Home  |  Contact

UniProtKB/Swiss-Prot Q96B26: Variant p.Ala2Val

Exosome complex component RRP43
Gene: EXOSC8
Variant information

Variant position:  2
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 Alanine (A) to Valine (V) at position 2 (A2V, p.Ala2Val).
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 small size and hydrophobic (A) to medium size and hydrophobic (V)
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:  Pontocerebellar hypoplasia 1C (PCH1C) [MIM:616081]: A severe autosomal recessive neurodegenerative disease characterized by cerebellar and corpus callosum hypoplasia, abnormal myelination of the central nervous system, and spinal motor neuron disease. Affected individuals manifest failure to thrive, severe muscle weakness, spasticity and psychomotor retardation. Vision and hearing are impaired. {ECO:0000269|PubMed:24989451}. Note=The disease is caused by mutations affecting the gene represented in this entry. EXOSC8 dysfunction causes myelin disruption through an imbalanced supply of myelin proteins due to dysregulation of their ARE-containing mRNAs (PubMed:24989451). {ECO:0000269|PubMed:24989451}.
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 PCH1C.
Any additional useful information about the variant.

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

Sequence information

Variant position:  2
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  276
The length of the canonical sequence.

Location on the sequence:   M  A AGFKTVEPLEYYRRFLKENC
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                         MAAGFKTVEPLEYYRRFLKENC

Mouse                         MAAGFKTVEPLEYYRRFLKENC

Bovine                        MAAGFKTVEPLEYYRRFLKENC

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.

Initiator methionine 1 – 1 Removed
Chain 2 – 276 Exosome complex component RRP43
Modified residue 2 – 2 N-acetylalanine

Literature citations

EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia.
Boczonadi V.; Muller J.S.; Pyle A.; Munkley J.; Dor T.; Quartararo J.; Ferrero I.; Karcagi V.; Giunta M.; Polvikoski T.; Birchall D.; Princzinger A.; Cinnamon Y.; Lutzkendorf S.; Piko H.; Reza M.; Florez L.; Santibanez-Koref M.; Griffin H.; Schuelke M.; Elpeleg O.; Kalaydjieva L.; Lochmuller H.; Elliott D.J.; Chinnery P.F.; Edvardson S.; Horvath R.;
Nat. Commun. 5:4287-4287(2014)

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.