OMIA:002240-9615 : Ataxia, cerebellar, KCNIP4-related in Canis lupus familiaris (dog)

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 608182 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2020

Species-specific name: Progressive cerebellar ataxia

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."

Clinical features: Affected Norwegian Buhunds generally present as puppies with slowly progressing abnormalities in gait and balance. There is generally no irregularity of behaviour or demeanour, however they have a broad-based stance and hypermetria in all limbs, truncal ataxia and persistent head tremors (Mari et al., 2018). A bilaterally reduced menace response may be present, however no other abnormalities are likely on physical exam, CBC or serum biochemistry, and no abnormalities have been noted on MRI imaging or CSF sampling in known cases (Mari et al., 2018). IT thanks DVM student Teresa McIntyre, who provided the basis of this contribution in May 2023.

Pathology: Histopathology will find mild evidence of neuronal degeneration and reduced Purkinje fibre differentiation in regions of the cerebellum (Mari et al., 2018). IT thanks DVM student Teresa McIntyre, who provided the basis of this contribution in May 2023.

Breed: Norwegian Buhund (Dog) (VBO_0200953).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

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 Year Published PubMed ID(s) Acknowledgements
1154 Norwegian Buhund (Dog) 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

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002240-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset].


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.

2023 Stee, K., Van Poucke, M., Lowrie, M., Van Ham, L., Peelman, L., Olby, N., Bhatti, S.F.M. :
Phenotypic and genetic aspects of hereditary ataxia in dogs. J Vet Intern Med 37:1306-1322, 2023. Pubmed reference: 37341581. DOI: 10.1111/jvim.16742.
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.

Edit History

  • Created by Frank Nicholas on 03 Feb 2020
  • Changed by Frank Nicholas on 03 Feb 2020
  • Changed by Imke Tammen2 on 05 Jun 2023