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UniProtKB/Swiss-Prot Q9NZC7: Variant p.Pro47Thr

WW domain-containing oxidoreductase
Gene: WWOX
Chromosomal location: 16q23.3-q24.1
Variant information

Variant position:  47
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 Proline (P) to Threonine (T) at position 47 (P47T, p.Pro47Thr).
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 hydrophobic (P) to medium size and polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
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:  Spinocerebellar ataxia, autosomal recessive, 12 (SCAR12) [MIM:614322]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR12 is additionally characterized by onset of generalized seizures in infancy, and delayed psychomotor development with mental retardation. Some patients may also show spasticity. {ECO:0000269|PubMed:24369382, ECO:0000269|PubMed:24456803}. 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 SCAR12.
Any additional useful information about the variant.

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



Sequence information

Variant position:  47
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  414
The length of the canonical sequence.

Location on the sequence:   TKDGWVYYANHTEEKTQWEH  P KTGKRKRVAGDLPYGWEQET
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                         TKDGWVYYANHTEEKTQWEHPKTGKRKRVAGDLPYGWEQET

Mouse                         TKDGWVYYANHTEEKTQWEHPKTGKRKRVAGDLPYGWEQET

Chicken                       TKDGWVYYANHLEEKTQWEHPKSGKRKRVAGGLPYGWEQET

Zebrafish                     TKDGWVYYANHEEMKTQWEHPKTGKKKRCAGALPYGWEQET

Drosophila                    TDDGTVCYVNQQGKTSQWTHPRTGRSKRITGELPLGWEKYY

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 1 – 414 WW domain-containing oxidoreductase
Domain 16 – 49 WW 1
Modified residue 33 – 33 Phosphotyrosine
Alternative sequence 36 – 36 N -> K. In isoform 4.
Alternative sequence 37 – 414 Missing. In isoform 4.
Mutagenesis 28 – 28 K -> T. No effect on interaction with TP53. Abolishes interaction with MAPK8; when associated with V-29.
Mutagenesis 29 – 29 D -> V. No effect on interaction with TP53. Abolishes interaction with MAPK8; when associated with T-28.
Mutagenesis 33 – 33 Y -> F. Loss of phosphorylation.
Mutagenesis 33 – 33 Y -> R. Abolishes interaction with TP53, TP73, MAPK8 and ERBB4. Partial loss of interaction with TFAP2C. Loss of phosphorylation. Loss of the proapoptotic activity.
Mutagenesis 44 – 47 WEHP -> FEHA. Abolishes interaction with LITAF.
Mutagenesis 61 – 61 Y -> R. No effect on interaction with TP73.


Literature citations

The tumour suppressor gene WWOX is mutated in autosomal recessive cerebellar ataxia with epilepsy and mental retardation.
Mallaret M.; Synofzik M.; Lee J.; Sagum C.A.; Mahajnah M.; Sharkia R.; Drouot N.; Renaud M.; Klein F.A.; Anheim M.; Tranchant C.; Mignot C.; Mandel J.L.; Bedford M.; Bauer P.; Salih M.A.; Schuele R.; Schoels L.; Aldaz C.M.; Koenig M.;
Brain 137:411-419(2014)
Cited for: VARIANTS SCAR12 THR-47 AND ARG-372;

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.