Human Gene L2HGDH (uc001wxu.3)
  Description: Homo sapiens L-2-hydroxyglutarate dehydrogenase (L2HGDH), nuclear gene encoding mitochondrial protein, mRNA.
RefSeq Summary (NM_024884): This gene encodes L-2-hydroxyglutarate dehydrogenase, a FAD-dependent enzyme that oxidizes L-2-hydroxyglutarate to alpha-ketoglutarate in a variety of mammalian tissues. Mutations in this gene cause L-2-hydroxyglutaric aciduria, a rare autosomal recessive neurometabolic disorder resulting in moderate to severe cognitive disability. [provided by RefSeq, Jul 2008].
Transcript (Including UTRs)
   Position: hg19 chr14:50,709,152-50,778,947 Size: 69,796 Total Exon Count: 10 Strand: -
Coding Region
   Position: hg19 chr14:50,713,776-50,778,868 Size: 65,093 Coding Exon Count: 10 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr14:50,709,152-50,778,947)mRNA (may differ from genome)Protein (463 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMalacards
MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: L2HDH_HUMAN
DESCRIPTION: RecName: Full=L-2-hydroxyglutarate dehydrogenase, mitochondrial; EC=1.1.99.2; AltName: Full=Duranin; Flags: Precursor;
CATALYTIC ACTIVITY: (S)-2-hydroxyglutarate + acceptor = 2- oxoglutarate + reduced acceptor.
COFACTOR: FAD.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=800 uM for L-2-hydroxyglutarate;
SUBCELLULAR LOCATION: Mitochondrion.
TISSUE SPECIFICITY: Widely expressed. Highly expressed in brain, testis and muscle. Expressed to a lower extent in lymphocytes, fibroblasts, keratinocytes, placenta, bladder, small intestine, liver and bone marrow.
DISEASE: Defects in L2HGDH are the cause of L-2-hydroxyglutaric aciduria (L2HGA) [MIM:236792]. L2HGA is a rare autosomal recessive disorder clinically characterized by mild psychomotor delay in the first years of life, followed by progressive cerebellar ataxia, dysarthria and moderate to severe mental retardation. Diagnosis is based on the presence of an excess of L-2-hydroxyglutaric acid in urine, blood and cerebrospinal fluid.
MISCELLANEOUS: Was named 'duranin' in honor of Marinus Duran, who first described L-2-hydroxyglutaric aciduria.
SIMILARITY: Belongs to the L2HGDH family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/L2HGDH";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): L2HGDH
CDC HuGE Published Literature: L2HGDH
Positive Disease Associations: Waist Circumference
Related Studies:
  1. Waist Circumference
    , , . [PubMed 0]

-  MalaCards Disease Associations
  MalaCards Gene Search: L2HGDH
Diseases sorted by gene-association score: l-2-hydroxyglutaric aciduria* (1726), 2-hydroxyglutaric aciduria (74), d-2-hydroxyglutaric aciduria (15), amino acid metabolic disorder (5), cerebellar ataxia (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 4.02 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 62.03 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -29.0079-0.367 Picture PostScript Text
3' UTR -1490.744624-0.322 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR006076 - FAD-dep_OxRdtase

Pfam Domains:
PF01266 - FAD dependent oxidoreductase

SCOP Domains:
51735 - NAD(P)-binding Rossmann-fold domains
51905 - FAD/NAD(P)-binding domain
51971 - Nucleotide-binding domain

ModBase Predicted Comparative 3D Structure on Q9H9P8
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0016491 oxidoreductase activity
GO:0047545 2-hydroxyglutarate dehydrogenase activity

Biological Process:
GO:0006103 2-oxoglutarate metabolic process
GO:0044267 cellular protein metabolic process
GO:0055114 oxidation-reduction process

Cellular Component:
GO:0005739 mitochondrion
GO:0005743 mitochondrial inner membrane
GO:0016021 integral component of membrane
GO:0031305 integral component of mitochondrial inner membrane


-  Descriptions from all associated GenBank mRNAs
  BC006117 - Homo sapiens L-2-hydroxyglutarate dehydrogenase, mRNA (cDNA clone MGC:12994 IMAGE:3504996), complete cds.
JF432174 - Synthetic construct Homo sapiens clone IMAGE:100073328 L-2-hydroxyglutarate dehydrogenase (L2HGDH) gene, encodes complete protein.
KJ903253 - Synthetic construct Homo sapiens clone ccsbBroadEn_12647 L2HGDH gene, encodes complete protein.
KR710070 - Synthetic construct Homo sapiens clone CCSBHm_00009296 L2HGDH (L2HGDH) mRNA, encodes complete protein.
KR710071 - Synthetic construct Homo sapiens clone CCSBHm_00009301 L2HGDH (L2HGDH) mRNA, encodes complete protein.
KR710072 - Synthetic construct Homo sapiens clone CCSBHm_00009304 L2HGDH (L2HGDH) mRNA, encodes complete protein.
KR710073 - Synthetic construct Homo sapiens clone CCSBHm_00009306 L2HGDH (L2HGDH) mRNA, encodes complete protein.
LF384855 - JP 2014500723-A/192358: Polycomb-Associated Non-Coding RNAs.
AK292627 - Homo sapiens cDNA FLJ76725 complete cds, highly similar to Homo sapiens L-2-hydroxyglutarate dehydrogenase (L2HGDH), mRNA.
AK022680 - Homo sapiens cDNA FLJ12618 fis, clone NT2RM4001666, weakly similar to HYPOTHETICAL 48.6 KD PROTEIN IN ALPA-GABP INTERGENIC REGION.
AY757363 - Homo sapiens putative L-2-hydroxyglutarate dehydrogenase (L2HGDH) mRNA, complete cds.
MA620432 - JP 2018138019-A/192358: Polycomb-Associated Non-Coding RNAs.
JD203248 - Sequence 184272 from Patent EP1572962.
JD203247 - Sequence 184271 from Patent EP1572962.
JD214362 - Sequence 195386 from Patent EP1572962.
JD457573 - Sequence 438597 from Patent EP1572962.
JD293525 - Sequence 274549 from Patent EP1572962.
JD293524 - Sequence 274548 from Patent EP1572962.
JD518536 - Sequence 499560 from Patent EP1572962.
JD518535 - Sequence 499559 from Patent EP1572962.
JD446574 - Sequence 427598 from Patent EP1572962.
JD457164 - Sequence 438188 from Patent EP1572962.
JD335361 - Sequence 316385 from Patent EP1572962.
JD442954 - Sequence 423978 from Patent EP1572962.
JD532258 - Sequence 513282 from Patent EP1572962.
JD446573 - Sequence 427597 from Patent EP1572962.
JD558765 - Sequence 539789 from Patent EP1572962.
JD430944 - Sequence 411968 from Patent EP1572962.
JD118440 - Sequence 99464 from Patent EP1572962.
JD326919 - Sequence 307943 from Patent EP1572962.
JD388337 - Sequence 369361 from Patent EP1572962.
JD247807 - Sequence 228831 from Patent EP1572962.
JD335360 - Sequence 316384 from Patent EP1572962.
JD131894 - Sequence 112918 from Patent EP1572962.
JD279578 - Sequence 260602 from Patent EP1572962.
JD499296 - Sequence 480320 from Patent EP1572962.
JD277639 - Sequence 258663 from Patent EP1572962.
JD508280 - Sequence 489304 from Patent EP1572962.
JD295497 - Sequence 276521 from Patent EP1572962.
JD092913 - Sequence 73937 from Patent EP1572962.
JD373897 - Sequence 354921 from Patent EP1572962.
JD214535 - Sequence 195559 from Patent EP1572962.
JD241995 - Sequence 223019 from Patent EP1572962.
JD553895 - Sequence 534919 from Patent EP1572962.
JD078948 - Sequence 59972 from Patent EP1572962.
JD056106 - Sequence 37130 from Patent EP1572962.
JD179073 - Sequence 160097 from Patent EP1572962.
JD421456 - Sequence 402480 from Patent EP1572962.
JD526611 - Sequence 507635 from Patent EP1572962.
JD514912 - Sequence 495936 from Patent EP1572962.
AK309294 - Homo sapiens cDNA, FLJ99335.
CU675259 - Synthetic construct Homo sapiens gateway clone IMAGE:100019415 5' read L2HGDH mRNA.
JD541042 - Sequence 522066 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00650 - Butanoate metabolism

Reactome (by CSHL, EBI, and GO)

Protein Q9H9P8 (Reactome details) participates in the following event(s):

R-HSA-880050 (S)-2-hydroxyglutarate + FAD => 2-oxoglutarate + FADH2
R-HSA-880009 Interconversion of 2-oxoglutarate and 2-hydroxyglutarate
R-HSA-71406 Pyruvate metabolism and Citric Acid (TCA) cycle
R-HSA-1428517 The citric acid (TCA) cycle and respiratory electron transport
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: C14orf160, L2HDH_HUMAN, NM_024884, NP_079160, Q9BRR1, Q9H9P8
UCSC ID: uc001wxu.3
RefSeq Accession: NM_024884
Protein: Q9H9P8 (aka L2HDH_HUMAN)
CCDS: CCDS9698.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_024884.2
exon count: 10CDS single in 3' UTR: no RNA size: 6111
ORF size: 1392CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2984.00frame shift in genome: no % Coverage: 99.74
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: yes # AT/AC introns 0
selenocysteine: no end bleed into intron: 4607# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.