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

    Gene ID: 79944, updated on 28-Oct-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
    mouse all
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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 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
    		Compare labs

    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)

    Genotypes

    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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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