ALDH2

protein-coding

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

Gene summary

This protein belongs to the aldehyde dehydrogenase family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. Two major liver isoforms of aldehyde dehydrogenase, cytosolic and mitochondrial, can be distinguished by their electrophoretic mobilities, kinetic properties, and subcellular localizations. Most Caucasians have two major isozymes, while approximately 50% of East Asians have the cytosolic isozyme but not the mitochondrial isozyme. A remarkably higher frequency of acute alcohol intoxication among East Asians than among Caucasians could be related to the absence of a catalytically active form of the mitochondrial isozyme. The increased exposure to acetaldehyde in individuals with the catalytically inactive form may also confer greater susceptibility to many types of cancer. This gene encodes a mitochondrial isoform, which has a low Km for acetaldehydes, and is localized in mitochondrial matrix. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Nov 2016]

MANE transcript

NM_000690.4

Inheritance

—

ClinVar variants

U:40B:13

Top phenotype

ALDH2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chr12:111,766,887-111,817,532

External References & Databases

Ensembl (ENSG00000111275)

Transcript & Mutation Effects

hg38 • Region Span ~50.6 kb

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GenCC 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 ALDH2 variants in ClinVar

10 Conditions Cataloged

not specifiedTotal: 26

not providedTotal: 15

ALDH2-related disorderTotal: 7

Alcohol sensitivity, acuteTotal: 3

ethanol response - ToxicityTotal: 1

Alcohol dependenceTotal: 1

NITROGLYCERIN, POOR RESPONSE TOTotal: 1

Susceptibility to hangoverTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000690.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	3 clinvar	5 clinvar	10
missense			32 clinvar	3 clinvar	2 clinvar	37
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	40	6	7	53

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 118 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000690.4	RefSeq	NP_000681.2	13	MANE Select
ENST00000261733.7	Ensembl	ENSP00000261733.2	13	MANE Select
NM_001204889.2	RefSeq	NP_001191818.1	12	Standard
ENST00000416293.7	Ensembl	ENSP00000403349.3	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

carbohydrate metabolic process
alcohol metabolic process
ethanol catabolic process
ethanol oxidation
electron transport chain

Molecular Function

aldehyde dehydrogenase (NAD) activity
aldehyde dehydrogenase [NAD(P)+] activity
electron transfer activity
glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity
NAD binding

Cellular Component

mitochondrial matrix
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000261733
Coding exons: 13
Length: 43092
Individuals with no LoFs: 125623
Homozygous LoFs: 1
Heterozygous LoFs: 123
Defined: 125747
p: 0.000493

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.32	250	316	0.791	0.0000195	3345
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.0019	0.0019	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00082	0.00082	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00032	0.00032	rare
South Asian	0.00023	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.670

Intolerance Scores

LoFtool: 0.727
RVIS EVS: -0.84
RVIS percentile EVS: 11.18

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.886

Gene Damage Prediction

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