DMGDH

Protein identityUniProt · HPA

UniProt accession

Q9UI17

Gene

DMGDH

Ensembl

ENSG00000132837

Chromosome

5

Canonical length

866 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

866 residues, UniProt reviewed canonical sequence.

>Q9UI17|DMGDH
     1  MLRPGAQLLR GLLLRSCPLQ GSPGRPRSVC GREGEEKPPL SAETQWKDRA ETVIIGGGCV
    61  GVSLAYHLAK AGMKDVVLLE KSELTAGSTW HAAGLTTYFH PGINLKKIHY DSIKLYEKLE
   121  EETGQVVGFH QPGSIRLATT PVRVDEFKYQ MTRTGWHATE QYLIEPEKIQ EMFPLLNMNK
   181  VLAGLYNPGD GHIDPYSLTM ALAAGARKCG ALLKYPAPVT SLKARSDGTW DVETPQGSMR
   241  ANRIVNAAGF WAREVGKMIG LEHPLIPVQH QYVVTSTISE VKALKRELPV LRDLEGSYYL
   301  RQERDGLLFG PYESQEKMKV QDSWVTNGVP PGFGKELFES DLDRIMEHIK AAMEMVPVLK
   361  KADIINVVNG PITYSPDILP MVGPHQGVRN YWVAIGFGYG IIHAGGVGKY LSDWILHGEP
   421  PFDLIELDPN RYGKWTTTQY TEAKARESYG FNNIVGYPKE ERFAGRPTQR VSGLYQRLES
   481  KCSMGFHAGW EQPHWFYKPG QDTQYRPSFR RTNWFEPVGS EYKQVMQRVA VTDLSPFGKF
   541  NIKGQDSIRL LDHLFANVIP KVGFTNISHM LTPKGRVYAE LTVSHQSPGE FLLITGSGSE
   601  LHDLRWIEEE AVKGGYDVEI KNITDELGVL GVAGPQARKV LQKLTSEDLS DDVFKFLQTK
   661  SLKVSNIPVT AIRISYTGEL GWELYHRRED SVALYDAIMN AGQEEGIDNF GTYAMNALRL
   721  EKAFRAWGLE MNCDTNPLEA GLEYFVKLNK PADFIGKQAL KQIKAKGLKR RLVCLTLATD
   781  DVDPEGNESI WYNGKVVGNT TSGSYSYSIQ KSLAFAYVPV QLSEVGQQVE VELLGKNYPA
   841  VIIQEPLVLT EPTRNRLQKK GGKDKT

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DMGDH can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.22

Highest tissue expression

265 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DMGDH.

Disease | AllUniProt

Conditions DMGDH is implicated in, by any mechanism.

• DMGDH deficiency (DMGDHD) MIM:605850

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 192 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Dimethylglycine dehydrogenase deficiency

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.17

gnomAD pLI

0

gnomAD missense Z

0.56

DepMap mean gene effect

0.01

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• amino-acid betaine catabolic process
• choline catabolic process
• choline metabolic process

Molecular functions

• electron transfer activity
• RNA binding
• dimethylglycine dehydrogenase activity

Cellular components

• cytoplasm
• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• FAD dependent oxidoreductase
• GCVT, N-terminal domain
• Aminomethyltransferase, C-terminal domain
• Aminomethyltransferase superfamily
• Aminomethyltransferase-like
• Glycine cleavage T-protein/YgfZ, C-terminal
• FAD dependent oxidoreductase, central domain
• FAD/NAD(P)-binding domain superfamily
• FAD dependent oxidoreductase
• GCVT N-terminal domain
• Glycine cleavage T-protein C-terminal barrel domain
• FAD dependent oxidoreductase central domain

KeywordsUniProt

• Acetylation
• FAD
• Flavoprotein
• Mitochondrion
• Oxidoreductase
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of DMGDH in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FLAD1