OMIA:002618-9615 : Nephropathy, COL4A4 related in Canis lupus familiaris (dog)

Categories: Renal / urinary system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 120131 (gene) , 203780 (trait) , 141200 (trait)

Links to relevant human diseases in MONDO:

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".

Prevalence: Prevalence: Andrade et al. (2020) reported the frequency of the c.115T variant as 0.9% in English Cocker Spaniels in Brazil.

Breeds: English Cocker Spaniel (Dog) (VBO_0200486), English Springer Spaniel (Dog) (VBO_0200497).
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
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 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

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002618-9615: 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.

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.

Edit History

  • Created by Imke Tammen2 on 01 Feb 2023
  • Changed by Imke Tammen2 on 01 Feb 2023
  • Changed by Imke Tammen2 on 12 Jun 2023