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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 56

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 1 and 2-Hydroxyglutaric Aciduria. Among its related pathways are Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. and Pyruvate metabolism and Citric Acid (TCA) cycle. Gene Ontology (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

GeneHancer (GH) Regulatory Elements for D2HGDH Gene

Promoters and enhancers for D2HGDH Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02I241733 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 568.5 +0.4 432 2.1 HDGF MLX ARID4B SIN3A FEZF1 DMAP1 ZNF143 SP5 ZHX2 MXD4 D2HGDH GC02P241738 PIR35530 ENSG00000215692 ENSG00000223374 ENSG00000235351 SNED1 FARP2 DTYMK ING5
GH02I241732 Enhancer 0.9 Ensembl ENCODE 550.8 -1.9 -1912 0.7 CTCF ATF1 SIN3A EBF1 RAD21 CTBP1 ZNF143 ATF7 RCOR1 IKZF2 D2HGDH ENSG00000235351 ING5 ATG4B ENSG00000224272 GC02P241729
GH02I241742 Promoter 0.8 EPDnew 550.4 +6.8 6765 0.1 GATA3 NFIB POLR2A CREB1 FOS D2HGDH ENSG00000215023 NEU4 ING5 ENSG00000215692 GC02P241747
GH02I241734 Enhancer 0.5 ENCODE 550.8 -1.1 -1068 0 PKNOX1 ESRRA MNT FOS D2HGDH ENSG00000215692 GC02P241738 PIR35530 GC02P241729
GH02I241769 Enhancer 1.6 FANTOM5 Ensembl ENCODE dbSUPER 38.4 +36.9 36861 3.2 HDGF PKNOX1 FOXA2 MLX ZFP64 ARID4B DMAP1 ZNF48 ETS1 YY1 LOC105373976 D2HGDH GAL3ST2 NEU4 GC02P241774
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around D2HGDH on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the D2HGDH gene promoter:

Genomic Locations for D2HGDH Gene

Genomic Locations for D2HGDH Gene
chr2:241,734,579-241,768,816
(GRCh38/hg38)
Size:
34,238 bases
Orientation:
Plus strand
chr2:242,673,994-242,708,231
(GRCh37/hg19)

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:
    Q8N465-D2HDH_HUMAN
    Recommended name:
    D-2-hydroxyglutarate dehydrogenase, mitochondrial
    Protein Accession:
    Q8N465
    Secondary Accessions:
    • B4E3L6
    • E7ENP2
    • Q6IQ24
    • Q8N5Q8

    Protein attributes for D2HGDH Gene

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

    Alternative splice isoforms for D2HGDH Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for D2HGDH Gene

Selected DME Specific Peptides for D2HGDH Gene

Q8N465:
  • CQAGCVLE
  • LDPKGILNPYK
  • AKHVVGYGHLGDGNLHLNVT

Post-translational modifications for D2HGDH Gene

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

Q8N465

UniProtKB/Swiss-Prot:

D2HDH_HUMAN :
  • Belongs to the FAD-binding oxidoreductase/transferase type 4 family.
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,IEA 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

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 D2HGDH gene
Compartment Confidence
mitochondrion 5
cytosol 2
nucleus 1

Subcellular locations from the

Human Protein Atlas (HPA)

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

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,IEA 15070399
GO:0010043 response to zinc ion IEA,ISS 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 174

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
2-hydroxyglutarate
D-2-Hydroxyglutaric acid
  • (R)-2-hydroxy-Pentanedioate
  • (R)-2-hydroxy-Pentanedioic acid
  • (R)-2-Hydroxyglutarate
  • (R)-2-Hydroxyglutaric acid
  • (R)-a-Hydroxyglutarate
2889-31-8
Oxoglutaric acid
  • 2-Ketoglutarate
  • 2-Ketoglutaric acid
  • 2-Oxo-1,5-pentanedioate
  • 2-Oxo-1,5-pentanedioic acid
  • 2-Oxoglutarate
328-50-7
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: - - -
SP6:
SP7: - -
SP8:

Relevant External Links for D2HGDH Gene

GeneLoc Exon Structure for
D2HGDH
ECgene alternative splicing isoforms for
D2HGDH

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:

D2HGDH

SOURCE GeneReport for Unigene cluster for D2HGDH Gene:

Hs.516813

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
Systems:
  • cardiovascular
  • digestive
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • chin
  • ear
  • epiglottis
  • face
  • forehead
  • head
  • jaw
  • larynx
  • mandible
  • maxilla
  • mouth
  • neck
  • pharynx
  • skull
  • vocal cord
Thorax:
  • aorta
  • bronchus
  • esophagus
  • heart
  • heart valve
  • lung
  • trachea
Abdomen:
  • kidney
  • stomach
General:
  • 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
chimpanzee
(Pan troglodytes)
Mammalia D2HGDH 33 34
  • 98.13 (n)
dog
(Canis familiaris)
Mammalia D2HGDH 33 34
  • 85.07 (n)
cow
(Bos Taurus)
Mammalia D2HGDH 33 34
  • 81.76 (n)
mouse
(Mus musculus)
Mammalia D2hgdh 33 16 34
  • 79.66 (n)
rat
(Rattus norvegicus)
Mammalia D2hgdh 33
  • 79.49 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia D2HGDH 34
  • 76 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia D2HGDH 34
  • 71 (a)
OneToOne
chicken
(Gallus gallus)
Aves D2HGDH 33 34
  • 70.33 (n)
lizard
(Anolis carolinensis)
Reptilia D2HGDH 34
  • 65 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia d2hgdh 33
  • 63.67 (n)
zebrafish
(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)
worm
(Caenorhabditis elegans)
Secernentea CELE_F54D5.12 33
  • 48.95 (n)
F54D5.12 34
  • 44 (a)
OneToOne
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)
OneToMany
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)
OneToOne
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

ENSEMBL:
Gene Tree for D2HGDH (if available)
TreeFam:
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 Variation AA Info Type
rs1001658835 uncertain-significance, D-2-hydroxyglutaric aciduria 241,734,647(+) C/G/T 5_prime_UTR_variant, genic_upstream_transcript_variant, non_coding_transcript_variant, upstream_transcript_variant
rs1020849176 uncertain-significance, D-2-hydroxyglutaric aciduria 241,734,656(+) C/T 5_prime_UTR_variant, genic_upstream_transcript_variant, non_coding_transcript_variant, upstream_transcript_variant
rs1022772084 uncertain-significance, D-2-hydroxyglutaric aciduria 241,768,522(+) G/A/C/T 3_prime_UTR_variant, genic_downstream_transcript_variant, non_coding_transcript_variant
rs1105273 likely-benign, benign, not specified, D-2-hydroxyglutaric aciduria 241,751,330(+) C/T coding_sequence_variant, downstream_transcript_variant, genic_downstream_transcript_variant, intron_variant, missense_variant, non_coding_transcript_variant
rs1106639 likely-benign, benign, not specified, D-2-hydroxyglutaric aciduria 241,751,260(+) G/A 3_prime_UTR_variant, coding_sequence_variant, genic_downstream_transcript_variant, intron_variant, missense_variant, non_coding_transcript_variant, synonymous_variant

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)

Additional Variant Information for D2HGDH Gene

Human Gene Mutation Database (HGMD)
D2HGDH
SNPedia medical, phenotypic, and genealogical associations of SNPs for
D2HGDH

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, GTR, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
d-2-hydroxyglutaric aciduria 1
  • d2hga1
2-hydroxyglutaric aciduria
  • combined d-2- and l-2-hydroxyglutaric aciduria
hypotonia
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

D2HDH_HUMAN
  • 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.

Additional Disease Information for D2HGDH

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 58
  2. Identification of a dehydrogenase acting on D-2-hydroxyglutarate. (PMID: 15070399) Achouri Y … Van Schaftingen E (The Biochemical journal 2004) 2 3 4 58
  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 58
  4. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. (PMID: 15815621) Hillier LW … Wilson RK (Nature 2005) 3 4 58
  5. Phenotypic heterogeneity in the presentation of D-2-hydroxyglutaric aciduria in monozygotic twins. (PMID: 16081310) Misra VK … Innis JW (Molecular genetics and metabolism 2005) 3 4 58

Products for D2HGDH Gene

Sources for D2HGDH Gene

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