GSTP1

Chr 11

glutathione S-transferase pi 1

Also known as: DFN7, FAEES3, GST3, GSTP, GSTP1-1, HEL-S-22, PI

NCBI Gene: 2950 ENSG00000084207 UniProt: P09211

Glutathione S-transferase Pi 1 catalyzes the conjugation of reduced glutathione to hydrophobic electrophiles for detoxification and negatively regulates ferroptosis by detoxifying reactive aldehydes. This gene is highly tolerant to loss-of-function variants and has not been definitively associated with Mendelian disease, though polymorphisms may influence susceptibility to various conditions including cancer.

ResearchSummary from RefSeq, UniProt

Glutathione S-transferases (GSTs) are a family of enzymes that play an important role in detoxification by catalyzing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. Based on their biochemical, immunologic, and structural properties, the soluble GSTs are categorized into 4 main classes: alpha, mu, pi, and theta. This GST family member is a polymorphic gene encoding active, functionally different GSTP1 variant proteins that are thought to function in xenobiotic metabolism and play a role in susceptibility to cancer, and other diseases. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

280

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.85

LOEUF

Multiple*

Mechanism· predicted

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?

0.85LOEUF

pLI 0.014

Z-score 1.93

OE 0.41 (0.21–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.33Z-score

OE missense 1.09 (0.94–1.26)

129 obs / 118.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.41 (0.21–0.85)

0≤0.351.4

Missense OE?1.09 (0.94–1.26)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 5 / 12.3Missense obs/exp: 129 / 118.8Syn Z: 1.00

Background carrier burden — how many people carry a rare variant somewhere in GSTP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

313 rare PASS variants

Rare truncating (LoF)

1 in 1,800

75 rare PASS variants

Rare synonymous (reference)

1 in 540

138 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GSTP1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 200	1 in 2,700
South Asian	~43k	1 in 110	1 in 2,600
Remaining (unassigned)	~30k	1 in 130	1 in 390
European (Finnish)	~27k	1 in 350	none seen
Admixed American	~22k	1 in 230	1 in 4,500
African / African American	~21k	1 in 130	1 in 2,400
East Asian	~20k	1 in 170	1 in 3,100
Ashkenazi Jewish	~13k	1 in 300	none seen
Middle Eastern	~2,884	1 in 160	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 7 coding exons well covered in gnomAD exomes; exon 1 poorly covered; exon 3 marginal. Genomes: all 7.? see exons ↓