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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O95140: Variant p.Arg104Trp

Mitofusin-2
Gene: MFN2
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Variant information Variant position: help 104 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Arginine (R) to Tryptophan (W) at position 104 (R104W, p.Arg104Trp). 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: help Change from large size and basic (R) to large size and aromatic (W) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -3 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
Variant description: help In CMT2A2A and HMSN6A; likely pathogenic. Any additional useful information about the variant.


Sequence information Variant position: help 104 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 757 The length of the canonical sequence.
Location on the sequence: help KVRGISEVLARRHMKVAFFG R TSNGKSTVINAMLWDKVLPS 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         KVRGISEVLARRHMKVAFFGRTSNGKSTVINAMLWDKVLPS

Mouse                         KVRGISEVLARRHMKVAFFGRTSNGKSTVINAMLWDKVLPS

Rat                           KVRGISEVLARRHMKVAFFGRTSNGKSTVINAMLWDKVLPS
Sequence annotation in neighborhood: help 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 1 – 757 Mitofusin-2
Topological domain 1 – 604 Cytoplasmic
Domain 93 – 342 Dynamin-type G
Region 103 – 110 G1 motif
Modified residue 111 – 111 Phosphothreonine; by PINK1
Alternative sequence 1 – 302 Missing. In isoform 2.
Mutagenesis 109 – 109 K -> AT. Does not affect its ability to cluster mitochondria; when overexpressed.
Mutagenesis 110 – 110 S -> N. Does not affect its ability to cluster mitochondria; when overexpressed.
Mutagenesis 111 – 111 T -> A. Diminishes interaction with PRKN in presence of PINK1. Abolishes phosphorylation by PINK1 and interaction with PRKN in presence of PINK1; when associated with Ala-442.
Mutagenesis 111 – 111 T -> E. Interacts with PRKN in absence of PINK1; when associated with Glu-442.



Literature citations
Cerebral involvement in axonal Charcot-Marie-Tooth neuropathy caused by mitofusin2 mutations.
Brockmann K.; Dreha-Kulaczewski S.; Dechent P.; Boennemann C.; Helms G.; Kyllerman M.; Brueck W.; Frahm J.; Huehne K.; Gaertner J.; Rautenstrauss B.;
J. Neurol. 255:1049-1058(2008)
Cited for: VARIANT CMT2A2A TRP-104; Mutated mitofusin 2 presents with intrafamilial variability and brain mitochondrial dysfunction.
Del Bo R.; Moggio M.; Rango M.; Bonato S.; D'Angelo M.G.; Ghezzi S.; Airoldi G.; Bassi M.T.; Guglieri M.; Napoli L.; Lamperti C.; Corti S.; Federico A.; Bresolin N.; Comi G.P.;
Neurology 71:1959-1966(2008)
Cited for: VARIANT CMT2A2A TRP-104; Genotype-phenotype correlations in Charcot-Marie-Tooth disease type 2 caused by mitofusin 2 mutations.
Calvo J.; Funalot B.; Ouvrier R.A.; Lazaro L.; Toutain A.; De Mas P.; Bouche P.; Gilbert-Dussardier B.; Arne-Bes M.C.; Carriere J.P.; Journel H.; Minot-Myhie M.C.; Guillou C.; Ghorab K.; Magy L.; Sturtz F.; Vallat J.M.; Magdelaine C.;
Arch. Neurol. 66:1511-1516(2009)
Cited for: VARIANTS CMT2A2B ARG-108 AND TRP-707; VARIANTS HMSN6A TRP-94; TRP-104 AND ARG-276; VARIANTS CMT2A2A ARG-128; ILE-156; MET-236; MET-244; TYR-277; PRO-364; GLN-364; SER-665; CYS-740; PRO-745 AND THR-747;
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.