HAGH

Summary

HAGH (hydroxyacylglutathione hydrolase, HGNC:4805) is a protein-coding gene on chromosome 16p13.3, encoding Hydroxyacylglutathione hydrolase, mitochondrial (Q16775). Thiolesterase that catalyzes the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid.

The enzyme encoded by this gene is classified as a thiolesterase and is responsible for the hydrolysis of S-lactoyl-glutathione to reduced glutathione and D-lactate. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3029 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 71 total
• Phenotypes (HPO): 2
• Druggable target: yes
• MANE Select transcript: NM_005326

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4805
Approved symbol	HAGH
Name	hydroxyacylglutathione hydrolase
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	GLO2, GLXII, HAGH1
Ensembl gene	ENSG00000063854
Ensembl biotype	protein_coding
OMIM	138760
Entrez	3029

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 13 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000397353, ENST00000397356, ENST00000455446, ENST00000564445, ENST00000564518, ENST00000565097, ENST00000566644, ENST00000566709, ENST00000567190, ENST00000567398, ENST00000569339, ENST00000569700, ENST00000851988, ENST00000851989, ENST00000851990, ENST00000945501, ENST00000945502, ENST00000945503

RefSeq mRNA: 5 — MANE Select: NM_005326 NM_001040427, NM_001286249, NM_001363912, NM_001363914, NM_005326

CCDS: CCDS10447, CCDS32366, CCDS66900, CCDS86494

Canonical transcript exons

ENST00000397356 — 9 exons

Exon	Start	End
ENSE00001908102	1826712	1826825
ENSE00002590337	1807629	1809382
ENSE00003380977	1819115	1819223
ENSE00003503337	1809754	1809833
ENSE00003569659	1822865	1823037
ENSE00003606766	1819897	1820014
ENSE00003608952	1816893	1816994
ENSE00003637443	1817168	1817271
ENSE00003649660	1822300	1822364

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.5134 / max 290.2111, expressed in 1814 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155875	19.6244	1811
155874	2.8890	1280

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.53	gold quality
right lobe of liver	UBERON:0001114	98.37	gold quality
right adrenal gland	UBERON:0001233	98.02	gold quality
right adrenal gland cortex	UBERON:0035827	98.00	gold quality
left adrenal gland	UBERON:0001234	97.98	gold quality
gastrocnemius	UBERON:0001388	97.96	gold quality
left adrenal gland cortex	UBERON:0035825	97.94	gold quality
prefrontal cortex	UBERON:0000451	97.74	gold quality
adrenal cortex	UBERON:0001235	97.64	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.63	gold quality
left testis	UBERON:0004533	97.61	gold quality
muscle of leg	UBERON:0001383	97.51	gold quality
right testis	UBERON:0004534	97.50	gold quality
right atrium auricular region	UBERON:0006631	97.28	gold quality
right frontal lobe	UBERON:0002810	97.21	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.21	gold quality
cerebellar hemisphere	UBERON:0002245	97.13	gold quality
cerebellar cortex	UBERON:0002129	97.11	gold quality
heart left ventricle	UBERON:0002084	97.09	gold quality
cingulate cortex	UBERON:0003027	96.97	gold quality
anterior cingulate cortex	UBERON:0009835	96.97	gold quality
adenohypophysis	UBERON:0002196	96.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.94	gold quality
cardiac ventricle	UBERON:0002082	96.91	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.88	gold quality
liver	UBERON:0002107	96.61	gold quality
cardiac atrium	UBERON:0002081	96.59	gold quality
pituitary gland	UBERON:0000007	96.58	gold quality
nucleus accumbens	UBERON:0001882	96.53	gold quality
cerebellum	UBERON:0002037	96.43	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	51.97
E-MTAB-10042	yes	33.61
E-MTAB-9221	yes	14.55
E-HCAD-9	yes	7.05
E-MTAB-7606	no	885.08
E-ENAD-17	no	874.22
E-MTAB-5061	no	3.11
E-HCAD-10	no	2.94
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP73

miRNA regulators (miRDB)

13 targeting HAGH, 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-340-5P	100.00	72.50	4437
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-1537-5P	98.70	68.33	999
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-4675	97.69	64.82	774
HSA-MIR-4741	97.69	64.14	883

Literature-anchored findings (GeneRIF, showing 15)

• hydroxyacylglutathione hydrolase (HAGH) gene encodes both cytosolic and mitochondrial forms of glyoxalase II (PMID:15117945)
• Overexpression of glyoxalase II is associated with kidney tumor (PMID:16803681)
• Data show that the GLX2 gene, which encodes glyoxalase II enzyme, is up-regulated by p63 and p73. (PMID:16831876)
• In androgen-dependent prostate cancer cells, testosterone upregulates GLO2 mRNA levels. In androgen-independent prostate cancer cells, it downregulates GLO2 mRNA. (PMID:18344682)
• Human glyoxalase II contains an Fe(II)Zn(II) center but is active as a mononuclear Zn(II) enzyme (PMID:19413286)
• No association between genetic variants of the HAGH gene and autism spectrum disorder was found. (PMID:24671236)
• This study suggested that HAGH, rs11859266 and rs3743852 showed significant associations with schizophrenia in males at allelic and genotype levels. (PMID:25645869)
• Studies indicate that the most extensively investigated The most extensively investigated glyoxalase enzymes are glyoxalase I and glyoxalase II (Glo1 and Glo2). (PMID:26552067)
• epidermal expression stronger in older skin donors (PMID:26914966)
• This article reports for the first time a possible additional role of Glo2 that, after interacting with a target protein, is able to promote S-glutathionylation. (PMID:27935136)
• The critical role of glyoxalases as regulators of tumorigenesis in the prostate through modulation of various critical signaling pathways, and an overview of the current knowledge on glyoxalases in bladder, kidney and testis cancers is reviewed. (GLO1, GLO2) (PMID:29385039)
• Down regulation of Glyoxalase II was observed in cases of diabetic retinopathy as compared to controls. (PMID:29950256)
• CDH6 and HAGH protein levels in plasma associate with Alzheimer’s disease in APOE epsilon4 carriers. (PMID:32427856)
• Sirtuin 2 Regulates Protein LactoylLys Modifications. (PMID:33725370)
• Overexpression of Glyoxalase 2 in Human Breast Cancer Cells: Implications for Cell Proliferation and Doxorubicin Resistance. (PMID:39456676)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hagh	ENSDARG00000025338
mus_musculus	Hagh	ENSMUSG00000024158
rattus_norvegicus	Hagh	ENSRNOG00000014743
drosophila_melanogaster	tzn	FBGN0037024
caenorhabditis_elegans		WBGENE00012459

Paralogs (4): HAGHL (ENSG00000103253), ETHE1 (ENSG00000105755), PNKD (ENSG00000127838), MBLAC2 (ENSG00000176055)

Protein

Protein identifiers

Hydroxyacylglutathione hydrolase, mitochondrial — Q16775 (reviewed: Q16775)

Alternative names: Glyoxalase II

All UniProt accessions (5): Q16775, H3BPK3, H3BPQ4, H3BQW8, H3BV79

UniProt curated annotations — full annotation on UniProt →

Function. Thiolesterase that catalyzes the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid.

Subunit / interactions. Monomer.

Subcellular location. Mitochondrion matrix Cytoplasm.

Tissue specificity. Expressed in liver and kidney.

Cofactor. Binds 2 Zn(2+) ions per subunit.

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

Miscellaneous. Produced by alternative splicing. Also produced by alternative initiation at Met-49 of isoform 1.

Similarity. Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q16775-1	1	yes
Q16775-2	2
Q16775-3	3

RefSeq proteins (5): NP_001035517, NP_001273178, NP_001350841, NP_001350843, NP_005317* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001279	Metallo-B-lactamas	Domain
IPR017782	Hydroxyacylglutathione_Hdrlase	Family
IPR032282	HAGH_C	Domain
IPR035680	Clx_II_MBL	Domain
IPR036866	RibonucZ/Hydroxyglut_hydro	Homologous_superfamily

Pfam: PF00753, PF16123

Enzyme classification (BRENDA):

• EC 3.1.2.6 — hydroxyacylglutathione hydrolase (BRENDA: 38 organisms, 111 substrates, 135 inhibitors, 161 Km, 77 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
S-D-LACTOYLGLUTATHIONE	0.055–5.782	51
S-LACTOYLGLUTATHIONE	0.0007–0.6	20
S-(2-HYDROXYACYL)GLUTATHIONE	0.152–0.283	9
S-ACETYLGLUTATHIONE	0.034–0.83	9
S-ACETOACETYLGLUTATHIONE	0.054–0.841	8
S-SUCCINYLGLUTATHIONE	0.134–0.535	8
S-PROPIONYLGLUTATHIONE	0.213–1.2	7
S-D-MANDELOYLGLUTATHIONE	0.0166–0.0365	5
S-MANDELOYLGLUTATHIONE	0.014–0.0164	5
(S)-D-LACTOYLGLUTATHIONE	0.15–0.29	4
MONO-(LACTOYL)TRYPANOTHIONE	0.039–0.108	4
S-GLYCOLYLGLUTATHIONE	0.07–1.16	4
S-(BETA-ETHOXY-ALPHA-D-HYDROXYBUTYRYL)GLUTATHION	0.044–0.703	3
S-FORMYLGLUTATHIONE	0.153–0.213	3
BIS-(LACTOYL)TRYPANOTHIONE	0.086	2

Catalyzed reactions (Rhea), 2 shown:

• an S-(2-hydroxyacyl)glutathione + H2O = a 2-hydroxy carboxylate + glutathione + H(+) (RHEA:21864)
• (R)-S-lactoylglutathione + H2O = (R)-lactate + glutathione + H(+) (RHEA:25245)

UniProt features (48 total): strand 13, binding site 11, helix 9, turn 4, modified residue 3, splice variant 3, sequence conflict 3, transit peptide 1, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1QH5	X-RAY DIFFRACTION	1.45
1QH3	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16775-F1	91.57	0.86

Functional residue map

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

Ligand- & substrate-binding residues (11): 221–223; 221; 297–300; 102; 104; 106; 107; 158; 182; 182; 191–193

Post-translational modifications (3): 116, 229, 229

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-70268	Pyruvate metabolism

MSigDB gene sets: 243 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_ALDEHYDE_CATABOLIC_PROCESS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_KETONE_METABOLIC_PROCESS, GOBP_PEPTIDE_METABOLIC_PROCESS, MODULE_66, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4

GO Biological Process (3): glutathione metabolic process (GO:0006749), glutathione biosynthetic process (GO:0006750), obsolete methylglyoxal catabolic process to pyruvate via (R)-S-lactoyl-glutathione (GO:0019243)

GO Molecular Function (4): hydroxyacylglutathione hydrolase activity (GO:0004416), metal ion binding (GO:0046872), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (4): cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	2
modified amino acid metabolic process	1
sulfur compound metabolic process	1
glutathione metabolic process	1
nonribosomal peptide biosynthetic process	1
modified amino acid biosynthetic process	1
sulfur compound biosynthetic process	1
thiolester hydrolase activity	1
cation binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

2060 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HAGH	GLO1	P78375	992
HAGH	CES5A	Q6NT32	771
HAGH	ASIC4	Q96FT7	767
HAGH	CES2	O00748	765
HAGH	ESD	P10768	756
HAGH	PGP	A6NDG6	734
HAGH	CES3	Q6UWW8	673
HAGH	ADH5	P11766	614
HAGH	PGM3	O95394	610
HAGH	CES1	P23141	555
HAGH	PARK7	Q99497	550
HAGH	GSR	P00390	502
HAGH	TPI1	P00938	488
HAGH	MBLAC1	A4D2B0	479
HAGH	GPX6	P59796	464
HAGH	GPX7	Q96SL4	464

IntAct

49 interactions, top by confidence:

A	B	Type	Score
AURKB	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
HAGH	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
PPP1R16B	USP11	psi-mi:“MI:0914”(association)	0.420
PPP1R16B	USP11	psi-mi:“MI:2364”(proximity)	0.420
TNFAIP3	LRRIQ3	psi-mi:“MI:0914”(association)	0.420
PCNA	HAGH	psi-mi:“MI:0915”(physical association)	0.370
HAGH	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
HAGH	BST2	psi-mi:“MI:0915”(physical association)	0.370
SOD1	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
GATA4	PCCA	psi-mi:“MI:0914”(association)	0.350
NKX2-5		psi-mi:“MI:0914”(association)	0.350
FLT3	LANCL1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
HAGH	CKM	psi-mi:“MI:0914”(association)	0.350
FECH	GTPBP10	psi-mi:“MI:0914”(association)	0.350
HRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
NRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
AIFM1	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
AURKAIP1	VWA8	psi-mi:“MI:2364”(proximity)	0.270
	VWA8	psi-mi:“MI:2364”(proximity)	0.270
BET1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
HSPD1	VWA8	psi-mi:“MI:2364”(proximity)	0.270
COX4I1	HAX1	psi-mi:“MI:2364”(proximity)	0.270
EEA1	PPIP5K2	psi-mi:“MI:2364”(proximity)	0.270
GOLGA2	MYO1C	psi-mi:“MI:2364”(proximity)	0.270
HK1	ANXA2P2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (102): HAGH (Co-fractionation), HSPE1 (Co-fractionation), LACTB2 (Co-fractionation), HAGH (Affinity Capture-MS), HAGH (Affinity Capture-MS), HAGH (Proximity Label-MS), HAGH (Affinity Capture-MS), HAGH (Affinity Capture-MS), HAGH (Affinity Capture-MS), HAGH (Proximity Label-MS), HAGH (Proximity Label-MS), HAGH (Proximity Label-MS), HAGH (Proximity Label-MS), HAGH (Proximity Label-MS), HAGH (Proximity Label-MS)

ESM2 similar proteins: A0A067XMV3, A0A179HLJ8, A0A1L9WLF1, A0A2I1C3U0, A0A411PQM3, A0A4P8DJU1, A0A5B8YUX5, A0A7R7ZLL0, A1D8J2, A2QX23, B6HN76, B8M9J8, C3K630, C5FM60, D4CZZ5, D7PHZ8, E1ACR1, E4V2N5, F2PWS8, F2S702, F2T0M3, G3KLH5, K3VFR8, M1WCF7, M3ANL0, P0CM88, P0CM89, P0CT90, P0CU68, P9WEG2, Q0CCY4, Q0CCY5, Q0CJ62, Q0CS61, Q0CS91, Q16775, Q26547, Q28333, Q4W945, Q4WA58

Diamond homologs: A1IPQ8, A1RK78, A1S6T3, A1WXD9, A3QET2, A4G7G5, A4Y6B8, A4YKS8, A5F635, A5VSR1, A6VVZ9, A6WXE0, A7MY07, A7YY46, A9M8S2, B0BZI8, B0CIU0, B0JW10, B0KN02, B0RTE9, B0TRL8, B1WUT9, B1XQ70, B2IVH7, B2S889, B3R1Y0, B4F6K2, B4RJC7, B5F9V3, B6EJV4, B7K3R6, B7KEB4, B7VIP5, B8HMJ9, C0RFI1, C3LPP0, C5BEP2, C6DC67, O24496, O35952

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1846 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1816889:TCA:T	donor_loss	1.0000
16:1816890:CA:C	donor_loss	1.0000
16:1816891:A:AC	donor_gain	1.0000
16:1816891:AC:A	donor_gain	1.0000
16:1816892:C:CA	donor_loss	1.0000
16:1816892:C:CC	donor_gain	1.0000
16:1816892:CC:C	donor_gain	1.0000
16:1816991:CTCT:C	acceptor_gain	1.0000
16:1816993:CT:C	acceptor_gain	1.0000
16:1816994:TCTGA:T	acceptor_loss	1.0000
16:1816995:C:CA	acceptor_loss	1.0000
16:1816995:C:CC	acceptor_gain	1.0000
16:1817166:A:AC	donor_gain	1.0000
16:1817167:C:CC	donor_gain	1.0000
16:1819892:CTTA:C	donor_loss	1.0000
16:1819893:TTACC:T	donor_loss	1.0000
16:1819894:TA:T	donor_loss	1.0000
16:1819895:A:AG	donor_loss	1.0000
16:1822294:ACTT:A	donor_loss	1.0000
16:1822295:CTTA:C	donor_loss	1.0000
16:1822296:TTA:T	donor_loss	1.0000
16:1822297:TACCA:T	donor_loss	1.0000
16:1822298:ACCAG:A	donor_loss	1.0000
16:1822377:C:CT	acceptor_gain	1.0000
16:1822377:C:T	acceptor_gain	1.0000
16:1822861:GCACC:G	donor_loss	1.0000
16:1822862:CACCT:C	donor_loss	1.0000
16:1822864:CCTT:C	donor_gain	1.0000
16:1822899:T:TA	donor_gain	1.0000
16:1823037:CCT:C	acceptor_loss	1.0000

AlphaMissense

1986 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1816950:A:C	F230L	0.999
16:1816950:A:T	F230L	0.999
16:1816952:A:G	F230L	0.999
16:1817268:T:A	D182V	0.999
16:1820008:A:C	H107Q	0.999
16:1820008:A:T	H107Q	0.999
16:1820010:G:C	H107D	0.999
16:1822310:G:C	H102D	0.999
16:1809771:G:C	N270K	0.998
16:1809771:G:T	N270K	0.998
16:1816957:A:G	L228P	0.998
16:1816979:G:C	H221D	0.998
16:1817268:T:C	D182G	0.998
16:1817268:T:G	D182A	0.998
16:1817269:C:G	D182H	0.998
16:1817271:C:A	G181V	0.998
16:1817271:C:T	G181D	0.998
16:1819120:A:G	F179S	0.998
16:1819164:A:C	C164W	0.998
16:1819184:G:C	H158D	0.998
16:1820009:T:G	H107P	0.998
16:1820012:T:G	D106A	0.998
16:1822308:G:C	H102Q	0.998
16:1822308:G:T	H102Q	0.998
16:1809765:G:C	F272L	0.997
16:1809765:G:T	F272L	0.997
16:1809767:A:G	F272L	0.997
16:1817267:G:C	D182E	0.997
16:1817267:G:T	D182E	0.997
16:1819163:A:C	Y165D	0.997

dbSNP variants (sampled 300 via entrez): RS1000004031 (16:1828829 G>A,T), RS1000056645 (16:1828977 C>T), RS1000094485 (16:1810197 C>T), RS1000113892 (16:1824819 A>G), RS1000156824 (16:1815191 C>T), RS1000235137 (16:1824965 C>T), RS1000242089 (16:1812897 G>C), RS1000698723 (16:1811063 C>G,T), RS1000832803 (16:1817074 C>A,T), RS1000835537 (16:1823940 T>C), RS1000843231 (16:1822740 C>A,T), RS1000886231 (16:1819873 G>A), RS1001173851 (16:1818346 C>T), RS1001194665 (16:1807636 T>C), RS1001364100 (16:1814740 T>C)

Disease associations

OMIM: gene MIM:138760 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0003258	Glyoxalase deficiency

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2261 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.92	Ki	1200	nM	CHEMBL1160349
5.47	Ki	3400	nM	CHEMBL1160350

PubChem BioAssay actives

2 with measured affinity, of 7 total; 2 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
2-amino-5-[[3-[(4-bromophenyl)-hydroxycarbamoyl]sulfanyl-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	74125: Inhibition constants obtained from using the enediol analogs as competitive inhibitors for the inhibition of the hydrolysis of S-D-lactoylglutathione by glyoxalase II	ki	1.2000	uM
2-amino-5-[[1-(carboxymethylamino)-3-[(4-chlorophenyl)-hydroxycarbamoyl]sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	74125: Inhibition constants obtained from using the enediol analogs as competitive inhibitors for the inhibition of the hydrolysis of S-D-lactoylglutathione by glyoxalase II	ki	3.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Smoke	decreases expression, increases abundance, increases expression	3
Troglitazone	decreases activity	2
Benzo(a)pyrene	decreases expression	2
Valproic Acid	affects expression, increases methylation	2
Aflatoxin B1	affects expression, decreases methylation	2
aristolochic acid I	increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
trichostatin A	affects expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	increases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Rosiglitazone	decreases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Carmustine	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	increases secretion, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diazinon	increases methylation	1
Ivermectin	decreases expression	1
Selenium	increases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5040687	Binding	Inhibition of recombinant human Glyoxalase-2 assessed as reduction of substrate level using S-D-lactoylglutathione as substrate by spectrophotometric method	1,2,4-Triazole-3-thione compounds with a 4-ethyl alkyl/aryl sulfide substituent are broad-spectrum metallo-β-lactamase inhibitors with re-sensitization activity. — Eur J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1TF	Abcam HeLa HAGH KO	Cancer cell line	Female
CVCL_SQ87	HAP1 HAGH (-) 1	Cancer cell line	Male
CVCL_SQ88	HAP1 HAGH (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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