GSTM4

protein-coding

glutathione S-transferase mu 4, the group of Soluble glutathione S-transferases

Gene summary

Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Diversification of these genes has occurred in regions encoding substrate-binding domains, as well as in tissue expression patterns, to accommodate an increasing number of foreign compounds. Multiple transcript variants, each encoding a distinct protein isoform, have been identified. [provided by RefSeq, Jul 2008]

MANE transcript

NM_000850.5

Inheritance

—

ClinVar variants

U:41

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.01

Max pathogenic AF

—

Genomic locus

chr1:109,656,099-109,665,496

External References & Databases

Transcript & Mutation Effects

hg38 • Region Span ~9.4 kb
Loading mutation effect viewer...

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 GSTM4 variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 32
not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000850.5. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
1
missense
34
clinvar
34
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
6
clinvar
6
Total00410041
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000850.5RefSeqNP_000841.18MANE Select
ENST00000369836.9EnsemblENSP00000358851.48MANE Select
NM_147148.3RefSeqNP_671489.18Standard
ENST00000326729.10EnsemblENSP00000316471.58Standard

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

  • glutathione metabolic process
  • nitrobenzene metabolic process
  • xenobiotic catabolic process
  • long-chain fatty acid biosynthetic process
  • glutathione derivative biosynthetic process

Molecular Function

  • glutathione transferase activity
  • protein binding
  • enzyme binding
  • protein homodimerization activity
  • glutathione binding

Cellular Component

  • cytoplasm
  • cytosol
  • intercellular bridge

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000369836
Coding exons
8
Length
9416
Individuals with no LoFs
125194
Homozygous LoFs
2
Heterozygous LoFs
552
Defined
125748
p
0.00221
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.1331171210.9660.000007051446
Missense (PolyPhen)3030.1280.99575378
Synonymous-1.655944.91.310.00000268381
Loss of Function-0.03551211.91.015.15e-7152

Population LoF Frequency

PopulationCAFp-valueStatus
African0.00330.0033notable
Latino/Admixed American0.000810.00081rare
Ashkenazi Jewish0.00280.0028notable
East Asian0.00150.0015notable
Finnish0.00120.0012notable
European (Non-Finnish)0.00310.0031notable
South Asian0.000910.00091rare
Other0.00210.0021notable

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Active on 1- chloro-2,4-dinitrobenzene.;

Recessive Scores

pRec
0.0957

Intolerance Scores

LoFtool
0.971
RVIS EVS
1.28
RVIS percentile EVS
93.71

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.859

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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