MGST1

protein-coding

microsomal glutathione S-transferase 1, the group of Microsomal glutathione S-transferases

Gene summary

The MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) family consists of six human proteins, two of which are involved in the production of leukotrienes and prostaglandin E, important mediators of inflammation. Other family members, demonstrating glutathione S-transferase and peroxidase activities, are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. This gene encodes a protein that catalyzes the conjugation of glutathione to electrophiles and the reduction of lipid hydroperoxides. This protein is localized to the endoplasmic reticulum and outer mitochondrial membrane where it is thought to protect these membranes from oxidative stress. Several transcript variants, some non-protein coding and some protein coding, have been found for this gene. [provided by RefSeq, May 2012]

Previous symbols:

GST12

MANE transcript

NM_020300.5

Inheritance

—

ClinVar variants

U:24B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.83

Max pathogenic AF

—

Genomic locus

chr12:16,347,142-16,609,259

External References & Databases

Ensembl (ENSG00000008394)

Transcript & Mutation Effects

hg38 • Region Span ~262.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MGST1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 24

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020300.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			22 clinvar	2 clinvar		24
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	24	3	0	27

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 122 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020300.5	RefSeq	NP_064696.1	3	MANE Select
ENST00000396210.8	Ensembl	ENSP00000379513.3	3	MANE Select
NM_001260511.2	RefSeq	NP_001247440.1	3	Standard
NM_001260512.2	RefSeq	NP_001247441.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
mgst1.1	Danio rerio	Structure: whole organism Quality: decreased process quality abnormal

Gene / Model

Organism

Observed Phenotype

mgst1.1

Danio rerio

Structure: whole organism

Quality: decreased process quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glutathione metabolism - Homo sapiens (human)
Hepatocellular carcinoma - Homo sapiens (human)
Fluid shear stress and atherosclerosis - Homo sapiens (human)
Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human)
Drug metabolism - other enzymes - Homo sapiens (human)

Biological Process

prostaglandin biosynthetic process
glutathione metabolic process
xenobiotic metabolic process
response to organonitrogen compound
response to lipopolysaccharide

Molecular Function

glutathione transferase activity
glutathione peroxidase activity
protein binding
protein homodimerization activity
glutathione binding

Cellular Component

nucleus
mitochondrion
mitochondrial outer membrane
peroxisomal membrane
endoplasmic reticulum

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000396209
Coding exons: 3
Length: 262118
Individuals with no LoFs: 125472
Homozygous LoFs: 3
Heterozygous LoFs: 266
Defined: 125741
p: 0.00107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.495	98	85.1	1.15	0.00000438	1007
Missense (PolyPhen)		26	24.354	1.0676		313
Synonymous	0.528	27	30.7	0.879	0.00000147	312
Loss of Function	0.338	4	4.80	0.834	2.65e-7	63

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.0031	0.0029	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.0051	0.0051	notable
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Has a wide substrate specificity.;

Recessive Scores

pRec: 0.229

Intolerance Scores

LoFtool: 0.910
RVIS EVS: -0.23
RVIS percentile EVS: 36.86

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.735

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium