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UniProtKB/Swiss-Prot Q9UI17: Variant p.His109Arg

Dimethylglycine dehydrogenase, mitochondrial
Gene: DMGDH
Variant information

Variant position:  109
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Histidine (H) to Arginine (R) at position 109 (H109R, p.His109Arg).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and polar (H) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in 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.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In DMGDHD; shows 10 fold lower catalytic efficiency due to lower cofactor saturation and reduced thermal stability.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  109
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  866
The length of the canonical sequence.

Location on the sequence:   TWHAAGLTTYFHPGINLKKI  H YDSIKLYEKLEEETGQVVGF
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         TWHAAGLTTYFHPGINLKKIHYDSIKLYEKLEEETGQVVGF

Mouse                         TWHAAGLTTYFHPGINLKKIHYDSIKLYERLEEETGQVVGF

Rat                           TWHAAGLTTYFHPGINLKKIHYDSIKLYERLEEETGQVVGF

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 51 – 866 Dimethylglycine dehydrogenase, mitochondrial
Modified residue 91 – 91 Tele-8alpha-FAD histidine
Modified residue 114 – 114 N6-acetyllysine
Alternative sequence 19 – 398 Missing. In isoform 2.
Helix 105 – 123


Literature citations

Cloning of dimethylglycine dehydrogenase and a new human inborn error of metabolism, dimethylglycine dehydrogenase deficiency.
Binzak B.A.; Wevers R.A.; Moolenaar S.H.; Lee Y.-M.; Hwu W.-L.; Poggi-Bach J.; Engelke U.F.H.; Hoard H.M.; Vockley J.G.; Vockley J.;
Am. J. Hum. Genet. 68:839-847(2001)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANTS GLY-530 AND PRO-646; VARIANT DMGDHD ARG-109;

Structure and biochemical properties of recombinant human dimethylglycine dehydrogenase and comparison to the disease-related H109R variant.
Augustin P.; Hromic A.; Pavkov-Keller T.; Gruber K.; Macheroux P.;
FEBS J. 283:3587-3603(2016)
Cited for: X-RAY CRYSTALLOGRAPHY (3.09 ANGSTROMS) OF 29-866 IN COMPLEX WITH FAD; CHARACTERIZATION OF VARIANT DMGDHD ARG-109; FUNCTION; CATALYTIC ACTIVITY; COFACTOR; BIOPHYSICOCHEMICAL PROPERTIES; ENZYME KINETICS;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.