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UniProtKB/Swiss-Prot Q9UBP0: Variant p.Ser44Leu

Chromosomal location: 2p21
Variant information

Variant position:  44
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
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 Serine (S) to Leucine (L) at position 44 (S44L, p.Ser44Leu).
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 small size and polar (S) to medium size and hydrophobic (L)
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

Variant description:  Rare polymorphism; acts as a disease modifier; patients carrying a mutated allele of spastin and L-44 on the other allele are affected by severe spastic paraplegia with an early age of onset; may decrease the activity of the alternative promoter which directs the synthesis of isoform 3 and isoform 4.
Any additional useful information about the variant.

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

Sequence information

Variant position:  44
The position of the amino-acid change on the UniProtKB canonical protein sequence.

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

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                         PPPPCLAPAPPAAGPAPPPESP---------------HKRNLYYFSYPLFVGFA-LL

Mouse                         RPPPPAAVPAPAAGPAPAAGSP---------------PKRN

Rat                           RPPPPAAVPAPAAGPAPAPGSP---------------HKRN

Pig                           PPPPCLASSRPAPRPAPPPQSP---------------HKRN

Bovine                        PPPPCQARSRPAPKPAPPPQSP---------------HKRN

Chicken                       APSGPAPPAPPAGAAAAAAASP---------------HKRN

Xenopus laevis                SPTTPPS-TETQVVLAPP--SP---------------HKRN

Xenopus tropicalis            PPTPPPPPAETQVLLAPP--SL---------------HKRN

Zebrafish                     RACGPVSDGSARGN--------------------------R

Caenorhabditis elegans        -----------------------------------------


Slime mold                    NFYNSLEDDDYLLNNQTTKVSL------------------Y

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.

Chain 1 – 616 Spastin
Topological domain 1 – 56 Cytoplasmic
Region 1 – 300 Required for interaction with RTN1
Region 1 – 194 Required for midbody localization
Region 1 – 80 Required for interaction with ATL1
Region 1 – 50 Required for nuclear localization
Alternative sequence 1 – 86 Missing. In isoform 3 and isoform 4.

Literature citations

A cryptic promoter in the first exon of the SPG4 gene directs the synthesis of the 60-kDa spastin isoform.
Mancuso G.; Rugarli E.I.;
BMC Biol. 6:31-31(2008)

Mutation analysis of the spastin gene (SPG4) in patients with hereditary spastic paraparesis.
Lindsey J.C.; Lusher M.E.; McDermott C.J.; White K.D.; Reid E.; Rubinsztein D.C.; Bashir R.; Hazan J.; Shaw P.J.; Bushby K.M.D.;
J. Med. Genet. 37:759-765(2000)

Intragenic modifiers of hereditary spastic paraplegia due to spastin gene mutations.
Svenson I.K.; Kloos M.T.; Gaskell P.C.; Nance M.A.; Garbern J.Y.; Hisanaga S.; Pericak-Vance M.A.; Ashley-Koch A.E.; Marchuk D.A.;
Neurogenetics 5:157-164(2004)

Infantile hereditary spastic paraparesis due to codominant mutations in the spastin gene.
Chinnery P.F.; Keers S.M.; Holden M.J.; Ramesh V.; Dalton A.;
Neurology 63:710-712(2004)
Cited for: VARIANT SPG4 LEU-361; VARIANT LEU-44;

Seven novel mutations and four exon deletions in a collection of Norwegian patients with SPG4 hereditary spastic paraplegia.
Erichsen A.K.; Inderhaug E.; Mattingsdal M.; Eiklid K.; Tallaksen C.M.;
Eur. J. Neurol. 14:809-814(2007)
Cited for: VARIANTS SPG4 THR-364; HIS-380 AND HIS-579; VARIANT LEU-44;

Unique spectrum of SPAST variants in Estonian HSP patients: presence of benign missense changes but lack of exonic rearrangements.
Braschinsky M.; Tamm R.; Beetz C.; Sachez-Ferrero E.; Raukas E.; Luus S.M.; Gross-Paju K.; Boillot C.; Canzian F.; Metspalu A.; Haldre S.;
BMC Neurol. 10:17-17(2010)
Cited for: VARIANTS LEU-44 AND GLY-229; VARIANTS SPG4 ILE-162; PHE-426 AND SER-460;

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-; 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.