GSTA4

Chr 6

glutathione S-transferase alpha 4

Also known as: GSTA4-4, GTA4

NCBI Gene: 2941ENSG00000170899UniProt: O15217

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]

37
ClinVar variants
9
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— GSTA4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 25 VUS of 37 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.90LOEUF
pLI 0.011
Z-score 1.81
OE 0.43 (0.22–0.90)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.27Z-score
OE missense 0.93 (0.80–1.09)
110 obs / 118.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.43 (0.22–0.90)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.80–1.09)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.22
0≤1.21.6
LoF obs/exp: 5 / 11.7Missense obs/exp: 110 / 118.1Syn Z: -1.15

ClinVar Variant Classifications

37 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic2
VUS25
Likely Benign2
Benign1
7
Pathogenic
2
Likely Pathogenic
25
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
2
0
2
VUS
0
22
3
0
25
Likely Benign
0
1
1
0
2
Benign
0
0
0
1
1
Total02313137

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GSTA4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Retracing from Outcomes to Causes: NRF2-Driven GSTA4 Transcriptional Regulation Controls Chronic Inflammation and Oxidative Stress in Atopic Dermatitis Recurrence.
Ma X et al.·J Invest Dermatol
2025
Curzerene suppresses progression of human glioblastoma through inhibition of glutathione S-transferase A4.
Cheng B et al.·CNS Neurosci Ther
2022
An overview of the role of lipid peroxidation-derived 4-hydroxynonenal in osteoarthritis.
Abusarah J et al.·Inflamm Res
2017Review
Substrate specificity combined with stereopromiscuity in glutathione transferase A4-4-dependent metabolism of 4-hydroxynonenal.
Balogh LM et al.·Biochemistry
2010
Collateral sensitivity to cisplatin in KB-8-5-11 drug-resistant cancer cells.
Doherty B et al.·Anticancer Res
2014
Development of a custom next-generation sequencing panel for the determination of bladder cancer risk in a Tunisian cohort.
Hemissi I et al.·Mol Biol Rep
2022Cohort
An integrated co-expression network analysis reveals novel genetic biomarkers for immune cell infiltration in chronic kidney disease.
Xia J et al.·Front Immunol
2023
Polymorphisms of glutathione S-transferase genes and survival of resected hepatocellular carcinoma patients.
Qu K et al.·World J Gastroenterol
2015Cohort
Expression profiling of adrenocortical neoplasms suggests a molecular signature of malignancy.
Velázquez-Fernández D et al.·Surgery
2005
A genome-wide association study and biological pathway analysis of epilepsy prognosis in a prospective cohort of newly treated epilepsy.
Speed D et al.·Hum Mol Genet
2014Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools