ALDH2

aldehyde dehydrogenase 2 family member, the group of Aldehyde dehydrogenases|MicroRNA protein coding host genes

Basic information

Region (hg38): 12:111766886-111817532

Links

ENSG00000111275 ∙ NCBI:217 ∙ OMIM:100650 ∙ HGNC:404 ∙ Uniprot:P05091 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALDH2 gene.

• Inborn genetic diseases (12 variants)
• not provided (11 variants)
• Alcohol sensitivity, acute (3 variants)
• ethanol response - Toxicity (1 variants)
• Susceptibility to hangover (1 variants)
• Sublingual nitroglycerin, susceptibility to poor response to (1 variants)
• Alcohol dependence (1 variants)
• Esophageal cancer, alcohol-related, susceptibility to (1 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 ALDH2 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				2	4	6
missense			13	2	2	17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	13	5	6

Variants in ALDH2

This is a list of pathogenic ClinVar variants found in the ALDH2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-111767072-G-T		not specified	Uncertain significance (Mar 07, 2023)
12-111781924-A-G		ALDH2-related disorder	Benign/Likely benign (Aug 28, 2019)
12-111782000-G-C		not specified	Uncertain significance (Jun 29, 2023)
12-111782020-A-G		not specified	Uncertain significance (Apr 18, 2023)
12-111783212-C-A			Benign (Dec 31, 2019)
12-111783242-G-A		not specified	Uncertain significance (Oct 12, 2022)
12-111783251-C-T			Benign (Jul 12, 2018)
12-111783275-G-A		not specified	Uncertain significance (Jul 13, 2021)
12-111783279-G-A		not specified	Uncertain significance (Jun 11, 2021)
12-111783284-C-T		not specified	Uncertain significance (Jun 28, 2022)
12-111783288-C-T			Uncertain significance (-)
12-111789833-G-A		not specified	Uncertain significance (Mar 29, 2022)
12-111789919-C-T			Likely benign (May 09, 2018)
12-111790444-C-T		not specified	Uncertain significance (Nov 08, 2022)
12-111790445-G-A		ALDH2-related disorder	Benign (Jul 29, 2019)
12-111791355-C-T		Alcohol sensitivity, acute • ALDH2-related disorder	Benign/Likely benign (Aug 12, 2021)
12-111792067-C-T		Alcohol sensitivity, acute	Uncertain significance (Aug 07, 2018)
12-111792115-T-C			Benign (May 21, 2018)
12-111792160-G-A		not specified	Uncertain significance (Aug 30, 2021)
12-111792609-G-A		ALDH2-related disorder	Benign (Jun 24, 2019)
12-111792717-G-A		not specified	Uncertain significance (Jul 28, 2021)
12-111792724-G-C		not specified	Uncertain significance (Apr 22, 2022)
12-111792743-C-T			Likely benign (Jun 12, 2018)
12-111799896-C-T			Likely benign (May 21, 2018)
12-111799980-G-A		ALDH2-related disorder	Benign/Likely benign (Mar 01, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALDH2	protein_coding	protein_coding	ENST00000261733	13	43092

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.40e-10	0.515	125623	1	123	125747	0.000493

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.32	250	316	0.791	0.0000195	3345
Missense in Polyphen		91	129.82	0.70098		1419
Synonymous	-0.548	143	135	1.06	0.00000915	1038
Loss of Function	1.20	18	24.4	0.738	0.00000104	301

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00194	0.00194
Ashkenazi Jewish	0.00	0.00
East Asian	0.000820	0.000816
Finnish	0.00	0.00
European (Non-Finnish)	0.000322	0.000316
Middle Eastern	0.000820	0.000816
South Asian	0.000233	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Pathway: Tryptophan metabolism - Homo sapiens (human);Pyruvate metabolism - Homo sapiens (human);Arginine and proline metabolism - Homo sapiens (human);Glycolysis / Gluconeogenesis - Homo sapiens (human);Glycerolipid metabolism - Homo sapiens (human);beta-Alanine metabolism - Homo sapiens (human);Lysine degradation - Homo sapiens (human);Histidine metabolism - Homo sapiens (human);Fatty acid degradation - Homo sapiens (human);Ascorbate and aldarate metabolism - Homo sapiens (human);Valine, leucine and isoleucine degradation - Homo sapiens (human);Cyclophosphamide Pathway, Pharmacodynamics;Ifosfamide Pathway, Pharmacodynamics;Carnosinuria, carnosinemia;Ureidopropionase deficiency;Pyruvate Dehydrogenase Complex Deficiency;GABA-Transaminase Deficiency;Disulfiram Action Pathway;3-Methylglutaconic Aciduria Type I;Valine, Leucine and Isoleucine Degradation;2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency;3-Phosphoglycerate dehydrogenase deficiency;Histidine Metabolism;Non Ketotic Hyperglycinemia;Glycine and Serine Metabolism;Beta-Alanine Metabolism;Primary hyperoxaluria II, PH2;Pyruvate kinase deficiency;Leigh Syndrome;Isovaleric Aciduria;3-Methylcrotonyl Coa Carboxylase Deficiency Type I;Propionic Acidemia;Maple Syrup Urine Disease;Histidinemia;3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency;Oxidation of Branched Chain Fatty Acids;Isobutyryl-coa dehydrogenase deficiency;3-hydroxyisobutyric aciduria;3-hydroxyisobutyric acid dehydrogenase deficiency;Ethanol Degradation;Isovaleric acidemia;Tryptophan Metabolism;Pyruvate Metabolism;Methylmalonate Semialdehyde Dehydrogenase Deficiency;Pyruvate Decarboxylase E1 Component Deficiency (PDHE1 Deficiency);Dimethylglycine Dehydrogenase Deficiency;Hyperglycinemia, non-ketotic;Methylmalonic Aciduria;3-Methylglutaconic Aciduria Type IV;3-Methylglutaconic Aciduria Type III;Dimethylglycine Dehydrogenase Deficiency;Sarcosinemia;Beta-Ketothiolase Deficiency;Dihydropyrimidine Dehydrogenase Deficiency (DHPD);Fatty Acid Omega Oxidation;Ethanol effects on histone modifications;Tryptophan metabolism;Phase I - Functionalization of compounds;ethanol degradation II;Glutamate Glutamine metabolism;Glycolysis and Gluconeogenesis;Leukotriene metabolism;Ethanol oxidation;Biological oxidations;Metabolism;Lysine degradation;oxidative ethanol degradation III;ethanol degradation IV;Propanoate metabolism;Neuronal System;Histidine metabolism;Lysine metabolism;Tryptophan metabolism;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;Valine, leucine and isoleucine degradation;Butanoate metabolism;Propanoate metabolism;Bile acid biosynthesis;Glycerophospholipid metabolism;Arginine Proline metabolism;Pyruvate metabolism;phenylethylamine degradation I;Metabolism of serotonin;Serotonin clearance from the synaptic cleft;Neurotransmitter clearance;serotonin degradation;Tryptophan degradation;superpathway of tryptophan utilization;Transmission across Chemical Synapses;Valine Leucine Isoleucine degradation;noradrenaline and adrenaline degradation;Histidine degradation;putrescine degradation III (Consensus)

Recessive Scores

• pRec: 0.670

Intolerance Scores

• loftool: 0.727
• rvis_EVS: -0.84
• rvis_percentile_EVS: 11.18

Haploinsufficiency Scores

• pHI: 0.486
• hipred: N
• hipred_score: 0.212
• ghis: 0.506

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.886

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Aldh2
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; pigmentation phenotype; neoplasm; 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); reproductive system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; skeleton phenotype; renal/urinary system phenotype

Gene ontology

• Biological process: carbohydrate metabolic process;alcohol metabolic process;ethanol catabolic process;ethanol oxidation;electron transport chain
• Cellular component: mitochondrial matrix;extracellular exosome
• Molecular function: aldehyde dehydrogenase (NAD) activity;aldehyde dehydrogenase [NAD(P)+] activity;electron transfer activity;glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity;NAD binding