OMIA:002618-9615 : Nephropathy, COL4A4 related in Canis lupus familiaris (dog)
Categories: Renal / urinary system phene
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2007
Species-specific name: Autosomal recessive hereditary nephropathy; Alport syndrome; autosomal recessive nephritis
Species-specific symbol: ARNH
Species-specific description: For other types of hereditary nephritis/nephropathy see also: 'OMIA:001112-9615: Nephritis, X-linked'; 'OMIA:001114-9615 Nephritis, autosomal dominant'; OMIA000708-9615: Nephritis' and 'OMIA:000413-9615 Glomerulonephritis'.
Molecular basis: By sequencing the most obvious candidate gene, Davidson et al. (2007) identified a causal mutation as "a single nucleotide substitution at base 115 as the cause of ARHN in English Cocker Spaniels. This mutation, which causes a premature stop codon in exon 3 of COL4A4 was segregated with clinical status in all affected dogs and obligate carriers".
Nowend et al. (2012) reported a different mutation in the same gene in English Springer Spaniels: "a single nucleotide substitution in COL4A4 at base 2806 resulting in a premature stop codon".
Have human generated variants been created, e.g. through genetic engineering and gene editing
Prevalence: Prevalence: Andrade et al. (2020) reported the frequency of the c.115T variant as 0.9% in English Cocker Spaniels in Brazil.
English Cocker Spaniel (Dog) (VBO_0200486),
English Springer Spaniel (Dog) (VBO_0200497).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|COL4A4||collagen, type IV, alpha 4||Canis lupus familiaris||25||NC_051829.1 (40223035..40097773)||COL4A4||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|
|278||English Springer Spaniel (Dog)||Nephropathy||COL4A4||nonsense (stop-gain)||Naturally occurring variant||CanFam3.1||25||g.39893376G>A||c.2713C>T||p.(Q905*)||NM_001031818.1; NP_001026988.1; published as c.2806C>T and p.(Q904*)||2012||22369189|
|277||English Cocker Spaniel (Dog)||Nephropathy||COL4A4||nonsense (stop-gain)||Naturally occurring variant||CanFam3.1||25||g.39953906T>A||c.115A>T||p.(K39*)||2007||17552442||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool|
Cite this entry
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||Andrade, L.R., Caceres, A.M., Trecenti, A.S., Borges, A.S., Oliveira-Filho, J.P. :|
|Allele frequency of nonsense mutation responsible for hereditary nephropathy in English cocker spaniel dogs. Vet Anim Sci 9:100114, 2020. Pubmed reference: 32734115. DOI: 10.1016/j.vas.2020.100114.|
|2013||Lees, G.E. :|
|Kidney diseases caused by glomerular basement membrane type IV collagen defects in dogs. J Vet Emerg Crit Care (San Antonio) 23:184-93, 2013. Pubmed reference: 23464675. DOI: 10.1111/vec.12031.|
|2012||Nowend, K.L., Starr-Moss, A.N., Lees, G.E., Berridge, B.R., Clubb, F.J., Kashtan, C.E., Nabity, M.B., Murphy, K.E. :|
|Characterization of the genetic basis for autosomal recessive hereditary nephropathy in the English Springer Spaniel. J Vet Intern Med 26:294-301, 2012. Pubmed reference: 22369189. DOI: 10.1111/j.1939-1676.2012.00888.x.|
|2007||Davidson, AG., Bell, RJ., Lees, GE., Kashtan, CE., Davidson, GS., Murphy, KE. :|
|Genetic cause of autosomal recessive hereditary nephropathy in the English Cocker Spaniel. J Vet Intern Med 21:394-401, 2007. Pubmed reference: 17552442.|
|2005||Wiersma, A.C., Millon, L.V., Hestand, M.S., Van Oost, B.A., Bannasch, D.L. :|
|Canine COL4A3 and COL4A4: sequencing, mapping and genomic organization. DNA Seq 16:241-51, 2005. Pubmed reference: 16147883. DOI: 10.1080/10425170500136822.|
|2002||Kashtan, C.E. :|
|Animal models of Alport syndrome. Nephrol Dial Transplant 17:1359-62, 2002. Pubmed reference: 12147777. DOI: 10.1093/ndt/17.8.1359.|
|1998||Lees, G.E., Helman, R.G., Homco, L.D., Millichamp, N.J., Hunter, J.F., Frey, M.S. :|
|Early diagnosis of familial nephropathy in English Cocker Spaniels Journal of the American Animal Hospital Association 34:189-195, 1998. Pubmed reference: 9590445.|
|Lees, G.E., Helman, R.G., Kashtan, C.E., Michael, A.F., Homco, L.D., Millichamp, N.J., Ninomiya, Y., Sado, Y., Naito, I., Kim, Y. :|
|A model of autosomal recessive Alport-syndrome in English Cocker Spaniel dogs Kidney International 54:706-719, 1998. Pubmed reference: 9734596. DOI: 10.1046/j.1523-1755.1998.00062.x.|
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