ADH1A

Summary

ADH1A (alcohol dehydrogenase 1A (class I), alpha polypeptide, HGNC:249) is a protein-coding gene on chromosome 4q23, encoding Alcohol dehydrogenase 1A (P07327). Alcohol dehydrogenase.

This gene encodes a member of the alcohol dehydrogenase family. The encoded protein is the alpha subunit of class I alcohol dehydrogenase, which consists of several homo- and heterodimers of alpha, beta and gamma subunits. Alcohol dehydrogenases catalyze the oxidation of alcohols to aldehydes. This gene is active in the liver in early fetal life but only weakly active in adult liver. This gene is found in a cluster with six additional alcohol dehydrogenase genes, including those encoding the beta and gamma subunits, on the long arm of chromosome 4. Mutations in this gene may contribute to variation in certain personality traits and substance dependence.

Source: NCBI Gene 124 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 58 total — 4 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_000667

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:249
Approved symbol	ADH1A
Name	alcohol dehydrogenase 1A (class I), alpha polypeptide
Location	4q23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187758
Ensembl biotype	protein_coding
OMIM	103700
Entrez	124

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000209668, ENST00000503461, ENST00000511656, ENST00000908165, ENST00000908166, ENST00000908167, ENST00000908168, ENST00000908169, ENST00000908170, ENST00000908171, ENST00000908172, ENST00000908173, ENST00000908174, ENST00000908175, ENST00000908176, ENST00000908177, ENST00000908178

RefSeq mRNA: 1 — MANE Select: NM_000667 NM_000667

CCDS: CCDS3648

Canonical transcript exons

ENST00000209668 — 9 exons

Exon	Start	End
ENSE00001131569	99276369	99276648
ENSE00001388966	99290897	99290985
ENSE00002461263	99280144	99280279
ENSE00002483914	99284399	99284618
ENSE00002488520	99279426	99279564
ENSE00002492009	99284716	99284803
ENSE00002504155	99282346	99282606
ENSE00003570834	99286850	99286988
ENSE00003594736	99287564	99287665

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 98.86.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.0185 / max 1153.9673, expressed in 18 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53260	2.0185	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.86	gold quality
liver	UBERON:0002107	98.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.15	gold quality
mucosa of paranasal sinus	UBERON:0005030	82.48	silver quality
omental fat pad	UBERON:0010414	78.30	gold quality
peritoneum	UBERON:0002358	78.23	gold quality
adipose tissue of abdominal region	UBERON:0007808	77.04	gold quality
superficial temporal artery	UBERON:0001614	76.95	silver quality
descending thoracic aorta	UBERON:0002345	76.80	gold quality
gall bladder	UBERON:0002110	76.46	gold quality
right coronary artery	UBERON:0001625	76.41	gold quality
right lung	UBERON:0002167	75.46	gold quality
subcutaneous adipose tissue	UBERON:0002190	74.90	gold quality
left coronary artery	UBERON:0001626	74.79	gold quality
coronary artery	UBERON:0001621	74.58	gold quality
duodenum	UBERON:0002114	74.29	gold quality
vena cava	UBERON:0004087	74.21	silver quality
thoracic aorta	UBERON:0001515	73.70	gold quality
ascending aorta	UBERON:0001496	73.40	gold quality
hindlimb stylopod muscle	UBERON:0004252	73.27	gold quality
adipose tissue	UBERON:0001013	72.50	gold quality
mucosa of stomach	UBERON:0001199	72.50	gold quality
connective tissue	UBERON:0002384	71.30	gold quality
aorta	UBERON:0000947	71.21	gold quality
pancreatic ductal cell	CL:0002079	70.14	gold quality
right uterine tube	UBERON:0001302	69.77	gold quality
epithelial cell of pancreas	CL:0000083	69.72	silver quality
diaphragm	UBERON:0001103	69.53	gold quality
popliteal artery	UBERON:0002250	69.51	gold quality
tibial artery	UBERON:0007610	69.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	31.29
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, DBP, FOXA2, GATA2, HNF1A, TBP, USF1

miRNA regulators (miRDB)

19 targeting ADH1A, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-135A-2-3P	98.40	66.74	442
HSA-MIR-135B-3P	98.40	67.35	426
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-3943	95.87	64.57	523
HSA-MIR-5002-3P	95.75	67.04	542

Literature-anchored findings (GeneRIF, showing 16)

• Structural aspects that influence dimer-tetramer formation. (PMID:12081471)
• GATA-2 and HNF-3beta regulate the human alcohol dehydrogenase 1A (ADH1A) gene. (PMID:16153155)
• The oxidative pathway of ethanol metabolism via ADH and ALDH does not play a role in pancreatic carcinogenesis. (PMID:17632320)
• Alleles of ADH7 SNPs were associated with the early stages of alcohol metabolism, with additional effects in the ADH1A, ADH1B and ADH4 regions. (PMID:19193628)
• ADH1A variation predisposes to personality traits and substance dependence (PMID:19526455)
• High ADH1 is associated with endometrial cancer. (PMID:20872569)
• common ADH variants conferred risk for both schizophrenia in African-Americans and autism in European-Americans. (PMID:23468174)
• high levels of ADH1 transcription are implicated in fluconazole resistance in C. albicans and that the mRNA expression levels of ADH1 are positively correlated with those of CDR1, CDR2 and FLU1. (PMID:23769565)
• Unde-rexpression of the ADH1 gene, which influences the transformation of the extracellular matrix, plays a probable role in the etiology of uterine fibroid. (PMID:23891545)
• Data indicate that the up-regulation of aldehyde dehydrogenase-1 (ALDH1) after neoadjuvant chemotherapy (NAC) predicts poor survival in locally advanced breast cancer. (PMID:24762066)
• Results suggest a potential role of alcohol dehydrogenase (ADH) class I as a marker for renal cell carcinoma (RCC). (PMID:27086037)
• High ADH expression is associated with Prostate Cancer. (PMID:28870918)
• 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)
• The activity of total alcohol dehydrogenase (ADH) and class I isoenzymes in the sera of autoimmune hepatitis patients is increased and aldehyde dehydrogenase (ALDH) levels were unchanged. (PMID:29739065)
• Variation of ADH1A was significantly associated with blood acetaldehyde concentrations, which may contribute to slow alcohol metabolism and result in increased blood acetaldehyde levels in Korean subjects. (PMID:31002879)
• Contrary to consensus, oxidation of ethanol by human alcohol dehydrogenase (ADH) 1A is activated by ATP. (PMID:34742856)

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	Adh1	ENSMUSG00000074207
rattus_norvegicus	Adh1c	ENSRNOG00000012436
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), ADH7 (ENSG00000196344), ADH1B (ENSG00000196616), ADH5 (ENSG00000197894), ADH4 (ENSG00000198099), CRYZL1 (ENSG00000205758), ADH1C (ENSG00000248144)

Protein

Protein identifiers

Alcohol dehydrogenase 1A — P07327 (reviewed: P07327)

Alternative names: Alcohol dehydrogenase subunit alpha

All UniProt accessions (1): P07327

UniProt curated annotations — full annotation on UniProt →

Function. Alcohol dehydrogenase. Oxidizes primary as well as secondary alcohols. Ethanol is a very poor substrate.

Subunit / interactions. Dimer of identical or heterodimer of closely related subunits alpha, beta, or gamma that are encoded by genes ADH1A, ADH1B, and ADH1C, respectively.

Subcellular location. Cytoplasm.

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

Miscellaneous. There are 7 different ADH’s isozymes in human: three belongs to class-I: ADH1A, ADH1B, and ADH1C, one to class-II: ADH4, one to class-III: ADH5, one to class-IV: ADH7 and one to class-V: ADH6.

Similarity. Belongs to the zinc-containing alcohol dehydrogenase family.

RefSeq proteins (1): NP_000658* (*=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
IPR020843	ER	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF00107, PF08240

Catalyzed reactions (Rhea), 4 shown:

• a primary alcohol + NAD(+) = an aldehyde + NADH + H(+) (RHEA:10736)
• a secondary alcohol + NAD(+) = a ketone + NADH + H(+) (RHEA:10740)
• butan-1-ol + NAD(+) = butanal + NADH + H(+) (RHEA:33199)
• 1-propanol + NAD(+) = propanal + NADH + H(+) (RHEA:50704)

UniProt features (62 total): strand 21, helix 18, binding site 15, turn 4, modified residue 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1U3T	X-RAY DIFFRACTION	2.49
1HSO	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07327-F1	97.97	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.

Ligand- & substrate-binding residues (15): 200–205; 224; 229; 270; 293–295; 318–320; 370; 47; 48–52; 68; 98; 101 …

Post-translational modifications (2): 2, 23

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-2161541	Abacavir metabolism
R-HSA-5365859	RA biosynthesis pathway
R-HSA-71384	Ethanol oxidation
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-211859	Biological oxidations
R-HSA-211945	Phase I - Functionalization of compounds
R-HSA-2161522	Abacavir ADME
R-HSA-5362517	Signaling by Retinoic Acid
R-HSA-9006931	Signaling by Nuclear Receptors
R-HSA-9748784	Drug ADME

MSigDB gene sets: 126 (showing top): MODULE_93, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_RETINOL_METABOLIC_PROCESS, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, MODULE_66, CAIRO_HEPATOBLASTOMA_CLASSES_DN, MARTINEZ_RB1_TARGETS_DN, DELYS_THYROID_CANCER_DN, HSIAO_LIVER_SPECIFIC_GENES, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_RETINOIC_ACID_METABOLIC_PROCESS, MODULE_373, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (3): alcohol metabolic process (GO:0006066), retinol metabolic process (GO:0042572), retinoic acid metabolic process (GO:0042573)

GO Molecular Function (7): alcohol dehydrogenase (NAD+) activity (GO:0004022), all-trans-retinol dehydrogenase (NAD+) activity (GO:0004745), zinc ion binding (GO:0008270), butanol dehydrogenase (NAD+) activity (GO:1990362), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872)

GO Cellular Component (7): nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), cilium (GO:0005929), ciliary transition zone (GO:0035869), ciliary basal body (GO:0036064), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Abacavir ADME	1
Signaling by Retinoic Acid	1
Phase I - Functionalization of compounds	1
Metabolism	1
Biological oxidations	1
Drug ADME	1
Signaling by Nuclear Receptors	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
retinoid metabolic process	2
hormone metabolic process	2
alcohol dehydrogenase (NAD+) activity	2
cilium	2
small molecule metabolic process	1
primary alcohol metabolic process	1
olefinic compound metabolic process	1
monocarboxylic acid metabolic process	1
alcohol dehydrogenase [NAD(P)+] activity	1
transition metal ion binding	1
binding	1
catalytic activity	1
cation binding	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
microtubule organizing center	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2032 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADH1A	AVP	P01185	963
ADH1A	ALDH2	P05091	907
ADH1A	ALDH1A1	P00352	853
ADH1A	RBP1	P09455	655
ADH1A	CDH2	P19022	639
ADH1A	ADH1B	P00325	629
ADH1A	CYP2E1	P05181	608
ADH1A	CHD7	Q9P2D1	602
ADH1A	TAS2R16	Q9NYV7	590
ADH1A	AVIL	O75366	588
ADH1A	ANKK1	Q8NFD2	569
ADH1A	ALDH1B1	P30837	539
ADH1A	GSTP1	P09211	517
ADH1A	CLC	Q05315	517
ADH1A	HPGDS	O60760	510
ADH1A	ALDH9A1	P49189	510

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ADH1A	CSNK2A2	psi-mi:“MI:0915”(physical association)	0.370
HADH	ADH1A	psi-mi:“MI:0915”(physical association)	0.370
ADH1A	ADH1B	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): ADH1B (Affinity Capture-MS), HPN (Affinity Capture-MS), ADH1A (Cross-Linking-MS (XL-MS)), CSNK2A2 (Two-hybrid), HADH (Two-hybrid)

ESM2 similar proteins: A0A2U1Q018, A1L4Y2, O46649, O57380, O74540, O97959, P00325, P00326, P00327, P00328, P00329, P07327, P08319, P14139, P22797, P25405, P25406, P26325, P28332, P28469, P40394, P41680, P41681, P41682, P78870, P80338, P80360, P80468, P80512, P80572, P81431, P81601, P86883, P86885, P93629, Q03505, Q0DWH1, Q0V7W6, Q5R1W2, Q5R7Z8

Diamond homologs: A0A0C5DM37, A0A2I7G3B2, A0A2I7G3B3, A0A2U1Q018, A1A835, A1L4Y2, A2XAZ3, A7ZIA4, A7ZX04, B1J085, B1LIP1, O19053, O74540, O97959, P00325, P00326, P00327, P00328, P00329, P00333, P04707, P05336, P06525, P06757, P07327, P08319, P0CL53, P10847, P10848, P11766, P12711, P12886, P13603, P14139, P14219, P14673, P14674, P14675, P17648, P19631

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	44
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
151714	GRCh38/hg38 4q22.1-24(chr4:92610413-101521991)x1	Pathogenic
3062757	GRCh37/hg19 4q23-24(chr4:99355670-107274288)x1	Pathogenic
3062772	GRCh37/hg19 4q23-25(chr4:100172302-107880077)x1	Pathogenic
443286	GRCh37/hg19 4q22.1-24(chr4:92201567-103043808)x1	Pathogenic
980109	GRCh37/hg19 4q22.2-24(chr4:94692345-101308220)x1	Likely pathogenic

SpliceAI

940 predictions. Top by Δscore:

Variant	Effect	Δscore
4:99276649:C:CC	acceptor_gain	1.0000
4:99282340:ACAT:A	donor_loss	1.0000
4:99282341:CAT:C	donor_loss	1.0000
4:99282342:AT:A	donor_loss	1.0000
4:99282343:TAC:T	donor_loss	1.0000
4:99282344:A:AC	donor_gain	1.0000
4:99282344:A:AG	donor_loss	1.0000
4:99282345:C:CC	donor_gain	1.0000
4:99282616:C:CT	acceptor_gain	1.0000
4:99282617:A:T	acceptor_gain	1.0000
4:99284617:CA:C	acceptor_gain	1.0000
4:99284619:C:CC	acceptor_gain	1.0000
4:99284624:CAG:C	acceptor_gain	1.0000
4:99284626:G:C	acceptor_gain	1.0000
4:99284626:G:GC	acceptor_gain	1.0000
4:99284714:A:AC	donor_gain	1.0000
4:99284715:C:CC	donor_gain	1.0000
4:99284715:CT:C	donor_gain	1.0000
4:99286985:CCAT:C	acceptor_gain	1.0000
4:99286986:CATC:C	acceptor_gain	1.0000
4:99287663:TACC:T	acceptor_loss	1.0000
4:99287664:ACC:A	acceptor_loss	1.0000
4:99287665:CCT:C	acceptor_loss	1.0000
4:99287667:T:A	acceptor_loss	1.0000
4:99276647:TA:T	acceptor_gain	0.9900
4:99282605:ACC:A	acceptor_loss	0.9900
4:99282607:C:G	acceptor_loss	0.9900
4:99282608:T:C	acceptor_loss	0.9900
4:99282609:G:C	acceptor_gain	0.9900
4:99282609:G:GC	acceptor_gain	0.9900

AlphaMissense

2463 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:99280238:A:C	S290R	0.989
4:99280238:A:T	S290R	0.989
4:99280240:T:G	S290R	0.989
4:99282586:A:C	C196W	0.986
4:99280259:A:C	C283W	0.985
4:99282538:A:C	C212W	0.982
4:99284794:A:T	V90D	0.981
4:99282584:G:T	A197D	0.980
4:99282540:A:G	C212R	0.979
4:99282542:C:T	G211D	0.979
4:99282577:A:C	F199L	0.978
4:99282577:A:T	F199L	0.978
4:99282579:A:G	F199L	0.978
4:99282605:A:T	V190D	0.978
4:99282379:A:C	F265L	0.977
4:99282379:A:T	F265L	0.977
4:99282381:A:G	F265L	0.977
4:99282509:G:T	A222E	0.977
4:99284427:C:T	G180D	0.977
4:99280165:A:G	W315R	0.976
4:99280165:A:T	W315R	0.976
4:99282503:T:A	D224V	0.976
4:99280170:C:G	R313P	0.975
4:99282588:A:G	C196R	0.974
4:99284531:G:C	S145R	0.974
4:99284531:G:T	S145R	0.974
4:99284533:T:G	S145R	0.974
4:99282504:C:G	D224H	0.973
4:99282575:C:T	G200D	0.973
4:99282594:A:G	S194P	0.973

dbSNP variants (sampled 300 via entrez): RS1000054449 (4:99279931 G>A), RS1000362821 (4:99287271 T>A,C), RS1001678004 (4:99281340 G>A), RS1001730198 (4:99281587 C>G,T), RS1001865521 (4:99286880 C>T), RS1001942969 (4:99281258 G>A), RS1001967932 (4:99288727 T>G), RS1002317053 (4:99288361 G>A), RS1002507867 (4:99276164 A>T), RS1002685581 (4:99282819 T>A,C), RS1002916933 (4:99290380 C>A,T), RS1002970291 (4:99276442 T>A), RS1003378466 (4:99290902 C>T), RS1003470506 (4:99292706 G>A), RS1003571788 (4:99277946 G>T)

Disease associations

OMIM: gene MIM:103700 | disease phenotypes: MIM:180500

GenCC curated gene-disease

Mondo (1): Axenfeld-Rieger syndrome type 1 (MONDO:0008386)

Orphanet (1): Axenfeld-Rieger syndrome (Orphanet:782)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001883_1	Alcohol dependence	3.000000e-21
GCST006921_3	Regular attendance at a pub or social club	4.000000e-25
GCST007328_29	Alcohol consumption (drinks per week)	3.000000e-11
GCST009733_6	Urinary metabolite levels in chronic kidney disease	1.000000e-21
GCST011955_1	Alcohol dependence	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009592	social interaction measurement
EFO:0005116	urinary metabolite measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1970 (SINGLE PROTEIN), CHEMBL2096668 (PROTEIN FAMILY), CHEMBL2363044 (PROTEIN COMPLEX GROUP)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1229976	Metabolism/PK	3	acetaldehyde

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs931635	ADH1A		0.00	0
rs1229967	ADH1A		0.00	0
rs1229976	ADH1A	3	1.50	1	acetaldehyde
rs1826909	ADH1A		0.00	0
rs2276332	ADH1A		0.00	0
rs6811453	ADH1A		0.00	0

ChEMBL bioactivities

25 potent at pChembl≥5 of 31 total, top 25 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	Kd	2	nM	CHEMBL1231859
8.70	Ki	2	nM	CHEMBL1231859
8.40	Ki	4	nM	CHEMBL1231859
8.22	Ki	6	nM	CHEMBL1231859
6.44	Ki	360	nM	CYCLOBUTYL(CYCLOPENTYL)FORMAMIDE
6.40	Ki	400	nM	CHEMBL1161866
6.34	IC50	460	nM	CHEMBL4465918
6.06	Ki	880	nM	CHEMBL45704
5.75	Ki	1800	nM	CHEMBL297125
5.72	Ki	1900	nM	CHEMBL46655
5.64	Ki	2300	nM	CYCLOHEXYLFORMAMIDE
5.44	Ki	3600	nM	HEPTYLFORMAMIDE
5.44	Ki	3600	nM	CHEMBL291214
5.42	Ki	3800	nM	CHEMBL49774
5.41	Ki	3900	nM	CHEMBL295789
5.35	Ki	4500	nM	CHEMBL300291
5.35	Ki	4500	nM	CHEMBL45526
5.26	Ki	5500	nM	CHEMBL45705
5.26	Ki	5500	nM	CHEMBL299094
5.25	IC50	5600	nM	CHEMBL4473548
5.25	Ki	5600	nM	CHEMBL297216
5.23	Ki	5900	nM	CHEMBL294911
5.16	Ki	7000	nM	CHEMBL48122
5.14	Ki	7200	nM	CHEMBL45466
5.13	Ki	7400	nM	CHEMBL47168

PubChem BioAssay actives

25 with measured affinity, of 67 total; 22 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
[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4R,5S)-5-(5-carbamoyl-3-pyridinyl)-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate	33705: Dissociation constant against mammalian liver alcohol dehydrogenase (ADH)	kd	0.0020	uM
N-cyclobutyl-N-cyclopentylformamide	34039: Inhibition of human alcohol dehydrogenase alpha activity	ki	0.3600	uM
[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(3R,4S)-5-(3-carbamoyl-4H-pyridin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate	33707: Inhibition constant against mammalian liver alcohol dehydrogenase (ADH)	ki	0.4000	uM
1,5-bis[(1S)-1-(chloromethyl)-5-hydroxy-1,2-dihydrobenzo[e]indol-3-yl]pentane-1,5-dione	1575465: Inhibition of ADH1 (unknown origin) preincubated for 2 hrs followed by substrate/NAD+ addition	ic50	0.4600	uM
N-cyclopentyl-N-cyclopropylformamide	34039: Inhibition of human alcohol dehydrogenase alpha activity	ki	0.8800	uM
N,N-di(cyclobutyl)formamide	34039: Inhibition of human alcohol dehydrogenase alpha activity	ki	1.8000	uM
N-cyclopropyl-N-heptylformamide	34039: Inhibition of human alcohol dehydrogenase alpha activity	ki	1.9000	uM
N-cyclohexylformamide	34039: Inhibition of human alcohol dehydrogenase alpha activity	ki	2.3000	uM
N-(cyclohexylmethyl)formamide	34039: Inhibition of human alcohol dehydrogenase alpha activity	ki	3.6000	uM
N-heptylformamide	34039: Inhibition of human alcohol dehydrogenase alpha activity	ki	3.6000	uM
N-cyclobutylformamide	34039: Inhibition of human alcohol dehydrogenase alpha activity	ki	3.8000	uM
N-cyclopentylformamide	34039: Inhibition of human alcohol dehydrogenase alpha activity	ki	3.9000	uM
N-cyclopentyl-N-propylformamide	34039: Inhibition of human alcohol dehydrogenase alpha activity	ki	4.5000	uM
N-cyclohexyl-N-ethylformamide	34039: Inhibition of human alcohol dehydrogenase alpha activity	ki	4.5000	uM
N-cyclohexyl-N-methylformamide	34039: Inhibition of human alcohol dehydrogenase alpha activity	ki	5.5000	uM
N-(2-methylpropyl)formamide	34039: Inhibition of human alcohol dehydrogenase alpha activity	ki	5.5000	uM
1,5-bis[(1S)-5-hydroxy-1-methyl-1,2-dihydrobenzo[e]indol-3-yl]pentane-1,5-dione	1575465: Inhibition of ADH1 (unknown origin) preincubated for 2 hrs followed by substrate/NAD+ addition	ic50	5.6000	uM
N-propylformamide	34039: Inhibition of human alcohol dehydrogenase alpha activity	ki	5.6000	uM
N-cyclohexyl-N-cyclopropylformamide	34039: Inhibition of human alcohol dehydrogenase alpha activity	ki	5.9000	uM
N-octan-2-ylformamide	34039: Inhibition of human alcohol dehydrogenase alpha activity	ki	7.0000	uM
N-butylformamide	34039: Inhibition of human alcohol dehydrogenase alpha activity	ki	7.2000	uM
N,N-dicyclopentylformamide	34039: Inhibition of human alcohol dehydrogenase alpha activity	ki	7.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Ethanol	increases oxidation, decreases reaction, increases expression	3
Tetrachlorodibenzodioxin	decreases expression, decreases reaction, affects reaction, affects cotreatment	3
perfluorooctane sulfonic acid	decreases expression	2
Acetaminophen	affects cotreatment, decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Dexamethasone	increases expression, affects cotreatment	2
Valproic Acid	decreases expression	2
Cyclosporine	increases expression, decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation, increases expression	2
apocarotenal	increases expression	1
senecionine	decreases expression	1
senkirkine	decreases expression	1
enilconazole	affects cotreatment, decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
potassium bromate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
pregna-4,17-diene-3,16-dione	decreases expression, decreases reaction, increases expression	1
2,2’-thiodiethanol	affects metabolic processing	1
cylindrospermopsin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
GW 4064	decreases reaction, increases expression, decreases expression	1
thiacloprid	affects cotreatment, decreases expression	1
clothianidin	affects cotreatment, decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid	decreases expression	1
walrycin A	increases expression	1
Zoledronic Acid	decreases expression	1
Arsenic Trioxide	increases expression	1

ChEMBL screening assays

18 unique, capped per target: 17 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4373595	Binding	Inhibition of ADH1 (unknown origin) preincubated for 2 hrs followed by substrate/NAD+ addition	Bifunctional Duocarmycin Analogues as Inhibitors of Protein Tyrosine Kinases. — J Nat Prod
CHEMBL706662	Functional	Duration of action where maximum inhibition of LTB4 formation is achieved at 3 mg/kg po	Substituted chromenes as potent, orally active 5-lipoxygenase inhibitors. — J Med Chem

Clinical trials (associated diseases)

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