GGT6

Chr 17

gamma-glutamyltransferase 6

NCBI Gene: 124975 ENSG00000167741 UniProt: Q6P531 OMIM: 612341

The protein hydrolyzes and transfers gamma-glutamyl moieties from glutathione and other gamma-glutamyl compounds to acceptors, playing a key role in glutathione homeostasis by providing substrates for glutathione synthesis. No established human disease associations have been reported for mutations in this gene. The gene shows low constraint to loss-of-function variation.

OMIM ResearchSummary from RefSeq, UniProt

GGT6 belongs to the gamma-glutamyltransferase (GGT; EC 2.3.2.2) gene family. GGT is a membrane-bound extracellular enzyme that cleaves gamma-glutamyl peptide bonds in glutathione and other peptides and transfers the gamma-glutamyl moiety to acceptors. GGT is also key to glutathione homeostasis because it provides substrates for glutathione synthesis (Heisterkamp et al., 2008 [PubMed 18357469]).[supplied by OMIM, Oct 2008]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.51

Clinical Summary— GGT6

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

87 VUS of 102 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.51LOEUF

pLI 0.000

Z-score 0.20

OE 0.94 (0.60–1.51)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.32Z-score

OE missense 0.95 (0.85–1.05)

264 obs / 279.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.94 (0.60–1.51)

0≤0.351.4

Missense OE?0.95 (0.85–1.05)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 12 / 12.8Missense obs/exp: 264 / 279.1Syn Z: -0.33

This gene — mechanism propensity

0.5870th %ile

GOF

0.6637th %ile

LOF

0.4038th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

102 submitted variants in ClinVar

ClinVar

Classification Summary

VUS87

Likely Benign11

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	87	0	87
Likely Benign	11	0	11
Benign	1	1	2
Total	99	1	100

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap GGT6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →