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UniProtKB/Swiss-Prot Q9UBP0: Variant p.Leu378Gln

Spastin
Gene: SPAST
Chromosomal location: 2p21
Variant information

Variant position:  378
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 Leucine (L) to Glutamine (Q) at position 378 (L378Q, p.Leu378Gln).
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 medium size and polar (Q)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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.



Sequence information

Variant position:  378
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:   VILPSLRPELFTGLRAPARG  L LLFGPPGNGKTMLAKAVAAE
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                         VILPSLRPELFTGLRAPARGLLLFGPPGNGKTMLAKAVAAE

Mouse                         VILPSLRPELFTGLRAPARGLLLFGPPGNGKTMLAKAVAAE

Rat                           VILPSLRPELFTGLRAPARGLLLFGPPGNGKTMLAKAVAAE

Pig                           VILPSLRPELFTGLRAPARGLLLFGPPGNGKTMLAKAVAAE

Bovine                        VILPSLRPELFTGLRAPARGLLLFGPPGNGKTMLAKAVAAE

Chicken                       VILPSLRPELFTGLRAPARGLLLFGPPGNGKTMLAKAVAAE

Xenopus laevis                VILPSIRPELFTGLRAPARGLLLFGPPGNGKTMLAKAVAAE

Xenopus tropicalis            VILPSIRPELFTGLRAPARGLLLFGPPGNGKTMLAKAVAAE

Zebrafish                     VILPALRPELFTGLRAPARGLLLFGPPGNGKTMLAKAVAME

Caenorhabditis elegans        VILPALNPNLFKGLRQPVKGILLFGPPGNGKTLLAKAVAGE

Drosophila                    VILPSVRPELFTGLRAPAKGLLLFGPPGNGKTLLARAVATE

Slime mold                    VILPNLRPDVFTGLRAPPKGLLLFGPPGNGKTMIAKAVAYE

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 228 – 616 Sufficient for microtubule severing
Mutagenesis 388 – 388 K -> A. Abrogates ATPase activity and abolishes microtubule severing.
Beta strand 376 – 383


Literature citations

Three novel mutations of the spastin gene in Chinese patients with hereditary spastic paraplegia.
Tang B.; Zhao G.; Xia K.; Pan Q.; Luo W.; Shen L.; Long Z.; Dai H.; Zi X.; Jiang H.;
Arch. Neurol. 61:49-55(2004)
Cited for: VARIANTS SPG4 GLN-378; VAL-390 AND LEU-515 DEL;

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.