GGT1

Chr 22AR

gamma-glutamyltransferase 1

Also known as: CD224, D22S672, D22S732, GGT, GGT 1, GGTD, GTG

NCBI Gene: 2678ENSG00000100031UniProt: P19440

The enzyme encoded by this gene is a type I gamma-glutamyltransferase that catalyzes the transfer of the glutamyl moiety of glutathione to a variety of amino acids and dipeptide acceptors. The enzyme is composed of a heavy chain and a light chain, which are derived from a single precursor protein. It is expressed in tissues involved in absorption and secretion and may contribute to the etiology of diabetes and other metabolic disorders. Multiple alternatively spliced variants have been identified. There are a number of related genes present on chromosomes 20 and 22, and putative pseudogenes for this gene on chromosomes 2, 13, and 22. [provided by RefSeq, Jan 2014]

Primary Disease Associations & Inheritance

?GlutathioninuriaMIM #231950
AR
UniProtGlutathionuria
309
ClinVar variants
48
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GGT1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
48 Pathogenic / Likely Pathogenic· 182 VUS of 309 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.74LOEUF
pLI 0.000
Z-score 2.55
OE 0.45 (0.28–0.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.86Z-score
OE missense 0.87 (0.79–0.96)
310 obs / 355.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.45 (0.28–0.74)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.79–0.96)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 11 / 24.7Missense obs/exp: 310 / 355.5Syn Z: 0.09

ClinVar Variant Classifications

309 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic11
VUS182
Likely Benign27
Benign34
37
Pathogenic
11
Likely Pathogenic
182
VUS
27
Likely Benign
34
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
37
0
37
Likely Pathogenic
0
0
11
0
11
VUS
0
124
58
0
182
Likely Benign
0
13
4
10
27
Benign
0
2
27
5
34
Total013913715291

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

View in ClinVar →

Protein Context — Lollipop Plot

GGT1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Glutathioninuria

MIM #231950

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Demarcating the Development of Cirrhosis and Its Complications via Plasma Proteomic Features in an Asymptomatic Population.
Liang Z et al.·J Proteome Res
2025
Family-based analysis of GGT1 and HNF1A gene polymorphisms in patients with polycystic ovary syndrome.
Xu X et al.·Reprod Biomed Online
2018Cohort
Targeting protein prenylation for cancer therapy.
Berndt N et al.·Nat Rev Cancer
2011
The human gamma-glutamyltransferase gene family.
Heisterkamp N et al.·Hum Genet
2008
The discovery of GGT1 as a novel gene for ischemic stroke conferring protection against disease risk in non-smokers and non-abusers of alcohol.
Solodilova M et al.·J Stroke Cerebrovasc Dis
2024
Ropivacaine as a novel AKT1 specific inhibitor regulates the stemness of breast cancer.
Ding L et al.·J Exp Clin Cancer Res
2024
Lewis antigen‑negative pancreatic cancer: An aggressive subgroup.
Liu C et al.·Int J Oncol
2020
GGT5 facilitates migration and invasion through the induction of epithelial-mesenchymal transformation in gastric cancer.
Luo Z et al.·BMC Med Genomics
2024
Interactive effects of a common γ-glutamyltransferase 1 variant and low high-density lipoprotein-cholesterol on diabetic macro- and micro-angiopathy.
Jinnouchi H et al.·Cardiovasc Diabetol
2015
γ-glutamyl transpeptidase deficiency caused by a large homozygous intragenic deletion in GGT1.
Darin N et al.·Eur J Hum Genet
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools