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.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 1.51
Clinical SummaryGGT6
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 unique Pathogenic / Likely Pathogenic· 104 VUS of 146 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.51LOEUF
pLI 0.000
Z-score 0.20
OE 0.94 (0.601.51)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.32Z-score
OE missense 0.95 (0.851.05)
264 obs / 279.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.94 (0.601.51)
00.351.4
Missense OE0.95 (0.851.05)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 12 / 12.8Missense obs/exp: 264 / 279.1Syn Z: -0.33
DN
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

146 submitted variants in ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic1
VUS104
Likely Benign13
Benign2
22
Pathogenic
1
Likely Pathogenic
104
VUS
13
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
1
0
1
VUS
0
87
17
0
104
Likely Benign
0
11
2
0
13
Benign
0
1
0
1
2
Total099421142

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

View in ClinVar →

Protein Context — Lollipop Plot

GGT6 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found