OMIA:002240-9615 : Ataxia, cerebellar, KCNIP4-related in Canis lupus familiaris
Categories: Nervous system phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 608182 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2020
Molecular basis: By whole-genome sequencing two affected Norwegian Buhund sibs, comparing these sequences against 405 whole-genome sequences from other breeds, and then extensively genotyping the most likely variant, Jenkins et al. (2020) identified the most likely causal variant as "a T to C single nucleotide polymorphism (SNP) (NC_006585.3:g.88890674T>C), [that] is predicted to cause a tryptophan to arginine substitution in a highly conserved region of the potassium voltage-gated channel interacting protein KCNIP4. This gene has not been implicated previously in hereditary ataxia in any species. Evaluation of KCNIP4 protein expression through western blot and immunohistochemical analysis using cerebellum tissue of affected and control dogs demonstrated that the mutation causes a dramatic reduction of KCNIP4 protein expression. The expression of alternative KCNIP4 transcripts within the canine cerebellum, and regional differences in KCNIP4 protein expression, were characterised through RT-PCR and immunohistochemistry respectively. The voltage-gated potassium channel protein KCND3 has previously been implicated in spinocerebellar ataxia, and our findings suggest that the Kv4 channel complex KCNIP accessory subunits also have an essential role in voltage-gated potassium channel function in the cerebellum and should be investigated as potential candidate genes for cerebellar ataxia in future studies in other species."
Breed: Norwegian Buhund.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|KCNIP4||Kv channel interacting protein 4||Canis lupus familiaris||3||NC_051807.1 (88754615..89880267)||KCNIP4||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1154||Norwegian Buhund||Ataxia, cerebellar, KCNIP4-related||KCNIP4||missense||Naturally occurring variant||CanFam3.1||3||g.88890674T>C||c.436T>C||p.(T146R)||XM_005618660.3; XP_005618717.1||2020||31999692|
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2020||Jenkins, C.A., Kalmar, L., Matiasek, K., Mari, L., Kyöstilä, K., Lohi, H., Schofield, E.C., Mellersh, C.S., De Risio, L., Ricketts, S.L. :|
|Characterisation of canine KCNIP4: A novel gene for cerebellar ataxia identified by whole-genome sequencing two affected Norwegian Buhund dogs. PLoS Genet 16:e1008527, 2020. Pubmed reference: 31999692 . DOI: 10.1371/journal.pgen.1008527.|
|2018||Mari, L., Matiasek, K., Jenkins, C.A., De Stefani, A., Ricketts, S.L., Forman, O., De Risio, L. :|
|Hereditary ataxia in four related Norwegian Buhunds. J Am Vet Med Assoc 253:774-780, 2018. Pubmed reference: 30179085 . DOI: 10.2460/javma.253.6.774.|
- Created by Frank Nicholas on 03 Feb 2020
- Changed by Frank Nicholas on 03 Feb 2020