UniProtKB/SwissProt variant VAR

Variant information

Variant position:

283

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 Arginine (R) to Tryptophan (W) at position 283 (R283W, p.Arg283Trp).

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 basic (R) to large size and aromatic (W)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-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

Involvement in disease:

Charcot-Marie-Tooth disease 4B1 (CMT4B1) [MIM:601382]: A recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. {ECO:0000269|PubMed:10802647, ECO:0000269|PubMed:12398840}. 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 CMT4B1.

Any additional useful information about the variant.

Sequence information

Variant position:

283

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

Protein sequence length:

643

The length of the canonical sequence.

Location on the sequence:

SRGRIPVLSWIHPESQATIT R CSQPMVGVSGKRSKEDEKYL

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                         SRGRIPVLSWIHPESQATITRCSQPMVGVSGKRSKEDEKYL

Mouse                         SRGRIPVLSWIHPESQATVTRCSQPMVGVSGKRSKEDEKYL

Bovine                        SRGRIPVLSWIHPESQATITRCSQPMVGVSGKRSKEDEKYL

Chicken                       SRGRIPVLSWIHPESQATITRCSQPMVGVSGKRSKEDEKYL

Zebrafish                     AKGRIPVLSWIHPESQAAVVRSSQPMVGQNGRRCKEDEKLL

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.

Type	Positions	Description
Chain	1 – 643	Myotubularin-related protein 2
Domain	205 – 580	Myotubularin phosphatase
Beta strand	280 – 284

Literature citations

A novel homozygous missense mutation in the myotubularin-related protein 2 gene associated with recessive Charcot-Marie-Tooth disease with irregularly folded myelin sheaths.
Nelis E.; Erdem S.; Tan E.; Loefgren A.; Ceuterick C.; De Jonghe P.; Van Broeckhoven C.; Timmerman V.; Topaloglu H.;
Neuromuscul. Disord. 12:869-873(2002)
Cited for: VARIANT CMT4B1 TRP-283;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q13614: Variant p.Arg283Trp