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DMGDH dimethylglycine dehydrogenase [ Homo sapiens (human) ]

Gene ID: 29958, updated on 11-Apr-2024

Summary

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Official Symbol
DMGDHprovided by HGNC
Official Full Name
dimethylglycine dehydrogenaseprovided by HGNC
Primary source
HGNC:HGNC:24475
See related
Ensembl:ENSG00000132837 MIM:605849; AllianceGenome:HGNC:24475
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
DMGDHD; ME2GLYDH
Summary
This gene encodes an enzyme involved in the catabolism of choline, catalyzing the oxidative demethylation of dimethylglycine to form sarcosine. The enzyme is found as a monomer in the mitochondrial matrix, and uses flavin adenine dinucleotide and folate as cofactors. Mutation in this gene causes dimethylglycine dehydrogenase deficiency, characterized by a fishlike body odor, chronic muscle fatigue, and elevated levels of the muscle form of creatine kinase in serum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
Expression
Biased expression in kidney (RPKM 31.5), liver (RPKM 24.3) and 1 other tissue See more
Orthologs
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Genomic context

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Location:
5q14.1
Exon count:
17
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (78997564..79069674, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (79478676..79550778, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (78293387..78365497, complement)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124900191 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr5:77995230-77996429 Neighboring gene Sharpr-MPRA regulatory region 2428 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16125 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22715 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22716 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22717 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22718 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22719 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:78105507-78106007 Neighboring gene arylsulfatase B Neighboring gene Sharpr-MPRA regulatory region 14877 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22720 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16126 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:78270456-78270975 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:78270976-78271494 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16127 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr5:78293710-78294909 Neighboring gene IMPACT pseudogene Neighboring gene NANOG hESC enhancer GRCh37_chr5:78317526-78318027 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:78407958-78408802 Neighboring gene uncharacterized LOC124901012 Neighboring gene betaine--homocysteine S-methyltransferase 2 Neighboring gene betaine--homocysteine S-methyltransferase

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. Nonalcoholic steatohepatitis is associated with a state of betaine-insufficiency. Sookoian S, et al. Liver Int, 2017 Apr. PMID 27614103
  2. Structure and biochemical properties of recombinant human dimethylglycine dehydrogenase and comparison to the disease-related H109R variant. Augustin P, et al. FEBS J, 2016 Oct. PMID 27486859, Free PMC Article
  3. Dimethylglycine Deficiency and the Development of Diabetes. Magnusson M, et al. Diabetes, 2015 Aug. PMID 25795213, Free PMC Article
  4. Molecular basis of dimethylglycine dehydrogenase deficiency associated with pathogenic variant H109R. McAndrew RP, et al. J Inherit Metab Dis, 2008 Dec. PMID 18937046, Free PMC Article
  5. Structure and analysis of the human dimethylglycine dehydrogenase gene. Binzak BA, et al. Mol Genet Metab, 2000 Mar. PMID 10767172

See all (30) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Our study suggested markers in BHMT/BHMT2 and DMGDH might affect the risk of NSCL/P through pairwise interaction.
    Title: Evidence of interaction between genes in the folate/homocysteine metabolic pathway in controlling risk of non-syndromic oral cleft.
  2. In nonalcoholic fatty liver disease patient, the missense variant p.Ser646Pro (rs1805074) in DMGDH gene was significantly associated with disease severity and circulating levels of dimethylglycine.
    Title: Nonalcoholic steatohepatitis is associated with a state of betaine-insufficiency.
  3. The structure-based analysis provided new insights into the kinetic properties of dimethylglycine dehydrogenase in particular with respect to oxygen reactivity.
    Title: Structure and biochemical properties of recombinant human dimethylglycine dehydrogenase and comparison to the disease-related H109R variant.
  4. In agreement with previous studies, we show that the genetic variant rs921943 in DMGDH is significantly associated with selenium status in United Kingdom pregnant women.
    Title: Genetic polymorphisms that affect selenium status and response to selenium supplementation in United Kingdom pregnant women.
  5. Genetic variation of DMGDH was associated with higher plasma insulin, increased insulin resistance and increased risk of incident diabetes.
    Title: Dimethylglycine Deficiency and the Development of Diabetes.
  6. Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
    Title: Polymorphisms located in the region containing BHMT and BHMT2 genes as maternal protective factors for orofacial clefts.
  7. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
    Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
  8. Observational study of gene-disease association. (HuGE Navigator)
    Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
  9. analysis of dimethylglycine dehydrogenase deficiency associated with pathogenic variant H109R
    Title: Molecular basis of dimethylglycine dehydrogenase deficiency associated with pathogenic variant H109R.
  10. Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
    Title: Oral facial clefts and gene polymorphisms in metabolism of folate/one-carbon and vitamin A: a pathway-wide association study.
Submit: New GeneRIF Correction

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
Dimethylglycine dehydrogenase deficiency
MedGen: C1853892 OMIM: 605850 GeneReviews: Not available
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EBI GWAS Catalog

Description
An atlas of genetic influences on human blood metabolites.
EBI GWAS Catalog
Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes.
EBI GWAS Catalog
Genome-wide association study identifies loci affecting blood copper, selenium and zinc.
EBI GWAS Catalog
Genome-wide association study of selenium concentrations.
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

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables RNA binding HDA PubMed 
enables dimethylglycine dehydrogenase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables dimethylglycine dehydrogenase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables electron transfer activity NAS
Non-traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in amino-acid betaine catabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in choline catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in choline metabolic process NAS
Non-traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in mitochondrial matrix IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrial matrix NAS
Non-traceable Author Statement
more info
 PubMed 
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
dimethylglycine dehydrogenase, mitochondrial
NP_037523.2
XP_006714660.1
XP_011541657.1
XP_054208450.1
XP_054208451.1

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_012164.1 RefSeqGene

    Range
    4953..77063
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_013391.3 → NP_037523.2  dimethylglycine dehydrogenase, mitochondrial precursor

    See identical proteins and their annotated locations for NP_037523.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the supported protein.
    Source sequence(s)
    AA676742, AC008502, AF111858, AK057641, BP276968, CA397896
    Consensus CDS
    CCDS4044.1
    UniProtKB/Swiss-Prot
    B2RBN0, B4E1J9, Q9UI17
    UniProtKB/TrEMBL
    B3KQ84
    Related
    ENSP00000255189.3, ENST00000255189.8
    Conserved Domains (6) summary
    COG0404
    Location:464 → 857
    GcvT; Glycine cleavage system T protein (aminomethyltransferase) [Amino acid transport and metabolism]
    COG0665
    Location:47 → 435
    DadA; Glycine/D-amino acid oxidase (deaminating) [Amino acid transport and metabolism]
    pfam01571
    Location:482 → 745
    GCV_T; Aminomethyltransferase folate-binding domain
    pfam08669
    Location:753 → 845
    GCV_T_C; Glycine cleavage T-protein C-terminal barrel domain
    pfam16350
    Location:417 → 472
    FAO_M; FAD dependent oxidoreductase central domain
    cl21454
    Location:44 → 90
    NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

RNA

  1. NR_104002.3 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks three internal exons and contains an alternate 3' terminal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AC008502, AC020937, AF111858, AI302996, AK300894, BC022388, BP276968, BP425307
    Related
    ENST00000523732.1

  2. NR_104003.3 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks five internal exons and contains an alternate 3' terminal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AC008502, AC020937, AI302996, AK303873, BC022388, BP276968, BP425307

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    78997564..79069674 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011543355.3 → XP_011541657.1  dimethylglycine dehydrogenase, mitochondrial isoform X2

    UniProtKB/TrEMBL
    B3KQ84
    Conserved Domains (5) summary
    COG0404
    Location:464 → 750
    GcvT; Glycine cleavage system T protein (aminomethyltransferase) [Amino acid transport and metabolism]
    COG0665
    Location:47 → 435
    DadA; Glycine/D-amino acid oxidase (deaminating) [Amino acid transport and metabolism]
    pfam01571
    Location:482 → 745
    GCV_T; Aminomethyltransferase folate-binding domain
    pfam16350
    Location:417 → 472
    FAO_M; FAD dependent oxidoreductase central domain
    cl21454
    Location:44 → 90
    NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

  2. XM_006714597.3 → XP_006714660.1  dimethylglycine dehydrogenase, mitochondrial isoform X1

    UniProtKB/TrEMBL
    B3KQ84
    Conserved Domains (5) summary
    COG0404
    Location:464 → 751
    GcvT; Glycine cleavage system T protein (aminomethyltransferase) [Amino acid transport and metabolism]
    COG0665
    Location:47 → 435
    DadA; Glycine/D-amino acid oxidase (deaminating) [Amino acid transport and metabolism]
    pfam01571
    Location:482 → 745
    GCV_T; Aminomethyltransferase folate-binding domain
    pfam16350
    Location:417 → 472
    FAO_M; FAD dependent oxidoreductase central domain
    cl21454
    Location:44 → 90
    NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    79478676..79550778 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054352476.1 → XP_054208451.1  dimethylglycine dehydrogenase, mitochondrial isoform X2

  2. XM_054352475.1 → XP_054208450.1  dimethylglycine dehydrogenase, mitochondrial isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9UI17.2 GenPept UniProtKB/Swiss-Prot:Q9UI17

Gene LinkOut

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