ADH6: Alcohol Dehydrogenase 6 (Class V)
Genetic and Functional Insights into ADH6, a Class V Alcohol Dehydrogenase Involved in Ethanol Metabolism and Retinoid Oxidation
Gene Information Card
| Symbol | ADH6 |
|---|---|
| Full Name | Alcohol Dehydrogenase 6 (Class V) |
| Gene Type | Protein coding |
| Chromosomal Location | 4q23 |
| NCBI Gene ID | 130 ncbi.nlm.nih.gov/gene/130 |
| Ensembl ID | ENSG00000172955 |
| UniProt ID | P28332 |
| OMIM ID | 103735 |
| HGNC ID | 255 |
| Aliases | ADH-6, ADHX, ADH5 (formerly, but distinct from ADH5) |
Description
ADH6 encodes alcohol dehydrogenase 6, a member of the class V alcohol dehydrogenase family. This enzyme catalyzes the oxidation of ethanol and other primary alcohols, as well as the oxidation of retinol (vitamin A) to retinaldehyde, playing a role in ethanol metabolism and retinoid signaling. The gene is located on chromosome 4q23 within the alcohol dehydrogenase gene cluster.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alcohol Dependence | Polymorphisms in ADH6 may alter ethanol oxidation rate, influencing alcohol metabolism and risk of dependence. | PMID: 19012866; ClinVar |
| Fetal Alcohol Spectrum Disorders (FASD) | Variants affecting retinol oxidation may disrupt retinoid signaling during development. | PMID: 23571566 |
| Cancer (gastric, liver) | Altered ADH6 expression linked to retinoic acid metabolism dysregulation in tumorigenesis. | COSMIC; PMID: 25691468 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 3.2 | Low |
| Kidney | 1.8 | Low |
| Stomach | 4.5 | Medium |
| Small Intestine | 2.1 | Low |
| Adrenal Gland | 1.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 2.5 | Hepatocellular carcinoma cell line |
| MCF7 | 0.8 | Breast cancer cell line |
| A549 | 1.2 | Lung carcinoma cell line |
| K562 | 0.5 | Chronic myeloid leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs4147541 (c.87G>A, p.Thr29=) | Synonymous | 0.12 (gnomAD) | Likely benign; no functional change |
| rs1229984 (c.143A>G, p.His48Arg) | Missense | 0.05 (East Asian) | Alters enzyme kinetics; reduced ethanol oxidation activity |
| c.1A>G (p.Met1Val) | Start loss | <0.01 | Loss of translation initiation; likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Start loss variants (e.g., p.Met1Val) or nonsense mutations that truncate the protein lead to loss of enzymatic activity.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in ADH6.
Dominant Negative (DN)
No evidence for dominant-negative effects; ADH6 functions as a dimer, but no dominant-negative variants described.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004022 - alcohol dehydrogenase (NAD+) activity | • GO:0004745 - retinol dehydrogenase activity |
| • GO:0006067 - ethanol metabolic process | • GO:0001523 - retinoid metabolic process |
| • GO:0005737 - cytoplasm |
Pathways
• Ethanol oxidation (Reactome: R-HSA-71311)
• Retinol metabolism (Reactome: R-HSA-5365859)
• Metabolism of vitamins and cofactors (Reactome: R-HSA-196854)
Protein Summary
Alcohol dehydrogenase 6 (ADH6) is a 40.5 kDa cytosolic enzyme that forms homodimers. It uses NAD+ as a cofactor to oxidize ethanol to acetaldehyde and retinol to retinaldehyde. ADH6 is expressed primarily in the stomach and liver, with lower levels in kidney and small intestine. Its activity contributes to the first-pass metabolism of ethanol and to retinoid homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADH6 Knockout HEK293 Cell Line | EDJ-KQ3359 | Human | 130 | Details Get a Quote |
| ADH6 Knockout HeLa Cell Line | EDJ-KQ52560 | Human | 130 | Details Get a Quote |
| ADH6 Knockout A-549 Cell Line | EDJ-KQ61041 | Human | 130 | Details Get a Quote |
| ADH6 Knockout HCT 116 Cell Line | EDJ-KQ69518 | Human | 130 | Details Get a Quote |
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