activity	IEA
GO:0004357	Function	Glutamate-cysteine ligase activity	IMP	9841880, 12663448, 16183645
GO:0005515	Function	Protein binding	IPI	9675072, 9841880, 28514442, 33961781
GO:0005524	Function	ATP binding	IEA
GO:0005739	Component	Mitochondrion	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006534	Process	Cysteine metabolic process	IDA	2294991
GO:0006536	Process	Glutamate metabolic process	IDA	2294991, 9841880, 12663448
GO:0006749	Process	Glutathione metabolic process	IEA
GO:0006750	Process	Glutathione biosynthetic process	IBA
GO:0006750	Process	Glutathione biosynthetic process	IDA	8104187, 9675072, 10395918
GO:0006750	Process	Glutathione biosynthetic process	IEA
GO:0006750	Process	Glutathione biosynthetic process	IEA
GO:0006750	Process	Glutathione biosynthetic process	IMP	12663448
GO:0006979	Process	Response to oxidative stress	IDA	10395918, 11972604
GO:0006979	Process	Response to oxidative stress	IEA
GO:0007584	Process	Response to nutrient	IEA
GO:0009408	Process	Response to heat	IDA	8104187
GO:0009410	Process	Response to xenobiotic stimulus	IEA
GO:0009725	Process	Response to hormone	IDA	8104187
GO:0014823	Process	Response to activity	IEA
GO:0016595	Function	Glutamate binding	IDA	9841880
GO:0016874	Function	Ligase activity	IEA
GO:0017109	Component	Glutamate-cysteine ligase complex	IBA
GO:0017109	Component	Glutamate-cysteine ligase complex	IDA	9675072, 9841880
GO:0017109	Component	Glutamate-cysteine ligase complex	IEA
GO:0019852	Process	L-ascorbic acid metabolic process	IEA
GO:0031397	Process	Negative regulation of protein ubiquitination	IEA
GO:0032436	Process	Positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IEA
GO:0032869	Process	Cellular response to insulin stimulus	IEA
GO:0035729	Process	Cellular response to hepatocyte growth factor stimulus	IEA
GO:0043066	Process	Negative regulation of apoptotic process	IDA	10439045
GO:0043066	Process	Negative regulation of apoptotic process	IEA
GO:0043524	Process	Negative regulation of neuron apoptotic process	IEA
GO:0043531	Function	ADP binding	IDA	24639
GO:0044344	Process	Cellular response to fibroblast growth factor stimulus	IEA
GO:0044752	Process	Response to human chorionic gonadotropin	IEA
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0045454	Process	Cell redox homeostasis	IDA	10439045
GO:0045892	Process	Negative regulation of DNA-templated transcription	IDA	10439045
GO:0046685	Process	Response to arsenic-containing substance	IEA
GO:0046686	Process	Response to cadmium ion	IEA
GO:0051409	Process	Response to nitrosative stress	IEA
GO:0051900	Process	Regulation of mitochondrial depolarization	IEA
GO:0070555	Process	Response to interleukin-1	IEA
GO:0071260	Process	Cellular response to mechanical stimulus	IEA
GO:0071333	Process	Cellular response to glucose stimulus	IEA
GO:0071372	Process	Cellular response to follicle-stimulating hormone stimulus	IEA
GO:0097069	Process	Cellular response to thyroxine stimulus	IEA
GO:0097746	Process	Blood vessel diameter maintenance	IMP	12598062
GO:1901029	Process	Negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway	IEA
GO:2000490	Process	Negative regulation of hepatic stellate cell activation	IEA
GO:2001237	Process	Negative regulation of extrinsic apoptotic signaling pathway	IEA

MIM	HGNC	e!Ensembl
606857	4311	ENSG00000001084

P48506

Protein name

Glutamate--cysteine ligase catalytic subunit (EC 6.3.2.2) (GCS heavy chain) (Gamma-ECS) (Gamma-glutamylcysteine synthetase)

Protein function

Catalyzes the ATP-dependent ligation of L-glutamate and L-cysteine and participates in the first and rate-limiting step in glutathione biosynthesis.

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF03074	GCS	236 → 608	Glutamate-cysteine ligase	Family

Sequence

MGLLSQGSPLSWEETKRHADHVRRHGILQFLHIYHAVKDRHKDVLKWGDEVEYMLVSFDH
ENKKVRLVLSGEKVLETLQEKGERTNPNHPTLWRPEYGSYMIEGTPGQPYGGTMSEFNTV
EANMRKRRKEATSILEENQALCTITSFPRLGCPGFTLPEVKPNPVEGGASKSLFFPDEAI
NKHPRFSTLTRNIRHRRGEKVVINVPIFKDKNTPSPFIETFTEDDEASRASKPDHIYMDA
MGFGMGNCCLQVTFQACSISEARYLYDQLATICPIVMALSAASPFYRGYVSDIDCRWGVI
SASVDDRTREERGLEPLKNNNYRISKSRYDSIDSYLSKCGEKYNDIDLTIDKEIYEQLLQ
EGIDHLLAQHVAHLFIRDPLTLFEEKIHLDDANESDHFENIQSTNWQTMRFKPPPPNSDI
GWRVEFRPMEVQLTDFENSAYVVFVVLLTRVILSYKLDFLIPLSKVDENMKVAQKRDAVL
QGMFYFRKDICKGGNAVVDGCGKAQNSTELAAEEYTLMSIDTIINGKEGVFPGLIPILNS
YLENMEVDVDTRCSILNYLKLIKKRASGELMTVARWMREFIANHPDYKQDSVITDEMNYS
LILKCNQIANELCECPELLGSAFRKVKYSGSKTDSSN

Sequence length

637

Interactions

View interactions

	KEGG		Reactome
	Cysteine and methionine metabolism Glutathione metabolism Metabolic pathways Biosynthesis of cofactors Ferroptosis		Glutathione synthesis and recycling Defective GCLC causes Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency (HAGGSD)

Show/Hide Causal Diseases (1)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Causal Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
Gamma-glutamylcysteine synthetase deficiency	Pathogenic	rs121907946	RCV000004164

Show/Hide Unknown Diseases (13)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Unknown Diseases with uncertain, conflicting, or no pathogenic evidence in ClinVar
Acute myeloid leukemia	Benign	rs2066507	RCV005912313
Cervical cancer	Benign	rs2066507	RCV005912316
Familial cancer of breast	Benign; Conflicting classifications of pathogenicity	rs185146268, rs199775302	RCV005922580 RCV005910902
Familial pancreatic carcinoma	Benign	rs2066507	RCV005912317
Gastric cancer	Benign	rs2066507	RCV005912319
GCLC-related disorder	Likely benign; Uncertain significance; Benign; Conflicting classifications of pathogenicity	rs141946881, rs201680153, rs3830798, rs2066509, rs80120302, rs181411098, rs368832845, rs2066508	RCV003956442 RCV003921548 RCV003929620 RCV003962423 RCV003983239 RCV003930716 RCV003925840 RCV003918592 RCV003973178
Hepatocellular carcinoma	Benign	rs2066507	RCV005912314
Malignant lymphoma, large B-cell, diffuse	Benign	rs2066507	RCV005912318
Malignant tumor of esophagus	Benign	rs2066507	RCV005912315
Melanoma	Likely benign	rs760538542	RCV005930530
Myocardial infarction, susceptibility to	Benign	rs17883901	RCV001839455
Thymoma	Benign	rs2066507	RCV005912320
Uterine corpus endometrial carcinoma	Benign	rs185146268	RCV005922581

Show/Hide Text Mining Associations (51)

Disease Name	Relationship Type	References
Associations from Text MiningDisease associations identified through Pubtator
Adenocarcinoma of Lung	Associate	29474642, 36359768, 39259123, 39735553
Alzheimer Disease	Associate	29091582
Anemia Hemolytic	Associate	10733484, 2294991
Breast Neoplasms	Associate	23443115, 28411284
Burkitt Lymphoma	Associate	37917375
Carcinoma Renal Cell	Associate	26040780
Cardiovascular Diseases	Associate	12598062
Cerebral Infarction	Associate	40420234
Conotruncal cardiac defects	Associate	24535845, 24585533, 25275547
Cystic Disease Of Lung	Associate	16690975
Cystic Fibrosis	Associate	16690975, 23758905
Diabetes Mellitus	Associate	29751399
Diabetes Mellitus Type 1	Associate	21962117
Drug Hypersensitivity	Associate	22824134
Drug Related Side Effects and Adverse Reactions	Associate	25789740
Fetal Growth Retardation	Associate	33896778
Gamma Glutamylcysteine Synthetase Deficiency Hemolytic Anemia due to	Associate	10733484
Head and Neck Neoplasms	Associate	36139430
Heart Defects Congenital	Associate	25846410
HIV Infections	Associate	22824134
Hypoglycemia	Stimulate	18926903
Hypoxia Brain	Stimulate	8065332
Ichthyosis Vulgaris	Stimulate	20664557
Inflammation	Associate	11429414, 37446045
Kidney Diseases	Associate	21962117
Leukemia	Associate	8663001
Liver Failure	Associate	33162398
Lung Neoplasms	Associate	10370789, 23947958, 25789740, 9569044
Mesothelioma Malignant	Associate	33544514
Metabolic Syndrome	Associate	24665821
Mitochondrial Diseases	Associate	23152058
Myocardial Infarction	Associate	12598062
Myocardial Ischemia	Associate	28757675
Neoplasms	Associate	12079521, 19153097, 39742570, 9569044
Neuroblastoma	Associate	20180881
Obesity	Associate	25275547, 25846410
Obesity Maternal	Associate	25275547
Osteoarthritis	Associate	39258983
Ovarian Neoplasms	Associate	9119751
Peritonitis	Associate	35194192
Preeclamptic toxemia	Inhibit	25323968
Pulmonary Disease Chronic Obstructive	Associate	22044695, 23688726, 40161396
Pulmonary Disease Chronic Obstructive	Inhibit	32000766
Radiation Injuries	Associate	19153097
Renal Insufficiency Chronic	Associate	27975059
Rhinitis Vasomotor	Associate	12598062
Schizophrenia	Associate	17921251
Spinocerebellar Degenerations	Associate	2294991
Stomach Neoplasms	Associate	35241341
Stroke	Associate	40420234
Vascular Diseases	Associate	12598062

GCLC (glutamate-cysteine ligase catalytic subunit)