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, ch... See more...

Aliases for DMGDH Gene

Aliases for DMGDH Gene

  • Dimethylglycine Dehydrogenase 2 3 5
  • Dimethylglycine Dehydrogenase, Mitochondrial 3 4
  • ME2GLYDH 3 4
  • EC 1.5.8.4 4
  • DMGDHD 3

External Ids for DMGDH Gene

Previous GeneCards Identifiers for DMGDH Gene

  • GC05M077099
  • GC05M078530
  • GC05M078332
  • GC05M078377
  • GC05M078329
  • GC05M073499
  • GC05M078293

Summaries for DMGDH Gene

Entrez Gene Summary for DMGDH Gene

  • 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]

GeneCards Summary for DMGDH Gene

DMGDH (Dimethylglycine Dehydrogenase) is a Protein Coding gene. Diseases associated with DMGDH include Dimethylglycine Dehydrogenase Deficiency and Sarcosinemia. Among its related pathways are Metabolism and Glycine, serine and threonine metabolism. Gene Ontology (GO) annotations related to this gene include electron transfer activity. An important paralog of this gene is SARDH.

UniProtKB/Swiss-Prot Summary for DMGDH Gene

  • Catalyzes the demethylation of N,N-dimethylglycine to sarcosine. Also has activity with sarcosine in vitro.

Additional gene information for DMGDH Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for DMGDH Gene

Genomics for DMGDH Gene

GeneHancer (GH) Regulatory Elements for DMGDH Gene

Promoters and enhancers for DMGDH Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH05J079069 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas 500.1 +166.2 166186 1.7 POLR2G ZBTB7A RBM25 EZH2 SIN3A ZNF316 NFIC TFDP1 SAP130 MAFK BHMT2 DMGDH BHMT piR-30325-011 lnc-DMGDH-1
GH05J079234 Promoter/Enhancer 1.7 Ensembl ENCODE CraniofacialAtlas 512.1 -1.7 -1663 5.8 FOXK2 ZNF217 EP300 ZSCAN5C SIN3A NRF1 MYC POLR2G USF1 GTF2E2 DMGDH JMY lnc-DMGDH-1 SCAMP1 BHMT ENSG00000251050 SCAMP1-AS1 BHMT2 RF00017-4755 piR-48759-248
GH05J079253 Enhancer 1 Ensembl ENCODE 23.7 -20.1 -20063 5.4 CTCF ZIC2 ATF2 CTBP1 ZNF341 WT1 ZNF316 ZNF263 RAD21 ARNT DMGDH BHMT BHMT2 JMY piR-48759-248 RF00017-4755 RF00017-4756
GH05J079261 Enhancer 0.7 Ensembl ENCODE 24.2 -26.8 -26816 3.5 TCF12 PAX5 NFIC CHD7 NANOG EED RUNX3 SCRT2 ZEB1 DMGDH JMY BHMT BHMT2 piR-48759-248 RF00017-4755 RF00017-4756
GH05J078359 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 4.7 +875.2 875237 3.6 ZBTB40 ZNF217 EP300 CTCF NRF1 TCF12 POLR2G SP1 GTF2E2 PHF8 SCAMP1 SCAMP1-AS1 NONHSAG040805.2 piR-39799 ENSG00000213757 RPL7P23 JMY DMGDH piR-56341-184
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around DMGDH on UCSC Golden Path with GeneCards custom track

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

Top Transcription factor binding sites by QIAGEN in the DMGDH gene promoter:
  • AML1a
  • AREB6
  • ARP-1
  • ITF-2
  • MZF-1
  • Pax-2
  • Pax-2a
  • Pax-2b
  • Pax-5
  • Tal-1beta

Genomic Locations for DMGDH Gene

Genomic Locations for DMGDH Gene
chr5:78,997,564-79,236,038
(GRCh38/hg38)
Size:
238,475 bases
Orientation:
Minus strand
chr5:78,293,429-78,531,861
(GRCh37/hg19)
Size:
238,433 bases
Orientation:
Minus strand

Genomic View for DMGDH Gene

Genes around DMGDH on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for DMGDH Gene

Proteins for DMGDH Gene

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

    Protein Symbol:
    Q9UI17-M2GD_HUMAN
    Recommended name:
    Dimethylglycine dehydrogenase, mitochondrial
    Protein Accession:
    Q9UI17
    Secondary Accessions:
    • B2RBN0
    • B4E1J9

    Protein attributes for DMGDH Gene

    Size:
    866 amino acids
    Molecular mass:
    96811 Da
    Cofactor:
    Name=FAD; Xref=ChEBI:CHEBI:57692;
    Quaternary structure:
    • Monomer.

    Three dimensional structures from OCA and Proteopedia for DMGDH Gene

    Alternative splice isoforms for DMGDH Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for DMGDH Gene

Post-translational modifications for DMGDH Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibody Products

  • Abcam antibodies for DMGDH

No data available for DME Specific Peptides for DMGDH Gene

Domains & Families for DMGDH Gene

Gene Families for DMGDH Gene

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

Protein Domains for DMGDH Gene

Blocks:
  • Glycine cleavage T protein (aminomethyl transferase)
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for DMGDH Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ50354, highly similar to Dimethylglycine dehydrogenase, mitochondrial (EC 1.5.99.2) (B4E1J9_HUMAN)
  • ME2GLYDH (M2GD_HUMAN)
  • DMGDH protein (Q8TCC6_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9UI17

UniProtKB/Swiss-Prot:

M2GD_HUMAN :
  • Belongs to the GcvT family.
Family:
  • Belongs to the GcvT family.
genes like me logo Genes that share domains with DMGDH: view

Function for DMGDH Gene

Molecular function for DMGDH Gene

UniProtKB/Swiss-Prot Function:
Catalyzes the demethylation of N,N-dimethylglycine to sarcosine. Also has activity with sarcosine in vitro.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(6S)-5,6,7,8-tetrahydrofolyl-(gamma-L-Glu)n + H(+) + N,N-dimethylglycine + oxidized [electron-transfer flavoprotein] = (6R)-5,10-methylenetetrahydrofolyl-(gamma-L-Glu)(n) + reduced [electron-transfer flavoprotein] + sarcosine; Xref=Rhea:RHEA:52856, Rhea:RHEA-COMP:10685, Rhea:RHEA-COMP:10686, Rhea:RHEA-COMP:13257, Rhea:RHEA-COMP:14738, ChEBI:CHEBI:15378, ChEBI:CHEBI:57433, ChEBI:CHEBI:57692, ChEBI:CHEBI:58251, ChEBI:CHEBI:58307, ChEBI:CHEBI:136572, ChEBI:CHEBI:141005; EC=1.5.8.4; Evidence=. ;.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=1.4 mM for N,N-dimethylglycine {ECO:0000269 PubMed:27486859}; Vmax=22.1 umol/min/mg enzyme; Note=kcat is 213 min(-1) for N,N-dimethylglycine. {ECO:0000269 PubMed:27486859};

Enzyme Numbers (IUBMB) for DMGDH Gene

Phenotypes From GWAS Catalog for DMGDH Gene

Gene Ontology (GO) - Molecular Function for DMGDH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003723 RNA binding HDA 22658674
GO:0005515 protein binding IEA --
GO:0009055 electron transfer activity NAS 10767172
GO:0016491 oxidoreductase activity IEA,IBA 21873635
GO:0047865 dimethylglycine dehydrogenase activity IBA,IMP 11231903
genes like me logo Genes that share ontologies with DMGDH: view
genes like me logo Genes that share phenotypes with DMGDH: view

Human Phenotype Ontology for DMGDH Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for DMGDH Gene

MGI Knock Outs for DMGDH:
  • Dmgdh Dmgdh<tm1a(KOMP)Wtsi>

Animal Model Products

CRISPR Products

Clone Products

No data available for Transcription Factor Targets and HOMER Transcription for DMGDH Gene

Localization for DMGDH Gene

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

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for DMGDH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA 21873635
GO:0005739 mitochondrion IDA --
GO:0005759 mitochondrial matrix TAS --
genes like me logo Genes that share ontologies with DMGDH: view

Pathways & Interactions for DMGDH Gene

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

UniProtKB/Swiss-Prot Q9UI17-M2GD_HUMAN

  • Pathway: Amine and polyamine degradation; betaine degradation; sarcosine from betaine: step 2/2.

Gene Ontology (GO) - Biological Process for DMGDH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006579 amino-acid betaine catabolic process IEA --
GO:0019695 choline metabolic process NAS 10767172
GO:0022900 electron transport chain IEA --
GO:0042426 choline catabolic process IMP,TAS --
GO:0055114 oxidation-reduction process IEA --
genes like me logo Genes that share ontologies with DMGDH: view

No data available for SIGNOR curated interactions for DMGDH Gene

Drugs & Compounds for DMGDH Gene

(10) Drugs for DMGDH Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Formaldehyde Approved, Vet_approved Pharma 136
FAD Approved Pharma 0
Water Approved Pharma 0
dimethylglycine Experimental Pharma 0
putrescine Experimental Pharma Antagonist, Pore Blocker 0

(3) Additional Compounds for DMGDH Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
N1-acetylspermine
  • N'-acetylspermine
  • N'-monoacetylspermine
  • N(1)-Acetylspermine
  • N-(3-((4-((3-Aminopropyl)amino)butyl)amino)propyl)-acetamide
  • N-Acetylspermine
25593-72-0
Norspermidine
  • 1,7-diamino-4-Azaheptane
  • 3,3'-Iminobis(propylamine)
  • 3,3'-Iminobispropylamine
  • 3,3'-Iminodi(propylamine)
  • 3,3-Diaminodipropylamine
56-18-8
genes like me logo Genes that share compounds with DMGDH: view

Transcripts for DMGDH Gene

mRNA/cDNA for DMGDH Gene

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

CRISPR Products

Clone Products

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

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14a · 14b ^ 15 ^ 16 ^ 17 ^ 18
SP1: - -
SP2: -
SP3: -
SP4:

Relevant External Links for DMGDH Gene

GeneLoc Exon Structure for
DMGDH

Expression for DMGDH Gene

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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for DMGDH Gene

This gene is overexpressed in Liver (x22.1) and Kidney - Cortex (x9.3).

Protein differential expression in normal tissues from HIPED for DMGDH Gene

This gene is overexpressed in Liver, secretome (46.5) and Liver (16.3).

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



Protein tissue co-expression partners for DMGDH Gene

- Elite partner

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

SOURCE GeneReport for Unigene cluster for DMGDH Gene:

Hs.655653

Evidence on tissue expression from TISSUES for DMGDH Gene

  • Liver(4.6)
  • Kidney(2.5)

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

Germ Layers:
  • mesoderm
Systems:
  • skeletal muscle
genes like me logo Genes that share expression patterns with DMGDH: view

No data available for mRNA Expression by UniProt/SwissProt for DMGDH Gene

Orthologs for DMGDH Gene

This gene was present in the common ancestor of animals.

Orthologs for DMGDH Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia DMGDH 31 30
  • 99.54 (n)
OneToOne
cow
(Bos Taurus)
Mammalia DMGDH 31 30
  • 91.64 (n)
OneToOne
dog
(Canis familiaris)
Mammalia DMGDH 31 30
  • 90.65 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Dmgdh 30
  • 86.14 (n)
mouse
(Mus musculus)
Mammalia Dmgdh 17 31 30
  • 85.86 (n)
oppossum
(Monodelphis domestica)
Mammalia DMGDH 31
  • 83 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia DMGDH 31
  • 83 (a)
OneToOne
chicken
(Gallus gallus)
Aves DMGDH 31 30
  • 77.19 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia DMGDH 31
  • 76 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia dmgdh 30
  • 73.9 (n)
zebrafish
(Danio rerio)
Actinopterygii dmgdh 31 30
  • 66.83 (n)
OneToOne
Dr.5571 30
worm
(Caenorhabditis elegans)
Secernentea Y37E3.17 31 32 30
  • 48.13 (n)
OneToOne
Y106G6H.5 32
  • 26 (a)
Species where no ortholog for DMGDH was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • 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)
  • fruit fly (Drosophila melanogaster)
  • 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)
  • 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 squirt (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 DMGDH Gene

ENSEMBL:
Gene Tree for DMGDH (if available)
TreeFam:
Gene Tree for DMGDH (if available)
Aminode:
Evolutionary constrained regions (ECRs) for DMGDH: view image

Paralogs for DMGDH Gene

Paralogs for DMGDH Gene

(2) SIMAP similar genes for DMGDH Gene using alignment to 7 proteins:

  • M2GD_HUMAN
  • B4E1J9_HUMAN
  • E5RG50_HUMAN
  • E5RGI4_HUMAN
  • E5RK15_HUMAN
  • F8W6P8_HUMAN
  • Q8TCC6_HUMAN
genes like me logo Genes that share paralogs with DMGDH: view

Variants for DMGDH Gene

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

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
668664 Likely Benign: not provided 79,028,654(-) C/T INTRON_VARIANT
681469 Likely Benign: not provided 79,063,706(-) A/G NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
682526 Likely Benign: not provided 79,028,663(-) C/A INTRON_VARIANT
726130 Likely Benign: not provided 78,998,219(-) G/A SYNONYMOUS_VARIANT
746214 Likely Benign: not provided 79,063,655(-) C/G NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for DMGDH Gene

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

Variant ID Type Subtype PubMed ID
esv2762527 CNV gain 21179565
nsv1022839 CNV gain 25217958
nsv462215 CNV gain 19166990
nsv462216 CNV loss 19166990
nsv519156 CNV gain 19592680
nsv598740 CNV gain 21841781
nsv598741 CNV loss 21841781

Variation tolerance for DMGDH Gene

Residual Variation Intolerance Score: 58.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 13.75; 95.78% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for DMGDH Gene

Human Gene Mutation Database (HGMD)
DMGDH
SNPedia medical, phenotypic, and genealogical associations of SNPs for
DMGDH

SNP Genotyping and Copy Number Assay Products

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

Disorders for DMGDH Gene

MalaCards: The human disease database

(5) MalaCards diseases for DMGDH Gene - From: UniProtKB/Swiss-Prot, OMIM, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
dimethylglycine dehydrogenase deficiency
  • dmgdhd
sarcosinemia
  • sarcos
aspartylglucosaminuria
  • agu
trimethylaminuria
  • tmau
argininosuccinic aciduria
  • argininosuccinase deficiency
- elite association - COSMIC cancer census association via MalaCards
Search DMGDH in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

M2GD_HUMAN
  • DMGDH deficiency (DMGDHD) [MIM:605850]: Disorder characterized by fish odor, muscle fatigue with increased serum creatine kinase. Biochemically it is characterized by an increase of N,N-dimethylglycine (DMG) in serum and urine. {ECO:0000269 PubMed:11231903, ECO:0000269 PubMed:27486859}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for DMGDH

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with DMGDH: view

No data available for Genatlas for DMGDH Gene

Publications for DMGDH Gene

  1. Cloning of dimethylglycine dehydrogenase and a new human inborn error of metabolism, dimethylglycine dehydrogenase deficiency. (PMID: 11231903) Binzak BA … Vockley J (American journal of human genetics 2001) 2 3 4 23 54
  2. Structure and analysis of the human dimethylglycine dehydrogenase gene. (PMID: 10767172) Binzak BA … Vockley J (Molecular genetics and metabolism 2000) 2 3 4 23 54
  3. Defect in dimethylglycine dehydrogenase, a new inborn error of metabolism: NMR spectroscopy study. (PMID: 10102904) Moolenaar SH … Wevers RA (Clinical chemistry 1999) 3 4 23 54
  4. Structure and biochemical properties of recombinant human dimethylglycine dehydrogenase and comparison to the disease-related H109R variant. (PMID: 27486859) Augustin P … Macheroux P (The FEBS journal 2016) 3 4 54
  5. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41 54

Products for DMGDH Gene

Sources for DMGDH Gene