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UniProtKB/Swiss-Prot Q12768: Variant p.Asn471Asp

WASH complex subunit 5
Gene: WASHC5
Variant information

Variant position:  471
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 Asparagine (N) to Aspartate (D) at position 471 (N471D, p.Asn471Asp).
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 polar (N) to medium size and acidic (D)
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:  Spastic paraplegia 8, autosomal dominant (SPG8) [MIM:603563]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. {ECO:0000269|PubMed:17160902, ECO:0000269|PubMed:20833645, ECO:0000269|PubMed:23085491, ECO:0000269|PubMed:23455931, ECO:0000269|PubMed:23881105, ECO:0000269|PubMed:25454649}. 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 SPG8; does not alter subcellular distribution; no effect on its binding to VCP; no effect on assembly in the WASH complex.
Any additional useful information about the variant.

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



Sequence information

Variant position:  471
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1159
The length of the canonical sequence.

Location on the sequence:   TELADVFSGVKPLTRVEKNE  N LQAWFREISKQILSLNYDDS
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                         TELADVFSGVKPLTRVEKNENLQAWFREISKQILSLNYDDS

Mouse                         TELADVFSGVKPLTRVEKNENLQAWFREISKQILSLNYDDS

Xenopus tropicalis            TELADVFSGVKPLTRVEKNEHLQAWFREIAKQIHSLNYDDS

Zebrafish                     MELAEVFSGVKPLTRVEKNENLQAWFREISKQIESLNYEDS

Drosophila                    NELSEAFAGSRPLSKIEQNPQLQQWFGEVAGRLQKLELSRP

Slime mold                    VELSEYFSGEKALTRVKKNENLQKWFGEISQKISQLDSTDS

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 – 1159 WASH complex subunit 5


Literature citations

Strumpellin is a novel valosin-containing protein binding partner linking hereditary spastic paraplegia to protein aggregation diseases.
Clemen C.S.; Tangavelou K.; Strucksberg K.H.; Just S.; Gaertner L.; Regus-Leidig H.; Stumpf M.; Reimann J.; Coras R.; Morgan R.O.; Fernandez M.P.; Hofmann A.; Muller S.; Schoser B.; Hanisch F.G.; Rottbauer W.; Blumcke I.; von Horsten S.; Eichinger L.; Schroder R.;
Brain 133:2920-2941(2010)
Cited for: SUBCELLULAR LOCATION; TISSUE SPECIFICITY; INTERACTION WITH VCP; FUNCTION; CHARACTERIZATION OF VARIANT SPG8 ASP-471;

The hereditary spastic paraplegia protein strumpellin: characterisation in neurons and of the effect of disease mutations on WASH complex assembly and function.
Freeman C.; Seaman M.N.; Reid E.;
Biochim. Biophys. Acta 1832:160-173(2013)
Cited for: FUNCTION; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS SPG8 ASP-471; PHE-619 AND PHE-626;

Mutations in the KIAA0196 gene at the SPG8 locus cause hereditary spastic paraplegia.
Valdmanis P.N.; Meijer I.A.; Reynolds A.; Lei A.; MacLeod P.; Schlesinger D.; Zatz M.; Reid E.; Dion P.A.; Drapeau P.; Rouleau G.A.;
Am. J. Hum. Genet. 80:152-161(2007)
Cited for: VARIANTS SPG8 ASP-471; PHE-619 AND PHE-626; CHARACTERIZATION OF VARIANTS SPG8 PHE-619 AND PHE-626;

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.