GSTT2

Chr 22

glutathione S-transferase theta 2 (gene/pseudogene)

NCBI Gene: 2953 ENSG00000099984 UniProt: P0CG30 OMIM: 600437

This protein conjugates reduced glutathione to hydrophobic electrophiles and has sulfatase activity, functioning in cellular detoxification pathways. The gene is poorly constrained to loss-of-function variation (LOEUF 1.61), and GSTT2 is a pseudogene in some populations, suggesting it may not be essential for normal human development. No established Mendelian diseases have been linked to GSTT2 mutations in pediatric populations.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene, glutathione S-transferase (GST) theta 2 (GSTT2), is a member of a superfamily of proteins that catalyze the conjugation of reduced glutathione to a variety of electrophilic and hydrophobic compounds. Human GSTs can be divided into five main classes: alpha, mu, pi, theta, and zeta. The theta class includes GSTT1, GSTT2, and GSTT2B. GSTT2 and GSTT2B are nearly identical to each other, and share 55% amino acid identity with GSTT1. All three genes may play a role in human carcinogenesis. The GSTT2 gene is a pseudogene in some populations. [provided by RefSeq, Sep 2015]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.61

Clinical Summary— GSTT2

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 10 VUS of 17 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.61LOEUF

pLI 0.015

Z-score 0.65

OE 0.67 (0.30–1.61)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.89Z-score

OE missense 0.63 (0.47–0.86)

30 obs / 47.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.67 (0.30–1.61)

0≤0.351.4

Missense OE?0.63 (0.47–0.86)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 3 / 4.5Missense obs/exp: 30 / 47.3Syn Z: 0.27

This gene — mechanism propensity

0.76top 25%

GOF

0.76top 25%

LOF

0.1895th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

17 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS10

Likely Pathogenic

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0	0
Likely Pathogenic	1	0	0	1
VUS	0	7	3	10
Likely Benign	0	0	0	0
Benign	0	0	0	0
Total	1	7	3	11

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

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58 pathogenic / likely-pathogenic (of 113) ClinVar copy-number / structural variants overlap GSTT2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →