GSTA3

protein-coding

glutathione S-transferase alpha 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. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. 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-tranferase belonging to the alpha class genes that are located in a cluster mapped to chromosome 6. Genes of the alpha class are highly related and encode enzymes with glutathione peroxidase activity. However, during evolution, this alpha class gene diverged accumulating mutations in the active site that resulted in differences in substrate specificity and catalytic activity. The enzyme encoded by this gene catalyzes the double bond isomerization of precursors for progesterone and testosterone during the biosynthesis of steroid hormones. An additional transcript variant has been identified, but its full length sequence has not been determined. [provided by RefSeq, Jul 2008]

MANE transcript

NM_000847.5

Inheritance

—

ClinVar variants

U:31B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr6:52,896,639-52,909,698

External References & Databases

Ensembl (ENSG00000174156)

Transcript & Mutation Effects

hg38 • Region Span ~13.1 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 GSTA3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 30

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000847.5. 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			30 clinvar		3 clinvar	33
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	31	0	3	34

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000847.5	RefSeq	NP_000838.3	6	MANE Select
ENST00000211122.4	Ensembl	ENSP00000211122.3	6	MANE Select
NM_001363542.2	RefSeq	NP_001350471.1	4	Standard
ENST00000370968.5	Ensembl	ENSP00000360007.1	4	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
glutathione derivative biosynthetic process

Molecular Function

glutathione transferase activity

Cellular Component

cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000211122
Coding exons: 6
Length: 13047
Individuals with no LoFs: 125696
Homozygous LoFs: 2
Heterozygous LoFs: 50
Defined: 125748
p: 0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.424	131	118	1.11	0.00000588	1459
Missense (PolyPhen)		21	20	1.05		249
Synonymous	-0.903	50	42.5	1.18	0.00000217	408
Loss of Function	1.31	6	10.6	0.567	5.11e-7	135

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.0021	0.0021	notable
East Asian	0	0.0	absent
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.00059	0.00052	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. Catalyzes isomerization reactions that contribute to the biosynthesis of steroid hormones. Efficiently catalyze obligatory double-bond isomerizations of delta(5)-androstene-3,17-dione and delta(5)- pregnene-3,20-dione, precursors to testosterone and progesterone, respectively. {ECO:0000269|PubMed:15595823, ECO:0000269|PubMed:20083122}.;

Intolerance Scores

LoFtool: 0.755
RVIS EVS: 0.6
RVIS percentile EVS: 82.66

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0637

Gene Damage Prediction

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