ADH5

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

Basic information

Region (hg38): 4:99070977-99088801

Previous symbols: [ "FDH" ]

Links

ENSG00000197894 ∙ NCBI:128 ∙ OMIM:103710 ∙ HGNC:253 ∙ Uniprot:P11766 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• AMED syndrome, digenic (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
AMED syndrome, digenic	Digenic	Hematologic; Oncologic	The condition can include bone marrow failure as well as predisposition to malignancy, and awareness may allow early diagnosis and management of these manifestations	Craniofacial; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Oncologic	33355142
The condition is described as being caused by bi-allelic variants in ADH5 and a specific allele in ALDH2

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADH5 gene.

• Inborn genetic diseases (11 variants)
• not provided (2 variants)
• AMED syndrome, digenic (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADH5 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			12			12
nonsense						0
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	1	0	12	0	0

Highest pathogenic variant AF is 0.00000657

Variants in ADH5

This is a list of pathogenic ClinVar variants found in the ADH5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-99072706-TC-T		AMED syndrome, digenic	Pathogenic (Oct 02, 2021)
4-99074925-G-T		not specified	Uncertain significance (May 31, 2023)
4-99074931-TTCCATG-T		AMED syndrome, digenic	Uncertain significance (Mar 29, 2024)
4-99074959-A-G		not specified	Uncertain significance (May 08, 2023)
4-99074995-C-T		not specified	Uncertain significance (Mar 21, 2023)
4-99075043-C-G		AMED syndrome, digenic	Pathogenic (Jan 21, 2021)
4-99075057-C-A			Likely benign (May 01, 2022)
4-99076364-C-G		not specified	Uncertain significance (Nov 08, 2022)
4-99076398-C-T		not specified	Uncertain significance (Jan 09, 2024)
4-99076464-C-A		not specified	Uncertain significance (Dec 21, 2023)
4-99076703-C-T		AMED syndrome, digenic	Pathogenic (Jan 21, 2021)
4-99076712-T-C		not specified	Uncertain significance (Mar 06, 2023)
4-99076804-A-G		not specified	Uncertain significance (Oct 25, 2022)
4-99076847-T-C		not specified	Uncertain significance (Aug 17, 2021)
4-99076876-G-T		not specified	Uncertain significance (Sep 17, 2021)
4-99082053-A-C		not specified	Uncertain significance (Apr 25, 2023)
4-99085122-C-T		not specified	Uncertain significance (Mar 16, 2022)
4-99085165-T-C		not specified	Uncertain significance (May 04, 2023)
4-99088692-G-C			Uncertain significance (May 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADH5	protein_coding	protein_coding	ENST00000296412	9	17821

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.54e-11	0.0398	124789	0	70	124859	0.000280

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.03	161	202	0.797	0.0000101	2419
Missense in Polyphen		45	69.623	0.64633		873
Synonymous	1.81	50	69.2	0.723	0.00000363	739
Loss of Function	-0.122	16	15.5	1.03	6.93e-7	223

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000810	0.000795
Ashkenazi Jewish	0.0000993	0.0000993
East Asian	0.000511	0.000498
Finnish	0.000466	0.000464
European (Non-Finnish)	0.000172	0.000168
Middle Eastern	0.000511	0.000498
South Asian	0.000238	0.000229
Other	0.000662	0.000660

dbNSFP

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}.
• Pathway: 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);Chemical carcinogenesis - Homo sapiens (human);Tyrosine metabolism - Homo sapiens (human);Cyclophosphamide Pathway, Pharmacodynamics;Ifosfamide Pathway, Pharmacodynamics;Folate-Alcohol and Cancer Pathway Hypotheses;Amino Acid metabolism;Phase I - Functionalization of compounds;Ethanol oxidation;Biological oxidations;Metabolism;Tyrosine metabolism;formaldehyde oxidation (Consensus)

Recessive Scores

• pRec: 0.344

Intolerance Scores

• loftool: 0.826
• rvis_EVS: 0.19
• rvis_percentile_EVS: 66.82

Haploinsufficiency Scores

• pHI: 0.264
• hipred: N
• hipred_score: 0.177
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.635

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Adh5
• Phenotype: homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: adh5
• Affected structure: liver
• Phenotype tag: abnormal
• Phenotype quality: increased size

Gene ontology

• Biological process: retinoid metabolic process;respiratory system process;ethanol oxidation;peptidyl-cysteine S-nitrosylation;electron transport chain;response to lipopolysaccharide;positive regulation of blood pressure;formaldehyde catabolic process;response to nitrosative stress;response to redox state
• Cellular component: mitochondrion;cytosol;extracellular exosome
• Molecular function: alcohol dehydrogenase (NAD) activity;alcohol dehydrogenase activity, zinc-dependent;fatty acid binding;zinc ion binding;electron transfer activity;formaldehyde dehydrogenase activity;protein homodimerization activity;S-(hydroxymethyl)glutathione dehydrogenase activity