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L2HGDH L-2-hydroxyglutarate dehydrogenase [ Homo sapiens (human) ]

Gene ID: 79944, updated on 2-Nov-2024

Summary

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Official Symbol
L2HGDHprovided by HGNC
Official Full Name
L-2-hydroxyglutarate dehydrogenaseprovided by HGNC
Primary source
HGNC:HGNC:20499
See related
Ensembl:ENSG00000087299 MIM:609584; AllianceGenome:HGNC:20499
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
L2HGA; C14orf160
Summary
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]
Expression
Ubiquitous expression in kidney (RPKM 5.2), fat (RPKM 1.8) and 25 other tissues See more
Orthologs
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Genomic context

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See L2HGDH in Genome Data Viewer
Location:
14q21.3
Exon count:
15
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (50242434..50312229, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (44448675..44518455, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (50709152..50778947, complement)

Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 1599 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8353 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr14:50605652-50606356 Neighboring gene valosin containing protein lysine methyltransferase Neighboring gene SOS Ras/Rho guanine nucleotide exchange factor 2 Neighboring gene NANOG hESC enhancer GRCh37_chr14:50692526-50693052 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5718 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8354 Neighboring gene MPRA-validated peak2154 silencer Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr14:50766206-50766899 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5720 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5721 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8355 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:50802261-50802882 Neighboring gene microRNA 4504 Neighboring gene Sharpr-MPRA regulatory region 14884 Neighboring gene distal membrane arm assembly component 2 like Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8356 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8357 Neighboring gene ReSE screen-validated silencer GRCh37_chr14:50832542-50832707 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:50838021-50838522 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:50838523-50839022 Neighboring gene cyclin dependent kinase like 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:50863511-50864010 Neighboring gene mitogen-activated protein kinase kinase kinase kinase 5 Neighboring gene zinc finger protein 678 pseudogene

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. L-2-Hydroxyglutaric aciduria: an inborn error of metabolism? Duran M, et al. J Inherit Metab Dis, 1980. PMID 6787330
  2. Elevated plasma 2-hydroxyglutarate in acute myeloid leukaemia: association with the IDH1 SNP rs11554137 and severe renal impairment. Wiseman DH, et al. Br J Haematol, 2014 Jul. PMID 24606602
  3. [Analysis of L2HGDH gene mutation in a patient with 2-hydroxyglutaric aciduria]. Deng Y, et al. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2016 Feb. PMID 26829733
  4. Exonic mutations in the L2HGDH gene in Staffordshire bull terriers. Short AD, et al. Vet Rec, 2010 Sep 18. PMID 20852250
  5. Identification of novel L2HGDH mutation in a large consanguineous Pakistani family- a case report. Ullah MI, et al. BMC Med Genet, 2018 Feb 20. PMID 29458334, Free PMC Article

See all (65) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Loss of function variants in L2HGDH gene causing L-2-hydroxyglutaric aciduria.
    Title: Loss of function variants in L2HGDH gene causing L-2-hydroxyglutaric aciduria.
  2. MYC Regulation of D2HGDH and L2HGDH Influences the Epigenome and Epitranscriptome.
    Title: MYC Regulation of D2HGDH and L2HGDH Influences the Epigenome and Epitranscriptome.
  3. Two novel L2HGDH mutations were identified in a Chinese family with L-2-hydroxyglutaric aciduria.
    Title: Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria.
  4. In this study, we describe a large pedigree from Pakistan showing multiple neurological symptoms. Homozygosity mapping and Sanger sequencing revealed a novel missense mutation in L2HGDH gene.
    Title: Identification of novel L2HGDH mutation in a large consanguineous Pakistani family- a case report.
  5. The mutations of the L2HGDH gene as the causes of L-2-hydroxyglutaric aciduria.
    Title: A novel compound heterozygous mutation of the L2HGDH gene in a Chinese boy with L-2-hydroxyglutaric aciduria: case report and literature review.
  6. c.845G>A (p.R282Q) in the exon 7 of the L2HGDH gene is associated with 2-hydroxyglutaric aciduria in Chinese family.
    Title: [Analysis of L2HGDH gene mutation in a patient with 2-hydroxyglutaric aciduria].
  7. Intragenic single nucleotide length polymorphisms and two extragenic microsatellites flanking the L2HGDH gene confirm the founder effect of c.241A>G mutation in the 14 studied cases.
    Title: Founder effect confirmation of c.241A>G mutation in the L2HGDH gene and characterization of oxidative stress parameters in six Tunisian families with L-2-hydroxyglutaric aciduria.
  8. modest increases in intracellular 2-HG in acute myeloid leukaemia cells, as seen with the rs11554137 SNP, might enhance chemoresistance, or promote acquisition of leukaemia-iniating mutations
    Title: Elevated plasma 2-hydroxyglutarate in acute myeloid leukaemia: association with the IDH1 SNP rs11554137 and severe renal impairment.
  9. Report ten novel mutations in the L2HGDH gene in patients with L-2-hydroxyglutaric aciduria from different ethnic backgrounds.
    Title: L-2-hydroxyglutaric aciduria: identification of ten novel mutations in the L2HGDH gene.
  10. Report three unrelated Tunisian families containing seven patients with L2HGA mutations and inter-familial phenotype variability.
    Title: L-2-hydroxyglutaric aciduria: clinical and molecular study in three Tunisian families. Identification of a new mutation and inter-familial phenotype variability.
Submit: New GeneRIF Correction See all GeneRIFs (22)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
L-2-hydroxyglutaric aciduria
MedGen: C1855995 OMIM: 236792 GeneReviews: Not available
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EBI GWAS Catalog

Description
Genome-wide association study of periodontal health measured by probing depth in adults ages 18-49 years.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ12618

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 2-hydroxyglutarate dehydrogenase activity EXP
Inferred from Experiment
more info
 PubMed 
enables 2-hydroxyglutarate dehydrogenase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables 2-hydroxyglutarate dehydrogenase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in 2-oxoglutarate metabolic process TAS
Traceable Author Statement
more info
  
involved_in small molecule metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrial inner membrane NAS
Non-traceable Author Statement
more info
 PubMed 
located_in mitochondrial inner membrane TAS
Traceable Author Statement
more info
  
located_in mitochondrion HTP PubMed 
located_in mitochondrion IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
L-2-hydroxyglutarate dehydrogenase, mitochondrial
Names
2-hydroxyglutarate dehydrogenase
L-alpha-hydroxyglutarate dehydrogenase
alpha-hydroxyglutarate oxidoreductase
alpha-ketoglutarate reductase
duranin
NP_001412141.1
NP_001412142.1
NP_001412143.1
NP_001412144.1
NP_001412145.1
NP_001412146.1
NP_001412147.1
NP_079160.1
XP_011535469.1
XP_011535470.1
XP_016877144.1
XP_054232700.1
XP_054232701.1
XP_054232702.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008092.1 RefSeqGene

    Range
    5001..74796
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001425212.1 → NP_001412141.1  L-2-hydroxyglutarate dehydrogenase, mitochondrial isoform 1

    Status: REVIEWED

    Source sequence(s)
    AL109758, AL359397
    UniProtKB/Swiss-Prot
    Q9BRR1, Q9H9P8
    Related
    ENSP00000405559.3, ENST00000421284.7

  2. NM_001425213.1 → NP_001412142.1  L-2-hydroxyglutarate dehydrogenase, mitochondrial isoform 2

    Status: REVIEWED

    Source sequence(s)
    AL109758, AL359397

  3. NM_001425214.1 → NP_001412143.1  L-2-hydroxyglutarate dehydrogenase, mitochondrial isoform 2

    Status: REVIEWED

    Source sequence(s)
    AL109758, AL359397

  4. NM_001425215.1 → NP_001412144.1  L-2-hydroxyglutarate dehydrogenase, mitochondrial isoform 3

    Status: REVIEWED

    Source sequence(s)
    AL109758, AL359397

  5. NM_001425216.1 → NP_001412145.1  L-2-hydroxyglutarate dehydrogenase, mitochondrial isoform 3

    Status: REVIEWED

    Source sequence(s)
    AL109758, AL359397

  6. NM_001425217.1 → NP_001412146.1  L-2-hydroxyglutarate dehydrogenase, mitochondrial isoform 3

    Status: REVIEWED

    Source sequence(s)
    AL109758, AL359397

  7. NM_001425218.1 → NP_001412147.1  L-2-hydroxyglutarate dehydrogenase, mitochondrial isoform 3

    Status: REVIEWED

    Source sequence(s)
    AL109758, AL359397

  8. NM_024884.3 → NP_079160.1  L-2-hydroxyglutarate dehydrogenase, mitochondrial isoform 1 precursor

    See identical proteins and their annotated locations for NP_079160.1

    Status: REVIEWED

    Source sequence(s)
    AK022680, AL109758, AY757363, CA424871
    Consensus CDS
    CCDS9698.1
    UniProtKB/Swiss-Prot
    Q9BRR1, Q9H9P8
    UniProtKB/TrEMBL
    A8K9B2
    Related
    ENSP00000267436.4, ENST00000267436.9
    Conserved Domains (2) summary
    PRK11728
    Location:61 → 457
    PRK11728; hydroxyglutarate oxidase; Provisional
    cl21454
    Location:31 → 448
    NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000014.9 Reference GRCh38.p14 Primary Assembly

    Range
    50242434..50312229 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017021655.3 → XP_016877144.1  L-2-hydroxyglutarate dehydrogenase, mitochondrial isoform X2

    UniProtKB/TrEMBL
    A8K9B2
    Conserved Domains (2) summary
    PRK11728
    Location:24 → 420
    PRK11728; hydroxyglutarate oxidase; Provisional
    cl21454
    Location:12 → 411
    NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

  2. XM_011537167.4 → XP_011535469.1  L-2-hydroxyglutarate dehydrogenase, mitochondrial isoform X3

    UniProtKB/TrEMBL
    A8K9B2
    Conserved Domains (2) summary
    PRK11728
    Location:16 → 412
    PRK11728; hydroxyglutarate oxidase; Provisional
    cl21454
    Location:2 → 403
    NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

  3. XM_011537168.4 → XP_011535470.1  L-2-hydroxyglutarate dehydrogenase, mitochondrial isoform X4

    See identical proteins and their annotated locations for XP_011535470.1

    Conserved Domains (1) summary
    cl21454
    Location:7 → 266
    NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

RNA

  1. XR_007064047.1 RNA Sequence

  2. XR_007064046.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060938.1 Alternate T2T-CHM13v2.0

    Range
    44448675..44518455 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054376725.1 → XP_054232700.1  L-2-hydroxyglutarate dehydrogenase, mitochondrial isoform X2

  2. XM_054376726.1 → XP_054232701.1  L-2-hydroxyglutarate dehydrogenase, mitochondrial isoform X3

  3. XM_054376727.1 → XP_054232702.1  L-2-hydroxyglutarate dehydrogenase, mitochondrial isoform X4

RNA

  1. XR_008488897.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9H9P8.3 GenPept UniProtKB/Swiss-Prot:Q9H9P8

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