UniProtKB/Swiss-Prot Q12756 : Variant p.Ala255Val
Kinesin-like protein KIF1A
Gene: KIF1A
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Variant information
Variant position:
255
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:
LP/P [Disclaimer : Variants classification is intended for research purposes only, not for clinical and diagnostic use . The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant. ]
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 Alanine (A) to Valine (V) at position 255 (A255V, p.Ala255Val).
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 hydrophobic (A) to medium size and hydrophobic (V)
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 SPG30; reduces accumulation in distal regions of the neurites; no effect on microtubule motility.
Any additional useful information about the variant.
Other resources:
Links to websites of interest for the variant.
Sequence information
Variant position:
255
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:
1690
The length of the canonical sequence.
Location on the sequence:
NITTEKVSKISLVDLAGSER
A DSTGAKGTRLKEGANINKSL
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 NITTEKVSKISLVDLAGSERA DSTGAKGTRLKEGANINKSL
Mouse NITTEKVSKISLVDLAGSERA DSTGAKGTRLKEGANINKSL
Rat NITTEKVSKISLVDLAGSERA DSTGAKGTRLKEGANINKSL
Drosophila NLTTEKVSKISLVDLAGSERA DSTGAKGTRLKEGANINKSL
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 – 1690
Kinesin-like protein KIF1A
Domain
5 – 354
Kinesin motor
Literature citations
Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis.
Erlich Y.; Edvardson S.; Hodges E.; Zenvirt S.; Thekkat P.; Shaag A.; Dor T.; Hannon G.J.; Elpeleg O.;
Genome Res. 21:658-664(2011)
Cited for: VARIANT SPG30 VAL-255;
KIF1A missense mutations in SPG30, an autosomal recessive spastic paraplegia: distinct phenotypes according to the nature of the mutations.
Klebe S.; Lossos A.; Azzedine H.; Mundwiller E.; Sheffer R.; Gaussen M.; Marelli C.; Nawara M.; Carpentier W.; Meyer V.; Rastetter A.; Martin E.; Bouteiller D.; Orlando L.; Gyapay G.; El-Hachimi K.H.; Zimmerman B.; Gamliel M.; Misk A.; Lerer I.; Brice A.; Durr A.; Stevanin G.;
Eur. J. Hum. Genet. 20:645-649(2012)
Cited for: VARIANTS SPG30 VAL-255 AND GLY-350;
De novo mutations in KIF1A cause progressive encephalopathy and brain atrophy.
Esmaeeli Nieh S.; Madou M.R.; Sirajuddin M.; Fregeau B.; McKnight D.; Lexa K.; Strober J.; Spaeth C.; Hallinan B.E.; Smaoui N.; Pappas J.G.; Burrow T.A.; McDonald M.T.; Latibashvili M.; Leshinsky-Silver E.; Lev D.; Blumkin L.; Vale R.D.; Barkovich A.J.; Sherr E.H.;
Ann. Clin. Transl. Neurol. 2:623-635(2015)
Cited for: VARIANTS MET-46; ASN-136; ILE-187; MET-205; ILE-220; ASP-233; VAL-336 AND HIS-355; VARIANTS NESCAVS MET-99; CYS-216; HIS-216; LYS-253 AND TRP-316; CHARACTERIZATION OF VARIANTS NESCAVS MET-99; CYS-216 AND LYS-253; CHARACTERIZATION OF VARIANT SPG30 VAL-255; CHARACTERIZATION OF VARIANT ILE-220;
De novo mutations in the motor domain of KIF1A cause cognitive impairment, spastic paraparesis, axonal neuropathy, and cerebellar atrophy.
Lee J.R.; Srour M.; Kim D.; Hamdan F.F.; Lim S.H.; Brunel-Guitton C.; Decarie J.C.; Rossignol E.; Mitchell G.A.; Schreiber A.; Moran R.; Van Haren K.; Richardson R.; Nicolai J.; Oberndorff K.M.; Wagner J.D.; Boycott K.M.; Rahikkala E.; Junna N.; Tyynismaa H.; Cuppen I.; Verbeek N.E.; Stumpel C.T.; Willemsen M.A.; de Munnik S.A.; Rouleau G.A.; Kim E.; Kamsteeg E.J.; Kleefstra T.; Michaud J.L.;
Hum. Mutat. 36:69-78(2015)
Cited for: VARIANTS NESCAVS LEU-58; MET-99; ASP-102; PHE-144; CYS-167; PRO-202; ARG-215; PRO-216; GLN-249; LYS-253 AND TRP-316; CHARACTERIZATION OF VARIANTS NESCAVS MET-99; PRO-202; ARG-215; PRO-216 AND LYS-253; CHARACTERIZATION OF VARIANTS SPG30 VAL-255 AND GLY-350; SUBCELLULAR LOCATION;
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.