DMGDH

dimethylglycine dehydrogenase

Basic information

Region (hg38): 5:78997563-79236038

Links

ENSG00000132837 ∙ NCBI:29958 ∙ OMIM:605849 ∙ HGNC:24475 ∙ Uniprot:Q9UI17 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dimethylglycine dehydrogenase deficiency (Supportive), mode of inheritance: AR
• dimethylglycine dehydrogenase deficiency (Limited), mode of inheritance: AR
• dimethylglycine dehydrogenase deficiency (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dimethylglycine dehydrogenase deficiency	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Musculoskeletal	10102904

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DMGDH gene.

• not provided (40 variants)
• not specified (35 variants)
• Inborn genetic diseases (30 variants)
• Dimethylglycine dehydrogenase deficiency (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DMGDH gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				15	4	19
missense		1	33	4	4	42
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region				7	1	8
non coding			1	14	15	30
Total	0	2	36	33	23

Highest pathogenic variant AF is 0.00138

Variants in DMGDH

This is a list of pathogenic ClinVar variants found in the DMGDH region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-78998074-G-A			Uncertain significance (Aug 01, 2016)
5-78998117-G-A		not specified	Uncertain significance (Nov 29, 2021)
5-78998138-A-G			Likely benign (Mar 01, 2022)
5-78998148-T-C		not specified • DMGDH-related disorder	Benign (Jul 14, 2019)
5-78998219-G-A			Likely benign (May 24, 2018)
5-78998233-T-A		not specified	Uncertain significance (Nov 07, 2023)
5-79005225-G-GT			Benign (Apr 16, 2019)
5-79005261-C-G		not specified	Likely benign (Aug 09, 2016)
5-79005262-T-G		not specified	Likely benign (Dec 15, 2016)
5-79005307-G-A		not specified	Uncertain significance (Dec 13, 2023)
5-79005349-C-T			Likely benign (Feb 01, 2023)
5-79005397-A-G		DMGDH-related disorder	Benign (Oct 28, 2019)
5-79005431-G-A			Benign (Feb 26, 2021)
5-79005503-A-G			Benign (Apr 16, 2019)
5-79005540-T-A			Benign (Apr 16, 2019)
5-79024136-A-G			Likely benign (Mar 17, 2021)
5-79024262-T-C		not specified • DMGDH-related disorder	Benign (Dec 18, 2019)
5-79024308-A-C		not specified	Uncertain significance (Jun 23, 2023)
5-79024325-G-A		not specified	Likely benign (Jul 05, 2017)
5-79026459-G-A		not specified	Uncertain significance (Feb 06, 2023)
5-79026459-G-T		not specified	Uncertain significance (Feb 22, 2023)
5-79026492-C-T		Dimethylglycine dehydrogenase deficiency	Uncertain significance (Mar 05, 2018)
5-79026539-A-G		not specified	Likely benign (Dec 14, 2022)
5-79026598-G-A		not specified	Likely benign (Mar 13, 2018)
5-79028332-TCA-T			Likely benign (Jul 02, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DMGDH	protein_coding	protein_coding	ENST00000255189	16	238424

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.05e-24	0.00276	125192	3	553	125748	0.00221

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.563	409	442	0.925	0.0000232	5598
Missense in Polyphen		146	176.15	0.82885		2078
Synonymous	-0.838	174	160	1.08	0.00000876	1711
Loss of Function	0.622	39	43.4	0.898	0.00000242	532

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00425	0.00425
Ashkenazi Jewish	0.00169	0.00169
East Asian	0.00207	0.00207
Finnish	0.00120	0.00120
European (Non-Finnish)	0.00208	0.00207
Middle Eastern	0.00207	0.00207
South Asian	0.00301	0.00301
Other	0.00358	0.00359

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the demethylation of N,N-dimethylglycine to sarcosine. Also has activity with sarcosine in vitro. {ECO:0000269|PubMed:27486859}.
• Disease: DISEASE: 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.
• Pathway: Glycine, serine and threonine metabolism - Homo sapiens (human);3-Phosphoglycerate dehydrogenase deficiency;Non Ketotic Hyperglycinemia;Glycine and Serine Metabolism;sarcosine oncometabolite pathway ;Dimethylglycine Dehydrogenase Deficiency;Hyperglycinemia, non-ketotic;Dimethylglycine Dehydrogenase Deficiency;Sarcosinemia;Dihydropyrimidine Dehydrogenase Deficiency (DHPD);One carbon metabolism and related pathways;Metabolism of amino acids and derivatives;Glycine Serine metabolism;Metabolism;Choline catabolism;glycine betaine degradation;superpathway of choline degradation to L-serine;Glycine, serine, alanine and threonine metabolism (Consensus)

Intolerance Scores

• loftool: 0.346
• rvis_EVS: 0.16
• rvis_percentile_EVS: 64.92

Haploinsufficiency Scores

• pHI: 0.0898
• hipred: N
• hipred_score: 0.457
• ghis: 0.410

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.840

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Dmgdh
• Phenotype: homeostasis/metabolism phenotype; immune system phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: amino-acid betaine catabolic process;choline metabolic process;electron transport chain;choline catabolic process
• Cellular component: cytoplasm;mitochondrion;mitochondrial matrix
• Molecular function: RNA binding;electron transfer activity;oxidoreductase activity;dimethylglycine dehydrogenase activity