ADH5: Alcohol Dehydrogenase 5 (Class III), Chi Polypeptide
A key enzyme in formaldehyde detoxification and nitric oxide metabolism
Gene Information Card
| Symbol | ADH5 |
|---|---|
| Full Name | Alcohol Dehydrogenase 5 (Class III), Chi Polypeptide |
| Gene Type | Protein coding |
| Chromosomal Location | 4q23 |
| NCBI Gene ID | 128 ncbi.nlm.nih.gov/gene/128 |
| Ensembl ID | ENSG00000198099 |
| UniProt ID | P11766 |
| OMIM ID | 103710 |
| HGNC ID | 253 |
| Aliases | ADHX, FDH, GSH-FDH, HEL-S-60p, ADH-3 |
Description
ADH5 encodes a member of the alcohol dehydrogenase family, class III (chi). This enzyme is a glutathione-dependent formaldehyde dehydrogenase, playing a critical role in the detoxification of formaldehyde and other alcohols. It also functions as an S-nitrosoglutathione reductase (GSNOR), regulating intracellular levels of S-nitrosoglutathione and thereby modulating nitric oxide signaling. ADH5 is ubiquitously expressed and is involved in cellular defense against oxidative stress and in the metabolism of endogenous and exogenous alcohols.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alcohol Dependence | ADH5 polymorphisms may influence alcohol metabolism and risk of dependence; altered enzyme activity affects acetaldehyde clearance. | NCBI Gene, OMIM |
| Cancer (various types) | ADH5 expression is altered in several cancers; GSNOR activity influences nitric oxide signaling and tumor progression. | COSMIC, NCBI Gene |
| Formaldehyde Toxicity | Deficiency in ADH5 leads to impaired formaldehyde detoxification, causing cellular damage and increased cancer risk. | UniProt, OMIM |
| Asthma | ADH5 polymorphisms have been associated with asthma susceptibility, possibly through modulation of nitrosative stress. | NCBI Gene, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 28.5 | High |
| Kidney | 18.2 | Medium |
| Lung | 15.1 | Medium |
| Brain | 12.3 | Medium |
| Heart | 10.8 | Medium |
| Skeletal Muscle | 8.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 32.1 | Hepatocellular carcinoma cell line |
| A549 | 22.4 | Lung carcinoma cell line |
| HEK293 | 19.7 | Embryonic kidney cells |
| HeLa | 16.5 | Cervical adenocarcinoma cells |
| MCF7 | 14.2 | Breast adenocarcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Likely loss of function; initiation codon disrupted |
| c.115C>T (p.Arg39Cys) | Missense | 0.02% | Reduced enzyme activity; associated with altered alcohol metabolism |
| c.374G>A (p.Arg125His) | Missense | 0.01% | Decreased catalytic efficiency |
| c.448C>T (p.Arg150*) | Nonsense | <0.01% | Premature stop; loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg150*, p.Met1?) that abolish or severely reduce enzyme activity, leading to impaired formaldehyde and GSNO metabolism.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in ADH5.
Dominant Negative (DN)
No evidence for dominant-negative effects; ADH5 functions as a dimer, but reported mutations are recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004022 - alcohol dehydrogenase (NAD+) activity | • GO:0004024 - alcohol dehydrogenase activity |
| • zinc-dependent | • GO:0016491 - oxidoreductase activity |
| • GO:0008270 - zinc ion binding | • GO:0051904 - S-nitrosoglutathione reductase activity |
| • GO:0006069 - ethanol oxidation | • GO:0046294 - formaldehyde catabolic process |
| • GO:0034614 - cellular response to reactive oxygen species |
Pathways
• Alcohol metabolism (Reactome: R-HSA-71311)
• Formaldehyde detoxification (Reactome: R-HSA-71384)
• Nitric oxide signaling (Reactome: R-HSA-202131)
• Metabolism of xenobiotics by cytochrome P450 (KEGG: hsa00980)
Protein Summary
ADH5 encodes a 40.5 kDa protein (374 amino acids) that belongs to the medium-chain alcohol dehydrogenase family. It is a homodimeric, zinc-dependent enzyme that catalyzes the oxidation of various alcohols, including ethanol and formaldehyde, using NAD+ as a cofactor. Its unique glutathione-dependent formaldehyde dehydrogenase activity is essential for detoxifying formaldehyde, a potent cellular toxin. Additionally, as S-nitrosoglutathione reductase (GSNOR), it regulates protein S-nitrosylation and nitric oxide signaling, impacting vascular tone, immune response, and cell survival. The protein is ubiquitously expressed, with highest levels in liver and kidney.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADH5 Knockout HEK293 Cell Line | EDJ-KQ4010 | Human | 128 | Details Get a Quote |
| ADH5 Knockout A-549 Cell Line | EDJ-KQ24993 | Human | 128 | Details Get a Quote |
| ADH5 Knockout HeLa Cell Line | EDJ-KQ26336 | Human | 128 | Details Get a Quote |
| ADH5 Knockout HCT 116 Cell Line | EDC08299 | Human | 128 | Details Get a Quote |
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