D2HGDH

Protein identityUniProt · HPA

UniProt accession

Q8N465

Gene

D2HGDH

Ensembl

ENSG00000180902

Chromosome

2

Canonical length

521 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

521 residues, UniProt reviewed canonical sequence.

>Q8N465|D2HGDH
     1  MLPRRPLAWP AWLLRGAPGA AGSWGRPVGP LARRGCCSAP GTPEVPLTRE RYPVRRLPFS
    61  TVSKQDLAAF ERIVPGGVVT DPEALQAPNV DWLRTLRGCS KVLLRPRTSE EVSHILRHCH
   121  ERNLAVNPQG GNTGMVGGSV PVFDEIILST ARMNRVLSFH SVSGILVCQA GCVLEELSRY
   181  VEERDFIMPL DLGAKGSCHI GGNVATNAGG LRFLRYGSLH GTVLGLEVVL ADGTVLDCLT
   241  SLRKDNTGYD LKQLFIGSEG TLGIITTVSI LCPPKPRAVN VAFLGCPGFA EVLQTFSTCK
   301  GMLGEILSAF EFMDAVCMQL VGRHLHLASP VQESPFYVLI ETSGSNAGHD AEKLGHFLEH
   361  ALGSGLVTDG TMATDQRKVK MLWALRERIT EALSRDGYVY KYDLSLPVER LYDIVTDLRA
   421  RLGPHAKHVV GYGHLGDGNL HLNVTAEAFS PSLLAALEPH VYEWTAGQQG SVSAEHGVGF
   481  RKRDVLGYSK PPGALQLMQQ LKALLDPKGI LNPYKTLPSQ A

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against D2HGDH can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

37 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about D2HGDH.

Disease | AllUniProt

Conditions D2HGDH is implicated in, by any mechanism.

• D-2-hydroxyglutaric aciduria 1 (D2HGA1) MIM:600721

Disease | GeneticClinVar

30 pathogenic / likely-pathogenic of 454 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• D-2-hydroxyglutaric aciduria 1
• D-2-hydroxyglutaric aciduria
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.58

gnomAD pLI

0.05

gnomAD missense Z

0.72

DepMap mean gene effect

-0.05

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• 2-oxoglutarate metabolic process
• lactate metabolic process
• malate metabolic process
• protein destabilization
• response to cobalt ion
• response to manganese ion
• response to zinc ion
• tartrate metabolic process

Molecular functions

• FAD binding
• zinc ion binding
• (R)-2-hydroxyglutarate dehydrogenase activity

Cellular components

• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• FAD-binding oxidoreductase/transferase, type 4, C-terminal
• FAD linked oxidase, N-terminal
• FAD-linked oxidase-like, C-terminal
• FAD-binding domain, PCMH-type
• FAD-binding, type PCMH, subdomain 1
• FAD-binding, type PCMH, subdomain 2
• Vanillyl-alcohol oxidase, C-terminal subdomain 2
• FAD-binding, type PCMH-like superfamily
• FAD binding domain
• FAD linked oxidases, C-terminal domain
• FAD-binding Oxidoreductase/Transferase Type 4

KeywordsUniProt

• FAD
• Flavoprotein
• Metal-binding
• Mitochondrion
• Oxidoreductase
• Transit peptide
• Zinc