GSTT2B

Chr 22

glutathione S-transferase theta 2B

Also known as: GSTT2P

NCBI Gene: 653689 ENSG00000133433 UniProt: P0CG30

Glutathione S-transferase theta 2B catalyzes the conjugation of reduced glutathione to electrophilic and hydrophobic compounds and has sulfatase activity as part of cellular detoxification pathways. This gene is a pseudogene in some populations and no definitive disease associations have been established from the provided data. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.708).

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene, glutathione S-transferase (GST) theta 2B (GSTT2B), 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 GSTT2B gene is a pseudogene in some populations. [provided by RefSeq, Sep 2015]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.71

Clinical Summary— GSTT2B

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.72) — some intolerance to loss-of-function variants.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 13 VUS of 16 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.71LOEUF

pLI 0.722

Z-score 1.90

OE 0.00 (0.00–0.71)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

0.72Z-score

OE missense 0.70 (0.53–0.94)

33 obs / 46.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.71)

0≤0.351.4

Missense OE?0.70 (0.53–0.94)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 0 / 4.2Missense obs/exp: 33 / 46.9Syn Z: 0.51

This gene — mechanism propensity

0.6937th %ile

GOF

0.79top 10%

LOF

0.2385th %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

16 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS13

Likely Benign2

Likely Pathogenic

VUS

Likely Benign

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	13	0	13
Likely Benign	0	0	2	2
Benign	0	0	0	0
Total	1	13	2	16

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

View in ClinVar →

58 pathogenic / likely-pathogenic (of 113) ClinVar copy-number / structural variants overlap GSTT2B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →