GSTA4

protein-coding

glutathione S-transferase alpha 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. 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. The alpha class genes, which are located in a cluster on chromosome 6, are highly related and encode enzymes with glutathione peroxidase activity that function in the detoxification of lipid peroxidation products. Reactive electrophiles produced by oxidative metabolism have been linked to a number of degenerative diseases including Parkinson's disease, Alzheimer's disease, cataract formation, and atherosclerosis. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001512.4

Inheritance

—

ClinVar variants

U:24B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr6:52,977,948-52,995,304

External References & Databases

Ensembl (ENSG00000170899)

Transcript & Mutation Effects

hg38 • Region Span ~17.4 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 GSTA4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 23

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001512.4. 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	1 clinvar		23
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	24	1	1	26

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 44 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001512.4	RefSeq	NP_001503.1	6	MANE Select
ENST00000370963.9	Ensembl	ENSP00000360002.4	6	MANE Select
ENST00000370959.1	Ensembl	ENSP00000359998.1	6	Standard
ENST00000370959.2	Ensembl	ENSP00000359998.1	6	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
xenobiotic metabolic process
glutathione derivative biosynthetic process

Molecular Function

glutathione transferase activity
protein binding
identical protein binding
protein homodimerization activity

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370963
Coding exons: 6
Length: 17426
Individuals with no LoFs: 125700
Homozygous LoFs: 0
Heterozygous LoFs: 47
Defined: 125747
p: 0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.266	110	118	0.931	0.00000561	1466
Missense (PolyPhen)		38	43.475	0.87406		569
Synonymous	-1.15	55	45.2	1.22	0.00000240	411
Loss of Function	1.81	5	11.7	0.429	5.80e-7	136

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.000060	0.000058	rare
Ashkenazi Jewish	0.0026	0.0026	notable
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.00024	0.00023	rare
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. This isozyme has a high catalytic efficiency with 4-hydroxyalkenals such as 4- hydroxynonenal (4-HNE). {ECO:0000269|PubMed:10329152, ECO:0000269|PubMed:20085333}.;

Recessive Scores

pRec: 0.209

Intolerance Scores

LoFtool: 0.736
RVIS EVS: -0.3
RVIS percentile EVS: 32.62

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.861

Gene Damage Prediction

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