ADH7

Summary

ADH7 (alcohol dehydrogenase 7 (class IV), mu or sigma polypeptide, HGNC:256) is a protein-coding gene on chromosome 4q23, encoding All-trans-retinol dehydrogenase [NAD(+)] ADH7 (P40394). Catalyzes the NAD-dependent oxidation of all-trans-retinol, alcohol, and omega-hydroxy fatty acids and their derivatives.

This gene encodes class IV alcohol dehydrogenase 7 mu or sigma subunit, which is 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 enzyme encoded by this gene is inefficient in ethanol oxidation, but is the most active as a retinol dehydrogenase; thus it may participate in the synthesis of retinoic acid, a hormone important for cellular differentiation. The expression of this gene is much more abundant in stomach than liver, thus differing from the other known gene family members. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 131 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 77 total
• Druggable target: yes
• MANE Select transcript: NM_000673

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:256
Approved symbol	ADH7
Name	alcohol dehydrogenase 7 (class IV), mu or sigma polypeptide
Location	4q23
Locus type	gene with protein product
Status	Approved
Aliases	ADH-4
Ensembl gene	ENSG00000196344
Ensembl biotype	protein_coding
OMIM	600086
Entrez	131

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000209665, ENST00000437033, ENST00000474027, ENST00000476959, ENST00000482593, ENST00000485660

RefSeq mRNA: 2 — MANE Select: NM_000673 NM_000673, NM_001166504

CCDS: CCDS34034, CCDS54781

Canonical transcript exons

ENST00000437033 — 9 exons

Exon	Start	End
ENSE00000733622	99418986	99419121
ENSE00000733625	99420533	99420793
ENSE00000733629	99427773	99427989
ENSE00000733632	99428087	99428174
ENSE00000801334	99415478	99415616
ENSE00001883960	99435216	99435342
ENSE00003512487	99428492	99428630
ENSE00003682844	99429532	99429633
ENSE00003921805	99412263	99413172

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 97.32.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5466 / max 180.8211, expressed in 46 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53277	0.3645	37
53279	0.0960	14
53276	0.0544	9
53278	0.0179	8
53280	0.0139	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.32	gold quality
esophagus mucosa	UBERON:0002469	97.19	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.93	gold quality
esophagus squamous epithelium	UBERON:0006920	96.30	gold quality
oral cavity	UBERON:0000167	95.31	gold quality
epithelium of esophagus	UBERON:0001976	95.02	gold quality
nasal cavity epithelium	UBERON:0005384	94.33	gold quality
tongue squamous epithelium	UBERON:0006919	93.79	gold quality
epithelium of nasopharynx	UBERON:0001951	92.64	gold quality
nasopharynx	UBERON:0001728	92.62	gold quality
nasal cavity mucosa	UBERON:0001826	92.38	gold quality
pharyngeal mucosa	UBERON:0000355	91.06	gold quality
squamous epithelium	UBERON:0006914	90.18	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.21	gold quality
gingiva	UBERON:0001828	87.02	gold quality
gingival epithelium	UBERON:0001949	85.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.76	gold quality
palpebral conjunctiva	UBERON:0001812	84.84	gold quality
body of tongue	UBERON:0011876	84.30	gold quality
bronchus	UBERON:0002185	83.35	gold quality
epithelium of bronchus	UBERON:0002031	83.23	gold quality
bronchial epithelial cell	CL:0002328	82.45	gold quality
tongue	UBERON:0001723	81.84	gold quality
trachea	UBERON:0003126	81.28	gold quality
cervix epithelium	UBERON:0004801	78.03	gold quality
superior surface of tongue	UBERON:0007371	76.38	gold quality
mucosa of stomach	UBERON:0001199	75.33	gold quality
esophagus	UBERON:0001043	75.07	gold quality
cervix squamous epithelium	UBERON:0006922	73.95	silver quality
tonsil	UBERON:0002372	73.69	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): JUN

miRNA regulators (miRDB)

58 targeting ADH7, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-4517	99.76	69.19	1867

Literature-anchored findings (GeneRIF, showing 17)

• the ADH7 variation may contribute to the genetic component of variation in personality traits, with the risk for SD and personality traits being partially shared. (PMID:17918242)
• A recombinational hotspot within intron 7 of the ADH7 gene were seen using 25 SNPs; haplotypes associated with inter-individual variation in the early stages of alcohol metabolism were identified. (PMID:17921519)
• Changes in the activity of class IV ADH in the sera of patients with gastric cancer seems to be caused by release of the isoenzyme from cancer cells. (PMID:18231859)
• Single Nucleotide Polymorphism in ADH7 gene is associated with upper aerodigestive cancer. (PMID:18500343)
• 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)
• ADH7 gene polymorphisms are associated with upper aerodigestive tract cancers. (PMID:19861527)
• An association between age at onset of regular alcohol use and a SNP just upstream of ADH7 (rs2654849, p = .003) was observed. (PMID:20158305)
• The current results support the ADH7 A92G SNP as a marker for the risk of SCCHN in non-Hispanic white populations. (PMID:20336794)
• The rs1573496 (ADH7) polymorphism was not associated with colorectal cancer risk overall in Western-European populations. However, the relationship between alcohol and colorectal cancer risk might be modulated by the rs1573496 (ADH7) polymorphism. (PMID:23149980)
• common ADH1-7 variants conferred risk for both schizophrenia in African-Americans and autism in European-Americans. (PMID:23468174)
• Transcriptional regulatory elements of ADH7 were identified that effect gene expression. (PMID:24512552)
• ADH1B-ADH1C-ADH7 cluster SNPs confer susceptibility to esophageal squamous cell carcinoma (PMID:24722735)
• These results suggest that variants near ADH7 may play a role in protection from alcohol dependence in this Mexican American cohort. (PMID:25527893)
• The results of the study do not support our hypothesis that ADH1B and ADH7 genotypes affect blood ethanol, and acetaldehyde concentration. (PMID:28731573)
• These results provide evidence that PAX6 might drive corneal epithelial differentiation by direct or indirect control of retinoic acid signaling processes through ADH7 and ALDH1A1. (PMID:30292490)
• Association of ADH7 Gene Polymorphism with Schizophrenia in the Han Population of Northern China: a Case-Control Study. (PMID:32388801)
• An alcohol dehydrogenase 7 gene polymorphism associates with both acute and chronic pain in sickle cell disease. (PMID:37712142)

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	Adh7	ENSMUSG00000055301
rattus_norvegicus	Adh7	ENSRNOG00000032959
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), ADH1B (ENSG00000196616), ADH5 (ENSG00000197894), ADH4 (ENSG00000198099), CRYZL1 (ENSG00000205758), ADH1C (ENSG00000248144)

Protein

Protein identifiers

All-trans-retinol dehydrogenase [NAD(+)] ADH7 — P40394 (reviewed: P40394)

Alternative names: Alcohol dehydrogenase class 4 mu/sigma chain, Alcohol dehydrogenase class IV mu/sigma chain, Gastric alcohol dehydrogenase, Omega-hydroxydecanoate dehydrogenase ADH7, Retinol dehydrogenase

All UniProt accessions (4): A0A0C4DG85, C9JP14, E9PFG0, P40394

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the NAD-dependent oxidation of all-trans-retinol, alcohol, and omega-hydroxy fatty acids and their derivatives. Oxidizes preferentially all trans-retinol, all-trans-4-hydroxyretinol, 9-cis-retinol, 2-hexenol, and long chain omega-hydroxy fatty acids such as juniperic acid. In vitro can also catalyze the NADH-dependent reduction of all-trans-retinal and aldehydes and their derivatives. Reduces preferentially all trans-retinal, all-trans-4-oxoretinal and hexanal. Catalyzes in the oxidative direction with higher efficiency. Therefore may participate in retinoid metabolism, fatty acid omega-oxidation, and elimination of cytotoxic aldehydes produced by lipid peroxidation.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Preferentially expressed in stomach.

Activity regulation. Retinol oxidation is inhibited by the detergent Tween 80. Ethanol inhibits both all-trans-retinol and 9-cis-retinol oxidation. 13-cis-retinol is an effective competitive inhibitor of the 9-cis-retinol oxidation. All-trans-retinoic acid is a powerful inhibitor of all-trans-retinol oxidation. 13-cis-retinoic acid is a powerful inhibitor of all-trans-retinol oxidation. Cimetidine competitively inhibited ethanol oxidation.

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-IV subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P40394-1	1	yes
P40394-2	2

RefSeq proteins (2): NP_000664, NP_001159976 (=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
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF00107, PF08240

Catalyzed reactions (Rhea), 12 shown:

• a primary alcohol + NAD(+) = an aldehyde + NADH + H(+) (RHEA:10736)
• 10-hydroxydecanoate + NAD(+) = 10-oxodecanoate + NADH + H(+) (RHEA:20880)
• all-trans-retinol + NAD(+) = all-trans-retinal + NADH + H(+) (RHEA:21284)
• 9-cis-retinol + NAD(+) = 9-cis-retinal + NADH + H(+) (RHEA:42052)
• all-trans-4-hydroxyretinol + NAD(+) = all-trans-4-hydroxyretinal + NADH + H(+) (RHEA:55936)
• all-trans-3,4-didehydroretinol + NAD(+) = all-trans-3,4-didehydroretinal + NADH + H(+) (RHEA:55940)
• all-trans-4-oxoretinol + NAD(+) = all-trans-4-oxoretinal + NADH + H(+) (RHEA:60632)
• hexan-1-ol + NAD(+) = hexanal + NADH + H(+) (RHEA:60972)
• (E)-4-hydroxynon-2-en-1-ol + NAD(+) = (E)-4-hydroxynon-2-enal + NADH + H(+) (RHEA:60976)
• 12-hydroxydodecanoate + NAD(+) = 12-oxododecanoate + NADH + H(+) (RHEA:60980)
• 16-hydroxyhexadecanoate + NAD(+) = 16-oxohexadecanoate + NADH + H(+) (RHEA:60984)
• (E)-hex-2-en-1-ol + NAD(+) = (E)-hex-2-enal + NADH + H(+) (RHEA:60988)

UniProt features (68 total): strand 20, helix 18, binding site 15, sequence conflict 9, turn 3, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1D1T	X-RAY DIFFRACTION	2.4
1D1S	X-RAY DIFFRACTION	2.5
1AGN	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40394-F1	95.13	0.94

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): 59; 235; 240; 281–283; 304–306; 329–331; 381; 60–64; 80; 110; 113; 116 …

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-211935	Fatty acids
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: 124 (showing top): GOBP_LIPID_MODIFICATION, MODULE_93, GOBP_RESPONSE_TO_ETHANOL, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_RETINOL_METABOLIC_PROCESS, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_RETINOIC_ACID_METABOLIC_PROCESS, MODULE_373, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, YAMASHITA_METHYLATED_IN_PROSTATE_CANCER, REACTOME_ETHANOL_OXIDATION

GO Biological Process (10): retinoid metabolic process (GO:0001523), response to bacterium (GO:0009617), fatty acid omega-oxidation (GO:0010430), retinol metabolic process (GO:0042572), retinoic acid metabolic process (GO:0042573), response to ethanol (GO:0045471), ethanol catabolic process (GO:0006068), lipid metabolic process (GO:0006629), monocarboxylic acid metabolic process (GO:0032787), small molecule metabolic process (GO:0044281)

GO Molecular Function (10): alcohol dehydrogenase (NAD+) activity (GO:0004022), aldehyde oxidase activity (GO:0004031), all-trans-retinol dehydrogenase (NAD+) activity (GO:0004745), zinc ion binding (GO:0008270), retinol binding (GO:0019841), ethanol binding (GO:0035276), receptor antagonist activity (GO:0048019), omega-hydroxydecanoate dehydrogenase activity (GO:0050153), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872)

GO Cellular Component (3): cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Cytochrome P450 - arranged by substrate type	1
Phase I - Functionalization of compounds	1
Metabolism	1
Biological oxidations	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
retinoid metabolic process	2
hormone metabolic process	2
alcohol binding	2
cellular anatomical structure	2
diterpenoid metabolic process	1
response to other organism	1
fatty acid oxidation	1
primary alcohol metabolic process	1
olefinic compound metabolic process	1
monocarboxylic acid metabolic process	1
response to alcohol	1
ethanol metabolic process	1
primary alcohol catabolic process	1
primary metabolic process	1
carboxylic acid metabolic process	1
metabolic process	1
alcohol dehydrogenase [NAD(P)+] activity	1
oxidoreductase activity, acting on the aldehyde or oxo group of donors, oxygen as acceptor	1
alcohol dehydrogenase (NAD+) activity	1
transition metal ion binding	1
retinoid binding	1
vitamin binding	1
anion binding	1
signaling receptor binding	1
signaling receptor inhibitor activity	1
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	1
catalytic activity	1
cation binding	1
cytoplasm	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1756 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADH7	AVP	P01185	955
ADH7	ALDH2	P05091	890
ADH7	ALDH1A1	P00352	741
ADH7	TAS2R16	Q9NYV7	726
ADH7	CHRM2	P08172	645
ADH7	ANKK1	Q8NFD2	641
ADH7	ALDH1B1	P30837	571
ADH7	ALDH3A2	P51648	554
ADH7	CYP2E1	P05181	545
ADH7	ALDH9A1	P49189	538
ADH7	ALDH3B2	P48448	532
ADH7	ALDH3A1	P30838	530
ADH7	LDHAL6B	Q9BYZ2	515
ADH7	OPRD1	P41143	514
ADH7	NRXN3	Q9Y4C0	514

IntAct

9 interactions, top by confidence:

A	B	Type	Score
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
PI4KA	A2ML1	psi-mi:“MI:0914”(association)	0.350
SRRT	A2ML1	psi-mi:“MI:0914”(association)	0.350
PI4KAP1	A2ML1	psi-mi:“MI:0914”(association)	0.350
PRXL2A	A2ML1	psi-mi:“MI:0914”(association)	0.350
BMP4	A2ML1	psi-mi:“MI:0914”(association)	0.350
OLFM4	SPINT1	psi-mi:“MI:0914”(association)	0.350
RSRP1	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): ADH7 (Affinity Capture-MS), ADH7 (Co-crystal Structure), ADH7 (Affinity Capture-MS), ADH7 (Affinity Capture-MS), ADH7 (Affinity Capture-MS), ADH7 (Affinity Capture-MS), ADH7 (Affinity Capture-MS), PRKACA (Cross-Linking-MS (XL-MS)), ADH7 (Affinity Capture-MS), ADH7 (Reconstituted Complex)

ESM2 similar proteins: A0A0C5DM37, A0A0U3S9Q3, A0A0U4BHM2, A0A161CAI1, A0A1B1FHP3, A0A2I7G3B2, A0A2I7G3B3, A0A2U1Q018, A0A9E7LUR3, A1L4Y2, B2NI93, E5AE42, O46649, O46650, O57380, O64969, O74540, O94564, P08319, P0CL53, P0DO83, P0DXF9, P0DXJ1, P22797, P25377, P26325, P28332, P30359, P30360, P39714, P40394, P41681, P41682, P48523, P78870, P80468, P86883, Q32L99, Q42726, Q5R7Z8

Diamond homologs: A0A072VPZ8, A0A075TMP0, A0A0U3S9Q3, A0A0U4AHM6, A0A0U4BHM2, A0A161CAI1, A0A1B1FHP3, A0A2P1GIW4, A0A9E7LUR3, B5LAT8, B6YTJ5, C0SPA5, E1ACQ9, O00097, O22380, O24562, O31186, O49482, O58389, O64969, O65621, O82035, O82056, O82515, O94038, P00331, P07246, P0A4X1, P0CH36, P0CH37, P0DO83, P0DXF9, P0DXJ1, P0DXJ3, P12311, P25377, P27250, P30359, P30360, P31655

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1318 predictions. Top by Δscore:

Variant	Effect	Δscore
4:99415473:GTTA:G	donor_loss	1.0000
4:99415474:TTA:T	donor_loss	1.0000
4:99415475:TACC:T	donor_loss	1.0000
4:99415476:A:AT	donor_loss	1.0000
4:99415477:C:CA	donor_loss	1.0000
4:99415613:AAACC:A	acceptor_loss	1.0000
4:99415614:AACCT:A	acceptor_loss	1.0000
4:99415615:ACC:A	acceptor_loss	1.0000
4:99415616:CCT:C	acceptor_loss	1.0000
4:99415617:C:CC	acceptor_gain	1.0000
4:99415617:CT:C	acceptor_loss	1.0000
4:99415618:T:A	acceptor_loss	1.0000
4:99418979:T:A	donor_gain	1.0000
4:99419000:C:A	donor_gain	1.0000
4:99427768:CTTA:C	donor_loss	1.0000
4:99427770:TACC:T	donor_loss	1.0000
4:99427771:ACCTT:A	donor_loss	1.0000
4:99427772:CCT:C	donor_loss	1.0000
4:99427985:TAATA:T	acceptor_gain	1.0000
4:99427986:AATA:A	acceptor_gain	1.0000
4:99427987:ATA:A	acceptor_gain	1.0000
4:99427987:ATAC:A	acceptor_loss	1.0000
4:99427988:TA:T	acceptor_gain	1.0000
4:99427989:AC:A	acceptor_loss	1.0000
4:99427990:C:CC	acceptor_gain	1.0000
4:99427990:CT:C	acceptor_loss	1.0000
4:99427991:T:G	acceptor_loss	1.0000
4:99428085:A:AC	donor_gain	1.0000
4:99428086:C:CT	donor_gain	1.0000
4:99428086:CT:C	donor_gain	1.0000

AlphaMissense

2445 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:99420773:G:C	C207W	0.997
4:99420725:A:C	C223W	0.996
4:99427905:A:C	S156R	0.996
4:99427905:A:T	S156R	0.996
4:99427907:T:G	S156R	0.996
4:99429539:C:G	R50P	0.995
4:99420727:A:G	C223R	0.994
4:99420768:A:T	V209D	0.994
4:99428612:A:G	C59R	0.994
4:99419080:G:C	S301R	0.993
4:99419080:G:T	S301R	0.993
4:99419082:T:G	S301R	0.993
4:99420726:C:T	C223Y	0.993
4:99420696:C:T	G233E	0.992
4:99420697:C:A	G233W	0.992
4:99419012:C:G	R324P	0.991
4:99420775:A:G	C207R	0.991
4:99427906:C:A	S156I	0.991
4:99428545:T:A	E81V	0.991
4:99419007:A:G	W326R	0.990
4:99419007:A:T	W326R	0.990
4:99420560:A:C	F278L	0.990
4:99420560:A:T	F278L	0.990
4:99420562:A:G	F278L	0.990
4:99420774:C:T	C207Y	0.990
4:99427801:C:T	G191E	0.990
4:99428610:A:C	C59W	0.990
4:99418988:C:T	G332E	0.989
4:99419101:G:C	C294W	0.989
4:99420762:C:T	G211D	0.989

dbSNP variants (sampled 300 via entrez): RS1000121445 (4:99434626 T>A), RS1000179416 (4:99436570 A>G), RS1000340010 (4:99416593 C>A,T), RS1000352361 (4:99430541 G>A,C,T), RS1000468492 (4:99430807 TA>T), RS1000472599 (4:99421271 A>C), RS1000518234 (4:99434895 T>G), RS1000588960 (4:99430481 G>A), RS1000698199 (4:99436730 A>C), RS1000700489 (4:99416287 G>C,T), RS1000713882 (4:99421505 A>G), RS1000866872 (4:99426357 A>G,T), RS1000877801 (4:99421540 T>C), RS1001043199 (4:99430229 C>T), RS1001114108 (4:99416046 G>T)

Disease associations

OMIM: gene MIM:600086 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000447_1	Hypertension	5.000000e-06
GCST001011_4	Oral cavity and pharyngeal cancer	9.000000e-17
GCST001883_1	Alcohol dependence	3.000000e-21
GCST001960_8	Eating disorders	8.000000e-06
GCST006054_6	High altitude adaptation	4.000000e-09
GCST006585_333	Blood protein levels	8.000000e-17
GCST006921_3	Regular attendance at a pub or social club	4.000000e-25
GCST007328_82	Alcohol consumption (drinks per week)	1.000000e-08
GCST008522_31	Bitter alcoholic beverage consumption	5.000000e-15
GCST012232_10	Lipoprotein (a) levels	4.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009105	high altitude adaptation
EFO:0009592	social interaction measurement
EFO:0010092	bitter alcoholic beverage consumption measurement
EFO:0006925	lipoprotein A measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2096668 (PROTEIN FAMILY), CHEMBL3867 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs729147	Toxicity	4	anthracyclines and related substances

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs729147	ADH7	4	-1.25	1	anthracyclines and related substances
rs1154461	ADH7		0.00	0
rs971074	ADH7		0.00	0

ChEMBL bioactivities

1 potent at pChembl≥5 of 8 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.13	Ki	740	nM	HEPTYLFORMAMIDE

PubChem BioAssay actives

1 with measured affinity, of 57 total; 1 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	34044: Inhibition of human alcohol dehydrogenase sigma activity	ki	0.7400	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Ethanol	decreases reaction, increases metabolic processing, increases oxidation	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
CBP30 compound	increases expression, decreases reaction	1
sodium arsenate	decreases expression, increases abundance	1
2,6-dichloro-4-nitrophenol	decreases reaction, increases metabolic processing	1
sodium arsenite	increases expression	1
CGP 52608	increases reaction, affects binding	1
bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV)	decreases expression	1
walrycin A	increases expression	1
Fomepizole	decreases reaction, increases oxidation	1
Acetaminophen	increases expression	1
Aerosols	decreases expression	1
Allergens	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Cannabidiol	increases expression	1
Cimetidine	decreases reaction, increases oxidation	1
Pentachlorophenol	decreases reaction, increases metabolic processing	1
Silicon Dioxide	decreases expression	1
Vitamin E	decreases expression	1
2-Propanol	increases oxidation	1
Ethylene Glycol	increases oxidation	1

ChEMBL screening assays

14 unique, capped per target: 14 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)

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