UniProtKB/Swiss-Prot Q9UBP0 : Variant p.Leu422Phe
Spastin
Gene: SPAST
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Variant information
Variant position:
422
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:
US
The variants are classified into three categories: LP/P, LB/B and US.LP/P: likely pathogenic or pathogenic. LB/B: likely benign or benign. US: uncertain significance
Residue change:
From Leucine (L) to Phenylalanine (F) at position 422 (L422F, p.Leu422Phe).
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 (L) to large size and aromatic (F)
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
Variant description:
In SPG4; uncertain significance.
Any additional useful information about the variant.
Other resources:
Links to websites of interest for the variant.
Sequence information
Variant position:
422
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:
TFFNISAASLTSKYVGEGEK
L VRALFAVARELQPSIIFIDE
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 TFFNISAASLTSKYVGEGEKL VRALFAVARELQPSIIFIDE
Mouse TFFNISAASLTSKYVGEGEKL VRALFAVARELQPSIIFIDE
Rat TFFNISAASLTSKYVGEGEKL VRALFAVARELQPSIIFIDE
Pig TFFNISAASLTSKYVGEGEKL VRALFAVARELQPSIIFIDE
Bovine TFFNISAASLTSKYVGEGEKL VRALFAVARELQPSIIFIDE
Chicken TFFNISAASLTSKYVGEGEKL VRALFAVARELQPSIIFIDE
Xenopus laevis TFFNISAASLTSKYVGEGEKL VRALFSVARELQPSIIFIDE
Xenopus tropicalis TFFNISAASLTSKYVGEGEKL VRALFSVARELQPSIIFIDE
Zebrafish TFFNISAATLTSKYVGEGEKL VRALFAVARELQPSIIFIDE
Caenorhabditis elegans MFFNISASSLTSKWVGDSEKT IRGLFQIARNAQPSIIFIDE
Drosophila TFLNISAASLTSKYVGDGEKL VRALFAVARHMQPSIIFIDE
Slime mold TFFSISSSSLTSKYVGDGEKL VRALFAVATHFQPSIIFIDE
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.
Type Positions Description
Chain
1 – 616
Spastin
Topological domain
78 – 616
Cytoplasmic
Region
228 – 616
Sufficient for microtubule severing
Mutagenesis
415 – 415
Y -> A. Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin, impairs ATPase activity and abolishes microtubule severing.
Mutagenesis
442 – 442
E -> Q. Abrogates ATP hydrolysis, abolishes microtubule severing, stabilizes the homohexameric form, and promotes microtubule binding and redistribution from the endosome to microtubules.
Literature citations
Hereditary spastic paraplegia due to SPAST mutations in 151 Dutch patients: new clinical aspects and 27 novel mutations.
de Bot S.T.; van den Elzen R.T.; Mensenkamp A.R.; Schelhaas H.J.; Willemsen M.A.; Knoers N.V.; Kremer H.P.; van de Warrenburg B.P.; Scheffer H.;
J. Neurol. Neurosurg. Psych. 81:1073-1078(2010)
Cited for: VARIANTS SPG4 ILE-162; LYS-356; SER-365; ARG-382; ILE-407; PHE-422; ASN-445; SER-460; LEU-482; GLU-512 DEL; VAL-534 AND PRO-562; VARIANT LEU-44;
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.