L2HGDH

L-2-hydroxyglutarate dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the L2HGDH gene, also known as C14orf160, on chromosome 14.[5][6]

L2HGDH
Identifiers
AliasesL2HGDH, C14orf160, L2HGA, L-2-hydroxyglutarate dehydrogenase
External IDsOMIM: 609584 MGI: 2384968 HomoloGene: 11767 GeneCards: L2HGDH
Gene location (Human)
Chr.Chromosome 14 (human)[1]
Band14q21.3Start50,237,563 bp[1]
End50,312,229 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

79944

217666

Ensembl

ENSG00000087299

ENSMUSG00000020988

UniProt

Q9H9P8

Q91YP0

RefSeq (mRNA)

NM_024884

NM_145443

RefSeq (protein)

NP_079160

NP_663418

Location (UCSC)Chr 14: 50.24 – 50.31 MbChr 12: 69.69 – 69.72 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

This gene encodes L-2-hydroxyglutarate dehydrogenase, a flavin adenine dinucleotide (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 mental retardation.[6]

L2HGDH codes for a protein that is 50 kDa in size. The L2HGDH protein contains a mitochondrial-targeting transit peptide[7] and is localized to the mitochondrial inner membrane inside mitochondria inside the cell. The L2HGDH protein catalyzes the following reaction, and requires flavin adenine dinucleotide (FAD) as a co-factor:

(S)-2-hydroxyglutarate + acceptor = 2-oxoglutarate + reduced acceptor.[5]

L-2-hydroxyglutarate is produced by promiscuous action of malate dehydrogenase on 2-oxoglutarate; the L2HGDH protein is thus an example of a metabolite repair enzyme because it reconverts the useless damage product L-2-hydroxyglutarate back to 2-oxoglutarate.

Clinical significance

Mutations in the L2HGDH gene cause L-2-hydroxyglutaric aciduria, a rare autosomal recessive neurometabolic disorder. Individuals with L2HGDH mutations present toxic accumulation of high concentration of L-2-hydroxyglutaric acid in the plasma and cerebrospinal fluid.[8] At least 70 disease-causing variants in the L2HGDH gene have been discovered in patients.[9] Patients with L-2-hydroxyglutaric aciduria are associated with moderate to severe mental retardation, psychomotor retardation, cerebellar ataxia, macrocephaly, or epilepsy.[9]

L2HGDH has a role in mediating differentiation in T-cells via its activity on S-2HG [10]

Molecular interactions

KLK10[11]

gollark: I *was* looking at the LG V20 as a cheap old device I can buy, they were very good for their time.
gollark: But there are... less bad ones?
gollark: Yes, I'm aware, I wrote a blog post about this thus I am an expert.
gollark: There are cheapish somewhat ruggedized phones available now, which is neat because I drop my phone a lot, subject it to water sometimes by accident, sort of thing, but they seem annoying to repair and have mediatek chipsets.
gollark: Oneplus 5s are apparently not too horrible to replace batteries in, and not terribly expensive I guess.

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000087299 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000020988 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Rzem R, Van Schaftingen E, Veiga-da-Cunha M (Jan 2006). "The gene mutated in l-2-hydroxyglutaric aciduria encodes l-2-hydroxyglutarate dehydrogenase". Biochimie. 88 (1): 113–116. doi:10.1016/j.biochi.2005.06.005. PMID 16005139.
  6. "Entrez Gene: L2HGDH L-2-hydroxyglutarate dehydrogenase".
  7. "L2HGDH - L-2-hydroxyglutarate dehydrogenase, mitochondrial precursor - Homo sapiens (Human) - L2HGDH gene & protein". www.uniprot.org.
  8. Vilarinho L, Tafulo S, Sibilio M, Kok F, Fontana F, Diogo L, Venâncio M, Ferreira M, Nogueira C, Valongo C, Parenti G, Amorim A, Azevedo L (Jan 2010). "Identification of novel L2HGDH gene mutations and update of the pathological spectrum". Journal of Human Genetics. 55 (1): 55–8. doi:10.1038/jhg.2009.110. PMID 19911013.
  9. Steenweg ME, Jakobs C, Errami A, van Dooren SJ, Adeva Bartolomé MT, Aerssens P, et al. (April 2010). "An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study". Human Mutation. 31 (4): 380–90. doi:10.1002/humu.21197. PMID 20052767.
  10. Tyrakis PA, Palazon A, Macias D, Lee KL, Phan AT, Veliça P, You J, Chia GS, Sim J, Doedens A, Abelanet A, Evans CE, Griffiths JR, Poellinger L, Goldrath AW, Johnson RS (Dec 2016). "S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate". Nature. 540 (7632): 236–241. doi:10.1038/nature20165. PMC 5149074. PMID 27798602.
  11. Huttlin EL, Ting L, Bruckner RJ, Gebreab F, Gygi MP, Szpyt J, et al. (Jul 2015). "The BioPlex Network: A Systematic Exploration of the Human Interactome". Cell. 162 (2): 425–40. doi:10.1016/j.cell.2015.06.043. PMC 4617211. PMID 26186194.

Further reading


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