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UniProtKB/Swiss-Prot O60282: Variant p.Glu237Lys

Kinesin heavy chain isoform 5C
Gene: KIF5C
Variant information

Variant position:  237
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 Glutamate (E) to Lysine (K) at position 237 (E237K, p.Glu237Lys).
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 large size and basic (K)
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

Involvement in disease:  Cortical dysplasia, complex, with other brain malformations 2 (CDCBM2) [MIM:615282]: A disorder of aberrant neuronal migration and disturbed axonal guidance. Clinical features include intrauterine growth retardation, fetal akinesia, seizures, microcephaly, lack of psychomotor development, and arthrogryposis. Brain imaging shows malformations of cortical development, including polymicrogyria, gyral simplification, and thin corpus callosum. {ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:23603762, ECO:0000269|PubMed:24812067, ECO:0000269|PubMed:29048727}. 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 CDCBM2; the mutation results in a significant decrease of excitatory post-synaptic currents when expressed in cultured primary hippocampal neurons; decreased localization to distal regions of dendrites; accumulates in dendrite cell body.
Any additional useful information about the variant.

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



Sequence information

Variant position:  237
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  957
The length of the canonical sequence.

Location on the sequence:   NVETEKKLSGKLYLVDLAGS  E KVSKTGAEGAVLDEAKNINK
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                         NVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLDEAKNINK

Mouse                         NVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLDEAKNINK

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 – 957 Kinesin heavy chain isoform 5C
Domain 8 – 327 Kinesin motor
Region 174 – 315 Microtubule-binding
Alternative sequence 233 – 238 LAGSEK -> MATYIH. In isoform 2.


Literature citations

Involvement of the kinesin family members KIF4A and KIF5C in intellectual disability and synaptic function.
Willemsen M.H.; Ba W.; Wissink-Lindhout W.M.; de Brouwer A.P.; Haas S.A.; Bienek M.; Hu H.; Vissers L.E.; van Bokhoven H.; Kalscheuer V.; Nadif Kasri N.; Kleefstra T.;
J. Med. Genet. 51:487-494(2014)
Cited for: FUNCTION; SUBCELLULAR LOCATION; VARIANT CDCBM2 LYS-237; CHARACTERIZATION OF VARIANT CDCBM2 LYS-237;

Diagnostic exome sequencing in persons with severe intellectual disability.
de Ligt J.; Willemsen M.H.; van Bon B.W.; Kleefstra T.; Yntema H.G.; Kroes T.; Vulto-van Silfhout A.T.; Koolen D.A.; de Vries P.; Gilissen C.; del Rosario M.; Hoischen A.; Scheffer H.; de Vries B.B.; Brunner H.G.; Veltman J.A.; Vissers L.E.;
N. Engl. J. Med. 367:1921-1929(2012)
Cited for: VARIANT CDCBM2 LYS-237;

Mutations of KIF5C cause a neurodevelopmental disorder of infantile-onset epilepsy, absent language, and distinctive malformations of cortical development.
Michels S.; Foss K.; Park K.; Golden-Grant K.; Saneto R.; Lopez J.; Mirzaa G.M.;
Am. J. Med. Genet. A 173:3127-3131(2017)
Cited for: VARIANT CDCBM2 LYS-237;

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.