UniProtKB/SwissProt variant VAR

Variant information

Variant position:

340

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 Cysteine (C) at position 340 (R340C, p.Arg340Cys).

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 (C)

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:

Neuropathy, hereditary motor and sensory, 6B (HMSN6B) [MIM:616505]: An autosomal recessive neurologic disorder characterized by early-onset optic atrophy, progressive visual loss, and peripheral sensorimotor neuropathy manifesting as axonal Charcot-Marie-Tooth disease, with variable age at onset and severity. Charcot-Marie-Tooth disease is 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. It is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies and primary peripheral axonal neuropathies. Peripheral axonal neuropathies are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, and normal or slightly reduced nerve conduction velocities. {ECO:0000269|PubMed:26168012}. 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 HMSN6B.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs746681765 [ dbSNP | Ensembl ]

Sequence information

Variant position:

340

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

Protein sequence length:

418

The length of the canonical sequence.

Location on the sequence:

NFAASLCSDVILYPLETVLH R LHIQGTRTIIDNTDLGYEVL

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                         NFAASLCSDVILYPLETVLHRLHIQGTRTIIDNTDLGYEVL

Mouse                         NFAASLCSDVILYPLETVLHRLHIQGTRTIIDNTDLGYEVL

Rat                           NFAASLCSDVILYPLETVLHRLHIQGTRTIIDNTDLGYEVL

Chicken                       SFAASLCADVMLYPLETVLHRLHIQGTRTIIDNTDLGYEVL

Xenopus tropicalis            NFAASLCADVLLYPLETVLHRLHIQGTRTIIDNTDLGHEVV

Zebrafish                     SFAASLCADVLLFPLETVLHRLHIQGTRTIIDNTDLGFEVL

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 – 418	Solute carrier family 25 member 46
Repeat	311 – 413	Solcar 2

Literature citations

Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder.
Abrams A.J.; Hufnagel R.B.; Rebelo A.; Zanna C.; Patel N.; Gonzalez M.A.; Campeanu I.J.; Griffin L.B.; Groenewald S.; Strickland A.V.; Tao F.; Speziani F.; Abreu L.; Schuele R.; Caporali L.; La Morgia C.; Maresca A.; Liguori R.; Lodi R.; Ahmed Z.M.; Sund K.L.; Wang X.; Krueger L.A.; Peng Y.; Prada C.E.; Prows C.A.; Schorry E.K.; Antonellis A.; Zimmerman H.H.; Abdul-Rahman O.A.; Yang Y.; Downes S.M.; Prince J.; Fontanesi F.; Barrientos A.; Nemeth A.H.; Carelli V.; Huang T.; Zuchner S.; Dallman J.E.;
Nat. Genet. 47:926-932(2015)
Cited for: FUNCTION; SUBCELLULAR LOCATION; INTERACTION WITH IMMT; INVOLVEMENT IN HMSN6B; VARIANTS HMSN6B ASP-249; LEU-333; ASP-335 AND CYS-340;

UniProtKB/Swiss-Prot Q96AG3: Variant p.Arg340Cys