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] See more...

Aliases for ADHFE1 Gene

Aliases for ADHFE1 Gene

  • Alcohol Dehydrogenase Iron Containing 1 2 3 5
  • Hydroxyacid-Oxoacid Transhydrogenase, Mitochondrial 3 4
  • Alcohol Dehydrogenase Iron-Containing Protein 1 3 4
  • EC 1.1.99.24 4 51
  • HOT 3 4
  • Fe-Containing Alcohol Dehydrogenase 1 3
  • Hydroxyacid-Oxoacid Transhydrogenase 2
  • Fe-Containing Alcohol Dehydrogenase 4
  • Alcohol Dehydrogenase 8 3
  • HMFT2263 3
  • FLJ32430 2
  • ADHFE1 5
  • ADHFe1 4
  • ADH8 3

External Ids for ADHFE1 Gene

Previous GeneCards Identifiers for ADHFE1 Gene

  • GC08P067067
  • GC08P067394
  • GC08P067507
  • GC08P067344
  • GC08P062834
  • GC08P066430

Summaries for ADHFE1 Gene

Entrez Gene Summary for ADHFE1 Gene

  • 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]

GeneCards Summary for ADHFE1 Gene

ADHFE1 (Alcohol Dehydrogenase Iron Containing 1) is a Protein Coding gene. Diseases associated with ADHFE1 include Flinders Island Spotted Fever and D-2-Hydroxyglutaric Aciduria 1. Among its related pathways are Pyruvate metabolism and Citric Acid (TCA) cycle and Metabolism. Gene Ontology (GO) annotations related to this gene include oxidoreductase activity and hydroxyacid-oxoacid transhydrogenase activity. An important paralog of this gene is ENSG00000285791.

UniProtKB/Swiss-Prot Summary for ADHFE1 Gene

  • 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.

Additional gene information for ADHFE1 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ADHFE1 Gene

Genomics for ADHFE1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ADHFE1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ADHFE1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ADHFE1

Top Transcription factor binding sites by QIAGEN in the ADHFE1 gene promoter:
  • AML1a
  • GR
  • GR-alpha
  • GR-beta
  • Nkx2-5
  • NRF-2

Genomic Locations for ADHFE1 Gene

Genomic Locations for ADHFE1 Gene
chr8:66,432,492-66,468,907
(GRCh38/hg38)
Size:
36,416 bases
Orientation:
Plus strand
chr8:67,342,420-67,383,836
(GRCh37/hg19)
Size:
41,417 bases
Orientation:
Plus strand

Genomic View for ADHFE1 Gene

Genes around ADHFE1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ADHFE1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ADHFE1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ADHFE1 Gene

Proteins for ADHFE1 Gene

  • Protein details for ADHFE1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8IWW8-HOT_HUMAN
    Recommended name:
    Hydroxyacid-oxoacid transhydrogenase, mitochondrial
    Protein Accession:
    Q8IWW8
    Secondary Accessions:
    • B4DTJ8
    • Q49A19
    • Q68CI7
    • Q6P2B6
    • Q96MF9

    Protein attributes for ADHFE1 Gene

    Size:
    467 amino acids
    Molecular mass:
    50308 Da
    Quaternary structure:
    No Data Available

    Alternative splice isoforms for ADHFE1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ADHFE1 Gene

Selected DME Specific Peptides for ADHFE1 Gene

Q8IWW8:
  • LADTLRKFL
  • VDHPLVPHGLSVVLTSPAVF
  • QMFPERHLE
  • GTLPQER
  • YQGSNPISD
  • LKRAVRNPDD
  • PLIAVPTT
  • GFGNAGVHLCHG
  • GTGSETTGVAIFD

Post-translational modifications for ADHFE1 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for ADHFE1 Gene

Gene Families for ADHFE1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for ADHFE1 Gene

InterPro:
Blocks:
  • Iron-containing alcohol dehydrogenase
ProtoNet:

Suggested Antigen Peptide Sequences for ADHFE1 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ59864, highly similar to Rattus norvegicus alcohol dehydrogenase, iron containing, 1 (Adhfe1), mRNA (B4DFI7_HUMAN)
  • cDNA FLJ53664, highly similar to Rattus norvegicus alcohol dehydrogenase, iron containing, 1 (Adhfe1), mRNA (B4DV11_HUMAN)
  • Fe-containing alcohol dehydrogenase (HOT_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8IWW8

UniProtKB/Swiss-Prot:

HOT_HUMAN :
  • Belongs to the iron-containing alcohol dehydrogenase family. Hydroxyacid-oxoacid transhydrogenase subfamily.
Family:
  • Belongs to the iron-containing alcohol dehydrogenase family. Hydroxyacid-oxoacid transhydrogenase subfamily.
genes like me logo Genes that share domains with ADHFE1: view

Function for ADHFE1 Gene

Molecular function for ADHFE1 Gene

UniProtKB/Swiss-Prot 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.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(S)-3-hydroxybutanoate + 2-oxoglutarate = (R)-2-hydroxyglutarate + acetoacetate; Xref=Rhea:RHEA:23048, ChEBI:CHEBI:11047, ChEBI:CHEBI:13705, ChEBI:CHEBI:15801, ChEBI:CHEBI:16810; EC=1.1.99.24; Evidence={ECO:0000269|PubMed:16435184};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=2-oxoglutarate + 4-hydroxybutanoate = (R)-2-hydroxyglutarate + succinate semialdehyde; Xref=Rhea:RHEA:24734, ChEBI:CHEBI:15801, ChEBI:CHEBI:16724, ChEBI:CHEBI:16810, ChEBI:CHEBI:57706; EC=1.1.99.24; Evidence={ECO:0000269|PubMed:16435184};.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=0.17 mM for GHB {ECO:0000269|PubMed:16435184}; KM=1.2 mM for 2-KG {ECO:0000269|PubMed:16435184}; KM=0.12 mM for D-2-HG {ECO:0000269|PubMed:16435184}; KM=0.04 mM for SSA {ECO:0000269|PubMed:16435184}; KM=0.8 mM for L-3-OHB {ECO:0000269|PubMed:16435184}; Vmax=16 nmol/h/mg enzyme with GHB and 2-KG as substrates {ECO:0000269|PubMed:16435184}; Vmax=0.5 nmol/h/mg enzyme with SSA and D-2-HG as substrates {ECO:0000269|PubMed:16435184}; Vmax=1.8 nmol/h/mg enzyme with L-3-OHB and 2-KG as substrates {ECO:0000269|PubMed:16435184}; pH dependence: Optimum pH is 7.5. {ECO:0000269|PubMed:16435184};

Enzyme Numbers (IUBMB) for ADHFE1 Gene

Phenotypes From GWAS Catalog for ADHFE1 Gene

Gene Ontology (GO) - Molecular Function for ADHFE1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004022 alcohol dehydrogenase (NAD) activity IBA 21873635
GO:0016491 oxidoreductase activity IEA --
GO:0046872 metal ion binding IEA --
GO:0047988 hydroxyacid-oxoacid transhydrogenase activity EXP,IDA 16435184
genes like me logo Genes that share ontologies with ADHFE1: view
genes like me logo Genes that share phenotypes with ADHFE1: view

Animal Model Products

CRISPR Products

miRNA for ADHFE1 Gene

miRTarBase miRNAs that target ADHFE1

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ADHFE1

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for ADHFE1 Gene

Localization for ADHFE1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ADHFE1 Gene

Mitochondrion.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ADHFE1 gene
Compartment Confidence
mitochondrion 5
plasma membrane 1
extracellular 1
cytoskeleton 1
peroxisome 1
nucleus 1
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for ADHFE1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IBA,ISS --
GO:0005759 mitochondrial matrix TAS --
genes like me logo Genes that share ontologies with ADHFE1: view

Pathways & Interactions for ADHFE1 Gene

genes like me logo Genes that share pathways with ADHFE1: view

Pathways by source for ADHFE1 Gene

Gene Ontology (GO) - Biological Process for ADHFE1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006103 2-oxoglutarate metabolic process TAS --
GO:0006539 glutamate catabolic process via 2-oxoglutarate IDA 16435184
GO:0055114 oxidation-reduction process IEA --
genes like me logo Genes that share ontologies with ADHFE1: view

No data available for SIGNOR curated interactions for ADHFE1 Gene

Drugs & Compounds for ADHFE1 Gene

(8) Drugs for ADHFE1 Gene - From: DrugBank and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Sodium oxybate Approved Pharma Enzyme, substrate 49
4-Hydroxybutyric acid Approved, Illicit, Investigational Pharma 0
Iron Approved, Experimental Pharma 1560
Isopropyl alcohol Approved, Investigational Pharma 0
Propyl alcohol Approved, Experimental Pharma 0

(7) Additional Compounds for ADHFE1 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
(S)-3-Hydroxybutyric acid
  • (+)-3-Hydroxybutyric acid
  • (3S)-3-Hydroxybutyric acid
  • (S)-3-Hydroxybutanoic acid
  • (S)-3Hb
  • (S)-beta-Hydroxybutyric acid
6168-83-8
1-Hexanol
  • 1-Hexyl alcohol
  • 1-Hydroxyhexane
  • Caproic alcohol
  • Hexanol
  • N-Hexyl alcohol
111-27-3
1-Pentanol
  • 1-Pentol
  • 1-Pentyl alcohol
  • Alcool amylique
  • Amyl alcohol, normal
  • Amylalkohol
71-41-0
2-hydroxyglutarate
  • alpha-Hydroxyglutaric acid
  • a-Hydroxyglutarate
  • a-Hydroxyglutaric acid
  • alpha-Hydroxyglutarate
  • α-hydroxyglutarate
D-2-Hydroxyglutaric acid
  • (R)-2-Hydroxyglutarate
  • (R)-Hydroxyglutarate
  • (R)-2-Hydroxyglutaric acid
  • D-2-Hydroxyglutarate
  • (R)-Hydroxyglutaric acid
13095-47-1
genes like me logo Genes that share compounds with ADHFE1: view

Transcripts for ADHFE1 Gene

mRNA/cDNA for ADHFE1 Gene

1 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
16 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ADHFE1

Alternative Splicing Database (ASD) splice patterns (SP) for ADHFE1 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b · 6c ^ 7 ^ 8a · 8b ^ 9a · 9b ^ 10a · 10b ^ 11a · 11b ^ 12 ^ 13a · 13b ^ 14 ^ 15a · 15b ^ 16a · 16b ·
SP1: - -
SP2: - - - -
SP3: - - -
SP4: - - - - -
SP5: - - - -
SP6: - -
SP7: - - - - -
SP8: - - - -
SP9: - - - -
SP10: -
SP11: - - -
SP12:
SP13: - - - -
SP14:
SP15: -

ExUns: 16c ^ 17
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9: -
SP10:
SP11:
SP12:
SP13:
SP14:
SP15:

Relevant External Links for ADHFE1 Gene

GeneLoc Exon Structure for
ADHFE1

Expression for ADHFE1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ADHFE1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for ADHFE1 Gene

This gene is overexpressed in Gallbladder (19.3), Heart (13.0), and Liver (10.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for ADHFE1 Gene



Protein tissue co-expression partners for ADHFE1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ADHFE1

SOURCE GeneReport for Unigene cluster for ADHFE1 Gene:

Hs.720023

mRNA Expression by UniProt/SwissProt for ADHFE1 Gene:

Q8IWW8-HOT_HUMAN
Tissue specificity: Only expressed in adult liver.

Evidence on tissue expression from TISSUES for ADHFE1 Gene

  • Nervous system(4.7)
  • Liver(4.6)
  • Muscle(4.5)
  • Pancreas(4.2)
  • Heart(2.2)
genes like me logo Genes that share expression patterns with ADHFE1: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for ADHFE1 Gene

Orthologs for ADHFE1 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for ADHFE1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia ADHFE1 30
  • 96.04 (n)
Dog
(Canis familiaris)
Mammalia ADHFE1 30 31
  • 90.54 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia ADHFE1 30 31
  • 88.32 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia ADHFE1 31
  • 88 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Adhfe1 30 17 31
  • 87.11 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Adhfe1 30
  • 85.05 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia ADHFE1 31
  • 84 (a)
OneToOne
Chicken
(Gallus gallus)
Aves ADHFE1 30 31
  • 77.75 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia ADHFE1 31
  • 78 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia adhfe1 30
  • 73.79 (n)
MGC75621 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.15864 30
Zebrafish
(Danio rerio)
Actinopterygii adhfe1 30 31
  • 69.15 (n)
OneToOne
Dr.16867 30
Fruit Fly
(Drosophila melanogaster)
Insecta T3dh 30 31
  • 59.71 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta HOT_ANOGA 30
  • 58.53 (n)
Worm
(Caenorhabditis elegans)
Secernentea Y38F1A.6 30 31
  • 52.25 (n)
OneToOne
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ADH4 31 33
  • 24 (a)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.4228 31
  • 62 (a)
OneToOne
Bread mold
(Neurospora crassa)
Ascomycetes NCU04078 30
  • 56.56 (n)
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.12418 30
Species where no ortholog for ADHFE1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for ADHFE1 Gene

ENSEMBL:
Gene Tree for ADHFE1 (if available)
TreeFam:
Gene Tree for ADHFE1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ADHFE1: view image

Paralogs for ADHFE1 Gene

Paralogs for ADHFE1 Gene

genes like me logo Genes that share paralogs with ADHFE1: view

Variants for ADHFE1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ADHFE1 Gene

SNP ID Clinical significance and condition Chr 08 pos Variation AA Info Type
rs1563493534 Uncertain Significance: not provided 66,456,830(+) T/TA NONSENSE
VAR_039470 A breast cancer sample p.Asp242Val
rs1060242 - p.Cys449Arg

Additional dbSNP identifiers (rs#s) for ADHFE1 Gene

Structural Variations from Database of Genomic Variants (DGV) for ADHFE1 Gene

Variant ID Type Subtype PubMed ID
esv3572801 CNV loss 25503493
esv3617484 CNV loss 21293372
nsv1026137 CNV loss 25217958
nsv1078616 CNV duplication 25765185
nsv465702 CNV loss 19166990
nsv611457 CNV loss 21841781
nsv6236 CNV deletion 18451855
nsv6237 CNV insertion 18451855

Variation tolerance for ADHFE1 Gene

Residual Variation Intolerance Score: 24.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.92; 35.65% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ADHFE1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
ADHFE1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ADHFE1 Gene

Disorders for ADHFE1 Gene

MalaCards: The human disease database

(9) MalaCards diseases for ADHFE1 Gene - From: DISEASES

- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for ADHFE1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with ADHFE1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ADHFE1 Gene

Publications for ADHFE1 Gene

  1. Cloning and characterization of a novel human alcohol dehydrogenase gene (ADHFe1). (PMID: 12592711) Deng Y … Mao Y (DNA sequence : the journal of DNA sequencing and mapping 2002) 2 3 4 23
  2. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 41
  3. Kinetic characterization of human hydroxyacid-oxoacid transhydrogenase: relevance to D-2-hydroxyglutaric and gamma-hydroxybutyric acidurias. (PMID: 16435184) Struys EA … Jakobs C (Journal of inherited metabolic disease 2005) 3 4
  4. Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas. (PMID: 15221005) Yamada S … Nakagawara A (Oncogene 2004) 3 4
  5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4

Products for ADHFE1 Gene

Sources for ADHFE1 Gene