GLO1

Chr 6

glyoxalase I

Also known as: GLOD1, GLYI, HEL-S-74

NCBI Gene: 2739ENSG00000124767UniProt: Q04760

The enzyme encoded by this gene is responsible for the catalysis and formation of S-lactoyl-glutathione from methylglyoxal condensation and reduced glutatione. Glyoxalase I is linked to HLA and is localized to 6p21.3-p21.1, between HLA and the centromere. [provided by RefSeq, Jul 2008]

23
ClinVar variants
6
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GLO1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 16 VUS of 23 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.
1.46LOEUF
pLI 0.000
Z-score 0.42
OE 0.87 (0.53–1.46)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.42Z-score
OE missense 0.88 (0.73–1.05)
82 obs / 93.4 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.0.87 (0.53–1.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.73–1.05)
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.1.02
0≤1.21.6
LoF obs/exp: 10 / 11.5Missense obs/exp: 82 / 93.4Syn Z: -0.08

ClinVar Variant Classifications

23 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
VUS16
Likely Benign1
6
Pathogenic
16
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
0
0
0
VUS
0
15
1
0
16
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total0158023

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

View in ClinVar →

Protein Context — Lollipop Plot

GLO1 · 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
GLYOXALASE I; GLO1
MIM #138750 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Dicarbonyls and glyoxalase in disease mechanisms and clinical therapeutics.
Rabbani N et al.·Glycoconj J
2016Review
Genomic Analysis Identifies Risk Factors in Restless Legs Syndrome.
Akçimen F et al.·Ann Neurol
2024Meta-analysis
Population genetics of human glyoxalases.
Thornalley PJ·Heredity (Edinb)
1991Review
Activity, regulation, copy number and function in the glyoxalase system.
Rabbani N et al.·Biochem Soc Trans
2014Review
Glyoxalase 1 Modulation in Obesity and Diabetes.
Rabbani N et al.·Antioxid Redox Signal
2019Review
Methylglyoxal and glyoxalase I in atherosclerosis.
Hanssen NM et al.·Biochem Soc Trans
2014Review
High expression of GLO1 indicates unfavorable clinical outcomes in glioma patients.
Tian X et al.·J Neurosurg Sci
2022Cohort
Methylglyoxal-Glyoxalase 1 Balance: The Root of Vascular Damage.
Nigro C et al.·Int J Mol Sci
2017Review
Targeting Methylglyoxal Metabolism to Enhance Ferroptosis Sensitivity in Tumor Therapy.
Zhang X et al.·Adv Sci (Weinh)
2025
Glyoxalase System in Breast and Ovarian Cancers: Role of MEK/ERK/SMAD1 Pathway.
Alhujaily M·Biomolecules
2024Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Systems genomics reveals age- and sex-dependent metabolic dysregulation from Glo1 reduction in mice.
Cely I et al.·Physiol Genomics
2026
Gender-Dependent Cognitive and Metabolic Benefits Due to Glyoxalase 1 (Glo1) Overexpression in Age-Accelerated SAMP8 Mice.
Dafre AL et al.·Antioxidants (Basel)
2025🔓 Open Access
Patient-derived TXNIP-deficient primary cells exhibit NRF2 activation linked to upregulation of glyoxalase 1 (GLO1).
Maimaiti S et al.·Free Radic Biol Med
2025
Protocatechualdehyde attenuates oxidative stress in diabetic cataract via GLO1-mediated inhibition of AGE/RAGE glycosylation.
Cheng X et al.·Front Pharmacol
2025🔓 Open Access
Paracrine Orchestration of Tumor Microenvironment Remodeling Induced by GLO1 Potentiates Lymph Node Metastasis in Breast Cancer.
Xie J et al.·Adv Sci (Weinh)
2025🔓 Open AccessFunctional
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