GLO1

Summary

GLO1 (glyoxalase I, HGNC:4323) is a protein-coding gene on chromosome 6p21.2, encoding Lactoylglutathione lyase (Q04760). Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione.

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.

Source: NCBI Gene 2739 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 18 total
• Druggable target: yes — 11 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006708

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4323
Approved symbol	GLO1
Name	glyoxalase I
Location	6p21.2
Locus type	gene with protein product
Status	Approved
Aliases	GLOD1
Ensembl gene	ENSG00000124767
Ensembl biotype	protein_coding
OMIM	138750
Entrez	2739

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000373365, ENST00000470973, ENST00000887176, ENST00000887177, ENST00000887178, ENST00000887179, ENST00000887180, ENST00000920550

RefSeq mRNA: 1 — MANE Select: NM_006708 NM_006708

CCDS: CCDS4837

Canonical transcript exons

ENST00000373365 — 6 exons

Exon	Start	End
ENSE00000750246	38682808	38682875
ENSE00000750268	38684374	38684514
ENSE00000750279	38686892	38686974
ENSE00001460407	38702971	38703145
ENSE00003423682	38675925	38677383
ENSE00003585652	38682012	38682101

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 131.2204 / max 1460.7060, expressed in 1826 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73463	99.2968	1823
73462	31.9236	1803

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	98.86	gold quality
middle temporal gyrus	UBERON:0002771	98.70	gold quality
jejunal mucosa	UBERON:0000399	98.57	gold quality
caput epididymis	UBERON:0004358	98.53	gold quality
gluteal muscle	UBERON:0002000	98.40	gold quality
choroid plexus epithelium	UBERON:0003911	98.38	gold quality
pigmented layer of retina	UBERON:0001782	98.34	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.30	gold quality
duodenum	UBERON:0002114	98.26	gold quality
ventricular zone	UBERON:0003053	98.22	gold quality
biceps brachii	UBERON:0001507	98.18	gold quality
jejunum	UBERON:0002115	98.18	gold quality
deltoid	UBERON:0001476	98.17	gold quality
vastus lateralis	UBERON:0001379	98.16	gold quality
body of tongue	UBERON:0011876	98.13	gold quality
triceps brachii	UBERON:0001509	98.12	gold quality
cartilage tissue	UBERON:0002418	98.11	gold quality
quadriceps femoris	UBERON:0001377	98.09	gold quality
pons	UBERON:0000988	98.04	gold quality
embryo	UBERON:0000922	98.03	gold quality
tongue squamous epithelium	UBERON:0006919	98.02	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.01	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.00	gold quality
endometrium epithelium	UBERON:0004811	97.93	gold quality
superior vestibular nucleus	UBERON:0007227	97.89	gold quality
ileal mucosa	UBERON:0000331	97.88	gold quality
skin of hip	UBERON:0001554	97.85	gold quality
orbitofrontal cortex	UBERON:0004167	97.84	gold quality
upper leg skin	UBERON:0004262	97.75	gold quality
ganglionic eminence	UBERON:0004023	97.74	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	36.49
E-GEOD-93593	yes	14.43
E-MTAB-6911	no	718.97
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

91 targeting GLO1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-181B-2-3P	99.81	70.06	1646

Literature-anchored findings (GeneRIF, showing 40)

• The analysis involved the data on nine polymorphic codominant loci: HP, GC, TF, PI, PGM1, GLO1, C3, ACP1, and ESD. The loci were selected by significance of differences in genotype frequencies between tuberculosis patients and healthy controls (PMID:12942785)
• the increase in glyoxalase I expression up to the age of 55 and progressively decreases thereafter. (PMID:15950319)
• The present study tested the hypothesis that this common genetic variant could confer susceptibility to panic disorder using an Italian population sample of 162 panic disorder patients and 288 matched controls. (PMID:16352396)
• In summary, our data suggest that a reduced glyoxalase I activity mimics some changes associated with neurodegeneration, such as neurite retraction and apoptotic cell death. (PMID:16555297)
• Overexpression of glyoxalase 1 is associated with kidney tumor (PMID:16803681)
• GLO1 gene variants do not confer autism vulnerability in this sample, but allele A419 apparently carries a protective effect, spurring interest into functional correlates of the C419A SNP (PMID:17346350)
• Polymorphism in this enzyme and paraoxonase I increase susceptibility to multiple sclerosis. (PMID:17463067)
• Therefore, we suggest that common variants in glyoxalase 1 are not significant susceptibility factors forautism spectrum disorders in the Finnish population. (PMID:17722011)
• Association of A419C polymorphism of the glyoxalase I gene with age receptor levels and show the genetic predisposition to vascular complications in hemodialysis patients. (PMID:18079478)
• In androgen-dependent and androgen-independent prostate cancer cells, testosterone upregulates GLO1 mRNA levels. (PMID:18344682)
• There was an association (odds ratio=2.9; 95% confidence interval=1.3-7.2) between the Glo1 A allele and T2DM in Zuni Indians. (PMID:18413187)
• Increased protection against dicarbonyl glycation of endothelial cell protein by transfected glyoxalase I protects hyperglycemia-induced angiogenesis deficit. (PMID:18448827)
• These results suggest that the aberrant expression of Glo1 might be involved in the pathophysiology of mood disorders. (PMID:18455873)
• the GLO1 gene is unlikely a major susceptible gene for autism in an ethnic Chinese population from Taiwan. (PMID:18721844)
• Glyoxalase I overexpression ameliorates renal ischemia-reperfusion injury in rats. (PMID:19211689)
• In the human lens, GLOI activity and immunoreactivity both decreased with age. (PMID:19238574)
• Results show that genetic polymorphisms in biotransformation enzymes CYP17, GSTP1, PON1 and GLO1 could be associated with the risk for breast cancer. (PMID:19379515)
• Report glyoxalase I Glu111Ala polymorphism in patients with breast cancer. (PMID:19452310)
• our data suggest a function of GLO1 in the regulation of detoxification and target adduction by the glycolytic byproduct methylglyoxal in malignant melanoma. (PMID:20093988)
• study shows for the first time a link between RAGE and GLO polymorphisms in the prognosis of hemodialysis patients (PMID:20185929)
• It did not show any difference in allelic and genotype frequencies in all glyoxalase I genes polymorphisms among the studied groups. (PMID:20398646)
• that Glo1 activity directly can be regulated by an oxidative posttranslational modification that was found in the native enzyme, i.e., glutathionylation (PMID:20454679)
• This study suggested that GLO1 is not involved into the acute panic response to CCK-4 in healthy volunteers. (PMID:20542521)
• GLO1-A is an amplified gene in cancer. (PMID:20544845)
• Glyoxalase I Ala111Glu gene polymorphism is not associated with breast cancer risk but correlates with the absence of progesterone receptor. (PMID:20712647)
• The expression and enzyme activity of GLO-I is significantly increased in endometrial cancer, which could promote abnormal proliferation and inhibit apoptosis in endometrial cancer cells. (PMID:21029593)
• in an in vivo model of diabetes that GLO-I overexpression reduces hyperglycemia-induced levels of carbonyl stress, AGEs, and oxidative stress (PMID:21056979)
• These findings suggest that deglycating enzymes Glyoxalase I and fructosamine-3-kinase may be involved in the malignant transformation of colon mucosa. (PMID:21253391)
• This study shows that only the GLO1 C-7T polymorphism, and not the GLO1 A419C and ALR C-106T polymorphisms, is associated with carotid atherosclerosis in Chinese patients with type 2 diabetes. (PMID:21294693)
• The expression of GLO-1 was increased in mononuclear leukocytes from diabetic patients. (PMID:21370249)
• Our findings suggest that GLO1 deficits and carbonyl stress are linked to the development of a certain subtype of schizophrenia.[review] (PMID:21386123)
• A non-conservative, non-synonymous single nucleotide polymorphism in the glyoxalase I gene may be an autism susceptibility factor. (PMID:21491613)
• GLO1 C-7T polymorphism alters promoter activity and confers susceptibility to nephropathy and retinopathy to Type 2 diabetic patients. (PMID:21738003)
• We conclude that dicarbonyl stress is countered by up-regulation of Glo1 in the Nrf2 stress-responsive system. (PMID:22188542)
• GLO1 expression was higher in gastric cancer tissues, compared with that in adjacent noncancerous tissues. (PMID:22479608)
• GLO1 is overexpressed in 79 percent of tumors and GLO1 up-regulation correlates with advanced tumor grade. (PMID:22614840)
• GLOI may be involved in prostate cancer progression via the control of key molecules in the mitochondrial apoptotic mechanism through the nuclear factor (NF)-kB signaling pathway. (PMID:22653787)
• No evidence of an association of RAGE or glyoxalase I single nucleotide polymorphisms with pathological pregnancy. (PMID:22771726)
• We showed for the first time an association between genetic variants with GLO1 enzyme activity in humans. SNPs in GLO1 can be used to predict enzyme activity and detoxifying capabilities. (PMID:23201419)
• Data suggest that GLO1 activity is lower in blood (in whole blood assay) in type 1 or type 2 diabetes with painful peripheral diabetic neuropathy as compared to control subjects; Glo1 activity negatively correlates with duration of type 1 diabetes. (PMID:23351995)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	glo1	ENSDARG00000068978
mus_musculus	Glo1	ENSMUSG00000024026
rattus_norvegicus	Glo1	ENSRNOG00000000541
drosophila_melanogaster	Glo1	FBGN0283450

Paralogs (1): GLOD4 (ENSG00000167699)

Protein

Protein identifiers

Lactoylglutathione lyase — Q04760 (reviewed: Q04760)

Alternative names: Aldoketomutase, Glyoxalase I, Ketone-aldehyde mutase, Methylglyoxalase, S-D-lactoylglutathione methylglyoxal lyase

All UniProt accessions (2): Q04760, X5DNM4

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione. Involved in the regulation of TNF-induced transcriptional activity of NF-kappa-B. Required for normal osteoclastogenesis.

Subunit / interactions. Homodimer.

Post-translational modifications. Glutathionylation at Cys-139 inhibits enzyme activity. Phosphorylated at Thr-107 in the presence of CaMK2. However, this is a consensus site for phosphorylation by CK2 so phosphorylation may be mediated by CK2 rather than CaMK2. Phosphorylation is induced by TNF and suppresses the TNF-induced transcriptional activity of NF-kappa-B. Exists in a nitric oxide (NO)-modified form. The exact nature of the modification is unknown, but it suppresses the TNF-induced transcriptional activity of NF-kappa-B.

Activity regulation. Regulated by oxidation of Cys-139 in response to the redox state of the cell. Results in the alternative formation of cystine or glutathione-bound cysteine, the latter modification leading to reduced enzyme activity.

Cofactor. Binds 1 zinc ion per subunit. In the homodimer, two zinc ions are bound between subunits.

Pathway. Secondary metabolite metabolism; methylglyoxal degradation; (R)-lactate from methylglyoxal: step 1/2.

Polymorphism. Exists in three separable isoforms which originate from two alleles in the genome. These correspond to two homodimers and one heterodimer composed of two subunits showing different electrophoretic properties.

Similarity. Belongs to the glyoxalase I family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q04760-1	1	yes
Q04760-2	2

RefSeq proteins (1): NP_006699* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004360	Glyas_Fos-R_dOase_dom	Domain
IPR004361	Glyoxalase_1	Family
IPR018146	Glyoxalase_1_CS	Conserved_site
IPR029068	Glyas_Bleomycin-R_OHBP_Dase	Homologous_superfamily
IPR037523	VOC_core	Domain

Pfam: PF00903

Enzyme classification (BRENDA):

• EC 4.4.1.5 — lactoylglutathione lyase (BRENDA: 77 organisms, 127 substrates, 282 inhibitors, 117 Km, 52 kcat entries)

Substrate kinetics (BRENDA)

33 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
METHYLGLYOXAL	0.016–3.5	28
GLUTATHIONE-METHYLGLYOXAL HEMITHIOACETAL	0.0089–11	14
(R)-S-LACTOYLGLUTATHIONE	0.016–0.12	11
PHENYLGLYOXAL	0.04–0.31	9
GLUTATHIONE	0.049–1.9	6
TRYPANOTHIONE	0.071–0.207	4
4,5-DIOXOVALERATE	0.87–1.2	2
GLUTATHIONE ETHYL ESTER	0.042–0.7	2
GLUTATHIONE ISOPROPYL ESTER	0.053–0.3	2
GLUTATHIONYLSPERMIDINE	0.008–0.014	2
N-[3-[(4-AMINOBUTYL)AMINO]PROPYL]-L-GAMMA-GLUTAM	0.064–0.148	2
2,4-DIMETHYLPHENYLGLYOXAL	0.07	1
4-BROMOPHENYLGLYOXAL	0.02	1
4-METHYLPHENYLGLYOXAL	0.02	1
ALPHA-DEUTERIOPHENYLGLYOXAL	0.06	1

Catalyzed reactions (Rhea), 1 shown:

• (R)-S-lactoylglutathione = methylglyoxal + glutathione (RHEA:19069)

UniProt features (58 total): mutagenesis site 13, binding site 10, strand 10, helix 9, modified residue 6, disulfide bond 2, sequence variant 2, initiator methionine 1, chain 1, domain 1, splice variant 1, active site 1, turn 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
3W0T	X-RAY DIFFRACTION	1.35
3VW9	X-RAY DIFFRACTION	1.47
7WSZ	X-RAY DIFFRACTION	1.52
3W0U	X-RAY DIFFRACTION	1.7
1QIP	X-RAY DIFFRACTION	1.72
9KEH	X-RAY DIFFRACTION	1.72
9KEG	X-RAY DIFFRACTION	1.8
9KEI	X-RAY DIFFRACTION	1.81
7WT1	X-RAY DIFFRACTION	1.85
1QIN	X-RAY DIFFRACTION	2
7WT0	X-RAY DIFFRACTION	2
7WT2	X-RAY DIFFRACTION	2
9KEE	X-RAY DIFFRACTION	2.08
9KEK	X-RAY DIFFRACTION	2.11
1BH5	X-RAY DIFFRACTION	2.2
1FRO	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q04760-F1	95.63	0.91

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 173 (proton donor/acceptor)

Ligand- & substrate-binding residues (10): 127 (in other chain); 127 (in other chain); 157–158 (in other chain); 173 (in other chain); 34; 34; 38; 100; 104; 123 (in other chain)

Post-translational modifications (6): 2, 88, 107, 139, 148, 148

Disulfide bonds (2): 19–20, 61–139

Mutagenesis-validated functional residues (13):

Position	Phenotype
19	no effect on no-mediated modification. impaired no-mediated modification; when associated with a-20. loss of no-mediated
20	no effect on no-mediated modification. impaired no-mediated modification; when associated with a-19. loss of no-mediated
34	reduces enzyme activity by 99%.
45	no effect on phosphorylation.
61	no effect on no-mediated modification.
69	no effect on phosphorylation.
94	no effect on phosphorylation.
98	no effect on phosphorylation.
100	reduces enzyme activity by over 99%.
102	no effect on phosphorylation.
107	loss of phosphorylation.
139	impaired no-mediated modification. loss of no-mediated modification; when associated with a-19 or a-20.
173	abolishes enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-70268	Pyruvate metabolism
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism

MSigDB gene sets: 223 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, HORIUCHI_WTAP_TARGETS_DN, FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, MORF_ESPL1, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, GOBP_KETONE_METABOLIC_PROCESS, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP, MARTINEZ_RB1_TARGETS_UP, UEDA_PERIFERAL_CLOCK, MODULE_239, MARTINEZ_RB1_TARGETS_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GOBP_AMIDE_METABOLIC_PROCESS, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_CIS

GO Biological Process (6): carbohydrate metabolic process (GO:0005975), regulation of transcription by RNA polymerase II (GO:0006357), glutathione metabolic process (GO:0006749), methylglyoxal metabolic process (GO:0009438), osteoclast differentiation (GO:0030316), negative regulation of apoptotic process (GO:0043066)

GO Molecular Function (5): lactoylglutathione lyase activity (GO:0004462), zinc ion binding (GO:0008270), protein binding (GO:0005515), lyase activity (GO:0016829), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
primary metabolic process	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
modified amino acid metabolic process	1
sulfur compound metabolic process	1
aldehyde metabolic process	1
ketone metabolic process	1
myeloid leukocyte differentiation	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
carbon-sulfur lyase activity	1
transition metal ion binding	1
binding	1
catalytic activity	1
cation binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
extracellular vesicle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

66 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
PUS10	GLO1	psi-mi:“MI:0915”(physical association)	0.560
GLO1	PUS10	psi-mi:“MI:0915”(physical association)	0.560
MRPL13	GTPBP10	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
LMTK3	GPI	psi-mi:“MI:0914”(association)	0.420
GLO1	MROH9	psi-mi:“MI:0915”(physical association)	0.400
GLO1	MEOX2	psi-mi:“MI:0915”(physical association)	0.370
IKBKG	GLO1	psi-mi:“MI:0915”(physical association)	0.370
MAP3K13	GLO1	psi-mi:“MI:0915”(physical association)	0.370
FOS	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
STAT1	KPNA6	psi-mi:“MI:0914”(association)	0.350
SOD1	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
DND1	RPSA2	psi-mi:“MI:0914”(association)	0.350
SHOC2	PNP	psi-mi:“MI:0914”(association)	0.350
Inpp5b	PSMD11	psi-mi:“MI:0914”(association)	0.350
SOS2	SAP18	psi-mi:“MI:0914”(association)	0.350

BioGRID (130): GLO1 (Affinity Capture-MS), ACY1 (Co-fractionation), AKR1B1 (Co-fractionation), AKR1B15 (Co-fractionation), ATIC (Co-fractionation), FABP5 (Co-fractionation), GLO1 (Co-fractionation), GLO1 (Co-fractionation), GLO1 (Co-fractionation), GLO1 (Co-fractionation), GLO1 (Co-fractionation), GLO1 (Co-fractionation), GLO1 (Co-fractionation), GLO1 (Co-fractionation), GLOD4 (Co-fractionation)

ESM2 similar proteins: A0A0U2WCB2, A4IG53, A6NK44, A7GNY8, A8WFT6, B7HNI5, B9IY29, F4ZGF2, O00116, O49818, P0C5H0, P32232, P35520, P97275, Q04760, Q05B89, Q0V9K2, Q28CR0, Q3T0H0, Q42891, Q4G064, Q4KLB0, Q4R510, Q4R5F2, Q4V7D6, Q4V7R3, Q502D1, Q54L71, Q58H57, Q5EA45, Q66L51, Q6DCP1, Q6JQN1, Q6NTR1, Q6P7Q4, Q6PCI6, Q8C0I1, Q8H0V3, Q8L5Z4, Q8ZM36

Diamond homologs: O04885, O49818, O65398, P0A0T2, P0A0T3, P0A1Q2, P0A1Q3, P0AC81, P0AC82, P0AC83, P16635, P44638, P46235, P50107, Q04760, Q09751, Q39366, Q42891, Q4R5F2, Q55595, Q6P7Q4, Q8H0V3, Q8W593, Q9CPU0, Q9HU72, Q9KT93, Q9ZS21, Q948T6, A1YPR3, A4IS40, A7GNY8, A7Z3A4, A8XX92, O31817, P39586, P45945, Q09253, Q739M9, Q8CXK5, Q9KBZ6

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
CAMK2A	“up-regulates activity”	GLO1	phosphorylation
FLT4	“up-regulates activity”	GLO1	phosphorylation
FGFR3	“up-regulates activity”	GLO1	phosphorylation
FGFR4	“up-regulates activity”	GLO1	phosphorylation
EPHA5	“up-regulates activity”	GLO1	phosphorylation
FGFR2	“up-regulates activity”	GLO1	phosphorylation
YES1	“up-regulates activity”	GLO1	phosphorylation
LYN	“up-regulates activity”	GLO1	phosphorylation
ABL1	“up-regulates activity”	GLO1	phosphorylation
FGR	“up-regulates activity”	GLO1	phosphorylation
SRC	“up-regulates activity”	GLO1	phosphorylation
FLT1	“up-regulates activity”	GLO1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 74 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SARS-CoV-2-host interactions	7	15.7×	5e-05
SARS-CoV-2 Infection	7	10.6×	5e-04
Signaling by Interleukins	7	8.5×	1e-03
SARS-CoV Infections	8	8.4×	5e-04
Viral Infection Pathways	13	7.5×	4e-06
Cytokine Signaling in Immune system	9	6.9×	5e-04
Infectious disease	14	6.6×	4e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

18 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1001 predictions. Top by Δscore:

Variant	Effect	Δscore
6:38682004:AGACT:A	donor_loss	1.0000
6:38682005:GACTC:G	donor_loss	1.0000
6:38682006:ACTCA:A	donor_loss	1.0000
6:38682007:CTCAC:C	donor_loss	1.0000
6:38682008:TCA:T	donor_loss	1.0000
6:38682009:CA:C	donor_loss	1.0000
6:38682010:A:AC	donor_gain	1.0000
6:38682011:C:CA	donor_loss	1.0000
6:38682011:C:CC	donor_gain	1.0000
6:38682118:C:CT	acceptor_gain	1.0000
6:38682118:C:T	acceptor_gain	1.0000
6:38682119:G:T	acceptor_gain	1.0000
6:38682127:C:CT	acceptor_gain	1.0000
6:38682128:A:T	acceptor_gain	1.0000
6:38682802:ACTT:A	donor_loss	1.0000
6:38682804:TTA:T	donor_loss	1.0000
6:38682805:TACC:T	donor_loss	1.0000
6:38682806:A:AC	donor_gain	1.0000
6:38682806:ACCGA:A	donor_loss	1.0000
6:38682807:C:CG	donor_gain	1.0000
6:38682807:CCG:C	donor_gain	1.0000
6:38682807:CCGA:C	donor_gain	1.0000
6:38682807:CCGAA:C	donor_gain	1.0000
6:38682871:AATTG:A	acceptor_gain	1.0000
6:38682872:ATTG:A	acceptor_gain	1.0000
6:38682873:TTG:T	acceptor_gain	1.0000
6:38682873:TTGC:T	acceptor_loss	1.0000
6:38682874:TG:T	acceptor_gain	1.0000
6:38682875:GCT:G	acceptor_loss	1.0000
6:38682876:C:CC	acceptor_gain	1.0000

AlphaMissense

1226 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:38677361:A:C	F163L	0.999
6:38677361:A:T	F163L	0.999
6:38677363:A:G	F163L	0.999
6:38682809:G:C	F125L	0.997
6:38682809:G:T	F125L	0.997
6:38682811:A:G	F125L	0.997
6:38684478:A:C	F68L	0.997
6:38684478:A:T	F68L	0.997
6:38684480:A:G	F68L	0.997
6:38682083:A:T	V132D	0.996
6:38682092:C:T	G129E	0.996
6:38684380:A:G	L101P	0.996
6:38686915:A:C	F48L	0.996
6:38686915:A:T	F48L	0.996
6:38686917:A:G	F48L	0.996
6:38677365:G:T	A162E	0.995
6:38682025:C:A	K151N	0.995
6:38682025:C:G	K151N	0.995
6:38682097:A:C	H127Q	0.995
6:38682097:A:T	H127Q	0.995
6:38682099:G:C	H127D	0.995
6:38682101:C:T	G126D	0.995
6:38682813:C:T	G124E	0.995
6:38682831:C:A	G118V	0.995
6:38684380:A:T	L101Q	0.995
6:38677359:A:T	I164N	0.994
6:38677362:A:G	F163S	0.994
6:38682827:A:C	N119K	0.994
6:38682827:A:T	N119K	0.994
6:38682831:C:T	G118D	0.994

dbSNP variants (sampled 300 via entrez): RS1000029718 (6:38681121 T>A,G), RS1000482457 (6:38686075 T>C), RS1000487665 (6:38681253 A>G), RS1000663196 (6:38692878 C>T), RS1000824429 (6:38693999 T>C), RS1001166575 (6:38693848 C>A,T), RS1001231250 (6:38681086 C>T), RS1001285679 (6:38688852 A>C), RS1001364077 (6:38687709 T>C), RS1001416645 (6:38688075 A>T), RS1001565790 (6:38701788 T>C), RS1001596859 (6:38701475 T>C,G), RS1001805845 (6:38695348 T>C,G), RS1001873795 (6:38680464 T>C), RS1001886183 (6:38693178 T>C)

Disease associations

OMIM: gene MIM:138750 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): autism, susceptibility to, 1 (MONDO:0800416)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005042_9	Restless legs syndrome	4.000000e-202
GCST005231_51	Major depressive disorder	4.000000e-06
GCST006585_1866	Blood protein levels	7.000000e-11
GCST011395_3	Tuberculosis susceptibility in HIV infection	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2424 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

11 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 551,944 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1020	TOLMETIN	4	60,332
CHEMBL15770	SULINDAC	4	80,712
CHEMBL189171	ACEMETACIN	4	17,027
CHEMBL6	INDOMETHACIN	4	156,366
CHEMBL140	CURCUMIN	3	93,882
CHEMBL50	QUERCETIN	3	74,559
CHEMBL10372	ZOPOLRESTAT	2	3,266
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL31574	FISETIN	2	7,745
CHEMBL8260	BAICALEIN	2	8,592
CHEMBL150	KAEMPFEROL	1	25,940

PharmGKB: 1 entry (VIP=true, CPIC=false)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Capzimin	IC50	340 nM	US-10005735: Inhibitors of RPN11

ChEMBL bioactivities

149 potent at pChembl≥5 of 246 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	Ki	0.3	nM	CHEMBL3629116
9.02	Ki	0.96	nM	CHEMBL4473806
9.00	Ki	1	nM	CHEMBL3629115
9.00	Ki	1	nM	CHEMBL4436073
8.92	Ki	1.2	nM	ZOPOLRESTAT
8.30	Ki	5	nM	CURCUMIN
8.15	Ki	7	nM	CHEMBL4450158
8.00	Ki	10	nM	CHEMBL4438930
7.96	IC50	11	nM	CHEMBL2203964
7.96	Ki	11	nM	CHEMBL2203964
7.85	Ki	14	nM	CHEMBL128872
7.85	Ki	14	nM	CHEMBL1160349
7.85	IC50	14	nM	CHEMBL2203978
7.85	Ki	14	nM	CHEMBL128935
7.80	Ki	16	nM	CHEMBL127840
7.75	Ki	18	nM	CHEMBL128836
7.72	Ki	19	nM	CHEMBL4559486
7.58	IC50	26.4	nM	CHEMBL3220929
7.40	IC50	40	nM	CHEMBL2203976
7.34	Ki	46	nM	CHEMBL1160350
7.34	IC50	45.8	nM	CHEMBL3220931
7.34	Ki	46	nM	CHEMBL131578
7.34	Ki	46	nM	CHEMBL3629119
7.29	IC50	51.3	nM	CHEMBL3220930
7.27	IC50	53.9	nM	CHEMBL3220932
7.10	Ki	80	nM	CHEMBL218644
6.89	Ki	130	nM	CHEMBL3629118
6.80	Ki	160	nM	CHEMBL128935
6.80	Ki	160	nM	CHEMBL1160353
6.77	Ki	170	nM	CHEMBL129965
6.77	Ki	170	nM	CHEMBL218644
6.75	Ki	180	nM	CHEMBL128447
6.64	Ki	230	nM	CHEMBL1234300
6.60	IC50	250	nM	CHEMBL2203975
6.58	IC50	260	nM	CHEMBL2203963
6.55	IC50	280	nM	CHEMBL2203974
6.52	IC50	300	nM	CHEMBL2203966
6.52	IC50	300	nM	CHEMBL2203965
6.48	Ki	330	nM	CHEMBL3629117
6.43	IC50	370	nM	CHEMBL4559294
6.34	IC50	460	nM	CHEMBL4516514
6.32	IC50	480	nM	CHEMBL2203977
6.32	IC50	480	nM	CHEMBL4543065
6.30	IC50	500	nM	CHEMBL4539074
6.29	IC50	510	nM	CHEMBL2203967
6.27	IC50	540	nM	CHEMBL4457949
6.25	IC50	560	nM	MYRICETIN
6.23	IC50	590	nM	CHEMBL4571524
6.19	IC50	640	nM	CHEMBL4573731
6.14	IC50	720	nM	CHEMBL4466017

PubChem BioAssay actives

144 with measured affinity, of 389 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[[3-[(4-bromophenyl)-hydroxycarbamoyl]sulfanyl-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-2-[[3-[2-[3-[[3-[2-[[3-[[3-[2-[3-[[4-[[3-[(4-bromophenyl)-hydroxycarbamoyl]sulfanyl-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-1-carboxy-4-oxobutyl]amino]propanoyloxy]ethylamino]-3-oxopropyl]amino]-3-oxopropanoyl]amino]ethylamino]-3-oxopropanoyl]amino]propanoylamino]ethoxy]-3-oxopropyl]amino]-5-oxopentanoic acid	1252520: Inhibition of 6-His tagged recombinant human glyoxalase 1 transfected in Escherichia coli BL21 (DE3) assessed as S-D-lactoylglutathione formation by spectrophotometer	ki	0.0003	uM
5-[[3-[(4-bromophenyl)-hydroxycarbamoyl]sulfanyl-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-2-[[3-[2-[2-[2-[2-[[8-[3-[2-[2-[3-[[8-[2-[2-[2-[2-[3-[[4-[[3-[(4-bromophenyl)-hydroxycarbamoyl]sulfanyl-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-1-carboxy-4-oxobutyl]amino]propanoyloxy]ethoxy]ethoxy]ethoxy]ethylamino]-8-oxooctanoyl]amino]propoxy]ethoxy]ethoxy]propylamino]-8-oxooctanoyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]-3-oxopropyl]amino]-5-oxopentanoic acid	1252520: Inhibition of 6-His tagged recombinant human glyoxalase 1 transfected in Escherichia coli BL21 (DE3) assessed as S-D-lactoylglutathione formation by spectrophotometer	ki	0.0010	uM
(2S)-2-[3-[3-[3-[3-[3-[3-[[8-[[3-[[3-[[3-[[3-[[3-[[3-[[(1S)-1-carboxy-4-[[(2R)-1-(carboxymethylamino)-3-[(4-chlorophenyl)-hydroxycarbamoyl]sulfanyl-1-oxopropan-2-yl]amino]-4-oxobutyl]amino]-3-oxopropyl]amino]-3-oxopropyl]amino]-3-oxopropyl]amino]-3-oxopropyl]amino]-3-oxopropyl]amino]-3-oxopropyl]amino]-8-oxooctanoyl]amino]propanoylamino]propanoylamino]propanoylamino]propanoylamino]propanoylamino]propanoylamino]-5-[[(2R)-1-(carboxymethylamino)-3-[(4-chlorophenyl)-hydroxycarbamoyl]sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1604825: Competitive inhibition of human Glyoxalase-1 using GSH and MGO as substrate by Michaelis-Menten analysis	ki	0.0010	uM
(2S)-2-amino-5-[[(2S)-1-(carboxymethylamino)-5-(3-ethynyl-N-hydroxyanilino)-1,5-dioxopentan-2-yl]amino]-5-oxopentanoic acid	1604824: Competitive inhibition of human Glyoxalase-1 using GSH and MGO as substrate	ki	0.0010	uM
2-[4-oxo-3-[[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]methyl]phthalazin-1-yl]acetic acid	1604827: Inhibition of human Glyoxalase-1 using GSH and MGO as substrate by Dixon plot analysis	ki	0.0012	uM
Curcumin	1604819: Inhibition of human erythrocyte Glyoxalase-1 using GSH and MGO as substrate by Dixon plot analysis	ki	0.0050	uM
(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-[(4-ethynylphenyl)-hydroxycarbamoyl]sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1604824: Competitive inhibition of human Glyoxalase-1 using GSH and MGO as substrate	ki	0.0070	uM
(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-[hydroxy-(4-iodophenyl)carbamoyl]sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1604818: Inhibition of human Glyoxalase-1	ki	0.0100	uM
1-hydroxy-6-[1-(3-methoxypropyl)pyrrolo[2,3-b]pyridin-5-yl]-4-phenylpyridin-2-one	1572176: Inhibition of human GLO1	ki	0.0110	uM
(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-[hydroxy(phenyl)carbamoyl]sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1572176: Inhibition of human GLO1	ki	0.0140	uM
2-amino-5-[[3-[(4-bromophenyl)-hydroxycarbamoyl]sulfanyl-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	74116: Tested for inhibitory activity against human erythrocyte glyoxalase I	ki	0.0140	uM
(2S)-2-amino-5-[[(2R)-3-[(4-bromophenyl)-hydroxycarbamoyl]sulfanyl-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1252523: Inhibition of human glyoxalase 1	ki	0.0140	uM
1-hydroxy-6-[1-(2-methoxyethyl)pyrrolo[2,3-b]pyridin-5-yl]-4-phenylpyridin-2-one	717339: Inhibition of human recombinant GLO1 expressed in Escherichia coli BL21 assessed as decrease in reduced glutathione level after 1 hr by Ellman’s method	ic50	0.0140	uM
(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-[hexyl(hydroxy)carbamoyl]sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	74115: Binding affinity for Glyoxalase I	ki	0.0160	uM
(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-[heptyl(hydroxy)carbamoyl]sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	74115: Binding affinity for Glyoxalase I	ki	0.0180	uM
(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-[(3-ethynylphenyl)-hydroxycarbamoyl]sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1604824: Competitive inhibition of human Glyoxalase-1 using GSH and MGO as substrate	ki	0.0190	uM
3-[[5-(1-hydroxy-6-oxo-4-phenyl-2-pyridinyl)pyrrolo[2,3-b]pyridin-1-yl]methyl]benzamide	717339: Inhibition of human recombinant GLO1 expressed in Escherichia coli BL21 assessed as decrease in reduced glutathione level after 1 hr by Ellman’s method	ic50	0.0400	uM
(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-[(4-chlorophenyl)-hydroxycarbamoyl]sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1158039: Competitive inhibition of GLO1 (unknown origin)	ki	0.0460	uM
5-[[1-(carboxymethylamino)-3-[(4-chlorophenyl)-hydroxycarbamoyl]sulfanyl-1-oxopropan-2-yl]amino]-2-[(3-ethoxy-3-oxopropyl)amino]-5-oxopentanoic acid	1252523: Inhibition of human glyoxalase 1	ki	0.0460	uM
2-amino-5-[[1-(carboxymethylamino)-3-[(4-chlorophenyl)-hydroxycarbamoyl]sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	74116: Tested for inhibitory activity against human erythrocyte glyoxalase I	ki	0.0460	uM
(2S)-2-amino-5-[[(2R)-3-[(4-bromophenyl)methylsulfanyl]-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1158036: Inhibition of GLO1 (unknown origin)	ki	0.0800	uM
5-[[1-(carboxymethylamino)-3-[(4-chlorophenyl)-hydroxycarbamoyl]sulfanyl-1-oxopropan-2-yl]amino]-5-oxo-2-(2-oxopropylamino)pentanoic acid	1252523: Inhibition of human glyoxalase 1	ki	0.1300	uM
2-amino-5-[[1-(carboxymethylamino)-3-[hydroxy(phenyl)carbamoyl]sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	74116: Tested for inhibitory activity against human erythrocyte glyoxalase I	ki	0.1600	uM
(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-[hydroxy(pentyl)carbamoyl]sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	74115: Binding affinity for Glyoxalase I	ki	0.1700	uM
(2S)-2-amino-5-[[(2R)-3-[butyl(hydroxy)carbamoyl]sulfanyl-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	74115: Binding affinity for Glyoxalase I	ki	0.1800	uM
methyl 4-(2,3-dihydroxy-5-methylphenoxy)-2-hydroxy-6-methylbenzoate	1572176: Inhibition of human GLO1	ki	0.2300	uM
1-hydroxy-6-(1H-indol-5-yl)-4-phenylpyridin-2-one	717339: Inhibition of human recombinant GLO1 expressed in Escherichia coli BL21 assessed as decrease in reduced glutathione level after 1 hr by Ellman’s method	ic50	0.2500	uM
1-hydroxy-6-[1-(2-methoxyethyl)indol-5-yl]-4-phenylpyridin-2-one	717339: Inhibition of human recombinant GLO1 expressed in Escherichia coli BL21 assessed as decrease in reduced glutathione level after 1 hr by Ellman’s method	ic50	0.2600	uM
1-hydroxy-4-phenyl-6-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyridin-2-one	717339: Inhibition of human recombinant GLO1 expressed in Escherichia coli BL21 assessed as decrease in reduced glutathione level after 1 hr by Ellman’s method	ic50	0.2800	uM
1-hydroxy-6-[1-(3-methoxypropyl)indol-5-yl]-4-phenylpyridin-2-one	717339: Inhibition of human recombinant GLO1 expressed in Escherichia coli BL21 assessed as decrease in reduced glutathione level after 1 hr by Ellman’s method	ic50	0.3000	uM
6-(1-butylpyrrolo[2,3-b]pyridin-5-yl)-1-hydroxy-4-phenylpyridin-2-one	717339: Inhibition of human recombinant GLO1 expressed in Escherichia coli BL21 assessed as decrease in reduced glutathione level after 1 hr by Ellman’s method	ic50	0.3000	uM
2-(3-aminopropanoylamino)-5-[[1-(carboxymethylamino)-3-[(4-chlorophenyl)-hydroxycarbamoyl]sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1252523: Inhibition of human glyoxalase 1	ki	0.3300	uM
N-[5-(3-chlorophenyl)quinolin-8-yl]pyridine-2-sulfonamide	1572164: Inhibition recombinant human N-terminal 6His-tagged GLO1 (2 to 184 residues) expressed in Escherichia coli using MG as substrate preincubated for 15 to 20 mins followed by substrate addition and measured every 1 min for 8 mins	ic50	0.3700	uM
N-[6-[2-(3,5-dimethoxyphenyl)ethyl]quinolin-8-yl]pyridine-2-sulfonamide	1572164: Inhibition recombinant human N-terminal 6His-tagged GLO1 (2 to 184 residues) expressed in Escherichia coli using MG as substrate preincubated for 15 to 20 mins followed by substrate addition and measured every 1 min for 8 mins	ic50	0.4600	uM
N-[5-(4-chlorophenyl)quinolin-8-yl]pyridine-2-sulfonamide	1572164: Inhibition recombinant human N-terminal 6His-tagged GLO1 (2 to 184 residues) expressed in Escherichia coli using MG as substrate preincubated for 15 to 20 mins followed by substrate addition and measured every 1 min for 8 mins	ic50	0.4800	uM
3-[[5-(1-hydroxy-6-oxo-4-phenyl-2-pyridinyl)indol-1-yl]methyl]benzamide	717339: Inhibition of human recombinant GLO1 expressed in Escherichia coli BL21 assessed as decrease in reduced glutathione level after 1 hr by Ellman’s method	ic50	0.4800	uM
N-(5-phenylquinolin-8-yl)pyridine-2-sulfonamide	1572164: Inhibition recombinant human N-terminal 6His-tagged GLO1 (2 to 184 residues) expressed in Escherichia coli using MG as substrate preincubated for 15 to 20 mins followed by substrate addition and measured every 1 min for 8 mins	ic50	0.5000	uM
1-hydroxy-6-(1-pentylpyrrolo[2,3-b]pyridin-5-yl)-4-phenylpyridin-2-one	717339: Inhibition of human recombinant GLO1 expressed in Escherichia coli BL21 assessed as decrease in reduced glutathione level after 1 hr by Ellman’s method	ic50	0.5100	uM
N-[5-(3,4-dichlorophenyl)quinolin-8-yl]pyridine-2-sulfonamide	1572164: Inhibition recombinant human N-terminal 6His-tagged GLO1 (2 to 184 residues) expressed in Escherichia coli using MG as substrate preincubated for 15 to 20 mins followed by substrate addition and measured every 1 min for 8 mins	ic50	0.5400	uM
3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one	381802: Inhibition of human recombinant His-tagged Glyoxalase 1 expressed in Sf21-Baculovirus system	ic50	0.5600	uM
N-[5-(3-chloro-4-methoxyphenyl)quinolin-8-yl]pyridine-2-sulfonamide	1572164: Inhibition recombinant human N-terminal 6His-tagged GLO1 (2 to 184 residues) expressed in Escherichia coli using MG as substrate preincubated for 15 to 20 mins followed by substrate addition and measured every 1 min for 8 mins	ic50	0.5900	uM
N-[5-(4-methoxyphenyl)quinolin-8-yl]pyridine-2-sulfonamide	1572164: Inhibition recombinant human N-terminal 6His-tagged GLO1 (2 to 184 residues) expressed in Escherichia coli using MG as substrate preincubated for 15 to 20 mins followed by substrate addition and measured every 1 min for 8 mins	ic50	0.6400	uM
N-[5-(4-fluorophenyl)quinolin-8-yl]pyridine-2-sulfonamide	1572164: Inhibition recombinant human N-terminal 6His-tagged GLO1 (2 to 184 residues) expressed in Escherichia coli using MG as substrate preincubated for 15 to 20 mins followed by substrate addition and measured every 1 min for 8 mins	ic50	0.7200	uM
4-[(E)-2-(3,5-dihydroxyphenyl)ethenyl]benzene-1,2-diol	1430278: Inhibition of human N-terminal His6-tagged GLO1 expressed in baculovirus infected sf21 cells assessed as reduction in S-D-lactoylglutathione formation measured for 5 mins in presence of glutathione by spectrophotometric method	ic50	0.7600	uM
N-[5-(2-phenylethyl)quinolin-8-yl]pyridine-2-sulfonamide	1572164: Inhibition recombinant human N-terminal 6His-tagged GLO1 (2 to 184 residues) expressed in Escherichia coli using MG as substrate preincubated for 15 to 20 mins followed by substrate addition and measured every 1 min for 8 mins	ic50	0.7900	uM
N-[5-[2-(4-fluorophenyl)ethyl]quinolin-8-yl]pyridine-2-sulfonamide	1572164: Inhibition recombinant human N-terminal 6His-tagged GLO1 (2 to 184 residues) expressed in Escherichia coli using MG as substrate preincubated for 15 to 20 mins followed by substrate addition and measured every 1 min for 8 mins	ic50	0.7900	uM
(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-[hydroxy(propyl)carbamoyl]sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	74115: Binding affinity for Glyoxalase I	ki	0.8000	uM
N-[5-(3-methoxyphenyl)quinolin-8-yl]pyridine-2-sulfonamide	1572164: Inhibition recombinant human N-terminal 6His-tagged GLO1 (2 to 184 residues) expressed in Escherichia coli using MG as substrate preincubated for 15 to 20 mins followed by substrate addition and measured every 1 min for 8 mins	ic50	1.0400	uM
1-hydroxy-4-[(4-methyl-3-sulfamoylphenyl)diazenyl]naphthalene-2-carboxylic acid	1721354: Inhibition of recombinant human N-terminal Met and 6-His-tagged Glyoxalase-1 (Ala2 to Met184 residues) using glutathione and methylglyoxal as substrates preincubated for 15 mins followed by enzyme addition by double beam UV-vis spectrophotometric method	ic50	1.1300	uM
(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-[ethyl(hydroxy)carbamoyl]sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	74115: Binding affinity for Glyoxalase I	ki	1.1800	uM

CTD chemical–gene interactions

65 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Pyruvaldehyde	affects reaction, affects expression, increases expression, affects binding, affects response to substance (+4 more)	7
bisphenol A	affects expression, decreases expression, increases expression	4
sodium arsenite	decreases reaction, increases activity, decreases expression, increases expression	3
Troglitazone	decreases reaction, decreases response to substance, decreases activity, decreases expression, increases response to substance	3
Benzo(a)pyrene	affects methylation, decreases expression, decreases reaction	2
dicrotophos	decreases expression	1
pimagedine	decreases expression, decreases reaction	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
protocatechualdehyde	decreases reaction, increases activity	1
chlorophyllin	decreases expression	1
ferric ammonium citrate	decreases reaction, increases expression	1
arsenite	affects binding, increases reaction	1
sulforaphane	decreases reaction, increases expression, decreases expression	1
bioallethrin	increases activity	1
cupric oxide	decreases expression	1
galangin	decreases activity, decreases expression	1
4-hydroxycoumarin	decreases activity	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
vanillin	decreases activity, decreases reaction	1
chloropicrin	affects expression	1
pterostilbene	decreases expression, decreases reaction	1
gambierol	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
monascin	increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
FPS-ZM1	affects cotreatment, decreases activity, decreases reaction	1

ChEMBL screening assays

72 unique, capped per target: 70 binding, 1 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1251073	Binding	Inhibition of human recombinant glyoxalase 1 assessed as S-D-lactoylglutathione after 15 mins by spectrophotometric analysis	Delphinidin, a dietary anthocyanidin in berry fruits, inhibits human glyoxalase I. — Bioorg Med Chem
CHEMBL4710826	ADMET	Inhibition of human Glyoxalase-1 expressed in Escherichia coli BL21 (DE3)	4-Amino-1,2,4-triazole-3-thione-derived Schiff bases as metallo-β-lactamase inhibitors. — Eur J Med Chem
CHEMBL684997	Functional	In vivo inhibitory activity against glyoxalase I in sheep liver; no inhibition	S-carbobenzoxyglutathione: a competitive inhibitor of mammalian glyoxalase II. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SQ04	HAP1 GLO1 (-) 1	Cancer cell line	Male
CVCL_XP15	HAP1 GLO1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.