ADHFE1

protein-coding

alcohol dehydrogenase iron containing 1, the group of Alcohol dehydrogenases

Gene summary

The ADHFE1 gene encodes hydroxyacid-oxoacid transhydrogenase (EC 1.1.99.24), which is responsible for the oxidation of 4-hydroxybutyrate in mammalian tissues (Kardon et al., 2006 [PubMed 16616524]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_144650.3

Inheritance

—

ClinVar variants

U:79B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr8:66,432,492-66,468,907

External References & Databases

Ensembl (ENSG00000147576)

Transcript & Mutation Effects

hg38 • Region Span ~36.4 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 ADHFE1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 76

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_144650.3. 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			75 clinvar	2 clinvar		77
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	79	2	0	81

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 70 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_144650.3	RefSeq	NP_653251.2	14	MANE Select
ENST00000396623.8	Ensembl	ENSP00000379865.3	14	MANE Select
ENST00000276576.11	Ensembl	ENSP00000276576.7	3	Standard
ENST00000396621.7	Ensembl	ENSP00000379864.3	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Interconversion of 2-oxoglutarate and 2-hydroxyglutarate
Pyruvate metabolism and Citric Acid (TCA) cycle
The citric acid (TCA) cycle and respiratory electron transport
Glycolysis and Gluconeogenesis
Leukotriene metabolism

Biological Process

2-oxoglutarate metabolic process
glutamate catabolic process via 2-oxoglutarate
oxidation-reduction process

Molecular Function

alcohol dehydrogenase (NAD) activity
metal ion binding
hydroxyacid-oxoacid transhydrogenase activity

Cellular Component

mitochondrion
mitochondrial matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000396623
Coding exons: 14
Length: 41417
Individuals with no LoFs: 125161
Homozygous LoFs: 14
Heterozygous LoFs: 573
Defined: 125748
p: 0.00234

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0612	265	262	1.01	0.0000139	2994
Missense (PolyPhen)		78	79.912	0.97608		856
Synonymous	0.442	100	106	0.945	0.00000621	974
Loss of Function	1.39	16	23.3	0.688	0.00000116	286

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00044	0.00043	rare
Latino/Admixed American	0.00062	0.00061	rare
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0.00038	0.00038	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00042	0.00042	rare
South Asian	0.017	0.016	notable
Other	0.0013	0.0013	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the cofactor-independent reversible oxidation of gamma-hydroxybutyrate (GHB) to succinic semialdehyde (SSA) coupled to reduction of 2-ketoglutarate (2-KG) to D-2- hydroxyglutarate (D-2-HG). D,L-3-hydroxyisobutyrate and L-3- hydroxybutyrate (L-3-OHB) are also substrates for HOT with 10-fold lower activities. {ECO:0000269|PubMed:16435184}.;

Recessive Scores

pRec: 0.594

Intolerance Scores

LoFtool: 0.649
RVIS EVS: -0.45
RVIS percentile EVS: 24.33

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0293

Gene Damage Prediction

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