Dimethylglycine dehydrogenase deficiency

Summary

Dimethylglycine dehydrogenase deficiency (MONDO:0011610) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 9
• Phenotypes (HPO): 5

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		1	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

5 HPO clinical features (Orphanet curated; top 5 by frequency):

HPO ID	Term	Frequency
HP:0001939	Abnormality of metabolism/homeostasis	Very frequent (80-99%)
HP:0003236	Elevated circulating creatine kinase concentration	Very frequent (80-99%)
HP:0003750	Increased muscle fatiguability	Very frequent (80-99%)
HP:0012379	Abnormal enzyme/coenzyme activity	Very frequent (80-99%)
HP:0410020	Fish odor	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	dimethylglycine dehydrogenase deficiency
Mondo ID	MONDO:0011610
MeSH	C565278
OMIM	605850
Orphanet	243343
DOID	DOID:0081446
SNOMED CT	719449007
UMLS	C1853892
MedGen	343006
GARD	0017185
Is cancer (heuristic)	no

Also known as: dimethylglycine dehydrogenase activity disease · dimethylglycine dehydrogenase deficiency · disorder of dimethylglycine dehydrogenase activity · DMG dehydrogenase deficiency · DMGDH deficiency · DMGDHD

Data availability: 9 ClinVar variants · 3 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › disorder of peptide and amine metabolism › disorder of methylamine metabolism › dimethylglycine dehydrogenase deficiency

Related subtypes (1): sarcosinemia

Subtypes (1): trimethylaminuria

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

9 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 3 conflicting classifications of pathogenicity, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3341079	NM_013391.3(DMGDH):c.269G>A (p.Trp90Ter)	DMGDH	Likely pathogenic	criteria provided, single submitter
4742	NM_013391.3(DMGDH):c.326A>G (p.His109Arg)	DMGDH	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3341080	NM_013391.3(DMGDH):c.236T>G (p.Leu79Arg)	DMGDH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
432171	NM_013391.3(DMGDH):c.101+2T>C	DMGDH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
781998	NM_013391.3(DMGDH):c.972G>A (p.Trp324Ter)	DMGDH	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1301702	NM_013391.3(DMGDH):c.696del (p.Glu233fs)	DMGDH	Uncertain significance	criteria provided, single submitter
225340	NM_013391.3(DMGDH):c.856C>T (p.Arg286Ter)	DMGDH	Uncertain significance	criteria provided, single submitter
2442124	NM_013391.3(DMGDH):c.1531C>T (p.Arg511Cys)	DMGDH	Uncertain significance	criteria provided, single submitter
548521	NM_013391.3(DMGDH):c.2122G>A (p.Asp708Asn)	DMGDH	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
DMGDH	Supportive	Autosomal recessive	dimethylglycine dehydrogenase deficiency	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DMGDH	Orphanet:243343	Dimethylglycine dehydrogenase deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DMGDH	HGNC:24475	ENSG00000132837	Q9UI17	Dimethylglycine dehydrogenase, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DMGDH	Dimethylglycine dehydrogenase, mitochondrial	Catalyzes the demethylation of N,N-dimethylglycine to sarcosine.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DMGDH	Enzyme (other)	yes	1.5.8.4	FAD-dep_OxRdtase, GCVT_N, GcvT_C

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
kidney epithelium	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DMGDH	188	ubiquitous	yes	kidney epithelium, right lobe of liver, liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DMGDH	1,847

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DMGDH	Q9UI17	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Choline catabolism	1	1427.5×	0.002	DMGDH
Metabolism of amino acids and derivatives	1	67.6×	0.022	DMGDH
Metabolism	1	11.6×	0.086	DMGDH

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
amino-acid betaine catabolic process	1	8426.0×	2e-04	DMGDH
choline metabolic process	1	5617.3×	2e-04	DMGDH
choline catabolic process	1	4213.0×	2e-04	DMGDH

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DMGDH	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DMGDH	1.5.8.4	dimethylglycine dehydrogenase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	DMGDH
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
DMGDH	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.