GeneBe

ADH5

protein-coding

alcohol dehydrogenase 5 (class III), chi polypeptide, the group of Alcohol dehydrogenases

Gene summary

This gene encodes 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 encoded protein forms a homodimer. It has virtually no activity for ethanol oxidation, but exhibits high activity for oxidation of long-chain primary alcohols and for oxidation of S-hydroxymethyl-glutathione, a spontaneous adduct between formaldehyde and glutathione. This enzyme is an important component of cellular metabolism for the elimination of formaldehyde, a potent irritant and sensitizing agent that causes lacrymation, rhinitis, pharyngitis, and contact dermatitis. The human genome contains several non-transcribed pseudogenes related to this gene. [provided by RefSeq, Oct 2008]

Previous symbols:
  • FDH

MANE transcript

NM_000671.4

Inheritance

AR, Digenic

ClinVar variants

P:4U:39B:2

Top phenotype

AMED syndrome, digenic

gnomAD constraint

pLI —, LoF o/e 1.03

Max pathogenic AF

—

Genomic locus

chr4:99,070,978-99,088,801

External References & Databases

Ensembl (ENSG00000197894)NCBI Gene (128)OMIM (103710)HGNC:253GenCCUniProt (P11766)AlphaFoldClinVar (ADH5)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~17.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

AMED syndrome, digenicSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030894

Submitter: PanelApp Australia

AMED syndrome, digenicLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030894

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

AMED syndrome, digenicDigenic

Manifestation: Craniofacial; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Oncologic

Intervention: Hematologic; Oncologic

Rationale: The condition can include bone marrow failure as well as predisposition to malignancy, and awareness may allow early diagnosis and management of these manifestations

Comments: The condition is described as being caused by bi-allelic variants in ADH5 and a specific allele in ALDH2

Refs: 33355142Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ADH5 variants in ClinVar

4 Conditions Cataloged
not specifiedTotal: 29
AMED syndrome, digenicTotal: 5
not providedTotal: 4
ADH5-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000671.4. 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
 2
missense
1
clinvar
35
clinvar
 36
nonsense
2
clinvar
 2
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
2
clinvar
2
clinvar
 4
Total40392045

Highest pathogenic variant AF is 0.000021171216

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000671.4RefSeqNP_000662.39MANE Select
ENST00000296412.14EnsemblENSP00000296412.89MANE Select
ENST00000502590.5EnsemblENSP00000422119.14Standard
ENST00000503130.5EnsemblENSP00000427049.15Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
adh5Danio rerio

Structure: liver

Quality: increased size

abnormal

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
  • respiratory system process
  • ethanol oxidation
  • peptidyl-cysteine S-nitrosylation
  • electron transport chain

Molecular Function

  • alcohol dehydrogenase (NAD) activity
  • alcohol dehydrogenase activity, zinc-dependent
  • fatty acid binding
  • zinc ion binding
  • electron transfer activity

Cellular Component

  • mitochondrion
  • cytosol
  • extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000296412
Coding exons
9
Length
17821
Individuals with no LoFs
124789
Homozygous LoFs
0
Heterozygous LoFs
70
Defined
124859
p
0.000280
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.031612020.7970.00001012419
Missense (PolyPhen)4569.6230.64633873
Synonymous1.815069.20.7230.00000363739
Loss of Function-0.1221615.51.036.93e-7223

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000400.00039rare
Latino/Admixed American0.000410.00041rare
Ashkenazi Jewish0.0000990.000099rare
East Asian0.000510.00050rare
Finnish0.000470.00046rare
European (Non-Finnish)0.000170.00017rare
South Asian0.000240.00023rare
Other0.000660.00066rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Class-III ADH is remarkably ineffective in oxidizing ethanol, but it readily catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione. {ECO:0000269|PubMed:8460164}.;

Recessive Scores

pRec
0.344

Intolerance Scores

LoFtool
0.826
RVIS EVS
0.19
RVIS percentile EVS
66.82

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.635

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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