ADH4
protein-codingalcohol dehydrogenase 4 (class II), pi polypeptide, the group of Alcohol dehydrogenases
Gene summary
This gene encodes class II alcohol dehydrogenase 4 pi subunit, which 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. Class II alcohol dehydrogenase is a homodimer composed of 2 pi subunits. It exhibits a high activity for oxidation of long-chain aliphatic alcohols and aromatic alcohols and is less sensitive to pyrazole. This gene is localized to chromosome 4 in the cluster of alcohol dehydrogenase genes. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~34.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ADH4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000670.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 58 | 1 | 59 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 59 | 1 | 0 | 60 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000661.2 | 9 | MANE Select | |
| Ensembl | ENSP00000265512.7 | 9 | MANE Select | |
| RefSeq | NP_001293100.1 | 9 | Standard | |
| RefSeq | NP_001293101.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Retinol metabolism - Homo sapiens (human)
- Glycolysis / Gluconeogenesis - Homo sapiens (human)
- Fatty acid degradation - Homo sapiens (human)
- Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human)
- Drug metabolism - cytochrome P450 - Homo sapiens (human)
Biological Process
- retinoid metabolic process
- alcohol metabolic process
- ethanol oxidation
- cellular aldehyde metabolic process
- retinol metabolic process
Molecular Function
- NADPH:quinone reductase activity
- alcohol dehydrogenase (NAD) activity
- alcohol dehydrogenase activity, zinc-dependent
- alditol:NADP+ 1-oxidoreductase activity
- retinol dehydrogenase activity
Cellular Component
- nucleus
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000265512
- Coding exons
- 9
- Length
- 34142
- Individuals with no LoFs
- 125622
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 123
- Defined
- 125745
- p
- 0.000489
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0325 | 199 | 200 | 0.994 | 0.00000941 | 2470 |
| Missense (PolyPhen) | 74 | 82.005 | 0.90238 | 1011 | ||
| Synonymous | 1.14 | 61 | 73.4 | 0.831 | 0.00000369 | 764 |
| Loss of Function | 0.815 | 11 | 14.3 | 0.768 | 5.97e-7 | 207 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0025 | 0.0025 | notable |
| Latino/Admixed American | 0.0011 | 0.0011 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00060 | 0.00060 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00024 | 0.00024 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.184
Intolerance Scores
- LoFtool
- 0.930
- RVIS EVS
- 0.17
- RVIS percentile EVS
- 65.96
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.277
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |