UniProtKB/SwissProt variant VAR

Variant information

Variant position:

165

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 165 (R165C, p.Arg165Cys).

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:

Friedreich ataxia (FRDA) [MIM:229300]: Autosomal recessive, progressive degenerative disease characterized by neurodegeneration and cardiomyopathy it is the most common inherited ataxia. The disorder is usually manifest before adolescence and is generally characterized by incoordination of limb movements, dysarthria, nystagmus, diminished or absent tendon reflexes, Babinski sign, impairment of position and vibratory senses, scoliosis, pes cavus, and hammer toe. In most patients, FRDA is due to GAA triplet repeat expansions in the first intron of the frataxin gene. But in some cases the disease is due to mutations in the coding region. {ECO:0000269|PubMed:10732799, ECO:0000269|PubMed:10874325, ECO:0000269|PubMed:19629184, ECO:0000269|PubMed:9150176, ECO:0000269|PubMed:9779809, ECO:0000269|PubMed:9989622, ECO:0000269|Ref.36, ECO:0000269|Ref.7, ECO:0000269|Ref.8}. 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 FRDA; mild form.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs138034837 [ dbSNP | Ensembl ]

Sequence information

Variant position:

165

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

Protein sequence length:

210

The length of the canonical sequence.

Location on the sequence:

INKQTPNKQIWLSSPSSGPK R YDWTGKNWVYSHDGVSLHEL

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                         INKQTPNKQIWLSSPSSGPKRYDW----TGKNWVYSHDGVSLHEL

Mouse                         INKQTPNKQIWLSSPSSGPKRYDW----TGKNWVYSHDGVS

Rat                           INKQTPLLYLWFSGPCSGPKRYDW----TGKNWVYSHDGVS

Bovine                        INKQTPNKQIWLSSPSSGPKRYDW----TGRNWVYSHDGVS

Caenorhabditis elegans        INKQSPNKQIWLSSPMSGPKRYDLE---EEGKWTYAHDGEQ

Drosophila                    INRQTPNKQIWLSSPTSGPKRYDFVGTVAAGRWIYKHSGQS

Slime mold                    INKQTPNRQIWWSSPLSGPKRFDYD--SVEKRWVDNRDGTP

Baker's yeast                 INKQPPNKQIWLASPLSGPNRFDL----LNGEWVSLRNGTK

Fission yeast                 INKQPPAHQIWLSSPVSGPKHYEYS--LKSKTWCSTRDEGT

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	42 – 210	Frataxin intermediate form
Chain	56 – 210	Frataxin(56-210)
Chain	78 – 210	Frataxin(78-210)
Chain	81 – 210	Frataxin mature form
Alternative sequence	161 – 210	SGPKRYDWTGKNWVYSHDGVSLHELLAAELTKALKTKLDLSSLAYSGKDA -> RLTWLLWLFHP. In isoform 2.
Alternative sequence	161 – 210	SGPKRYDWTGKNWVYSHDGVSLHELLAAELTKALKTKLDLSSLAYSGKDA -> RYVVDLSVMTGLGKTGCTPTTACPSMSCWPQSSLKP. In isoform 3.
Beta strand	164 – 168

Literature citations

The correlation of clinical phenotype in Friedreich ataxia with the site of point mutations in the FRDA gene.
Forrest S.M.; Knight M.; Delatycki M.B.; Paris D.; Williamson R.; King J.; Yeung L.; Nassif N.; Nicholson G.A.;
Neurogenetics 1:253-257(1998)
Cited for: VARIANTS FRDA VAL-130; CYS-165 AND PHE-182;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q16595: Variant p.Arg165Cys