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] See more...

Aliases for L2HGDH Gene

Aliases for L2HGDH Gene

  • L-2-Hydroxyglutarate Dehydrogenase 2 3 5
  • L-2-Hydroxyglutarate Dehydrogenase, Mitochondrial 3 4
  • 2-Hydroxyglutarate Dehydrogenase 2 3
  • EC 1.1.99.2 4 50
  • C14orf160 3 4
  • Duranin 3 4
  • L-Alpha-Hydroxyglutarate Dehydrogenase 3
  • Alpha-Hydroxyglutarate Oxidoreductase 3
  • Chromosome 14 Open Reading Frame 160 2
  • Alpha-Ketoglutarate Reductase 3
  • FLJ12618 2
  • L2HGDH 5
  • L2HGA 3

External Ids for L2HGDH Gene

Previous HGNC Symbols for L2HGDH Gene

  • C14orf160

Previous GeneCards Identifiers for L2HGDH Gene

  • GC14M049775
  • GC14M050704
  • GC14M030834

Summaries for L2HGDH Gene

Entrez Gene Summary for L2HGDH Gene

  • 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]

GeneCards Summary for L2HGDH Gene

L2HGDH (L-2-Hydroxyglutarate Dehydrogenase) is a Protein Coding gene. Diseases associated with L2HGDH include L-2-Hydroxyglutaric Aciduria and 2-Hydroxyglutaric Aciduria. Among its related pathways are Butanoate metabolism and Pyruvate metabolism and Citric Acid (TCA) cycle. Gene Ontology (GO) annotations related to this gene include oxidoreductase activity and 2-hydroxyglutarate dehydrogenase activity. An important paralog of this gene is DMGDH.

Gene Wiki entry for L2HGDH Gene

No data available for CIViC Summary , UniProtKB/Swiss-Prot Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for L2HGDH Gene

Genomics for L2HGDH Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for L2HGDH Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around L2HGDH on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for L2HGDH

Top Transcription factor binding sites by QIAGEN in the L2HGDH gene promoter:
  • C/EBPbeta
  • COUP
  • COUP-TF
  • COUP-TF1
  • HNF-4alpha1
  • HNF-4alpha2
  • Nkx2-5
  • PPAR-gamma1
  • PPAR-gamma2
  • STAT5B

Genomic Locations for L2HGDH Gene

Latest Assembly
chr14:50,237,563-50,312,229
(GRCh38/hg38)
Size:
74,667 bases
Orientation:
Minus strand

Previous Assembly
chr14:50,709,152-50,778,947
(GRCh37/hg19 by Entrez Gene)
Size:
69,796 bases
Orientation:
Minus strand

chr14:50,704,281-50,779,266
(GRCh37/hg19 by Ensembl)
Size:
74,986 bases
Orientation:
Minus strand

Genomic View for L2HGDH Gene

Genes around L2HGDH on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
L2HGDH Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for L2HGDH Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for L2HGDH Gene

Proteins for L2HGDH Gene

  • Protein details for L2HGDH Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9H9P8-L2HDH_HUMAN
    Recommended name:
    L-2-hydroxyglutarate dehydrogenase, mitochondrial
    Protein Accession:
    Q9H9P8
    Secondary Accessions:
    • Q9BRR1

    Protein attributes for L2HGDH Gene

    Size:
    463 amino acids
    Molecular mass:
    50316 Da
    Cofactor:
    Name=FAD; Xref=ChEBI:CHEBI:57692;
    Quaternary structure:
    No Data Available
    Miscellaneous:
    • Was named 'duranin' in honor of Marinus Duran, who first described L-2-hydroxyglutaric aciduria.

    Alternative splice isoforms for L2HGDH Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for L2HGDH Gene

Selected DME Specific Peptides for L2HGDH Gene

Q9H9P8:
  • SLKAKLCV
  • RGPAGVRAQA
  • FPFLGVHFT
  • NIYPVPD
  • HNSGVIH

Post-translational modifications for L2HGDH Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for L2HGDH Gene

Gene Families for L2HGDH Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for L2HGDH Gene

Suggested Antigen Peptide Sequences for L2HGDH Gene

GenScript: Design optimal peptide antigens:
  • Duranin (L2HDH_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9H9P8

UniProtKB/Swiss-Prot:

L2HDH_HUMAN :
  • Belongs to the L2HGDH family.
Family:
  • Belongs to the L2HGDH family.
genes like me logo Genes that share domains with L2HGDH: view

Function for L2HGDH Gene

Molecular function for L2HGDH Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(S)-2-hydroxyglutarate + A = 2-oxoglutarate + AH2; Xref=Rhea:RHEA:21252, ChEBI:CHEBI:13193, ChEBI:CHEBI:16782, ChEBI:CHEBI:16810, ChEBI:CHEBI:17499; EC=1.1.99.2; Evidence={ECO:0000269|PubMed:16005139};.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=800 uM for L-2-hydroxyglutarate {ECO:0000269|PubMed:16005139};

Enzyme Numbers (IUBMB) for L2HGDH Gene

Phenotypes From GWAS Catalog for L2HGDH Gene

Gene Ontology (GO) - Molecular Function for L2HGDH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003973 (S)-2-hydroxy-acid oxidase activity IBA 21873635
GO:0016491 oxidoreductase activity IEA --
GO:0047545 2-hydroxyglutarate dehydrogenase activity IBA,IDA 16005139
genes like me logo Genes that share ontologies with L2HGDH: view
genes like me logo Genes that share phenotypes with L2HGDH: view

Human Phenotype Ontology for L2HGDH Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

miRNA for L2HGDH Gene

miRTarBase miRNAs that target L2HGDH

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for L2HGDH

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for L2HGDH Gene

Localization for L2HGDH Gene

Subcellular locations from UniProtKB/Swiss-Prot for L2HGDH 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 L2HGDH gene
Compartment Confidence
mitochondrion 5
cytosol 2
plasma membrane 1
extracellular 1
cytoskeleton 1
peroxisome 1
nucleus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for L2HGDH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IBA,IDA 16005139
GO:0005743 mitochondrial inner membrane TAS --
GO:0016021 integral component of membrane IDA 16005139
GO:0031305 integral component of mitochondrial inner membrane NAS 16005139
genes like me logo Genes that share ontologies with L2HGDH: view

Pathways & Interactions for L2HGDH Gene

genes like me logo Genes that share pathways with L2HGDH: view

Gene Ontology (GO) - Biological Process for L2HGDH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006103 2-oxoglutarate metabolic process TAS --
GO:0044267 cellular protein metabolic process IDA 16005139
GO:0055114 oxidation-reduction process IEA --
genes like me logo Genes that share ontologies with L2HGDH: view

No data available for SIGNOR curated interactions for L2HGDH Gene

Drugs & Compounds for L2HGDH Gene

(2) Drugs for L2HGDH Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
FAD Approved Pharma 0
Oxogluric acid Experimental, Investigational Nutra 0

(3) Additional Compounds for L2HGDH Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
2-hydroxyglutarate
  • alpha-Hydroxyglutaric acid
  • alpha-Hydroxyglutarate
  • a-Hydroxyglutarate
  • a-Hydroxyglutaric acid
  • Α-hydroxyglutarate
2889-31-8
FADH
  • 1,5-Dihydro-fad
  • DIHYDROFLAVINE-adenine dinucleotide
  • Flavin adenine dinucleotide (reduced)
  • 1,5-Dihydro-p-5-ester with adenosine
  • 1,5-Dihydro-riboflavin 5'-(trihydrogen diphosphate) p'->5'-ester with adenosine
1910-41-4
L-2-Hydroxyglutaric acid
  • (S)-2-Hydroxyglutarate
  • (S)-2-Hydroxyglutaric acid
  • L-2-Hydroxyglutarate
  • (S)-Α-hydroxyglutarate
  • (S)-Α-hydroxyglutaric acid
13095-48-2
genes like me logo Genes that share compounds with L2HGDH: view

Transcripts for L2HGDH Gene

mRNA/cDNA for L2HGDH Gene

1 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for L2HGDH

Alternative Splicing Database (ASD) splice patterns (SP) for L2HGDH Gene

No ASD Table

Relevant External Links for L2HGDH Gene

GeneLoc Exon Structure for
L2HGDH

Expression for L2HGDH Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for L2HGDH Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

  • Kidney (Urinary System)
  • Heart (Cardiovascular System)

Protein differential expression in normal tissues from HIPED for L2HGDH Gene

This gene is overexpressed in Heart (10.5), Peripheral blood mononuclear cells (9.4), and Stomach (7.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for L2HGDH Gene



Protein tissue co-expression partners for L2HGDH Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for L2HGDH

SOURCE GeneReport for Unigene cluster for L2HGDH Gene:

Hs.256034

mRNA Expression by UniProt/SwissProt for L2HGDH Gene:

Q9H9P8-L2HDH_HUMAN
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.

Evidence on tissue expression from TISSUES for L2HGDH Gene

  • Liver(4.4)

Phenotype-based relationships between genes and organs from Gene ORGANizer for L2HGDH Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • immune
  • nervous
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cerebellum
  • cranial nerve
  • ear
  • eye
  • head
  • skull
Limb:
  • lower limb
  • upper limb
General:
  • peripheral nerve
  • peripheral nervous system
  • spinal cord
genes like me logo Genes that share expression patterns with L2HGDH: view

Primer products for research

No data available for mRNA differential expression in normal tissues for L2HGDH Gene

Orthologs for L2HGDH Gene

This gene was present in the common ancestor of animals.

Orthologs for L2HGDH Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia L2HGDH 29 30
  • 99.14 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia L2HGDH 29 30
  • 91.07 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia L2HGDH 29 30
  • 90.28 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia L2hgdh 29 16 30
  • 84.38 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia L2hgdh 29
  • 83.95 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia L2HGDH 30
  • 67 (a)
OneToOne
Chicken
(Gallus gallus)
Aves L2HGDH 29 30
  • 72.38 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia L2HGDH 30
  • 71 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia l2hgdh 29
  • 71.01 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.30010 29
Zebrafish
(Danio rerio)
Actinopterygii l2hgdh 29 30
  • 64.99 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta CG10639 29 30
  • 56.92 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP007868 29
  • 55.48 (n)
Worm
(Caenorhabditis elegans)
Secernentea Y45G12B.3 29 30
  • 56.85 (n)
OneToOne
Species where no ortholog for L2HGDH was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • 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 Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for L2HGDH Gene

ENSEMBL:
Gene Tree for L2HGDH (if available)
TreeFam:
Gene Tree for L2HGDH (if available)
Aminode:
Evolutionary constrained regions (ECRs) for L2HGDH: view image
Alliance of Genome Resources:
Additional Orthologs for L2HGDH

Paralogs for L2HGDH Gene

genes like me logo Genes that share paralogs with L2HGDH: view

Variants for L2HGDH Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for L2HGDH Gene

SNP ID Clinical significance and condition Chr 14 pos Variation AA Info Type
1007053 Uncertain Significance: L-2-hydroxyglutaric aciduria 50,278,520(-) C/T
NM_024884.3(L2HGDH):c.738G>A (p.Lys246=)
SYNONYMOUS
1010586 Uncertain Significance: L-2-hydroxyglutaric aciduria 50,312,033(-) C/G
NM_024884.3(L2HGDH):c.118G>C (p.Gly40Arg)
MISSENSE_VARIANT,INTRON
1010897 Uncertain Significance: L-2-hydroxyglutaric aciduria 50,294,222(-) C/T
NM_024884.3(L2HGDH):c.433G>A (p.Glu145Lys)
MISSENSE
1018292 Uncertain Significance: L-2-hydroxyglutaric aciduria 50,303,006(-) A/G
NM_024884.3(L2HGDH):c.152T>C (p.Ile51Thr)
MISSENSE
1028350 Uncertain Significance: L-2-hydroxyglutaric aciduria 50,302,003(-) A/G
NM_024884.3(L2HGDH):c.408+14T>C
INTRON

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for L2HGDH Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for L2HGDH Gene

Variant ID Type Subtype PubMed ID
esv2664640 CNV deletion 23128226
esv28926 CNV gain+loss 19812545
esv3551539 CNV deletion 23714750
esv3634474 CNV loss 21293372
esv3634475 CNV loss 21293372
esv3634476 CNV loss 21293372
nsv1052059 CNV loss 25217958
nsv1122900 CNV deletion 24896259
nsv564835 CNV gain 21841781
nsv832793 CNV loss 17160897

Variation tolerance for L2HGDH Gene

Residual Variation Intolerance Score: 45.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.72; 46.58% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for L2HGDH Gene

Human Gene Mutation Database (HGMD)
L2HGDH
SNPedia medical, phenotypic, and genealogical associations of SNPs for
L2HGDH
Leiden Open Variation Database (LOVD)
L2HGDH

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for L2HGDH Gene

Disorders for L2HGDH Gene

MalaCards: The human disease database

(14) MalaCards diseases for L2HGDH Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

L2HDH_HUMAN
  • L-2-hydroxyglutaric aciduria (L2HGA) [MIM:236792]: 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. {ECO:0000269 PubMed:15385440, ECO:0000269 PubMed:15548604, ECO:0000269 PubMed:16134148}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for L2HGDH

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with L2HGDH: view

No data available for Genatlas for L2HGDH Gene

Publications for L2HGDH Gene

  1. The gene mutated in l-2-hydroxyglutaric aciduria encodes l-2-hydroxyglutarate dehydrogenase. (PMID: 16005139) Rzem R … Veiga-da-Cunha M (Biochimie 2006) 2 3 4 22
  2. L-2-Hydroxyglutaric aciduria: identification of a mutant gene C14orf160, localized on chromosome 14q22.1. (PMID: 15385440) Topçu M … Fischer J (Human molecular genetics 2004) 3 4 22 72
  3. An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study. (PMID: 20052767) Steenweg ME … Salomons GS (Human mutation 2010) 3 22 72
  4. Novel L2HGDH mutations in 21 patients with L-2-hydroxyglutaric aciduria of Portuguese origin. (PMID: 16134148) Vilarinho L … Jakobs C (Human mutation 2005) 3 4 22
  5. A gene encoding a putative FAD-dependent L-2-hydroxyglutarate dehydrogenase is mutated in L-2-hydroxyglutaric aciduria. (PMID: 15548604) Rzem R … Van Schaftingen E (Proceedings of the National Academy of Sciences of the United States of America 2004) 3 4 22

Products for L2HGDH Gene

Sources for L2HGDH Gene