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UniProtKB/Swiss-Prot Q16595: Variant p.Asp122Tyr

Frataxin, mitochondrial
Gene: FXN
Chromosomal location: 9q13-q21.1
Variant information

Variant position:  122
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 Aspartate (D) to Tyrosine (Y) at position 122 (D122Y, p.Asp122Tyr).
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 medium size and acidic (D) to large size and aromatic (Y)
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.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  122
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:   TLDSLAEFFEDLADKPYTFE  D YDVSFGSGVLTVKLGGDLGT
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                         TLDSLAEFFEDLADKPYTFEDYDVSFGSGVLTVKLGGDLGT

Mouse                         TLDSLAEFFEDLADKPYTLEDYDVSFGDGVLTIKLGGDLGT

Rat                           TLDALAEFFEDLADKPYTLKDYDVSFGDGVLTIKLGGDLGT

Bovine                        TLDSLAEFFEDLADKPYTFEDYDVSFGSGVLTVKLGGDLGT

Caenorhabditis elegans        TLERLSDYFDQIADSFPVSEQFDVSHAMGVLTVNVSKSVGT

Drosophila                    TLDALCDYFEELTENASELQGTDVAYSDGVLTVNLGGQHGT

Slime mold                    EFELFVDRLEILSEA-NTCEGFEVEGNDGVLTIIVGNK-GT

Baker's yeast                 YLDHLLDSLEELSEAHPDCIP-DVELSHGVMTLEIPAF-GT

Fission yeast                 TLDVLNDTFEDLLEEVGK-KDYDIQYANGVITLMLGEK-GT

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.

TypePositionsDescription
Chain 42 – 210 Frataxin intermediate form
Chain 56 – 210 Frataxin(56-210)
Chain 78 – 210 Frataxin(78-210)
Chain 81 – 210 Frataxin mature form


Literature citations

Submission
Kostrzewa M.;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 89-128; VARIANT FRDA TYR-122;

A novel splice site mutation (384+1G-A) in the Friedreich's ataxia gene.
Doudney J.D.; Pook M.A.; Al-Mahdawi S.; Carvajal J.J.; Hillerman R.; Chamberlain S.;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 89-128; VARIANT FRDA TYR-122;

Friedreich's ataxia: point mutations and clinical presentation of compound heterozygotes.
Cossee M.; Duerr A.; Schmitt M.; Dahl N.; Trouillas P.; Allinson P.; Kostrzewa M.; Nivelon-Chevallier A.; Gustavson K.-H.; Kohlschuetter A.; Mueller U.; Mandel J.-L.; Brice A.; Koenig M.; Cavalcanti F.; Tammaro A.; de Michele G.; Filla A.; Cocozza S.; Labuda M.; Montermini L.; Poirier J.; Pandolfo M.;
Ann. Neurol. 45:200-206(1999)
Cited for: VARIANTS FRDA TYR-122 AND VAL-130;

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.