ADH4: Alcohol Dehydrogenase 4 (Class II), Pi Polypeptide
Genetic and functional insights into ADH4, a key enzyme in ethanol metabolism and its association with alcohol dependence, cancer risk, and metabolic disorders.
Gene Information Card
| Symbol | ADH4 |
|---|---|
| Full Name | Alcohol Dehydrogenase 4 (Class II), Pi Polypeptide |
| Gene Type | protein-coding |
| Chromosomal Location | 4q23 |
| NCBI Gene ID | 127 ncbi.nlm.nih.gov/gene/127 |
| Ensembl ID | ENSG00000198099 |
| UniProt ID | P08319 |
| OMIM ID | 103740 |
| HGNC ID | 251 |
| Aliases | ADH-2, ADH2, HEL-S-4, class II alcohol dehydrogenase |
Description
ADH4 encodes alcohol dehydrogenase 4 (class II), pi polypeptide, a member of the alcohol dehydrogenase family. This enzyme is primarily expressed in the liver and stomach and catalyzes the oxidation of ethanol to acetaldehyde, playing a key role in ethanol metabolism. Polymorphisms in ADH4 are associated with altered alcohol metabolism, alcohol dependence, and susceptibility to certain cancers, including gastric and liver cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alcohol Dependence | ADH4 variants alter ethanol oxidation rate, affecting acetaldehyde accumulation and drinking behavior | PMID: 19124644; ClinVar |
| Gastric Cancer | ADH4 polymorphisms influence local ethanol metabolism in gastric mucosa, modulating carcinogen exposure | PMID: 22922874; COSMIC |
| Liver Cancer | Altered ADH4 expression affects hepatic ethanol metabolism and oxidative stress, contributing to hepatocarcinogenesis | PMID: 25652308; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 38.2 | High |
| Stomach | 12.5 | Medium |
| Kidney | 4.1 | Low |
| Adrenal Gland | 3.8 | Low |
| Small Intestine | 2.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.3 | Hepatocellular carcinoma cell line |
| MKN45 | 8.7 | Gastric cancer cell line |
| HEK293 | 1.2 | Embryonic kidney cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1800759 (Arg48His) | Missense | 0.15 (East Asian) | Reduced enzyme activity; altered ethanol metabolism |
| rs1126671 (Arg370Cys) | Missense | 0.05 (European) | Decreased catalytic efficiency; associated with alcohol dependence |
| rs4148886 (Intronic) | Intron variant | 0.20 (Global) | Linked to altered ADH4 expression; cancer risk modifier |
Mutation functional classification
Loss of Function (LOF)
rs1800759 (Arg48His) reduces catalytic activity by ~50%, impairing ethanol oxidation.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in ADH4.
Dominant Negative (DN)
No evidence of dominant-negative effects for ADH4 variants.
View complete mutation data：
Gene Ontology (GO)
| • alcohol dehydrogenase (NAD+) activity | • zinc ion binding |
| • ethanol oxidation | • retinol dehydrogenase activity |
| • cellular response to ethanol |
Pathways
• Ethanol oxidation (Reactome: R-HSA-71311)
• Retinol metabolism (KEGG: hsa00830)
• Metabolism of xenobiotics by cytochrome P450 (KEGG: hsa00980)
Protein Summary
ADH4 encodes a 375-amino-acid protein (class II alcohol dehydrogenase) that forms homodimers and uses NAD+ as a cofactor to oxidize ethanol to acetaldehyde. It is highly expressed in the liver and stomach, with lower levels in other tissues. The enzyme also metabolizes retinol and other aliphatic alcohols. Structural differences from class I ADH enzymes include a narrower substrate-binding pocket, affecting substrate specificity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADH4 Knockout HEK293 Cell Line | EDJ-KQ2163 | Human | 127 | Details Get a Quote |
| ADH4 Knockout HeLa Cell Line | EDJ-KQ52559 | Human | 127 | Details Get a Quote |
| ADH4 Knockout A-549 Cell Line | EDJ-KQ61040 | Human | 127 | Details Get a Quote |
| ADH4 Knockout HCT 116 Cell Line | EDJ-KQ69517 | Human | 127 | Details Get a Quote |
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