PhenoModifier-Gene Detail

Gene "GCLC"

Found 6 records

Gene information

Gene symbol:

GCLC

See related:

Ensembl: ENSG00000001084, Gene ID: 2729

Additive variants :

Detected

Genetic interaction partners

Confidence	Stringent (ε>0.16 or ε<-0.12)	Intermediate (-0.16≤ε≤-0.08 or 0.08≤ε≤0.16)	Lenient (\|ε\|<0.08)
Positive interactions	USP14 VAC14 NCBP2 LEO1 SIN3A GCN1 CTDSPL2 TBK1 MTO1 DYNC2H1 KATNA1 LSM7 PPIP5K1 MOCS3 UBE2F-SCLY DUS2 UBA3 CDC73 RAB5B LENG8 ADI1 XPNPEP2 ARL14 KIAA1109 NMNAT1 RBM34 QPRT PPM1L PLAA RNASEH2A PGM2L1 TST CANX SH3YL1 RPL7 PFDN6 ALDH4A1 BRSK1 AGL RRP8 EPN3 USP33 CAPZB EDEM2 ZDHHC17 EP400 RPL21 PICALM PPME1 SLC30A8 EPS15 RAB7A URM1 PRKG2 ASNA1 TRMT12 SELENOO LTN1 MEF2A MGAM2 SNX8 RHOH SORD METTL2A FAAH RPSA POMT2 MAN1A2 SFN WIPI2 FAU SLC3A1 PPP6R3 ALG12 TGIF2 GALT RPS3A PGM1 CDC25B EIF2D DDX31 GLUD2 PIM3 LCMT2 PBLD show allhide
Negative interactions	BOLA3 LETM1 TEAD4 DLAT NF1 PDHA2 GTPBP3 AVL9 DDX59 PGAP1 TBL1XR1 ATP23 DPYD PABPN1 GATA2 OPLAH MPC1 SLC25A32 TXNL1 PGLS RCOR1 NFU1 USP35 RAB5B XPNPEP3 YEATS4 FASN RPS10 IMMP2L AGPAT4 USP35 CHD1L CHTF18 EDF1 UBE2V2 HMGB2 UBE2D3 ELOVL1 PPP6C HSPA4L RPL31 EEF1G POMT2 ELP3 SMS TOM1 MRE11 TXNRD1 RPS6 ANKZF1 ATG3 ATIC PEX13 UBA52 SRPK2 MSH3 BRD1 AMD1 SEC24D FKBP15 SLC44A3 TSTD1 CHKA IDH3B SRM IAH1 MLH1 PAN2 ATAD1 CHCHD2 CCNA2 GPT RPS16 RPS6KA1 OGG1 PITRM1 SDHB PEX5L WDR26 ANPEP LIAS RPS10 SBF1 EVI5 RPL22L1 TSR3 MAP3K4 TALDO1 HHATL HAO2 PRMT8 XRN1 AP3B2 CERK MTOR SMARCB1 BMP2K NFYB DPP6 EEF2 MRS2 ACER3 SLC35F5 KIF6 MBOAT4 SFXN1 PDHB AMPD1 TRIP12 TEX261 PHB2 TKFC PPM1B USP17L30 TXNDC9 DDX11 GLO1 PDK2 GLRX3 HIST2H4B ZDHHC18 CRLS1 ELOF1 UPF2 IMPA2 EXO1 SCYL2 TGIF2 GYS1 SDSL METTL11B ABCG2 LIG4 DPH1 RTN4IP1 BMP2K show allhide

Modifier statisitcs

Record:

Disorder:

Vriant:

Reference:

Effect type:

Expressivity(6)

Modifier effect:

Altered severity(5) ,Risk factor(1)

Details：

Variant 1:

GCLC:c.-594C>T

Gene:

GCLC

Genomic location:

chr6:53410037

dbSNP ID:

rs17883901

Alias:

GCLC:-129C>T, GCLC:c.-129T/C

Target disease:

Coronary Artery Disease(DOID_3393)

Effect type:

Expressivity

Modifier effect:

Risk factor

Evidence:

OR=3.22, P=0.03

Effect:

The two promoter polymorphisms of GCLM (-588C/T) and GCLC (-128T/C) are associated with an increased risk of IHD in Kazakhstan population.

Reference:

PMID28757675

Title:

Association of GCLM -588C/T and GCLC -129T/C Promoter Polymorphisms of Genes Coding the Subunits of Glutamate Cysteine Ligase with Ischemic Heart Disease Development in Kazakhstan Population.

Species studied:

Human

Abstract:

Glutamate cysteine ligase (GCL) is a rate-limiting enzyme in synthesis of glutathione. Evidence suggests that genetic variations in the promoter region of genes coding a catalytic subunit (GCLC -129T/C) and a modifier subunit (GCLM -588C/T) of GCL have a functional impact on their transcriptional activity and were associated with various disorders. Hence, we hypothesize whether these two polymorphic variants of GCLM and GCLC genes are associated with the risk of ischemic heart disease (IHD) development in the population of Kazakhstan.
Variant 2:

GCLC:c.-594C>T

Gene:

GCLC

Genomic location:

chr6:53410037

dbSNP ID:

rs17883901

Alias:

GCLC:-129C>T, GCLC:c.-129T/C

Target disease:

Cystic fibrosis(DOID_1485)

Effect type:

Expressivity

Modifier effect:

Altered severity

Evidence:

Balance testing accuracy=0.6824, P=0.008

Effect:

Polymorphisms in genes associated with metabolism of GSH act on the CF's severity.

Reference:

PMID23758905

Title:

Genetic interaction of GSH metabolic pathway genes in cystic fibrosis.

Species studied:

Human

Abstract:

Cystic fibrosis (CF) is a monogenic disease caused by CFTR gene mutations, with clinical expression similar to complex disease, influenced by genetic and environmental factors. Among the possible modifier genes, those associated to metabolic pathways of glutathione (GSH) have been considered as potential modulators of CF clinical severity. In this way it is of pivotal importance investigate gene polymorphisms at Glutamate-Cysteine Ligase, Catalytic Subunit (GCLC), Glutathione S-transferase Mu 1 (GSTM1), Glutathione S-transferase Theta 1 (GSTT1), and Glutathione S-transferase P1 (GSTP1), which have been associated to the GSH metabolic pathway and CF clinical severity.
Variant 3:

GCLC:c.-594C>T

Gene:

GCLC

Genomic location:

chr6:53410037

dbSNP ID:

rs17883901

Alias:

GCLC:-129C>T, GCLC:c.-129T/C

Target disease:

Cystic fibrosis(DOID_1485)

Effect type:

Expressivity

Modifier effect:

Altered severity

Evidence:

P=0.044

Effect:

CF severity is associated with polymorphisms in GSH pathways and CFTR mutations

Reference:

PMID24593045

Title:

Polymorphisms in the glutathione pathway modulate cystic fibrosis severity: a cross-sectional study.

Species studied:

Human

Abstract:

Cystic fibrosis (CF) clinically manifests with various levels of severity, which are thought to be modulated by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR), modifier genes, and the environment. This study verified whether polymorphisms in modifier genes associated with glutathione (GSH) metabolism influence CF severity.
Variant 4:

GCLC:c.-594C>T

Gene:

GCLC

Genomic location:

chr6:53410037

dbSNP ID:

rs17883901

Alias:

GCLC:-129C>T, GCLC:c.-129T/C

Target disease:

Nonalcoholic Fatty Liver Disease(DOID_0080208)

Effect type:

Expressivity

Modifier effect:

Altered severity

Evidence:

P=0.007

Effect:

Associated with the development NAFLD or disease severity.

Reference:

PMID26740948

Title:

Genetic analysis of nonalcoholic fatty liver disease within a Caribbean-Hispanic population.

Species studied:

Human

Abstract:

We explored potential genetic risk factors implicated in nonalcoholic fatty liver disease (NAFLD) within a Caribbean-Hispanic population in New York City. A total of 316 individuals including 40 subjects with biopsy-proven NAFLD, 24 ethnically matched non-NAFLD controls, and a 252 ethnically mixed random sampling of Bronx County, New York were analyzed. Genotype analysis was performed to determine allelic frequencies of 74 known single-nucleotide polymorphisms (SNPs) associated with NAFLD risk based on previous genome-wide association study (GWAS) and candidate gene studies. Additionally, the entire coding region of PNPLA3, a gene showing the strongest association to NAFLD was subjected to Sanger sequencing. Results suggest that both rare and common DNA variations in PNPLA3 and SAMM50 may be correlated with NAFLD in this small population study, while common DNA variations in CHUK and ERLIN1, may have a protective interaction. Common SNPs in ENPP1 and ABCC2 have suggestive association with fatty liver, but with less compelling significance. In conclusion, Hispanic patients of Caribbean ancestry may have different interactions with NAFLD genetic modifiers; therefore, further investigation with a larger sample size, into this Caribbean-Hispanic population is warranted.
Variant 5:

GCLC:c.-3506A>G

Gene:

GCLC

Genomic location:

dbSNP ID:

Target disease:

Cystic fibrosis(DOID_1485)

Effect type:

Expressivity

Modifier effect:

Altered severity

Evidence:

Balance testing accuracy=0.6824, P=0.008

Effect:

Polymorphisms in genes associated with metabolism of GSH act on the CF's severity.

Reference:

PMID23758905

Title:

Genetic interaction of GSH metabolic pathway genes in cystic fibrosis.

Species studied:

Human

Abstract:

Cystic fibrosis (CF) is a monogenic disease caused by CFTR gene mutations, with clinical expression similar to complex disease, influenced by genetic and environmental factors. Among the possible modifier genes, those associated to metabolic pathways of glutathione (GSH) have been considered as potential modulators of CF clinical severity. In this way it is of pivotal importance investigate gene polymorphisms at Glutamate-Cysteine Ligase, Catalytic Subunit (GCLC), Glutathione S-transferase Mu 1 (GSTM1), Glutathione S-transferase Theta 1 (GSTT1), and Glutathione S-transferase P1 (GSTP1), which have been associated to the GSH metabolic pathway and CF clinical severity.
Variant 6:

GCLC:c.-3506A>G

Gene:

GCLC

Genomic location:

dbSNP ID:

Target disease:

Cystic fibrosis(DOID_1485)

Effect type:

Expressivity

Modifier effect:

Altered severity

Evidence:

P=0.012

Effect:

CF severity is associated with polymorphisms in GSH pathways and CFTR mutations

Reference:

PMID24593045

Title:

Polymorphisms in the glutathione pathway modulate cystic fibrosis severity: a cross-sectional study.

Species studied:

Human

Abstract:

Cystic fibrosis (CF) clinically manifests with various levels of severity, which are thought to be modulated by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR), modifier genes, and the environment. This study verified whether polymorphisms in modifier genes associated with glutathione (GSH) metabolism influence CF severity.