ADH5

Summary

ADH5 (alcohol dehydrogenase 5 (class III), chi polypeptide, HGNC:253) is a protein-coding gene on chromosome 4q23, encoding Alcohol dehydrogenase class-3 (P11766). Catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione.

This gene encodes a member of the alcohol dehydrogenase family. Members of this family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. The encoded protein forms a homodimer. It has virtually no activity for ethanol oxidation, but exhibits high activity for oxidation of long-chain primary alcohols and for oxidation of S-hydroxymethyl-glutathione, a spontaneous adduct between formaldehyde and glutathione. This enzyme is an important component of cellular metabolism for the elimination of formaldehyde, a potent irritant and sensitizing agent that causes lacrymation, rhinitis, pharyngitis, and contact dermatitis. The human genome contains several non-transcribed pseudogenes related to this gene.

Source: NCBI Gene 128 — RefSeq curated summary.

At a glance

• Gene–disease (curated): AMED syndrome, digenic (Strong, GenCC)
• GWAS associations: 12
• Clinical variants (ClinVar): 53 total — 4 pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000671

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:253
Approved symbol	ADH5
Name	alcohol dehydrogenase 5 (class III), chi polypeptide
Location	4q23
Locus type	gene with protein product
Status	Approved
Aliases	ADH-3, ADHX, GSNOR
Ensembl gene	ENSG00000197894
Ensembl biotype	protein_coding
OMIM	103710
Entrez	128

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 11 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000296412, ENST00000502386, ENST00000502590, ENST00000503130, ENST00000505652, ENST00000507102, ENST00000508146, ENST00000508511, ENST00000512604, ENST00000512621, ENST00000512659, ENST00000512991, ENST00000626055, ENST00000885756, ENST00000885757, ENST00000885758, ENST00000885759, ENST00000885760, ENST00000885761, ENST00000929295, ENST00000929296

RefSeq mRNA: 1 — MANE Select: NM_000671 NM_000671

CCDS: CCDS47111

Canonical transcript exons

ENST00000296412 — 9 exons

Exon	Start	End
ENSE00001080651	99070978	99072441
ENSE00001134769	99072573	99072711
ENSE00003488268	99076704	99076923
ENSE00003491806	99085115	99085216
ENSE00003524132	99074914	99075049
ENSE00003608112	99081975	99082116
ENSE00003633866	99081365	99081452
ENSE00003790965	99076292	99076552
ENSE00003846062	99088689	99088788

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 99.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.5362 / max 1405.4008, expressed in 1808 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53245	47.2950	1808
53244	0.2412	88

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	99.26	gold quality
descending thoracic aorta	UBERON:0002345	99.14	gold quality
stromal cell of endometrium	CL:0002255	99.07	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.99	gold quality
lower esophagus	UBERON:0013473	98.96	gold quality
nephron tubule	UBERON:0001231	98.85	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.84	gold quality
thoracic aorta	UBERON:0001515	98.83	gold quality
corpus epididymis	UBERON:0004359	98.81	gold quality
ascending aorta	UBERON:0001496	98.80	gold quality
calcaneal tendon	UBERON:0003701	98.78	gold quality
aorta	UBERON:0000947	98.76	gold quality
popliteal artery	UBERON:0002250	98.71	gold quality
tibial artery	UBERON:0007610	98.71	gold quality
artery	UBERON:0001637	98.63	gold quality
ventricular zone	UBERON:0003053	98.60	gold quality
rectum	UBERON:0001052	98.58	gold quality
cauda epididymis	UBERON:0004360	98.58	gold quality
ganglionic eminence	UBERON:0004023	98.46	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.46	gold quality
caput epididymis	UBERON:0004358	98.32	gold quality
transverse colon	UBERON:0001157	98.31	gold quality
right coronary artery	UBERON:0001625	98.30	gold quality
smooth muscle tissue	UBERON:0001135	98.28	gold quality
sigmoid colon	UBERON:0001159	98.28	gold quality
left coronary artery	UBERON:0001626	98.25	gold quality
embryo	UBERON:0000922	98.20	gold quality
body of uterus	UBERON:0009853	98.18	gold quality
colon	UBERON:0001155	98.16	gold quality
germinal epithelium of ovary	UBERON:0001304	98.16	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-10290	no	457.15
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RARB, SP1, SP3, SP4, ZBTB7A

miRNA regulators (miRDB)

97 targeting ADH5, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509

Literature-anchored findings (GeneRIF, showing 29)

• POZ domain of FBI1 represses transcription of ADH5. (PMID:12004059)
• The structural determination of apo, binary alcohol, and inhibitory ternary FDH complexes provides new insight into the enzyme’s metal-assisted catalysis and substrate-binding properties. (PMID:12196016)
• Formation of a FDH-S-(hydroxymethyl)glutathione-NADH ternary complex causes movement of glutathione-dependent formaldehyde dehydrogenase catalytic domain toward the coenzyme-binding domain, and a change in active-site zinc coordination. (PMID:12484756)
• No evidence that alcohol dehydrogenase 3genotype modifies risk related to alcohol and lung cancer. (PMID:14608084)
• data suggest that genetic variation in S-nitrosoglutathione reductase (GSNOR) might play a role in asthma susceptibility (PMID:17543375)
• A statistically significant increase of class III alcohol dehydrogenase isoenzymes was found in the sera of pancreatic cancer patients. (PMID:18095160)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• GSNOR inhibitors to be novel tools for regulating nitric oxide bioactivity and assessing the role of SNOs in vivo. (PMID:19596685)
• Significant associations were found however, for reactions to alcohol with a SNP in ADH5 (rs6827292, p = .001) and a SNP just upstream of ADH5 (rs6819724, p = .0007) that is in strong LD with rs6827292. (PMID:20158305)
• Data suggest that GSNOR deficiency, through dysregulated S-nitrosylation, may promote hepatocellular carcinoma, possibly by inactivating a DNA repair system. (PMID:20371487)
• biological significance of SNPs rs11568816, rs17028487 and rs13832 (PMID:21920416)
• N6022 binds in the GSNO binding pocket like a competitive inhibitor, although in kinetic assays it behaves with a mixed uncompetitive mode of inhibition (MOI) toward GSNO and a mixed competitive MOI toward formaldehyde adduct S-hydroxymethylglutathione. (PMID:22335564)
• A decrease in ADH IB, rather than GSNOR, correlates with human lung cancer. (PMID:23285246)
• study compared individuals occupationally exposed to formaldehyde and controls to effects of XRCC3 Thr241Met, ADH5 Val309Ile and Asp353Glu polymorphisms; ADH5 polymorphisms did not show significant association with genotoxicity biomarkers (PMID:23355119)
• common ADH variants conferred risk for both schizophrenia in African-Americans and autism in European-Americans. (PMID:23468174)
• ADH5 counteracts neuronal differentiation of neural stem cells and this effect can be reversed by pharmacological inhibition of ADH5. (PMID:24895131)
• GSNOR expression has different effect on neuronal viability in dependence on the stimulus applied, and plays opposite roles in SH-SY5Y models of Parkinson’s disease and amyotrophic lateral sclerosis (PMID:26491229)
• It was concluded that in HepG2 cells, ADH5 is a source of formate for de novo purine biosynthesis, especially during folate deficiency when folate-dependent formate production is limited. (PMID:28228507)
• GSNOR represents the prototype enzyme to disclose how denitrosylation plays a crucial role in tuning NO-bioactivity and how much it deeply impacts on cell homeostasis and human pathophysiology. (Review) (PMID:28533171)
• Data (including data from studies using knockout and transgenic mice) suggest that obesity and diabetes are accompanied by decreases in GSNOR activity in hepatocytes engendering nitrosative stress; obesity promotes S-nitrosylation of lysosomal proteins in liver, thereby impairing lysosomal enzyme activities and compromising autophagy. (PMID:29074597)
• We demonstrated for the first time that rs1154402C>G change in in intron 1 of ADH5 might create a silencer, repressing ADH1A transcription via long-range interaction with ADH1A promoter (PMID:29248712)
• Our data indicates that nebivolol has no effect on GSNOR activity, nor does nebivolol inhibit thioredoxin reductase, two of the major protein denitrosylases. (PMID:30188599)
• nNOS/GSNOR interaction contributes to skeletal muscle differentiation and homeostasis in humans and mice. (PMID:31043586)
• Mitophagy contributes to alpha-tocopheryl succinate toxicity in GSNOR-deficient hepatocellular carcinoma. (PMID:32112881)
• Two Aldehyde Clearance Systems Are Essential to Prevent Lethal Formaldehyde Accumulation in Mice and Humans. (PMID:33147438)
• Analysis of disease model iPSCs derived from patients with a novel Fanconi anemia-like IBMFS ADH5/ALDH2 deficiency. (PMID:33512438)
• [Aldehyde degradation deficiency (ADD) syndrome: discovery of a novel fanconi anemia-like inherited BMF syndrome due to combined ADH5/ALDH2 deficiency]. (PMID:34219079)
• GSNOR deficiency promotes tumor growth via FAK1 S-nitrosylation. (PMID:36656716)
• Effects of the major formaldehyde catalyzer ADH5 on phenotypes of fanconi anemia zebrafish model. (PMID:37615925)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	adh8b	ENSDARG00000024278
danio_rerio	adh5l	ENSDARG00000087262
danio_rerio	zgc:77938	ENSDARG00000088366
danio_rerio	adh8a	ENSDARG00000091211
mus_musculus	Adh5	ENSMUSG00000028138
rattus_norvegicus	Adh5	ENSRNOG00000089438
drosophila_melanogaster	Drat	FBGN0033188
caenorhabditis_elegans		WBGENE00010790
caenorhabditis_elegans		WBGENE00010791
caenorhabditis_elegans		WBGENE00014096
caenorhabditis_elegans		WBGENE00017060

Paralogs (17): PTGR1 (ENSG00000106853), VAT1 (ENSG00000108828), TP53I3 (ENSG00000115129), MECR (ENSG00000116353), CRYZ (ENSG00000116791), RTN4IP1 (ENSG00000130347), PTGR2 (ENSG00000140043), SORD (ENSG00000140263), VAT1L (ENSG00000171724), ADH6 (ENSG00000172955), PTGR3 (ENSG00000180011), ADH1A (ENSG00000187758), ADH7 (ENSG00000196344), ADH1B (ENSG00000196616), ADH4 (ENSG00000198099), CRYZL1 (ENSG00000205758), ADH1C (ENSG00000248144)

Protein

Protein identifiers

Alcohol dehydrogenase class-3 — P11766 (reviewed: P11766)

Alternative names: Alcohol dehydrogenase 5, Alcohol dehydrogenase class chi chain, Alcohol dehydrogenase class-III, Glutathione-dependent formaldehyde dehydrogenase, S-(hydroxymethyl)glutathione dehydrogenase

All UniProt accessions (6): D6R9G2, D6RAY0, D6RFE4, P11766, H0YAG8, Q6IRT1

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione. Also oxidizes long chain omega-hydroxy fatty acids, such as 20-HETE, producing both the intermediate aldehyde, 20-oxoarachidonate and the end product, a dicarboxylic acid, (5Z,8Z,11Z,14Z)-eicosatetraenedioate. Class-III ADH is remarkably ineffective in oxidizing ethanol. Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage. Also acts as a S-nitroso-glutathione reductase by catalyzing the NADH-dependent reduction of S-nitrosoglutathione, thereby regulating protein S-nitrosylation.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Disease relevance. AMED syndrome, digenic (AMEDS) [MIM:619151] A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. AMEDS is an autosomal recessive, digenic form characterized by childhood onset of bone marrow failure resulting in aplastic anemia, in association with global developmental delay, intellectual disability, and poor overall growth with short stature. The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. AMEDS patients carry ADH5 biallelic variants and homozygous or heterozygous ALDH2 variant p.Glu504Lys, affecting protein activity. Cellular and animal studies demonstrate that the simultaneous loss of ALDH2 and ADH5 activities leads to an increase of cellular formaldehyde sensitivity and multisystem abnormalities including hematopoietic failure.

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

Miscellaneous. There are 7 different ADH’s isozymes in human: three belongs to class-I: alpha, beta, and gamma, one to class-II: pi, one to class-III: chi, one to class-IV: ADH7 and one to class-V: ADH6.

Similarity. Belongs to the zinc-containing alcohol dehydrogenase family. Class-III subfamily.

RefSeq proteins (1): NP_000662* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002328	ADH_Zn_CS	Conserved_site
IPR011032	GroES-like_sf	Homologous_superfamily
IPR013149	ADH-like_C	Domain
IPR013154	ADH-like_N	Domain
IPR014183	ADH_3	Family
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF00107, PF08240

Catalyzed reactions (Rhea), 7 shown:

• a primary alcohol + NAD(+) = an aldehyde + NADH + H(+) (RHEA:10736)
• a secondary alcohol + NAD(+) = a ketone + NADH + H(+) (RHEA:10740)
• S-(hydroxymethyl)glutathione + NADP(+) = S-formylglutathione + NADPH + H(+) (RHEA:19981)
• S-(hydroxymethyl)glutathione + NAD(+) = S-formylglutathione + NADH + H(+) (RHEA:19985)
• 20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + NAD(+) = 20-oxo-(5Z,8Z,11Z,14Z)-eicosatetraenoate + NADH + H(+) (RHEA:39799)
• 20-oxo-(5Z,8Z,11Z,14Z)-eicosatetraenoate + NAD(+) + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenedioate + NADH + 2 H(+) (RHEA:39803)
• S-nitrosoglutathione + NADH + H(+) = S-(hydroxysulfenamide)glutathione + NAD(+) (RHEA:78371)

UniProt features (65 total): strand 20, helix 19, binding site 7, modified residue 6, sequence variant 4, turn 3, sequence conflict 2, initiator methionine 1, chain 1, mutagenesis site 1, site 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
2FZW	X-RAY DIFFRACTION	1.84
2FZE	X-RAY DIFFRACTION	1.9
3QJ5	X-RAY DIFFRACTION	1.9
1M6H	X-RAY DIFFRACTION	2
1MP0	X-RAY DIFFRACTION	2.2
1M6W	X-RAY DIFFRACTION	2.3
1MA0	X-RAY DIFFRACTION	2.3
1MC5	X-RAY DIFFRACTION	2.6
1TEH	X-RAY DIFFRACTION	2.7
8GV3	ELECTRON MICROSCOPY	3.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11766-F1	98.13	0.99

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): 115 (important for fdh activity and activation by fatty acids)

Ligand- & substrate-binding residues (7): 45; 67; 97; 100; 103; 111; 174

Post-translational modifications (6): 2, 233, 247, 315, 324, 351

Mutagenesis-validated functional residues (1):

Position	Phenotype
115	loss of fdh activity and loss of activation by fatty acids.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-71384	Ethanol oxidation
R-HSA-1430728	Metabolism
R-HSA-211859	Biological oxidations
R-HSA-211945	Phase I - Functionalization of compounds

MSigDB gene sets: 259 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_LIPID_MODIFICATION, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, MORF_ATRX, GOBP_ALDEHYDE_CATABOLIC_PROCESS, GOBP_RESPIRATORY_SYSTEM_PROCESS, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, RODWELL_AGING_KIDNEY_NO_BLOOD_DN

GO Biological Process (10): retinoid metabolic process (GO:0001523), respiratory system process (GO:0003016), fatty acid omega-oxidation (GO:0010430), response to lipopolysaccharide (GO:0032496), positive regulation of blood pressure (GO:0045777), formaldehyde catabolic process (GO:0046294), response to nitrosative stress (GO:0051409), response to redox state (GO:0051775), lipid metabolic process (GO:0006629), small molecule metabolic process (GO:0044281)

GO Molecular Function (12): alcohol dehydrogenase (NAD+) activity (GO:0004022), fatty acid binding (GO:0005504), zinc ion binding (GO:0008270), electron transfer activity (GO:0009055), formaldehyde dehydrogenase (NAD+) activity (GO:0018467), identical protein binding (GO:0042802), S-(hydroxymethyl)glutathione dehydrogenase [NAD(P)+] activity (GO:0051903), S-nitrosoglutathione reductase (NADH) activity (GO:0080007), S-(hydroxymethyl)glutathione dehydrogenase (NADP+) activity (GO:0106321), S-(hydroxymethyl)glutathione dehydrogenase (NAD+) activity (GO:0106322), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872)

GO Cellular Component (4): mitochondrion (GO:0005739), cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Phase I - Functionalization of compounds	1
Metabolism	1
Biological oxidations	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	2
S-(hydroxymethyl)glutathione dehydrogenase [NAD(P)+] activity	2
cytoplasm	2
cellular anatomical structure	2
diterpenoid metabolic process	1
system process	1
respiratory gaseous exchange by respiratory system	1
fatty acid oxidation	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
regulation of blood pressure	1
small molecule catabolic process	1
aldehyde catabolic process	1
formaldehyde metabolic process	1
cellular detoxification of aldehyde	1
response to stress	1
response to stimulus	1
primary metabolic process	1
metabolic process	1
alcohol dehydrogenase [NAD(P)+] activity	1
lipid binding	1
monocarboxylic acid binding	1
transition metal ion binding	1
molecular_function	1
aldehyde dehydrogenase (NAD+) activity	1
protein binding	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2032 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADH5	AVP	P01185	917
ADH5	ALDH2	P05091	877
ADH5	ESD	P10768	847
ADH5	CES5A	Q6NT32	754
ADH5	CES2	O00748	694
ADH5	NOS1	P29475	694
ADH5	ALDH1A1	P00352	653
ADH5	MANBA	O00462	648
ADH5	HAGH	Q16775	614
ADH5	TXN	P10599	593
ADH5	CES3	Q6UWW8	581
ADH5	FABP2	P12104	559
ADH5	KDM4E	B2RXH2	555
ADH5	LDHAL6A	Q6ZMR3	545
ADH5	ALDH1B1	P30837	539

IntAct

22 interactions, top by confidence:

A	B	Type	Score
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
ADH5	POTEF	psi-mi:“MI:0915”(physical association)	0.400
ADH5	ARNT	psi-mi:“MI:0915”(physical association)	0.370
ESRRA	ADH5	psi-mi:“MI:0915”(physical association)	0.370
PRDX1	ADH5	psi-mi:“MI:0915”(physical association)	0.370
ADH5	VTN	psi-mi:“MI:0915”(physical association)	0.370
ADH5	SLC66A2	psi-mi:“MI:0915”(physical association)	0.370
ADH5	ADH5	psi-mi:“MI:0915”(physical association)	0.370
ADH5	CSNK2B	psi-mi:“MI:0915”(physical association)	0.370
PTPN4	GOLIM4	psi-mi:“MI:0914”(association)	0.350
KEAP1	ASNS	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
HDAC1	KPNA3	psi-mi:“MI:0914”(association)	0.350
U2AF1	MED19	psi-mi:“MI:2364”(proximity)	0.270
ZNF800	MED19	psi-mi:“MI:2364”(proximity)	0.270
CLU	ADH5	psi-mi:“MI:0915”(physical association)	0.000
ADH5	CHD3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (72): ADH5 (Co-fractionation), ADH5 (Co-fractionation), ALDH4A1 (Co-fractionation), ESD (Co-fractionation), ADH5 (Affinity Capture-MS), ADH5 (Affinity Capture-Western), ADH5 (Affinity Capture-MS), ADH5 (Proximity Label-MS), CHD3 (Two-hybrid), ADH5 (Proximity Label-MS), ADH5 (Proximity Label-MS), ADH5 (Proximity Label-MS), ADH5 (Proximity Label-MS), ADH5 (Proximity Label-MS), ADH5 (Co-crystal Structure)

ESM2 similar proteins: A2XAZ3, O19053, O74685, O97959, P00325, P00326, P00327, P00328, P00329, P06757, P07327, P11766, P12711, P14139, P19631, P19854, P22797, P23991, P25405, P25406, P28469, P28474, P41680, P41682, P46415, P49645, P79896, P80222, P80338, P80360, P80467, P80512, P80572, P81431, P81600, P81601, P86884, P86885, P93629, Q03505

Diamond homologs: A0A0C5DM37, A0A2I7G3B2, A0A2I7G3B3, A0A2U1Q018, A1A835, A1L4Y2, A2XAZ3, A7ZIA4, A7ZX04, B1J085, B1LIP1, O19053, O74540, O74685, O97959, P00325, P00327, P00329, P00333, P04707, P05336, P06525, P06757, P0CL53, P10847, P10848, P11766, P12711, P12886, P13603, P14219, P14673, P14674, P14675, P17648, P19631, P19854, P22797, P23991, P25141

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	31
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
4277919	NM_000671.4(ADH5):c.114+1G>A	Pathogenic
995825	NM_000671.4(ADH5):c.966del (p.Gly321_Trp322insTer)	Pathogenic
995826	NM_000671.4(ADH5):c.564+1G>A	Pathogenic
995827	NM_000671.4(ADH5):c.832G>C (p.Ala278Pro)	Pathogenic

SpliceAI

1440 predictions. Top by Δscore:

Variant	Effect	Δscore
4:99072709:ATCC:A	acceptor_loss	1.0000
4:99072711:CCTAA:C	acceptor_loss	1.0000
4:99072712:C:CA	acceptor_loss	1.0000
4:99072712:C:CC	acceptor_gain	1.0000
4:99072713:T:C	acceptor_loss	1.0000
4:99074909:ATTAC:A	donor_loss	1.0000
4:99074910:TTACC:T	donor_loss	1.0000
4:99074911:TAC:T	donor_loss	1.0000
4:99074912:A:C	donor_loss	1.0000
4:99074913:CCTCC:C	donor_loss	1.0000
4:99076284:ATAC:A	donor_loss	1.0000
4:99076285:TACT:T	donor_loss	1.0000
4:99076288:TCAC:T	donor_loss	1.0000
4:99076289:C:CG	donor_loss	1.0000
4:99076290:A:AC	donor_gain	1.0000
4:99076291:C:CC	donor_gain	1.0000
4:99076698:TCTTA:T	donor_loss	1.0000
4:99076699:CTTAC:C	donor_loss	1.0000
4:99076700:TTACC:T	donor_loss	1.0000
4:99076701:TACCT:T	donor_loss	1.0000
4:99076702:ACCTT:A	donor_loss	1.0000
4:99076919:TGACT:T	acceptor_gain	1.0000
4:99076920:GACT:G	acceptor_gain	1.0000
4:99076922:CT:C	acceptor_gain	1.0000
4:99076923:TC:T	acceptor_loss	1.0000
4:99076924:C:CC	acceptor_gain	1.0000
4:99076925:T:A	acceptor_loss	1.0000
4:99081360:CTAA:C	donor_loss	1.0000
4:99081361:TAA:T	donor_loss	1.0000
4:99081362:AAC:A	donor_loss	1.0000

AlphaMissense

2439 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:99076836:G:C	S144R	0.999
4:99076836:G:T	S144R	0.999
4:99076838:T:G	S144R	0.999
4:99081378:A:G	C111R	0.999
4:99081443:A:T	V89D	0.999
4:99082098:A:G	C45R	0.999
4:99074916:C:T	G320E	0.998
4:99075008:G:C	S289R	0.998
4:99075008:G:T	S289R	0.998
4:99075010:T:G	S289R	0.998
4:99076313:A:C	C268W	0.998
4:99076816:A:T	V151D	0.998
4:99076837:C:A	S144I	0.998
4:99081377:C:G	C111S	0.998
4:99081378:A:T	C111S	0.998
4:99082028:T:A	E68V	0.998
4:99082034:C:T	G66E	0.998
4:99082089:C:G	D48H	0.998
4:99082091:G:A	T47I	0.998
4:99082096:G:C	C45W	0.998
4:99082097:C:T	C45Y	0.998
4:99085122:C:G	R36P	0.998
4:99085125:A:T	V35D	0.998
4:99085194:A:T	V12D	0.998
4:99074935:A:G	W314R	0.997
4:99074935:A:T	W314R	0.997
4:99074940:C:G	R312P	0.997
4:99075029:A:C	C282W	0.997
4:99081376:G:C	C111W	0.997
4:99081377:C:T	C111Y	0.997

dbSNP variants (sampled 300 via entrez): RS1000110361 (4:99083370 C>A,T), RS1000272646 (4:99088927 C>G), RS1000646028 (4:99088821 T>C), RS1000838146 (4:99078841 G>A), RS1000876694 (4:99078181 T>C), RS1000947165 (4:99085463 T>C), RS1000996302 (4:99084262 G>C), RS1001110756 (4:99084510 G>A), RS1001122674 (4:99072142 A>C), RS1001245163 (4:99077864 A>C), RS1001347586 (4:99076666 T>C,G), RS1001477709 (4:99072237 G>A), RS1001568899 (4:99083579 G>A), RS1001600067 (4:99083851 A>C), RS1001773321 (4:99089467 C>T)

Disease associations

OMIM: gene MIM:103710 | disease phenotypes: MIM:619151

GenCC curated gene-disease

Disease	Classification	Inheritance
AMED syndrome, digenic	Strong	Autosomal recessive

Mondo (1): AMED syndrome, digenic (MONDO:0030894)

Orphanet (1): Aplastic anemia-intellectual disability-dwarfism syndrome (Orphanet:611216)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000013	Hypoplasia of the uterus
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000506	Telecanthus
HP:0000729	Autistic behavior
HP:0000835	Adrenal hypoplasia
HP:0000953	Hyperpigmentation of the skin
HP:0001249	Intellectual disability
HP:0001508	Failure to thrive
HP:0001873	Thrombocytopenia
HP:0001882	Decreased total leukocyte count
HP:0001903	Anemia
HP:0002863	Myelodysplasia
HP:0004322	Short stature
HP:0004808	Acute myeloid leukemia
HP:0005301	Persistent left superior vena cava
HP:0005528	Bone marrow hypocellularity
HP:0007018	Attention deficit hyperactivity disorder
HP:0010984	Digenic inheritance
HP:0032524	Long thumb
HP:0033044	Motor regression

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001762_291	Obesity-related traits	9.000000e-06
GCST001883_1	Alcohol dependence	3.000000e-21
GCST002223_8	HDL cholesterol	5.000000e-08
GCST002899_7	HDL cholesterol	1.000000e-08
GCST004232_83	HDL cholesterol levels	7.000000e-07
GCST004886_10	Alcohol consumption	1.000000e-09
GCST004886_17	Alcohol consumption	1.000000e-18
GCST004886_4	Alcohol consumption	1.000000e-10
GCST004887_4	Alcohol consumption in current drinkers	1.000000e-16
GCST006585_922	Blood protein levels	2.000000e-25
GCST006921_3	Regular attendance at a pub or social club	4.000000e-25
GCST90002400_434	Plateletcrit	4.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0003939	energy intake
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009592	social interaction measurement
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2096668 (PROTEIN FAMILY), CHEMBL4116 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 117 (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
CHEMBL1738699	N6022	3	117

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

Binding affinities (BindingDB)

43 measured of 43 human assays (43 total across all organisms); most potent 43 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(6R)-6-(3-ethoxy-4-hydroxy-5-nitrophenyl)-4,5-diphenyl-5,6-dihydro-1H-pyrimidin-2-one	IC50	11 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
(4S)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5,6-diphenyl-3,4-dihydro-1H-pyrimidin-2-one	IC50	11 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
3-ethoxy-2-hydroxy-5-[(6R)-4-(1-methylpyrazol-4-yl)-2-oxo-5-thiophen-3-yl-5,6-dihydro-1H-pyrimidin-6-yl]benzoic acid	IC50	13 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
3-ethoxy-2-hydroxy-5-[6-(1-methylpyrazol-4-yl)-2-oxo-5-thiophen-3-yl-1,3-diazinan-4-yl]benzoic acid	IC50	13 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
US8741915, 144	IC50	16 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
(4S)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-pyridin-3-yl-5-thiophen-3-yl-3,4-dihydro-1H-pyrimidin-2-one	IC50	16 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
(6R)-6-(3-ethoxy-4-hydroxy-5-nitrophenyl)-4-phenyl-5-thiophen-3-yl-5,6-dihydro-1H-pyrimidin-2-one	IC50	18 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
(4S)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-phenyl-5-thiophen-3-yl-3,4-dihydro-1H-pyrimidin-2-one	IC50	18 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
6-(3-ethoxy-4-hydroxy-5-nitrophenyl)-4-phenyl-5-thiophen-3-yl-5,6-dihydro-1H-pyrimidin-2-one	IC50	19 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-phenyl-5-thiophen-3-yl-3,4-dihydro-1H-pyrimidin-2-one	IC50	19 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
2-hydroxy-4-[(6R)-4-(1-methylpyrazol-4-yl)-2-oxo-5-thiophen-3-yl-5,6-dihydro-1H-pyrimidin-6-yl]benzoic acid	IC50	23 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
2-hydroxy-4-[6-(1-methylpyrazol-4-yl)-2-oxo-5-thiophen-3-yl-1,3-diazinan-4-yl]benzoic acid	IC50	23 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
6-(3-ethoxy-4-hydroxy-5-nitrophenyl)-4-pyridin-3-yl-5-thiophen-3-yl-5,6-dihydro-1H-pyrimidin-2-one	IC50	24 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-pyridin-3-yl-5-thiophen-3-yl-3,4-dihydro-1H-pyrimidin-2-one	IC50	24 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
3-ethoxy-2-hydroxy-5-[4-(1-methylpyrazol-4-yl)-2-oxo-5-thiophen-3-yl-5,6-dihydro-1H-pyrimidin-6-yl]benzoic acid	IC50	27 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
(6R)-6-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5-phenyl-4-pyridin-3-yl-5,6-dihydro-1H-pyrimidin-2-one	IC50	28 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
(4S)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5-phenyl-6-pyridin-3-yl-3,4-dihydro-1H-pyrimidin-2-one	IC50	28 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
6-(3-ethoxy-4-hydroxy-5-nitrophenyl)-4,5-diphenyl-5,6-dihydro-1H-pyrimidin-2-one	IC50	29 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5,6-diphenyl-3,4-dihydro-1H-pyrimidin-2-one	IC50	29 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
US8741915, 148	IC50	35 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
(4S)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-(1-methylpyrazol-3-yl)-5-thiophen-3-yl-3,4-dihydro-1H-pyrimidin-2-one	IC50	35 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
2-hydroxy-4-[4-(1-methylpyrazol-3-yl)-2-oxo-5-thiophen-3-yl-5,6-dihydro-1H-pyrimidin-6-yl]benzoic acid	IC50	39 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
6-(3-ethoxy-4-hydroxy-5-nitrophenyl)-4-(1-methylpyrazol-3-yl)-5-thiophen-3-yl-5,6-dihydro-1H-pyrimidin-2-one	IC50	40 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-(1-methylpyrazol-3-yl)-5-thiophen-3-yl-3,4-dihydro-1H-pyrimidin-2-one	IC50	40 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
6-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5-phenyl-4-pyridin-3-yl-5,6-dihydro-1H-pyrimidin-2-one	IC50	43 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5-phenyl-6-pyridin-3-yl-3,4-dihydro-1H-pyrimidin-2-one	IC50	43 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
3-ethoxy-2-hydroxy-5-[(6R)-2-oxo-4-pyridin-3-yl-5-thiophen-3-yl-5,6-dihydro-1H-pyrimidin-6-yl]benzoic acid	IC50	67 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
3-ethoxy-2-hydroxy-5-[(4R)-2-oxo-6-pyridin-3-yl-5-thiophen-3-yl-1,3-diazinan-4-yl]benzoic acid	IC50	67 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
3-ethoxy-2-hydroxy-5-(2-oxo-4-pyridin-3-yl-5-thiophen-3-yl-5,6-dihydro-1H-pyrimidin-6-yl)benzoic acid	IC50	150 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
3-ethoxy-2-hydroxy-5-(2-oxo-6-pyridin-3-yl-5-thiophen-3-yl-1,3-diazinan-4-yl)benzoic acid	IC50	150 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
3-ethoxy-2-hydroxy-5-[(6S)-4-(1-methylpyrazol-4-yl)-2-oxo-5-thiophen-3-yl-5,6-dihydro-1H-pyrimidin-6-yl]benzoic acid	IC50	580 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
(6S)-6-(3-ethoxy-4-hydroxy-5-nitrophenyl)-4-phenyl-5-thiophen-3-yl-5,6-dihydro-1H-pyrimidin-2-one	IC50	1820 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
(4R)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-phenyl-5-thiophen-3-yl-3,4-dihydro-1H-pyrimidin-2-one	IC50	1820 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
(4R)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-pyridin-3-yl-5-thiophen-3-yl-3,4-dihydro-1H-pyrimidin-2-one	IC50	1900 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
3-ethoxy-2-hydroxy-5-[(6S)-2-oxo-4-pyridin-3-yl-5-thiophen-3-yl-5,6-dihydro-1H-pyrimidin-6-yl]benzoic acid	IC50	3170 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
3-ethoxy-2-hydroxy-5-[(4S)-2-oxo-6-pyridin-3-yl-5-thiophen-3-yl-1,3-diazinan-4-yl]benzoic acid	IC50	3170 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
2-hydroxy-4-[(6S)-4-(1-methylpyrazol-4-yl)-2-oxo-5-thiophen-3-yl-5,6-dihydro-1H-pyrimidin-6-yl]benzoic acid	IC50	4250 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
(6S)-6-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5-phenyl-4-pyridin-3-yl-5,6-dihydro-1H-pyrimidin-2-one	IC50	6020 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
(4R)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5-phenyl-6-pyridin-3-yl-3,4-dihydro-1H-pyrimidin-2-one	IC50	6020 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
(6S)-6-(3-ethoxy-4-hydroxy-5-nitrophenyl)-4,5-diphenyl-5,6-dihydro-1H-pyrimidin-2-one	IC50	19700 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
(4R)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5,6-diphenyl-3,4-dihydro-1H-pyrimidin-2-one	IC50	19700 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
(6S)-6-(3-ethoxy-4-hydroxy-5-nitrophenyl)-4-(1-methylpyrazol-3-yl)-5-thiophen-3-yl-5,6-dihydro-1H-pyrimidin-2-one	IC50	31000 nM	US-8741915: Dihydropyrimidin-2(1H)-one compounds as S-nitrosoglutathione reductase inhibitors
(4R)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-(1-methylpyrazol-3-yl)-5-thiophen-3-yl-3,4-dihydro-1H-pyrimidin-2-one	IC50	31000 nM	US-8906933: Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists

ChEMBL bioactivities

85 potent at pChembl≥5 of 89 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.21	IC50	6.1	nM	CHEMBL4291042
8.04	IC50	9.2	nM	CHEMBL4290485
7.96	IC50	11	nM	CHEMBL3650413
7.96	IC50	11	nM	CHEMBL3661058
7.96	IC50	11	nM	CHEMBL4289979
7.92	IC50	12	nM	CHEMBL4294439
7.89	IC50	13	nM	CHEMBL3650428
7.89	IC50	13	nM	CHEMBL3661051
7.85	IC50	14	nM	CHEMBL4283184
7.85	IC50	14	nM	CHEMBL4289333
7.80	IC50	16	nM	CHEMBL3650426
7.80	IC50	16	nM	CHEMBL3661050
7.77	IC50	17	nM	CHEMBL4286132
7.75	IC50	18	nM	CHEMBL3650415
7.75	IC50	18	nM	CHEMBL3661059
7.72	IC50	19	nM	CHEMBL3650420
7.72	IC50	19	nM	CHEMBL3661042
7.70	IC50	20	nM	N6022
7.70	IC50	20	nM	CHEMBL4287066
7.70	IC50	20	nM	CHEMBL4283157
7.70	IC50	20	nM	CHEMBL4278220
7.66	IC50	22	nM	CHEMBL4290516
7.66	IC50	22	nM	CHEMBL4277254
7.64	IC50	23	nM	CHEMBL3650432
7.64	IC50	23	nM	CHEMBL3661057
7.62	IC50	24	nM	CHEMBL3650425
7.62	IC50	24	nM	CHEMBL3661044
7.62	IC50	24	nM	CHEMBL4286551
7.58	IC50	26	nM	CHEMBL4279145
7.57	IC50	27	nM	CHEMBL3650428
7.57	IC50	27	nM	CHEMBL3661049
7.57	IC50	27	nM	CHEMBL4281451
7.55	IC50	28	nM	CHEMBL3650417
7.55	IC50	28	nM	CHEMBL3661061
7.54	IC50	29	nM	CHEMBL3650419
7.54	IC50	29	nM	CHEMBL3661041
7.54	IC50	29	nM	CHEMBL4282722
7.54	IC50	29	nM	CHEMBL4285078
7.52	IC50	30	nM	CHEMBL4292916
7.50	IC50	32	nM	CHEMBL4279294
7.46	IC50	35	nM	CHEMBL3650430
7.46	IC50	35	nM	CHEMBL3661053
7.44	IC50	36	nM	CHEMBL4283715
7.43	IC50	37	nM	CHEMBL4282612
7.42	IC50	38	nM	CHEMBL4281650
7.41	IC50	39	nM	CHEMBL3650432
7.41	IC50	39	nM	CHEMBL3661055
7.41	IC50	39	nM	CHEMBL4285208
7.40	IC50	40	nM	CHEMBL3650429
7.40	IC50	40	nM	CHEMBL3661045

PubChem BioAssay actives

40 with measured affinity, of 84 total; 40 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-[4-(2-ethyl-4-imidazol-1-ylphenyl)phenyl]-2H-tetrazole	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0061	uM
5-[3-chloro-4-(4-imidazol-1-ylphenyl)phenyl]-2H-tetrazole	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0092	uM
5-[4-(2-ethyl-4-imidazol-1-ylphenyl)-3-fluorophenyl]-2H-tetrazole	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0110	uM
5-[3-chloro-4-(4-imidazol-1-yl-2-methylphenyl)phenyl]-2H-tetrazole	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0120	uM
5-[4-(4-imidazol-1-yl-2-methylphenyl)phenyl]-2H-tetrazole	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0140	uM
2-[2-fluoro-4-(2H-tetrazol-5-yl)phenyl]-5-imidazol-1-yl-3-methylpyridine	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0140	uM
5-imidazol-1-yl-3-methyl-2-[4-(2H-tetrazol-5-yl)phenyl]pyridine	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0170	uM
4-(4-imidazol-1-yl-2-methylphenyl)benzoic acid	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0200	uM
3-chloro-5-imidazol-1-yl-2-[4-(2H-tetrazol-5-yl)phenyl]pyridine	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0200	uM
5-[3-fluoro-4-(4-imidazol-1-ylphenyl)phenyl]-2H-tetrazole	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0200	uM
3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-imidazol-1-ylphenyl)pyrrol-2-yl]propanoic acid	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0200	uM
5-[4-(4-imidazol-1-ylphenyl)phenyl]-2H-tetrazole	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0220	uM
5-[4-(2-chloro-4-imidazol-1-ylphenyl)phenyl]-2H-tetrazole	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0220	uM
5-[4-[2-ethyl-4-(2-methylimidazol-1-yl)phenyl]phenyl]-2H-tetrazole	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0240	uM
5-[4-(4-imidazol-1-ylphenyl)-3-methylphenyl]-2H-tetrazole	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0260	uM
3-chloro-2-[2-fluoro-4-(2H-tetrazol-5-yl)phenyl]-5-imidazol-1-ylpyridine	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0270	uM
4-(4-imidazol-1-ylphenyl)-3-methylbenzoic acid	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0290	uM
3-fluoro-4-(4-imidazol-1-ylphenyl)benzoic acid	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0290	uM
3-chloro-4-(4-imidazol-1-ylphenyl)benzoic acid	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0300	uM
5-imidazol-1-yl-2-[4-(2H-tetrazol-5-yl)phenyl]pyridine	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0320	uM
3-fluoro-4-(5-imidazol-1-yl-3-methyl-2-pyridinyl)benzoic acid	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0360	uM
5-[3-chloro-4-[4-(2-methylimidazol-1-yl)phenyl]phenyl]-2H-tetrazole	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0370	uM
4-(4-imidazol-1-ylphenyl)-3-(trifluoromethyl)benzoic acid	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0380	uM
5-[4-(4-imidazol-1-ylphenyl)-3-(trifluoromethyl)phenyl]-2H-tetrazole	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0390	uM
4-(5-imidazol-1-yl-3-methyl-2-pyridinyl)benzoic acid	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0410	uM
5-imidazol-1-yl-2-[2-methyl-4-(2H-tetrazol-5-yl)phenyl]pyridine	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0440	uM
4-(2-chloro-4-imidazol-1-ylphenyl)benzoic acid	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0590	uM
4-(4-imidazol-1-ylphenyl)benzoic acid	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0620	uM
3-ethyl-2-[2-fluoro-4-(2H-tetrazol-5-yl)phenyl]-5-imidazol-1-ylpyridine	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0620	uM
3-ethyl-5-imidazol-1-yl-2-[4-(2H-tetrazol-5-yl)phenyl]pyridine	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0660	uM
3-cyclohexyl-5-imidazol-1-yl-2-[4-(2H-tetrazol-5-yl)phenyl]pyridine	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0740	uM
4-(3-chloro-5-imidazol-1-yl-2-pyridinyl)benzoic acid	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0890	uM
5-[4-[4-(2-methylimidazol-1-yl)phenyl]phenyl]-2H-tetrazole	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.0970	uM
3-[4-(4-imidazol-1-ylphenyl)phenyl]-4H-1,2,4-oxadiazol-5-one	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.1520	uM
4-(5-imidazol-1-yl-2-pyridinyl)benzoic acid	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.2140	uM
2-[2-chloro-4-(2H-tetrazol-5-yl)phenyl]-5-imidazol-1-ylpyridine	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.3080	uM
5-[3-chloro-4-[4-(1,2,4-triazol-4-yl)phenyl]phenyl]-2H-tetrazole	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.5930	uM
3-chloro-5-imidazol-1-yl-2-[2-methyl-4-(2H-tetrazol-5-yl)phenyl]pyridine	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	0.9350	uM
5-[4-[4-(2H-tetrazol-5-yl)phenyl]phenyl]-2H-tetrazole	1414305: Inhibition of human GSNOR assessed as reduction in NADH consumption after 3 mins by spectrophotometric analysis	ic50	3.2790	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147807: Binding affinity to human ADH5 incubated for 45 mins by Kinobead based pull down assay	kd	4.8886	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects expression	3
12-hydroxydodecanoic acid	affects binding, increases oxidation	3
Acetaminophen	decreases expression	3
Cadmium	decreases expression, decreases reaction, increases abundance, increases palmitoylation	2
Formaldehyde	increases metabolic processing, increases oxidation, increases reaction	2
Tretinoin	decreases expression, increases expression	2
S-Nitrosoglutathione	increases reduction, decreases reaction, increases oxidation, increases reaction	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
apocarotenal	increases expression	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	increases expression	1
pelargonic acid	decreases reaction, increases reduction	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
decabromobiphenyl ether	decreases expression	1
sebacic acid	increases reduction, decreases reaction	1
methylparaben	decreases expression	1
undecanoic acid	decreases reaction, increases reduction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
S-methyl glutathione	increases reduction, decreases reaction	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
potassium chromate(VI)	decreases expression	1
S-hydroxymethylglutathione	increases oxidation, decreases reaction	1
lauric acid	decreases reaction, increases reduction	1
decanoic acid	decreases reaction, increases reduction	1
octanoic acid	decreases reaction, increases reduction	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1

ChEMBL screening assays

19 unique, capped per target: 19 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3257323	Binding	Inhibition of alcohol dehydrogenase (unknown origin) assessed as dissociation constant for the complex of enzyme and DPNH	A manual method for applying the Hansch approach to drug design. — J Med Chem

Cellosaurus cell lines

11 cell lines: 4 induced pluripotent stem cell, 3 finite cell line, 3 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B5LY	AP57P	Finite cell line	Male
CVCL_B5LZ	AP57P(SVT)	Transformed cell line	Male
CVCL_B5M0	FA50P	Finite cell line	Female
CVCL_B5M1	FA50P-iPSC#1	Induced pluripotent stem cell	Female
CVCL_B5M2	AP39P-iPSC#1	Induced pluripotent stem cell	Female
CVCL_B5M3	FA50P-iPSC#2	Induced pluripotent stem cell	Female
CVCL_B5M4	AP39P-iPSC#2	Induced pluripotent stem cell	Female
CVCL_XD42	AP39P	Finite cell line	Female
CVCL_XD43	AP39P(SVT)	Transformed cell line	Female
CVCL_XD44	AP39P(L)	Transformed cell line	Female

Clinical trials (associated diseases)

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