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UniProtKB/Swiss-Prot Q9BQP7: Variant p.Tyr233Cys

Mitochondrial genome maintenance exonuclease 1
Gene: MGME1
Variant information

Variant position:  233
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 Tyrosine (Y) to Cysteine (C) at position 233 (Y233C, p.Tyr233Cys).
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 large size and aromatic (Y) to medium size and polar (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  Mitochondrial DNA depletion syndrome 11 (MTDPS11) [MIM:615084]: An autosomal recessive mitochondrial disorder characterized by onset in childhood or adulthood of progressive external ophthalmoplegia, muscle weakness and atrophy, exercise intolerance, and respiratory insufficiency due to muscle weakness. More variable features include spinal deformity, emaciation, and cardiac abnormalities. Skeletal muscle biopsies show deletion and depletion of mitochondrial DNA (mtDNA) with variable defects in respiratory chain enzyme activities. {ECO:0000269|PubMed:23313956}. Note=The disease may be 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 MTDPS11; impaired exonuclease activity.
Any additional useful information about the variant.

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

Sequence information

Variant position:  233
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  344
The length of the canonical sequence.

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.




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.

Chain 1 – 344 Mitochondrial genome maintenance exonuclease 1
Active site 238 – 238
Active site 251 – 251
Active site 253 – 253
Mutagenesis 251 – 251 D -> A. Abolishes catalytic activity.
Mutagenesis 253 – 253 K -> A. Abolishes catalytic activity.
Mutagenesis 253 – 253 K -> A. Abolishes exonuclease activity.
Beta strand 233 – 243

Literature citations

Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease.
Kornblum C.; Nicholls T.J.; Haack T.B.; Scholer S.; Peeva V.; Danhauser K.; Hallmann K.; Zsurka G.; Rorbach J.; Iuso A.; Wieland T.; Sciacco M.; Ronchi D.; Comi G.P.; Moggio M.; Quinzii C.M.; Dimauro S.; Calvo S.E.; Mootha V.K.; Klopstock T.; Strom T.M.; Meitinger T.; Minczuk M.; Kunz W.S.; Prokisch H.;
Nat. Genet. 45:214-219(2013)

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.