UniProtKB/Swiss-Prot Q9UBP0: Variant p.Glu464Ala

Spastin
Gene: SPAST
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Variant information Variant position:

464 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 Glutamate (E) to Alanine (A) at position 464 (E464A, p.Glu464Ala). 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 acidic (E) to small size and hydrophobic (A) 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
Variant description:

In SPG4; uncertain significance. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1553318251 [ dbSNP | Ensembl ]

Sequence information Variant position:

464 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:

DSLLCERREGEHDASRRLKT E FLIEFDGVQSAGDDRVLVMG 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                         DSLLCERREGEHDASRRLKTEFLIEFDGVQSAGD-DRVLVMG

Mouse                         DSLLCERREGEHDASRRLKTEFLIEFDGVQSAGD-DRVLVM

Rat                           DSLLCERREGEHDASRRLKTEFLIEFDGVQSAGD-DRVLVM

Pig                           DSLLRERREGEHDASRRLKTEFLIEFDGVQSAGD-DRVLVM

Bovine                        DSLLCERREGEHDASRRLKTEFLIEFDGVQSAGD-DRVLVM

Chicken                       DSLLCERREGEHDASRRLKTEFLIEFDGVQSSGE-DRILVM

Xenopus laevis                DSLLCERREGEHDASRRLKTEFLIEFDGVQSGGD-DRVLVM

Xenopus tropicalis            DSLLCERREGEHDASRRLKTEFLIEFDGVQSGGD-DRVLVM

Zebrafish                     DSLLCERREGEHDASRRLKTEFLIEFDGVQSGGD-ERVLVM

Caenorhabditis elegans        DSILCERSEKDAEVSRRMKTEFLVQFDGATSSAD-DRILVI

Drosophila                    DSLLSERSSSEHEASRRLKTEFLVEFDGLPGNPDGDRIVVL

Slime mold                    DSLLTERSSNESEASRRLKTEILVQFDGARTNGD-ERVLVM

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	448 – 448	C -> AG. Abolishes ATPase activity.
Mutagenesis	448 – 448	C -> S. Does not affect ATPase activity.
Mutagenesis	451 – 451	R -> G. Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin, impairs ATPase activity and abolishes microtubule severing.
Mutagenesis	457 – 457	A -> E. Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin and abolishes microtubule severing.
Helix	462 – 473

Literature citations
Mutation screening of spastin, atlastin, and REEP1 in hereditary spastic paraplegia.
McCorquodale D.S. III; Ozomaro U.; Huang J.; Montenegro G.; Kushman A.; Citrigno L.; Price J.; Speziani F.; Pericak-Vance M.A.; Zuchner S.;
Clin. Genet. 79:523-530(2011)
Cited for: VARIANTS SPG4 THR-97; ASP-201; SER-314; VAL-360; ALA-464; GLY-498 AND ILE-550;

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.