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D2HGDH Gene

protein-coding GIFtS: 44

GC02P242323

D-2-hydroxyglutarate dehydrogenase
Symbol approved by the HUGO Gene Nomenclature Committee (HGNC) database

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc , and/or ⁷Ensembl, ⁸miRBase)
About This Section

Aliases
D2HGD ^¹, ², ³, ⁵
EC 1.1.99.- ^³
FLJ42195 ^¹, ²
MGC25181 ^¹, ²

Descriptions
D-2-hydroxyglutarate dehydrogenase ^²

External Ids
HGNC: 28358¹
Entrez Gene: 728294²
UniProtKB: Q8N465³
Ensembl: ENSG00000180902⁷

Search outside databases for aliases for D2HGDH gene

Previous GC identifer: GC02P9M0151

(According to Entrez Gene, Wikipedia's Gene Wiki,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

EntrezGene summary for D2HGDH:

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]

UniProtKB/Swiss-Prot: D2HDH_HUMAN, Q8N465

Function: Catalyzes the oxidation of D-2-hydroxyglutarate to alpha-ketoglutarate

Gene Wiki entry for D2HGDH

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 36),
and/or miRBase,
Genomic Views according to UCSC and Ensembl, Transcription factor binding sites according to SABiosciences)
About This Section

Genomic View:

UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2q37.3 Ensembl cytogenetic band: 2q37.3 HGNC cytogenetic band: 2p25.3

D2HGDH Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)

GeneLoc gene densities for chromosome 2 GeneLoc Exon Structure

GeneLoc location for GC02P242323: (about GC identifiers)

Start:	242,322,690 bp from pter
End:	242,356,904 bp from pter
Size:	34,215 bases
Orientation:	plus strand

RefSeq DNA sequence:

NT_113880.1 NC_000002.10 NT_005416.12

(According to ¹UniProtKB, and/or Ensembl, Phosphorylation sites according to ²Phosphosite, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Enzo Life Sciences, Abnova, OriGene and/or, Abcam,
Biochemical Assays by Invitrogen, Millipore, R&D Systems, Cell Signaling Technology, and/or Enzo Life Sciences, Ontologies according to Gene Ontology Consortium 01 Apr 2009 and Entrez Gene, Antibodies by Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Cell Signaling Technology, Abcam, Abnova, and/or Novus Biologicals)
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UniProtKB/Swiss-Prot: D2HDH_HUMAN, Q8N465 (See protein sequence)

Recommended Name: D-2-hydroxyglutarate dehydrogenase, mitochondrial precursor

Size: 521 amino acids; 56416 Da

Cofactor: FAD (Potential)

Subcellular location: Mitochondrion (Probable)

Sequence caution: Sequence=AAH31817.2; Type=Miscellaneous discrepancy; Note=Intron retention;

Sequence=AAX82020.1; Type=Erroneous gene model prediction;

Secondary accessions: Q6IQ24 Q8N5Q8

Alternative splicing: 2 isoforms: Q8N465-1 Q8N465-2

REFSEQ proteins: NP_689996.4

ENSEMBL proteins:

ENSP00000315351 ENSP00000339536 ENSP00000384723

Human Recombinant Proteins

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1 Gene Ontology (GO) cellular component term (links to tree view):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005739	mitochondrion	ISS	15070399

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Antibodies for D2HGDH:

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Assays for D2HGDH:

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(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

Graphical View of Domain Structure for InterPro Entry Q8N465

ProtoNet protein and cluster: Q8N465

1 Blocks protein family: IPB004113 FAD linked oxidase

UniProtKB/Swiss-Prot: D2HDH_HUMAN, Q8N465

Similarity: Belongs to the FAD-binding oxidoreductase/transferase type 4 family

Similarity: Contains 1 FAD-binding PCMH-type domain

(According to MGI Jun 06 2009, UniProtKB, IUBMB,and/or Genatlas,
shRNA from OriGene, Sigma-Aldrich, RNAi from Sigma-Aldrich,
RNAi Products, Clones, and Q-PCR Products from Invitrogen, Millipore, OriGene, and/or Abnova, siRNAs from Applied Biosystems, SYBR primers from OriGene, Cell-based Assays from Millipore, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
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Inhib. RNA:		Browse Invitrogen for RNAi
		Browse for Gene Knock-down Tools from Millipore
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Browse Origene for 29mer shRNA kit in GFP-retroviral vector

Applied Biosystems Silencer® siRNAs for D2HGDH

Sigma-Aldrich siRNA for D2HGDH

Browse shRNA at Sigma-Aldrich

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Clones:		Invitrogen Clones for D2HGDH
		Browse Clones for the Expression of Recombinant Proteins Available from Millipore

OriGene GFP tagged cDNA clone in CMV expression vector: NM_152783
Myc/DDK tagged cDNA clone in CMV expression vector: NM_152783
untagged cDNA clones in CMV expression vector (see all 2): BC036604

Primers:

Browse Quantitative PCR Central at Invitrogen for Q-PCR LUX™ Primers

OriGene genome-wide validated SYBR primer pairs: NM_152783

UniProtKB/Swiss-Prot: D2HDH_HUMAN, Q8N465

Function: Catalyzes the oxidation of D-2-hydroxyglutarate to alpha-ketoglutarate

Catalytic activity: (R)-2-hydroxyglutarate + acceptor = 2-oxoglutarate + reduced acceptor

Enzyme regulation: Activated by zinc and cobalt

Enzyme Number (IUBMB): EC 1.1.99.-

4 Gene Ontology (GO) molecular function terms (links to tree view):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005515	protein binding	IPI	17353931
GO:0016491	oxidoreductase activity	IEA	--
GO:0050660	FAD binding	IEA	--
GO:0051990	(R)-2-hydroxyglutarate dehydrogenase activity	ISS	15070399

About this table

(Pathways according to Invitrogen (maps by GeneGo), Millipore, Cell Signaling Technology, Sigma-Aldrich, KEGG and/or UniProtKB,
Sets of similar genes according to GeneDecks, Proteins Network according to SABiosciences, Interactions according to ¹UniProtKB, ²MINT, and/or ³STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
About This Section

1 Interacting protein for D2HGDH (Q8N465¹) via UniProtKB, MINT, and/or STRING
Interactant Interaction Details
GeneCard External ID(s)
RAB25 P57735¹ EBI-1053783, EBI-1050500
About this table
5/7 Gene Ontology (GO) biological process terms (links to tree view) (see all 7 ):
GO ID Qualified GO term Evidence PubMed IDs
GO:0010042 response to manganese ion ISS 15070399
GO:0010043 response to zinc ion ISS 15070399
GO:0032025 response to cobalt ion ISS 15070399
GO:0032026 NOT response to magnesium ion ISS 15070399
GO:0044267 cellular protein metabolic process ISS 15070399
About this table

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, Sigma-Aldrich, Tocris Bioscience, and/or Novoseek and Drugs according to Enzo Life Sciences and/or PharmGKB)
About This Section

Browse drugs & compounds from Enzo Life Sciences

Browse Small Molecules at Sigma-Aldrich

Browse Tocris compounds for D2HGDH

(GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 219 Homo sapiens; Jun 2 2009) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView,
non coding RNAs according to RNAdb,
ESTs according to GeneTide,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from Invitrogen, Millipore, and/or Abnova,
siRNAs from Applied Biosystems, Sigma-Aldrich,
shRNA from Sigma-Aldrich, OriGene,
Tagged/untagged cDNA clones from OriGene,
Expression Assays from Applied Biosystems)
About This Section

Inhib. RNA:		Browse Invitrogen for RNAi
		Browse for Gene Knock-down Tools from Millipore
		Browse Abnova for Chimera RNAi Products

Browse Origene for 29mer shRNA kit in GFP-retroviral vector

Sigma-Aldrich siRNA for D2HGDH

Browse shRNA at Sigma-Aldrich

Explore Sigma-Aldrich super-pooled esiRNAs

Applied Biosystems Silencer® siRNAs:

NM_152783

REFSEQ mRNAs for D2HGDH gene:

NM_152783.3

Applied Biosystems TaqMan ® Gene Expression Assays:

NM_152783

              OriGene GFP tagged cDNA clone in CMV expression vector: NM_152783
                                 Myc/DDK tagged cDNA clone in CMV expression vector: NM_152783
                                 untagged cDNA clones in CMV expression vector (see all 2): BC036604

Additional cDNA sequence:

AK304773.1 AK311066.1

11 DOTS entries:

DT.92068331 DT.99969480 DT.75139555 DT.95211512 DT.108618 DT.121001808 DT.99937479 DT.108617

DT.100781756 DT.102828291 DT.121001801

highest scoring ESTs for D2HGDH:

AA478726 AA479430 AA700770 AF318334 AI283360 AI608921 AI927858 AI953659 AJ346772 AK027102

Unigene Clusters for D2HGDH:

D-2-hydroxyglutarate dehydrogenase

Hs.516813 [show with all ESTs], Hs.535639 [show with all ESTs]

Unigene Representative Sequences: BC036604, NM_152783

GeneLoc Exon Structure

5/8 Alternative Splicing Database (ASD) splice patterns (SP) for D2HGDH (see all 8 )

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:																															-		-		-

About this scheme

ECgene alternative splicing isoforms for D2HGDH

3 Ensembl transcripts including schematic representations:

ENST00000321264 ENST00000342518 ENST00000403782

(Experimental results according to ¹GeneNote and GNF BioGPS,
probe sets-to-genes annotations according to ²GeneAnnot , ³GeneTide , Sets of similar genes according to GeneDecks, Electronic Northern calculations according to data from UniGene (Build 219 Homo sapiens), SAGE tags according to CGAP, plus additional links to SOURCE, and/or GNF BioGPS, and/or EXPOLDB, and/or UniProtKB,
Expression Assays from Applied Biosystems )
About This Section

D2HGDH expression in normal and diseased human tissues

Applied Biosystems TaqMan ® Gene Expression Assays for D2HGDH

¹ / ² / ³

3 probe-sets matching D2HGDH gene

Affymetrix probe-set	Array	# genes	Sensitivity	Specificity	Correlation	Length	Gb_Accession	Consensus	Uniqueness	Score	Rank
Affymetrix probe-set	Array	GeneAnnot data			GeneNote data		GeneTide data
50086_at²^{, 3}	U95-B	2	1.00	0.50	1.00	1.00	AI927858	0.40	1.00	0.76	1
228738_at²^{, 3}	U133-B	2	1.00	0.50	--	--	AI927858	0.40	1.00	0.76	1
228738_at²	U133Plus2	2	1.00	0.50	--	--	--	--	--	--	--

About this table

Data from

(Publications) and GNF BioGPS
About these images
About these images

CGAP SAGE TAG: AATGTCCAGT

SOURCE GeneReport for Unigene clusters: Hs.516813 Hs.535639

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD and/or ⁵MGI Jun 06 2009, with possible further links to Flybase and/or WormBase, Gene Trees according to Ensembl)
About This Section

Orthologs for D2HGDH gene from 2 species

Organism	Gene	Locus	Description	Human Similarity	NCBI accessions
mouse (Mus musculus)	D2hgdh⁵	1	D-2-hydroxyglutarate dehydrogenase	--	CD544497
baker's yeast (Saccharomyces cerevisiae)	DLD2(YDL178W)⁴	4(139523-141115)	D-lactate dehydrogenase, located in the mitochondrial more	--	851376 NP_010103.1

About this table Species with no ortholog for D2HGDH

ENSEMBL Gene Tree for D2HGDH

(Paralogs according to ¹HomoloGene
and ²Ensembl, Pseudogenes according to ³Pseudogene.org)
About This Section

Paralogs for D2HGDH gene

LOC257054¹ LDHD² ENSG00000215692² AGPS²

(According to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, and UniProtKB, Linkage Disequilibrium by HapMap, Genotyping Reagents from Applied Biosystems)
About This Section

(in which this Gene is Involved, According to OMIM, UniProtKB, PharmGKB, Genatlas, GeneTests, Blood group antigen gene mutations by BGMUT, HGMD, GAD, HuGE Navigator, BCGD, and/or TGDB.)
About This Section

OMIM: 609186 disorders: 600721

UniProtKB/Swiss-Prot: D2HDH_HUMAN, Q8N465

Defects in D2HGDH are the cause of D-2-hydroxyglutaric aciduria (D2HGA) [MIM:600721].

D2HGA is 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

Human Gene Mutation Database: D2HGDH

(Possibly Related Articles in Doctor's Guide)
About This Section

(in PubMed. Associations of this gene to articles via ¹Novoseek, ²HGNC, ³Entrez Gene, ⁴UniProtKB/Swiss-Prot, ⁵UniProtKB/TrEMBL, ⁶GAD, and/or ⁷PharmGKB)
About This Section

10/14 PubMed articles for D2HGDH gene (see all 14 ):

Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria. (PubMed id 15609246)^{2, 3, 4} Struys E.A....Jakobs C. (2005)
Identification of a dehydrogenase acting on D-2-hydroxyglutarate. (PubMed id 15070399)^{2, 3, 4} Achouri Y....van Schaftingen E. (2004)
D-2-Hydroxyglutaric aciduria in three patients with proven SSADH deficiency: genetic coincidence or a related biochemical epiphenomenon? (PubMed id 16442322)^{3, 4} Struys E.A....Jakobs C. (2006)
Phenotypic heterogeneity in the presentation of D-2-hydroxyglutaric aciduria in monozygotic twins. (PubMed id 16081310)^{3, 4} Misra V.K.... Innis J.W. (2005)
Generation and annotation of the DNA sequences of human chromosomes 2 and 4. (PubMed id 15815621)^{3, 4} Hillier L.W....Wilson R.K. (2005)
Mutations in phenotypically mild D-2-hydroxyglutaric aciduria. (PubMed id 16037974)^{3, 4} Struys E.A.... Jakobs C. (2005)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{3, 4} Gerhard D.S....Malek J. (2004)
Large-scale mapping of human protein-protein interactions by mass spectrometry. (PubMed id 17353931)³ Ewing R.M....Figeys D. (2007)
Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. (PubMed id 16344560)³ Kimura K.... Sugano S. (2006)
Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)³ Ota T....Sugano S. (2004)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, and/or H-InvDB)
About This Section

Entrez Gene: 728294	HGNC: 28358	Ensembl:ENSG00000180902	euGenes: HUgn728294	ECgene: D2HGDH
H-InvDB: D2HGDH

(According to HUGE)
About This Section

(According to ATLAS, HORDE, IMGT, MTDB, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
GeneReviews	http://www.genetests.org/query?gene=D2HGDH

Licensable Technologies for D2HGDH
(Available from WIS Yeda, Salk, Tufts)

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(Reagents available from Applied Biosystems, Antibodies and assays by Cell Signaling Technology, Abcam, Novus Biologicals,
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Enzo Life Sciences, and/or Tocris Bioscience)
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Products for D2HGDH:

TaqMan ® Gene Expression Assays

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Free SNP selection tool

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D2HGDH Gene

protein-coding GIFtS: 44

Aliases &
Descriptions
for D2HGDH

Summaries
for D2HGDH

Genomic Location
for D2HGDH

Proteins
for D2HGDH

Protein Domains/
Families
for D2HGDH

Gene Function
for D2HGDH

Pathways & Interactions
for D2HGDH

Drugs & Compounds
for D2HGDH

Transcripts
for D2HGDH

Expression
for D2HGDH

Orthologs
for D2HGDH

Paralogs
for D2HGDH

SNPs/Variants
for D2HGDH

Disorders & Mutations
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Medical News
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for D2HGDH

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Specialized Databases showing D2HGDH

Licensable Technologies
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Gene Index: 3 5 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

D2HGDH Gene

protein-coding GIFtS: 44

Aliases & Descriptionsfor D2HGDH

Summariesfor D2HGDH

Genomic Locationfor D2HGDH

Proteinsfor D2HGDH

Protein Domains/Familiesfor D2HGDH

Gene Functionfor D2HGDH

Pathways & Interactionsfor D2HGDH

Drugs & Compoundsfor D2HGDH

Transcriptsfor D2HGDH

Expression for D2HGDH

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Paralogsfor D2HGDH

SNPs/Variantsfor D2HGDH

Disorders & Mutationsfor D2HGDH

Medical Newsfor D2HGDH

Publicationsfor D2HGDH

Search for D2HGDH

Genome Databases showing D2HGDH

Other Databases showing D2HGDH

Specialized Databases showing D2HGDH

Licensable Technologiesfor D2HGDH

Servicesfor D2HGDH

Gene Index: 3 5 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

Aliases &
Descriptions
for D2HGDH

Summaries
for D2HGDH

Genomic Location
for D2HGDH

Proteins
for D2HGDH

Protein Domains/
Families
for D2HGDH

Gene Function
for D2HGDH

Pathways & Interactions
for D2HGDH

Drugs & Compounds
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Transcripts
for D2HGDH

Expression
for D2HGDH

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for D2HGDH

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for D2HGDH

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