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UniProtKB/Swiss-Prot Q9UBP0: Variant p.Pro293Leu

Spastin
Gene: SPAST
Chromosomal location: 2p21
Variant information

Variant position:  293
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 Leucine (L) at position 293 (P293L, p.Pro293Leu).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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:  Spastic paraplegia 4, autosomal dominant (SPG4) [MIM:182601]: 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:10610178, ECO:0000269|PubMed:10699187, ECO:0000269|PubMed:11015453, ECO:0000269|PubMed:11039577, ECO:0000269|PubMed:11087788, ECO:0000269|PubMed:11309678, ECO:0000269|PubMed:11809724, ECO:0000269|PubMed:11843700, ECO:0000269|PubMed:11985387, ECO:0000269|PubMed:12124993, ECO:0000269|PubMed:12161613, ECO:0000269|PubMed:12163196, ECO:0000269|PubMed:12202986, ECO:0000269|PubMed:12460147, ECO:0000269|PubMed:12552568, ECO:0000269|PubMed:12939659, ECO:0000269|PubMed:14732620, ECO:0000269|PubMed:15159500, ECO:0000269|PubMed:15210521, ECO:0000269|PubMed:15248095, ECO:0000269|PubMed:15326248, ECO:0000269|PubMed:15482961, ECO:0000269|PubMed:15667412, ECO:0000269|PubMed:15716377, ECO:0000269|PubMed:15891913, ECO:0000269|PubMed:16339213, ECO:0000269|PubMed:16682546, ECO:0000269|PubMed:16684598, ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:17594340, ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:20214791, ECO:0000269|PubMed:20550563, ECO:0000269|PubMed:20562464, ECO:0000269|PubMed:20718791, ECO:0000269|PubMed:20932283, ECO:0000269|PubMed:21546041, ECO:0000269|PubMed:22960362, ECO:0000269|PubMed:23279441, ECO:0000269|PubMed:24824479, ECO:0000269|PubMed:25045380, ECO:0000269|PubMed:25421405, ECO:0000269|PubMed:28572275}. 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 SPG4.
Any additional useful information about the variant.

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



Sequence information

Variant position:  293
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  616
The length of the canonical sequence.

Location on the sequence:   SMVSGVKQGSGPAPTTHKGT  P KTNRTNKPSTPTTATRKKKD
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                         SMVSGVKQG--SGPAPTTHKGTP-KTNRTNKPSTPTTATRKKKD

Mouse                         SMVSGARPG--PGPAATTHKGTP-KPNRTNKPSTPTTAVRK

Rat                           SMVSGARPG--SGPAATTHKGTS-KPNRTNKPSTPTTAVRK

Pig                           SIVSGMRQG--PGPTTATHKSTP-KTNRTNKPSTPTTAPRK

Bovine                        SMVSGVRQG--PGSAAATHKSTP-KTNRTNKPSTPTTAARK

Chicken                       STASVSRPA--ANPATSTHKAAP-KNSRTNKPSTPTPAARK

Xenopus laevis                PTSARQA----GAHTPSNRGATGKNNTRTNKPATPTTAVR-

Xenopus tropicalis            SSSARQA----GPNAPSNRGAAGKNNTRTNKPTTPTTAVR-

Zebrafish                     NCTPSAAQSSRTGPQNNQKGPTVKGKNNVKASTTATASPQR

Caenorhabditis elegans        DTVHPEPP-----VQASNRKMETVKRVKVDKASLPMHQNPV

Drosophila                    TPPAVRRQFSSGRNTPPQRSRTPINNNGPSGSGASTPVVS-

Slime mold                    NTSTITSPGNKYGLQKSLSSTTLSLKKSSNSTNFQQPSPP-

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 – 616 Spastin
Topological domain 78 – 616 Cytoplasmic
Region 1 – 300 Required for interaction with RTN1
Region 228 – 616 Sufficient for microtubule severing
Region 270 – 328 Required for interaction with microtubules and microtubule severing
Modified residue 306 – 306 Phosphothreonine


Literature citations

Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia.
Alvarez V.; Sanchez-Ferrero E.; Beetz C.; Diaz M.; Alonso B.; Corao A.I.; Gamez J.; Esteban J.; Gonzalo J.F.; Pascual-Pascual S.I.; Lopez de Munain A.; Moris G.; Ribacoba R.; Marquez C.; Rosell J.; Marin R.; Garcia-Barcina M.J.; Del Castillo E.; Benito C.; Coto E.;
BMC Neurol. 10:89-89(2010)
Cited for: VARIANTS SPG4 THR-287 DEL; LEU-293; LEU-328; ARG-378; HIS-380; PRO-391; 393-LYS--ALA-396 DEL; THR-409; ARG-410; PRO-436; ASN-441; SER-460; ALA-463; PHE-492; GLY-498; ARG-503 INS; GLY-514 AND THR-580;

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.