UniProtKB/SwissProt variant VAR

Variant information

Variant position:

329

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 Histidine (H) at position 329 (R329H, p.Arg329His).

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 medium size and polar (H)

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:

Charcot-Marie-Tooth disease 2N (CMT2N) [MIM:613287]: An axonal 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). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269|PubMed:20045102, ECO:0000269|PubMed:22009580, ECO:0000269|PubMed:22206013}. 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 CMT2N; severely reduces enzyme activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs267606621 [ dbSNP | Ensembl ]

Sequence information

Variant position:

329

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

Protein sequence length:

968

The length of the canonical sequence.

Location on the sequence:

LADGGRPDNTGRGYVLRRIL R RAVRYAHEKLNASRGFFATL

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.

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 – 968	Alanine--tRNA ligase, cytoplasmic
Helix	319 – 339

Literature citations

A major determinant for binding and aminoacylation of tRNA(Ala) in cytoplasmic Alanyl-tRNA synthetase is mutated in dominant axonal Charcot-Marie-Tooth disease.
Latour P.; Thauvin-Robinet C.; Baudelet-Mery C.; Soichot P.; Cusin V.; Faivre L.; Locatelli M.C.; Mayencon M.; Sarcey A.; Broussolle E.; Camu W.; David A.; Rousson R.;
Am. J. Hum. Genet. 86:77-82(2010)
Cited for: VARIANT CMT2N HIS-329;

A recurrent loss-of-function alanyl-tRNA synthetase (AARS) mutation in patients with Charcot-Marie-Tooth disease type 2N (CMT2N).
McLaughlin H.M.; Sakaguchi R.; Giblin W.; Wilson T.E.; Biesecker L.; Lupski J.R.; Talbot K.; Vance J.M.; Zuchner S.; Lee Y.C.; Kennerson M.; Hou Y.M.; Nicholson G.; Antonellis A.;
Hum. Mutat. 33:244-253(2012)
Cited for: VARIANT CMT2N HIS-329; CHARACTERIZATION OF VARIANT CMT2N HIS-329;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P49588: Variant p.Arg329His