GSTM3

protein-coding

glutathione S-transferase mu 3, 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. Mutations of this class mu gene have been linked with a slight increase in a number of cancers, likely due to exposure with environmental toxins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2008]

MANE transcript

NM_000849.5

Inheritance

ClinVar variants

U:28

Top phenotype

cystic fibrosis

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr1:109,733,932-109,741,038

External References & Databases

Ensembl (ENSG00000134202)

Transcript & Mutation Effects

hg38 • Region Span ~7.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cystic fibrosisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009061

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GSTM3 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 21

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000849.5. 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						0
missense			24 clinvar			24
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	28	0	0	28

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000849.5	RefSeq	NP_000840.2	8	MANE Select
ENST00000361066.7	Ensembl	ENSP00000354357.2	8	MANE Select
ENST00000256594.7	Ensembl	ENSP00000256594.3	8	Standard
ENST00000256594.8	Ensembl	ENSP00000256594.3	8	Standard

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
establishment of blood-nerve barrier
nitrobenzene metabolic process
xenobiotic catabolic process
response to estrogen

Molecular Function

glutathione transferase activity
protein binding
enzyme binding
identical protein binding
protein homodimerization activity

Cellular Component

nucleus
cytoplasm
cytosol
sperm fibrous sheath
intercellular bridge

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000540225
Coding exons: 8
Length: 7831
Individuals with no LoFs: 125715
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 125748
p: 0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.936	99	129	0.768	0.00000678	1488
Missense (PolyPhen)		17	36.003	0.47218		408
Synonymous	-0.173	48	46.5	1.03	0.00000227	385
Loss of Function	1.04	12	16.6	0.724	9.35e-7	172

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.00033	0.00033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. May govern uptake and detoxification of both endogenous compounds and xenobiotics at the testis and brain blood barriers. {ECO:0000269|PubMed:10587441}.;

Recessive Scores

pRec: 0.346

Intolerance Scores

LoFtool: 0.827
RVIS EVS: 0.46
RVIS percentile EVS: 78.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.784

Gene Damage Prediction

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