ADH1B

Summary

ADH1B (alcohol dehydrogenase 1B (class I), beta polypeptide, HGNC:250) is a protein-coding gene on chromosome 4q23, encoding All-trans-retinol dehydrogenase [NAD(+)] ADH1B (P00325). Catalyzes the NAD-dependent oxidation of all-trans-retinol and its derivatives such as all-trans-4-hydroxyretinol and may participate in retinoid metabolism.

The protein encoded by this gene is a member of the alcohol dehydrogenase family. Members of this enzyme family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. This encoded protein, consisting of several homo- and heterodimers of alpha, beta, and gamma subunits, exhibits high activity for ethanol oxidation and plays a major role in ethanol catabolism. Three genes encoding alpha, beta and gamma subunits are tandemly organized in a genomic segment as a gene cluster. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 125 — RefSeq curated summary.

At a glance

• Gene–disease (curated): alcohol dependence (Limited, GenCC)
• GWAS associations: 81
• Clinical variants (ClinVar): 75 total
• Phenotypes (HPO): 2
• Druggable target: yes
• MANE Select transcript: NM_000668

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:250
Approved symbol	ADH1B
Name	alcohol dehydrogenase 1B (class I), beta polypeptide
Location	4q23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196616
Ensembl biotype	protein_coding
OMIM	103720
Entrez	125

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 14 protein_coding, 3 retained_intron

ENST00000305046, ENST00000504498, ENST00000506651, ENST00000515694, ENST00000625860, ENST00000632775, ENST00000881097, ENST00000881098, ENST00000881099, ENST00000881100, ENST00000881101, ENST00000881102, ENST00000881103, ENST00000881104, ENST00000881105, ENST00000881106, ENST00000881107

RefSeq mRNA: 2 — MANE Select: NM_000668 NM_000668, NM_001286650

CCDS: CCDS34033, CCDS68761

Canonical transcript exons

ENST00000305046 — 9 exons

Exon	Start	End
ENSE00002069705	99304971	99307864
ENSE00003458236	99318046	99318184
ENSE00003543818	99316215	99316302
ENSE00003546133	99315898	99316117
ENSE00003595688	99318785	99318886
ENSE00003597999	99311521	99311656
ENSE00003599852	99321314	99321401
ENSE00003657734	99313821	99314081
ENSE00003661534	99310765	99310903

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 99.66.

FANTOM5 (CAGE): breadth broad, TPM avg 44.4123 / max 7553.5483, expressed in 391 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53270	39.8704	366
53269	3.9394	242
53273	0.5575	46
203294	0.0450	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.66	gold quality
right coronary artery	UBERON:0001625	99.65	gold quality
lower lobe of lung	UBERON:0008949	99.64	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.61	gold quality
mucosa of stomach	UBERON:0001199	99.60	gold quality
peritoneum	UBERON:0002358	99.60	gold quality
omental fat pad	UBERON:0010414	99.60	gold quality
descending thoracic aorta	UBERON:0002345	99.52	gold quality
left coronary artery	UBERON:0001626	99.51	gold quality
coronary artery	UBERON:0001621	99.49	gold quality
right lung	UBERON:0002167	99.45	gold quality
superficial temporal artery	UBERON:0001614	99.36	gold quality
adipose tissue	UBERON:0001013	99.35	gold quality
left uterine tube	UBERON:0001303	99.28	gold quality
thoracic aorta	UBERON:0001515	99.24	gold quality
pericardium	UBERON:0002407	99.24	gold quality
ascending aorta	UBERON:0001496	99.20	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.05	gold quality
parietal pleura	UBERON:0002400	99.03	gold quality
tibial nerve	UBERON:0001323	98.98	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.84	gold quality
aorta	UBERON:0000947	98.81	gold quality
blood vessel layer	UBERON:0004797	98.78	gold quality
synovial joint	UBERON:0002217	98.74	gold quality
fundus of stomach	UBERON:0001160	98.73	gold quality
upper lobe of lung	UBERON:0008948	98.62	gold quality
upper lobe of left lung	UBERON:0008952	98.56	gold quality
lung	UBERON:0002048	98.53	gold quality
popliteal artery	UBERON:0002250	98.49	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.49	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	2984.23
E-CURD-122	yes	2960.52
E-CURD-126	yes	2799.53
E-MTAB-8221	yes	2797.92
E-HCAD-15	yes	1980.47
E-HCAD-11	yes	1165.04
E-HCAD-1	yes	88.56
E-MTAB-8410	yes	65.76
E-HCAD-9	yes	64.84
E-GEOD-135922	yes	49.63
E-MTAB-10553	yes	42.65
E-CURD-46	yes	26.34
E-MTAB-10287	yes	25.81
E-MTAB-9543	yes	23.37
E-GEOD-81547	yes	8.62

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, CEBPG, DBP, SMARCA5, SP1, TBP, USF1, ZNF236, ZNF91

miRNA regulators (miRDB)

69 targeting ADH1B, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733

Literature-anchored findings (GeneRIF, showing 23)

• we show that two co-transcribed Drosophila miRNAs, let-7 and miR-125, non-redundantly regulate a common target, the transcription factor Chronologically Inappropriate Morphogenesis (Chinmo). We first characterize novel adult phenotypes associated with loss of both let-7 and miR-125, which are derived from a common, polycistronic transcript that also encodes a third miRNA, miR-100. (PMID:27508495)
• During ovarian germline stem cell niche formation, the status of Notch signaling in the cell can be reprogrammed. This is controlled via steroid-induced miR-125, which targets a negative regulator of Notch signaling, Tom (PMID:29361571)
• let-7-Complex MicroRNAs Regulate Broad-Z3, Which Together with Chinmo Maintains Adult Lineage Neurons in an Immature State. (PMID:32071070)
• Sructural aspects that influence dimer-tetramer formation (PMID:12081471)
• There was a gene-environment interaction between the ADH2 polymorphism, alcohol consumption, and breast cancer risk. Breast cancer risk associated with alcohol consumption vary with the ADH2 polymorphism, probably due to differences in EtOH metabolism. (PMID:12189549)
• The ADH2*2 allele protects against alcohol dependence severity in Jewish samples. (PMID:12351924)
• Mutations that contribute to the risk of alcoholism affect European, Chinese, and Japanese populations differently. (PMID:12452180)
• Polymorphisms of alcohol-metabolizing enzymes: analyses of mutations on the CYP2E1, ADH2, ADH3 and ALDH2 genes in a Mexican-American population living in the Los Angeles area. (PMID:12554615)
• There is no significant interaction between alcohol consumption and ADH2 genotype. (PMID:12658118)
• Polymorphism is not associated with laryngeal cancer risk in Caucasians. (PMID:12668919)
• The alcohol-BP relationship was significantly stronger in men with ADH21/21 than in men with ADH21/22 or 22/22 in this Japanese rural population. (PMID:12777946)
• The ADH1B gene may interact with the dopamine D2 receptor (DRD2) gene in the development of anxiety-depressive alcohol dependence in the Taiwan Han Chinese population. (PMID:15084894)
• Risk of cerebral infarction is increased by the ADH2*1 allele. (PMID:15534263)
• Effect modification suggested of association between alcohol consumption and breast cancer risk by ADH1B genotype (PMID:15886702)
• Polymorphisms of the alcohol metabolism-related ADH2 gene are significantly different in Korean patients with alcoholism and Korean control subjects without alcoholism. (PMID:15902904)
• polymorphisms in ADH1C and ADH1B may have roles in the risk of alcoholism (PMID:16086315)
• Heterozygous alcohol dehydrogenase 2 genotype (ADH2*1/2*2) exhibited an association with the scant pancreatitis subgroup (P = 0.02). (PMID:16163053)
• No effects of the ADH1B*47His alleles on in vivo ethanol metabolism were observed. This implies that there is a major determinant of variation for in vivo alcohol metabolism in the ADH region that is not accounted for by this polymorphism. (PMID:16184481)
• interaction between ALDH2 and ADH2 polymorphisms may have a role in colorectal cancer in Japan (PMID:16332725)
• ADH1B*2 allele has been associated with lowr rates of alcohol dependence. (PMID:16404797)
• Data are consistent with the hypothesis that the maternal ADH1B*3 allele provides some protection to the fetus from prenatal alcohol exposure. (PMID:16423594)
• findings suggest that the alcohol dehydrogenase IB and IC genes are regulated by epigenetic mechanisms in human hepatoma cells (PMID:16737450)
• There were no differences in the frequencies of genotypes of ADH2 and ADH3 between trichloroethylene-induced medicamentosa-like dermatitis cases and exposed controls. (PMID:16758956)

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), ADH1A (ENSG00000187758), ADH7 (ENSG00000196344), ADH5 (ENSG00000197894), ADH4 (ENSG00000198099), CRYZL1 (ENSG00000205758), ADH1C (ENSG00000248144)

Protein

Protein identifiers

All-trans-retinol dehydrogenase [NAD(+)] ADH1B — P00325 (reviewed: P00325)

Alternative names: Alcohol dehydrogenase 1B, Alcohol dehydrogenase subunit beta

All UniProt accessions (3): P00325, D6RHZ6, V9HW50

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the NAD-dependent oxidation of all-trans-retinol and its derivatives such as all-trans-4-hydroxyretinol and may participate in retinoid metabolism. In vitro can also catalyze the NADH-dependent reduction of all-trans-retinal and its derivatives such as all-trans-4-oxoretinal. Catalyzes in the oxidative direction with higher efficiency. Has the same affinity for all-trans-4-hydroxyretinol and all-trans-4-oxoretinal.

Subunit / interactions. Dimer of identical or non-identical chains of three types; alpha, beta and gamma.

Subcellular location. Cytoplasm.

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

Polymorphism. Three alleles are known: ADH1B1 (ADH21) corresponding to variant beta-1, ADH1B2 (ADH22) corresponding to variant beta-2, ADH1B3 (ADH23) corresponding to variant beta-3. The sequence shown is that of allele ADH1B2. The ADH1B2 allele frequency in orientals is approximately 75%, whereas it is less than 5% in most Caucasian populations. The ADH1B*2 allele is associated with a lower risk of alcoholism. ADH1B variations have been associated with protection against alcohol dependence and alcohol-related aerodigestive tract cancer [MIM:103720].

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.

Isoforms (2)

UniProt ID	Names	Canonical?
P00325-1	1	yes
P00325-2	2

RefSeq proteins (2): NP_000659, NP_001273579 (=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), 3 shown:

• all-trans-retinol + NAD(+) = all-trans-retinal + NADH + H(+) (RHEA:21284)
• all-trans-4-hydroxyretinol + NAD(+) = all-trans-4-hydroxyretinal + NADH + H(+) (RHEA:55936)
• all-trans-4-oxoretinol + NAD(+) = all-trans-4-oxoretinal + NADH + H(+) (RHEA:60632)

UniProt features (74 total): strand 22, helix 18, binding site 12, sequence conflict 8, sequence variant 4, turn 4, modified residue 3, initiator methionine 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
1U3U	X-RAY DIFFRACTION	1.6
1U3V	X-RAY DIFFRACTION	1.65
1DEH	X-RAY DIFFRACTION	2.2
1HSZ	X-RAY DIFFRACTION	2.2
1HTB	X-RAY DIFFRACTION	2.4
1HDX	X-RAY DIFFRACTION	2.5
1HDY	X-RAY DIFFRACTION	2.5
1HDZ	X-RAY DIFFRACTION	2.5
3HUD	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00325-F1	97.86	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 (12): 224; 229; 293–295; 370; 47; 68; 98; 101; 104; 112; 175; 200–205

Post-translational modifications (3): 2, 23, 35

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: 138 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, LOPEZ_MESOTHELIOMA_SURVIVAL_OVERALL_UP, GOBP_REGULATION_OF_HORMONE_LEVELS, SMID_BREAST_CANCER_RELAPSE_IN_LUNG_DN, GOBP_RETINOL_METABOLIC_PROCESS, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, CAIRO_HEPATOBLASTOMA_CLASSES_DN, BOQUEST_STEM_CELL_CULTURED_VS_FRESH_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, DELYS_THYROID_CANCER_DN, HSIAO_LIVER_SPECIFIC_GENES, MODULE_99, VANHARANTA_UTERINE_FIBROID_DN, GOBP_RETINOIC_ACID_METABOLIC_PROCESS

GO Biological Process (4): retinoid metabolic process (GO:0001523), retinol metabolic process (GO:0042572), retinoic acid metabolic process (GO:0042573), lipid metabolic process (GO:0006629)

GO Molecular Function (6): alcohol dehydrogenase (NAD+) activity (GO:0004022), all-trans-retinol dehydrogenase (NAD+) activity (GO:0004745), zinc ion binding (GO:0008270), 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-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
cellular anatomical structure	4
retinoid metabolic process	2
hormone metabolic process	2
cilium	2
diterpenoid metabolic process	1
primary alcohol metabolic process	1
olefinic compound metabolic process	1
monocarboxylic acid metabolic process	1
primary metabolic process	1
alcohol dehydrogenase [NAD(P)+] activity	1
alcohol dehydrogenase (NAD+) 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

2062 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADH1B	ALDH2	P05091	984
ADH1B	AVP	P01185	969
ADH1B	CYP2E1	P05181	877
ADH1B	ALDH1A1	P00352	814
ADH1B	ANKK1	Q8NFD2	705
ADH1B	OPRM1	P35372	642
ADH1B	ADH1A	P07327	629
ADH1B	CHRM2	P08172	614
ADH1B	MTHFR	P42898	609
ADH1B	ALDH1B1	P30837	608
ADH1B	OPRD1	P41143	594
ADH1B	GABRA2	P47869	582
ADH1B	CHRNA5	P30532	578
ADH1B	CYP2C9	P11712	572
ADH1B	DLEC1	Q9Y238	566

IntAct

15 interactions, top by confidence:

A	B	Type	Score
ADH1C	ADH1B	psi-mi:“MI:0914”(association)	0.560
ADH1C	ADH1B	psi-mi:“MI:0915”(physical association)	0.560
ADH1B	PCNA	psi-mi:“MI:0915”(physical association)	0.370
ADH1B		psi-mi:“MI:0915”(physical association)	0.370
ADH1B	SERPINA3	psi-mi:“MI:0915”(physical association)	0.370
PML	ADH1B	psi-mi:“MI:0915”(physical association)	0.370
PDE4DIP	ADH1B	psi-mi:“MI:0915”(physical association)	0.370
RACK1	ADH1B	psi-mi:“MI:0915”(physical association)	0.370
IRAK3	ADH1B	psi-mi:“MI:0915”(physical association)	0.370
PPP1CA	ACO2	psi-mi:“MI:0914”(association)	0.350
ADH1A	ADH1B	psi-mi:“MI:0914”(association)	0.350
CTNNA1	ILVBL	psi-mi:“MI:0914”(association)	0.350
	ADH1B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): ADH1B (Affinity Capture-MS), ADH1B (Affinity Capture-MS), ADH1B (Affinity Capture-MS), ADH1B (Affinity Capture-MS), ADH1B (Affinity Capture-MS), ADH1B (Affinity Capture-MS), ADH1B (Affinity Capture-MS), ADH1B (Positive Genetic), ADH1B (Affinity Capture-MS), PDE4DIP (Two-hybrid), GNB2L1 (Two-hybrid), SERPINA3 (Two-hybrid), PML (Two-hybrid), IRAK3 (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, 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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	4
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

1186 predictions. Top by Δscore:

Variant	Effect	Δscore
4:99307865:C:CC	acceptor_gain	1.0000
4:99313815:ACAT:A	donor_loss	1.0000
4:99313816:CAT:C	donor_loss	1.0000
4:99313818:TA:T	donor_loss	1.0000
4:99313819:A:AC	donor_gain	1.0000
4:99313819:A:AT	donor_loss	1.0000
4:99313820:C:CC	donor_gain	1.0000
4:99313891:T:TA	donor_gain	1.0000
4:99314080:ACCT:A	acceptor_loss	1.0000
4:99314081:CC:C	acceptor_loss	1.0000
4:99314081:CCTG:C	acceptor_gain	1.0000
4:99314084:G:C	acceptor_gain	1.0000
4:99314084:G:GC	acceptor_gain	1.0000
4:99314091:C:CT	acceptor_gain	1.0000
4:99314092:A:T	acceptor_gain	1.0000
4:99314097:A:C	acceptor_gain	1.0000
4:99315892:TCTCA:T	donor_loss	1.0000
4:99315893:CTCA:C	donor_loss	1.0000
4:99315894:TCA:T	donor_loss	1.0000
4:99315895:CA:C	donor_loss	1.0000
4:99315897:CCTT:C	donor_loss	1.0000
4:99316123:CAG:C	acceptor_gain	1.0000
4:99316125:G:C	acceptor_gain	1.0000
4:99316125:G:GC	acceptor_gain	1.0000
4:99316213:A:AC	donor_gain	1.0000
4:99316214:C:CT	donor_gain	1.0000
4:99316214:CT:C	donor_gain	1.0000
4:99316214:CTCA:C	donor_gain	1.0000
4:99316214:CTCAT:C	donor_gain	1.0000
4:99316217:A:AC	donor_gain	1.0000

AlphaMissense

2448 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:99318166:A:G	C47R	0.993
4:99311615:G:C	S290R	0.992
4:99311615:G:T	S290R	0.992
4:99311617:T:G	S290R	0.992
4:99316030:G:C	S145R	0.992
4:99316030:G:T	S145R	0.992
4:99316032:T:G	S145R	0.992
4:99314061:A:C	C196W	0.991
4:99314013:A:C	C212W	0.990
4:99315942:A:G	C175R	0.990
4:99314015:A:G	C212R	0.989
4:99315926:C:T	G180D	0.989
4:99318164:A:C	C47W	0.989
4:99318099:T:A	E69V	0.988
4:99307860:G:T	R370S	0.987
4:99314017:C:T	G211D	0.987
4:99307859:C:G	R370P	0.986
4:99311636:A:C	C283W	0.986
4:99313852:G:C	S266W	0.986
4:99314044:C:T	G202E	0.986
4:99316293:A:T	V90D	0.986
4:99313978:T:A	D224V	0.985
4:99314059:G:T	A197D	0.985
4:99316031:C:A	S145I	0.985
4:99318165:C:T	C47Y	0.985
4:99314063:A:G	C196R	0.984
4:99318084:A:T	V74E	0.984
4:99318795:A:T	V37D	0.984
4:99313979:C:G	D224H	0.983
4:99314050:C:T	G200D	0.983

dbSNP variants (sampled 300 via entrez): RS1000003992 (4:99306430 G>C), RS1000102884 (4:99308659 G>A), RS1000312910 (4:99319187 G>A), RS1000358343 (4:99305248 T>C), RS10005290 (4:99308253 A>C,G,T), RS1000877928 (4:99307478 T>C), RS1000923337 (4:99322072 T>C), RS1000957458 (4:99308441 T>C), RS1000975210 (4:99321806 A>G), RS1001163963 (4:99315264 T>C), RS1001281246 (4:99314900 C>T), RS1001505455 (4:99318491 G>A), RS1001707692 (4:99311637 CAACAT>C), RS1001770249 (4:99320659 T>C), RS1002054501 (4:99313610 A>G,T)

Disease associations

OMIM: gene MIM:103720 | disease phenotypes: MIM:103780

GenCC curated gene-disease

Disease	Classification	Inheritance
alcohol dependence	Limited	Autosomal dominant

Mondo (1): alcohol dependence (MONDO:0007079)

Orphanet (0):

HPO phenotypes

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

HPO	Term
HP:0001426	Non-Mendelian inheritance
HP:0030955	Addictive alcohol use

GWAS associations

81 associations (top):

Study	Trait	p-value
GCST000466_2	Esophageal cancer	8.000000e-24
GCST001011_2	Oral cavity and pharyngeal cancer	1.000000e-20
GCST001281_6	Alcohol dependence	1.000000e-08
GCST001672_1	Esophageal cancer (alcohol interaction)	3.000000e-07
GCST001883_1	Alcohol dependence	3.000000e-21
GCST002065_5	Alcohol consumption	2.000000e-08
GCST003857_1	Oral cavity and pharyngeal cancer	2.000000e-15
GCST003858_2	Oral cavity cancer	1.000000e-09
GCST003859_2	Oropharynx cancer	9.000000e-09
GCST004404_4	Alcohol consumption (drinkers vs non-drinkers)	2.000000e-20
GCST004404_5	Alcohol consumption (drinkers vs non-drinkers)	4.000000e-07
GCST004405_5	Alcohol consumption (drinks per week)	3.000000e-32
GCST004405_6	Alcohol consumption (drinks per week)	3.000000e-06
GCST004711_2	Alcohol dependence	2.000000e-23
GCST004711_24	Alcohol dependence	2.000000e-22
GCST004711_25	Alcohol dependence	2.000000e-13
GCST004711_34	Alcohol dependence	4.000000e-06
GCST004711_42	Alcohol dependence	6.000000e-06
GCST004711_7	Alcohol dependence	6.000000e-17
GCST004711_8	Alcohol dependence	2.000000e-12
GCST004711_9	Alcohol dependence	3.000000e-12
GCST004712_10	Alcohol dependence	4.000000e-11
GCST004712_11	Alcohol dependence	2.000000e-09
GCST004712_12	Alcohol dependence	2.000000e-09
GCST004712_4	Alcohol dependence	1.000000e-31
GCST004748_39	Lung cancer	2.000000e-06
GCST004756_3	Alcohol dependence	2.000000e-08
GCST004886_13	Alcohol consumption	1.000000e-30
GCST004886_2	Alcohol consumption	4.000000e-13
GCST004886_6	Alcohol consumption	3.000000e-19

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0004329	alcohol drinking
EFO:0007835	alcohol dependence measurement
EFO:0008434	initial pursuit acceleration
EFO:0009592	social interaction measurement
EFO:0009270	heel bone mineral density
EFO:0008579	risk-taking behaviour
EFO:0007645	longitudinal alcohol consumption measurement
EFO:0009458	alcohol use disorder measurement
EFO:0010092	bitter alcoholic beverage consumption measurement
EFO:0009282	sodium measurement
EFO:0009793	isoleucine measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0010810	protein intake measurement
EFO:0010809	fat intake measurement
EFO:0007986	reticulocyte count
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2096668 (PROTEIN FAMILY), CHEMBL2363044 (PROTEIN COMPLEX GROUP), CHEMBL3284 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

5 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1229984	Metabolism/PK	3	ethanol
rs1229984	Metabolism/PK	3	acetaldehyde
rs1229984	Toxicity	3	ethanol	Alcohol abuse
rs2066702	Efficacy	3	naltrexone	Alcohol abuse
rs75967634	Toxicity	3	ethanol	Alcohol abuse

PharmGKB variants

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17033	ADH1B		0.00	0
rs1229984	ADH1B	3	7.25	3	ethanol;acetaldehyde
rs1229985	ADH1B		0.00	0
rs1789891	ADH1B		0.00	0
rs2018417	ADH1B		0.00	0
rs2066702	ADH1B	3	2.50	1	naltrexone
rs75967634	ADH1B	3	1.50	1	ethanol

ChEMBL bioactivities

9 potent at pChembl≥5 of 14 total, top 9 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.48	Ki	330	nM	CHEMBL46293
6.48	Ki	330	nM	HEPTYLFORMAMIDE
6.00	Ki	1000	nM	CHEMBL291214
5.77	Ki	1700	nM	CHEMBL48122
5.54	Ki	2900	nM	CHEMBL49774
5.47	Ki	3400	nM	CYCLOHEXYLFORMAMIDE
5.26	Ki	5500	nM	CHEMBL297216
5.19	Ki	6400	nM	CHEMBL49963
5.14	Ki	7300	nM	CHEMBL295789

PubChem BioAssay actives

9 with measured affinity, of 58 total; 9 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
N-heptylformamide	34040: Inhibition of human alcohol dehydrogenase beta 1 activity	ki	0.3300	uM
N-benzylformamide	34040: Inhibition of human alcohol dehydrogenase beta 1 activity	ki	0.3300	uM
N-(cyclohexylmethyl)formamide	34040: Inhibition of human alcohol dehydrogenase beta 1 activity	ki	1.0000	uM
N-octan-2-ylformamide	34040: Inhibition of human alcohol dehydrogenase beta 1 activity	ki	1.7000	uM
N-cyclobutylformamide	34040: Inhibition of human alcohol dehydrogenase beta 1 activity	ki	2.9000	uM
N-cyclohexylformamide	34040: Inhibition of human alcohol dehydrogenase beta 1 activity	ki	3.4000	uM
N-propylformamide	34040: Inhibition of human alcohol dehydrogenase beta 1 activity	ki	5.5000	uM
N-cyclopropylformamide	34040: Inhibition of human alcohol dehydrogenase beta 1 activity	ki	6.4000	uM
N-cyclopentylformamide	34040: Inhibition of human alcohol dehydrogenase beta 1 activity	ki	7.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Ethanol	affects metabolic processing, affects response to substance, increases metabolic processing, increases chemical synthesis, increases oxidation (+2 more)	7
Tetrachlorodibenzodioxin	decreases reaction, affects reaction, affects cotreatment, increases reaction, decreases expression	3
Valproic Acid	increases expression, decreases expression, decreases methylation	3
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
sodium arsenite	decreases expression	2
Acetaldehyde	increases chemical synthesis, increases metabolic processing, increases oxidation, decreases reaction	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Progesterone	increases expression	2
Aflatoxin B1	decreases methylation, affects expression, decreases expression	2
bisphenol F	increases expression	1
methyleugenol	decreases expression	1
lead acetate	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	increases abundance, increases expression	1
cupric chloride	decreases expression	1
9-cis-retinal	increases metabolic processing	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
fipronil	decreases expression	1
cylindrospermopsin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
entinostat	decreases expression	1
clothianidin	decreases expression	1
bisphenol B	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
bisphenol S	increases expression	1

ChEMBL screening assays

13 unique, capped per target: 13 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

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000437	PHASE4	COMPLETED	Tobacco Dependence in Alcoholism Treatment (Nicotine Patch/Naltrexone)
NCT00000438	PHASE4	COMPLETED	Naltrexone Treatment for Alcoholism
NCT00000441	PHASE4	COMPLETED	Drug Therapy for Alcohol Detoxification
NCT00000442	PHASE4	COMPLETED	Naltrexone for Relapse Prevention
NCT00000444	PHASE4	COMPLETED	Timing of Smoking Intervention in Alcohol Treatment (Nicotine Patch)
NCT00000445	PHASE4	COMPLETED	Use of Naltrexone in a Clinical Setting
NCT00000447	PHASE4	COMPLETED	Behavioral/Drug Therapy for Alcohol-Nicotine Dependence (Naltrexone/Nicotine Patch)
NCT00000448	PHASE4	COMPLETED	Naltrexone Treatment for Alcoholic Women
NCT00000449	PHASE4	COMPLETED	Behavior and Naltrexone Treatment for Alcoholics
NCT00000450	PHASE4	COMPLETED	Naltrexone Maintenance Treatment of Alcoholism
NCT00000452	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Dependence
NCT00000454	PHASE4	COMPLETED	Smoking Cessation in Alcoholism Treatment
NCT00000455	PHASE4	COMPLETED	Naltrexone for Early Problem Drinkers
NCT00000456	PHASE4	COMPLETED	Behavioral Therapy Plus Naltrexone for Alcoholism
NCT00004551	PHASE4	COMPLETED	Behavioral Counseling for Alcohol Dependent Smokers (Nicotine Patch)
NCT00004554	PHASE4	COMPLETED	Sertraline for Alcohol Dependence and Depression
NCT00006203	PHASE4	COMPLETED	Naltrexone, Craving, and Drinking
NCT00006204	PHASE4	COMPLETED	Drug Treatment for Depressed Alcoholics (Naltrexone/Fluoxetine)
NCT00006449	PHASE4	COMPLETED	Post-Treatment Effects of Naltrexone
NCT00006489	PHASE4	COMPLETED	Treatment for Alcoholism and Post-Traumatic Stress Disorder (Naltrexone)
NCT00018824	PHASE4	COMPLETED	Treating Alcohol Use In Older Adults With Depression
NCT00044434	PHASE4	COMPLETED	Bupropion as a Smoking Cessation Aid in Alcoholics
NCT00064844	PHASE4	COMPLETED	Combination Nicotine Replacement for Alcoholic Smokers
NCT00082199	PHASE4	COMPLETED	Study of Aripiprazole in Subjects With Alcoholism
NCT00115037	PHASE4	COMPLETED	Managing Alcoholism in People Who Do Not Respond to Naltrexone
NCT00120601	PHASE4	UNKNOWN	Trial for the Treatment of Alcohol Dependence
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148031	PHASE4	COMPLETED	Improving Hepatitis C Treatment in Injection Drug Users
NCT00159107	PHASE4	COMPLETED	Integrative Therapy in Alcoholism
NCT00167687	PHASE4	COMPLETED	Prazosin Alcohol Dependence IVR Study
NCT00223275	PHASE4	COMPLETED	Naltrexone for Bipolar Disorder and Alcohol Dependence
NCT00226109	PHASE4	SUSPENDED	Clinical Trial Studying the Effects of Spironolactone on Heart and Skeletal Muscle Function in Chronic Alcoholics
NCT00246441	PHASE4	COMPLETED	Paroxetine for Comorbid Social Anxiety Disorder and Alcoholism
NCT00249379	PHASE4	TERMINATED	Study of Acamprosate to Prevent Alcohol Relapse in Criminal Justice Supervisees
NCT00261872	PHASE4	COMPLETED	Treatment of Patients With Alcoholism and Attention Deficit Disorder
NCT00317031	PHASE4	COMPLETED	Individually Adapted Therapy of Alcoholism
NCT00325182	PHASE4	COMPLETED	The Effects of Levetiracetam on Alcohol Dependent Subjects
NCT00329407	PHASE4	COMPLETED	The Effects of Topiramate on Alcohol Use in Alcohol Dependent Subjects
NCT00330174	PHASE4	COMPLETED	Acamprosate in Alcoholics With Comorbid Anxiety or Depression
NCT00352469	PHASE4	COMPLETED	Trial of Seroquel SR for Alcohol Dependence and Comorbid Anxiety