Free for academic non-profit institutions. Other users need a Commercial license

Aliases for D2HGDH Gene

Aliases for D2HGDH Gene

  • D-2-Hydroxyglutarate Dehydrogenase 2 3 5
  • D2HGD 3 4
  • D-2-Hydroxyglutarate Dehydrogenase, Mitochondrial 3
  • EC 1.1.99.- 4
  • EC 1.1.99 58

External Ids for D2HGDH Gene

Previous GeneCards Identifiers for D2HGDH Gene

  • GC02P9M0151
  • GC02P242323
  • GC02P242673
  • GC02P234429

Summaries for D2HGDH Gene

Entrez Gene Summary for D2HGDH Gene

  • This gene encodes D-2hydroxyglutarate dehydrogenase, a mitochondrial enzyme belonging to the FAD-binding oxidoreductase/transferase type 4 family. This enzyme, which is most active in liver and kidney but also active in heart and brain, converts D-2-hydroxyglutarate to 2-ketoglutarate. Mutations in this gene are present in D-2-hydroxyglutaric aciduria, a rare recessive neurometabolic disorder causing developmental delay, epilepsy, hypotonia, and dysmorphic features. [provided by RefSeq, Jul 2008]

GeneCards Summary for D2HGDH Gene

D2HGDH (D-2-Hydroxyglutarate Dehydrogenase) is a Protein Coding gene. Diseases associated with D2HGDH include D-2-Hydroxyglutaric Aciduria and 2-Hydroxyglutaric Aciduria. Among its related pathways are Metabolism and Pyruvate metabolism and Citric Acid (TCA) cycle. GO annotations related to this gene include oxidoreductase activity and oxidoreductase activity, acting on CH-OH group of donors.

UniProtKB/Swiss-Prot for D2HGDH Gene

  • Catalyzes the oxidation of D-2-hydroxyglutarate to alpha-ketoglutarate.

Gene Wiki entry for D2HGDH Gene

Additional gene information for D2HGDH Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for D2HGDH Gene

Genomics for D2HGDH Gene

Regulatory Elements for D2HGDH Gene

Enhancers for D2HGDH Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH02H241769 1.9 FANTOM5 Ensembl ENCODE dbSUPER 38.4 +36.9 36862 3.2 HDGF PKNOX1 MLX ZFP64 ARID4B DMAP1 YY1 SLC30A9 ATF7 PAF1 D2HGDH ENSG00000223374 GAL3ST2 NEU4 GC02P241774 LOC105373976
GH02H241762 1.2 FANTOM5 ENCODE 37.7 +28.7 28688 2.1 PKNOX1 NFIB ZNF207 ATF7 RCOR1 RUNX3 IKZF2 JUNB ELF1 ZNF217 D2HGDH GAL3ST2 ENSG00000224272 ATG4B PDCD1 PIR37451 LOC105373976
GH02H241858 1.4 Ensembl ENCODE dbSUPER 21.5 +125.2 125165 3.1 HDGF PKNOX1 TBL1XR1 ZNF473 SIN3A BATF GLIS2 EGR1 HSF1 ZNF207 ENSG00000224272 D2HGDH NEU4 ENSG00000234793 ENSG00000215023 ATG4B ENSG00000223374 LOC285095 LINC01237 ENSG00000235151
GH02H241543 1.3 Ensembl ENCODE 20 -188.4 -188378 4.4 HDGF PKNOX1 ZNF133 ARID4B YBX1 ZNF2 ZNF121 ZNF766 FOS ZNF548 ENSG00000223374 MTERF4 ATG4B ANKMY1 ING5 CAPN10 FARP2 SNED1 D2HGDH DTYMK
GH02H241616 1.2 ENCODE dbSUPER 20.6 -115.6 -115573 4.1 HDGF PKNOX1 GLI4 YY1 ETS1 ZNF143 FOS SP3 YY2 REST ENSG00000223374 ING5 SNED1 ENSG00000235351 MTERF4 FARP2 BOK D2HGDH DTYMK SEPT2
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around D2HGDH on UCSC Golden Path with GeneCards custom track

Promoters for D2HGDH Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

Genomic Locations for D2HGDH Gene

Genomic Locations for D2HGDH Gene
34,238 bases
Plus strand

Genomic View for D2HGDH Gene

Genes around D2HGDH on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
D2HGDH Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for D2HGDH Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for D2HGDH Gene

Proteins for D2HGDH Gene

  • Protein details for D2HGDH Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    D-2-hydroxyglutarate dehydrogenase, mitochondrial
    Protein Accession:
    Secondary Accessions:
    • B4E3L6
    • E7ENP2
    • Q6IQ24
    • Q8N5Q8

    Protein attributes for D2HGDH Gene

    521 amino acids
    Molecular mass:
    56416 Da
    Name=FAD; Xref=ChEBI:CHEBI:57692;
    Quaternary structure:
    No Data Available
    • Sequence=AAX82020.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

    Alternative splice isoforms for D2HGDH Gene


neXtProt entry for D2HGDH Gene

Selected DME Specific Peptides for D2HGDH Gene


Post-translational modifications for D2HGDH Gene

  • Ubiquitination at posLast=6464
  • Modification sites at PhosphoSitePlus

Domains & Families for D2HGDH Gene

Gene Families for D2HGDH Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Predicted secreted proteins

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the FAD-binding oxidoreductase/transferase type 4 family.
  • Belongs to the FAD-binding oxidoreductase/transferase type 4 family.
genes like me logo Genes that share domains with D2HGDH: view

Function for D2HGDH Gene

Molecular function for D2HGDH Gene

UniProtKB/Swiss-Prot CatalyticActivity:
(R)-2-hydroxyglutarate + acceptor = 2-oxoglutarate + reduced acceptor.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by zinc and cobalt.
UniProtKB/Swiss-Prot Function:
Catalyzes the oxidation of D-2-hydroxyglutarate to alpha-ketoglutarate.

Enzyme Numbers (IUBMB) for D2HGDH Gene

Phenotypes From GWAS Catalog for D2HGDH Gene

Gene Ontology (GO) - Molecular Function for D2HGDH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004458 D-lactate dehydrogenase (cytochrome) activity IBA --
GO:0016491 oxidoreductase activity IEA --
GO:0016614 oxidoreductase activity, acting on CH-OH group of donors IEA --
GO:0050660 flavin adenine dinucleotide binding IEA --
GO:0051990 (R)-2-hydroxyglutarate dehydrogenase activity ISS 15070399
genes like me logo Genes that share ontologies with D2HGDH: view
genes like me logo Genes that share phenotypes with D2HGDH: view

Human Phenotype Ontology for D2HGDH Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

miRNA for D2HGDH Gene

miRTarBase miRNAs that target D2HGDH

Clone Products

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for D2HGDH Gene

Localization for D2HGDH Gene

Subcellular locations from UniProtKB/Swiss-Prot for D2HGDH Gene


Subcellular locations from

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 D2HGDH gene
Compartment Confidence
mitochondrion 5
cytosol 2
nucleus 1

Gene Ontology (GO) - Cellular Components for D2HGDH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion ISS 15070399
GO:0005759 mitochondrial matrix TAS --
genes like me logo Genes that share ontologies with D2HGDH: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for D2HGDH Gene

Pathways & Interactions for D2HGDH Gene

genes like me logo Genes that share pathways with D2HGDH: view

Gene Ontology (GO) - Biological Process for D2HGDH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006103 2-oxoglutarate metabolic process TAS --
GO:0010042 response to manganese ion ISS 15070399
GO:0010043 response to zinc ion ISS,IEA 15070399
GO:0019516 lactate oxidation IBA --
GO:0022904 respiratory electron transport chain IBA --
genes like me logo Genes that share ontologies with D2HGDH: view

No data available for SIGNOR curated interactions for D2HGDH Gene

Drugs & Compounds for D2HGDH Gene

(2) Drugs for D2HGDH Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
FAD Approved Pharma 0
Cobalt Pharma 172

(3) Additional Compounds for D2HGDH Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
D-2-Hydroxyglutaric acid
  • (R)-2-hydroxy-Pentanedioate
  • (R)-2-hydroxy-Pentanedioic acid
  • (R)-2-Hydroxyglutarate
  • (R)-2-Hydroxyglutaric acid
  • (R)-a-Hydroxyglutarate
Oxoglutaric acid
  • 2-Ketoglutarate
  • 2-Ketoglutaric acid
  • 2-Oxo-1,5-pentanedioate
  • 2-Oxo-1,5-pentanedioic acid
  • 2-Oxoglutarate
genes like me logo Genes that share compounds with D2HGDH: view

Transcripts for D2HGDH Gene

mRNA/cDNA for D2HGDH Gene

(33) REFSEQ mRNAs :
(10) Additional mRNA sequences :
(16) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for D2HGDH Gene

D-2-hydroxyglutarate dehydrogenase:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for D2HGDH Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7a · 7b · 7c ^ 8a · 8b ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13a · 13b · 13c
SP1: - - -
SP2: - - - - - - -
SP3: - - - - - - - -
SP4: - - - - - - - - -
SP5: - - -
SP7: - -

Relevant External Links for D2HGDH Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for D2HGDH Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for D2HGDH Gene

Protein differential expression in normal tissues from HIPED for D2HGDH Gene

This gene is overexpressed in Cervix (19.7), Liver (14.1), and Frontal cortex (10.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for D2HGDH Gene

NURSA nuclear receptor signaling pathways regulating expression of D2HGDH Gene:


SOURCE GeneReport for Unigene cluster for D2HGDH Gene:


Evidence on tissue expression from TISSUES for D2HGDH Gene

  • Nervous system(4.4)

Phenotype-based relationships between genes and organs from Gene ORGANizer for D2HGDH Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Head and neck:
  • brain
  • chin
  • ear
  • epiglottis
  • face
  • forehead
  • head
  • jaw
  • larynx
  • mandible
  • maxilla
  • mouth
  • neck
  • pharynx
  • skull
  • vocal cord
  • aorta
  • bronchus
  • esophagus
  • heart
  • heart valve
  • lung
  • trachea
  • kidney
  • stomach
  • blood
  • blood vessel
  • spinal cord
genes like me logo Genes that share expression patterns with D2HGDH: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein tissue co-expression partners and mRNA Expression by UniProt/SwissProt for D2HGDH Gene

Orthologs for D2HGDH Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for D2HGDH Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia D2HGDH 33 34
  • 98.13 (n)
(Canis familiaris)
Mammalia D2HGDH 33 34
  • 85.07 (n)
(Bos Taurus)
Mammalia D2HGDH 33 34
  • 81.76 (n)
(Mus musculus)
Mammalia D2hgdh 33 16 34
  • 79.66 (n)
(Rattus norvegicus)
Mammalia D2hgdh 33
  • 79.49 (n)
(Ornithorhynchus anatinus)
Mammalia D2HGDH 34
  • 76 (a)
(Monodelphis domestica)
Mammalia D2HGDH 34
  • 71 (a)
(Gallus gallus)
Aves D2HGDH 33 34
  • 70.33 (n)
(Anolis carolinensis)
Reptilia D2HGDH 34
  • 65 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia d2hgdh 33
  • 63.67 (n)
(Danio rerio)
Actinopterygii d2hgdh 33 34
  • 66.09 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP004195 33
  • 59.3 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG3835 33 34
  • 58.53 (n)
(Caenorhabditis elegans)
Secernentea CELE_F54D5.12 33
  • 48.95 (n)
F54D5.12 34
  • 44 (a)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ACL021C 33
  • 58.69 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0F05753g 33
  • 54.26 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes DLD2 33 34 36
  • 54.14 (n)
DLD3 34
  • 46 (a)
thale cress
(Arabidopsis thaliana)
eudicotyledons AT4G36400 33
  • 53.88 (n)
bread mold
(Neurospora crassa)
Ascomycetes NCU06441 33
  • 58.32 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 58 (a)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes SPBC713.03 33
  • 49.32 (n)
Species where no ortholog for D2HGDH was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • 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)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for D2HGDH Gene

Gene Tree for D2HGDH (if available)
Gene Tree for D2HGDH (if available)

Paralogs for D2HGDH Gene

genes like me logo Genes that share paralogs with D2HGDH: view

No data available for Paralogs for D2HGDH Gene

Variants for D2HGDH Gene

Sequence variations from dbSNP and Humsavar for D2HGDH Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type
rs121434360 Pathogenic, D-2-hydroxyglutaric aciduria 1 (D2HGA1) [MIM:600721] 241,767,734(+) CAATG(C/T)GACGG nc-transcript-variant, reference, missense, utr-variant-3-prime, stop-lost
rs121434361 Pathogenic, D-2-hydroxyglutaric aciduria 1 (D2HGA1) [MIM:600721] 241,742,524(+) GATCA(G/T)CCTCT nc-transcript-variant, reference, missense, utr-variant-5-prime
rs121434362 Pathogenic, D-2-hydroxyglutaric aciduria 1 (D2HGA1) [MIM:600721] 241,767,718(+) ATGGT(A/G)ACCTG nc-transcript-variant, reference, synonymous-codon, missense, utr-variant-3-prime
rs267606759 Pathogenic, D-2-hydroxyglutaric aciduria 1 (D2HGA1) [MIM:600721] 241,751,371(+) CCACC(A/G/T)ACCAG intron-variant, nc-transcript-variant, downstream-variant-500B, reference, missense, utr-variant-3-prime
rs587783517 Pathogenic 241,743,697(+) CATGC(C/T)GCTGG nc-transcript-variant, reference, missense

Structural Variations from Database of Genomic Variants (DGV) for D2HGDH Gene

Variant ID Type Subtype PubMed ID
nsv997984 CNV gain 25217958
nsv955300 CNV deletion 24416366
nsv584981 CNV loss 21841781
nsv584978 CNV gain+loss 21841781
nsv584977 CNV loss 21841781
nsv584976 CNV loss 21841781
nsv584975 CNV loss 21841781
nsv513026 CNV loss 21212237
nsv1143974 CNV deletion 24896259
nsv1136320 CNV deletion 24896259
nsv1072091 CNV deletion 25765185
nsv10230 CNV loss 18304495
nsv1006733 CNV gain 25217958
nsv1002941 CNV gain 25217958
esv988977 CNV gain 20482838
esv3893578 CNV loss 25118596
esv3594839 CNV loss 21293372
esv3561319 CNV deletion 23714750
esv2722025 CNV deletion 23290073
esv2722024 CNV deletion 23290073
esv2722023 CNV deletion 23290073
esv2722022 CNV deletion 23290073
esv2722021 CNV deletion 23290073
esv2722020 CNV deletion 23290073
esv2656823 CNV deletion 23128226
esv23937 CNV gain 19812545
esv1249069 CNV insertion 17803354
esv1008074 CNV deletion 20482838
dgv7395n54 CNV loss 21841781
dgv165e55 CNV loss 17911159

Variation tolerance for D2HGDH Gene

Residual Variation Intolerance Score: 69.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 11.04; 92.13% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for D2HGDH Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for D2HGDH Gene

Disorders for D2HGDH Gene

MalaCards: The human disease database

(3) MalaCards diseases for D2HGDH Gene - From: HGMD, OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
d-2-hydroxyglutaric aciduria
  • d-2-hga
2-hydroxyglutaric aciduria
  • combined d-2- and l-2-hydroxyglutaric aciduria
- elite association - COSMIC cancer census association via MalaCards


  • D-2-hydroxyglutaric aciduria 1 (D2HGA1) [MIM:600721]: A rare recessive neurometabolic disorder causing developmental delay, epilepsy, hypotonia, and dysmorphic features. Both a mild and a severe phenotype exist. The severe phenotype is homogeneous and is characterized by early infantile-onset epileptic encephalopathy and cardiomyopathy. The mild phenotype has a more variable clinical presentation. Diagnosis is based on the presence of an excess of D-2-hydroxyglutaric acid in the urine. {ECO:0000269 PubMed:15609246, ECO:0000269 PubMed:16037974, ECO:0000269 PubMed:16081310}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for D2HGDH

Human Genome Epidemiology (HuGE) Navigator
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with D2HGDH: view

No data available for Genatlas for D2HGDH Gene

Publications for D2HGDH Gene

  1. Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria. (PMID: 15609246) Struys EA … Jakobs C (American journal of human genetics 2005) 2 3 4 60
  2. Identification of a dehydrogenase acting on D-2-hydroxyglutarate. (PMID: 15070399) Achouri Y … Van Schaftingen E (The Biochemical journal 2004) 2 3 4 60
  3. D-2-hydroxyglutaric aciduria in three patients with proven SSADH deficiency: genetic coincidence or a related biochemical epiphenomenon? (PMID: 16442322) Struys EA … Jakobs C (Molecular genetics and metabolism 2006) 3 4 60
  4. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. (PMID: 15815621) Hillier LW … Wilson RK (Nature 2005) 3 4 60
  5. Mutations in phenotypically mild D-2-hydroxyglutaric aciduria. (PMID: 16037974) Struys EA … Jakobs C (Annals of neurology 2005) 3 4 60

Products for D2HGDH Gene

Sources for D2HGDH Gene

Loading form....