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Canine Mendelian disease record

X-Linked Hereditary Nephropathy (Discovered in the Samoyed; XLHN)

X-Linked Hereditary Nephropathy (Discovered in the Samoyed; XLHN). X-linked recessive. Observed in 0 of 266 breeds tested in the Sniff Atlas, with measured variant frequencies drawn from 242,650 dogs (Donner 2023). Whether a dog carrying this variant is at risk depends on the disease’s inheritance pattern; outcome also depends on penetrance, modifiers, and environment. The frequencies below describe variant prevalence, not confirmed disease incidence.

OMIA identifier
OMIA:001112-9615
X-linked recessive
Linked gene
COL4A5
Human counterpart
In humans, this gene is COL4A5. OMIM 303630 In people, variants in the COL4A5 gene have conflicting classifications in ClinVar, and none is expert-reviewed. The evidence is unsettled, not that variants here are benign.
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human X-linked Alport syndrome

Dogs with this condition carry a change in COL4A5. In people, changes in the same gene cause X-linked Alport syndrome. That makes affected dogs a naturally-occurring model of the human disease, and it is part of why studying dogs moves medicine forward for everyone. It does not mean your dog has the human disease. It means the two share an underlying biology.

In people, the disease is described as: X-linked form of Alport syndrome.

In humans it is also called: ATS, Alport syndrome 1, X-linked, X-linked dominant, Alport syndrome, X-linked, congenital hereditary hematuria, hemorrhagic familial nephritis.

MONDO:0010520 OMIM 301050

Mapped from OMIA via the human disease's OMIM entry to the Mondo Disease Ontology (Monarch Initiative, CC-BY 4.0). Sniff renders this as a model-of link; the canine disease remains the subject of this page.

About this disease

From OMIA's curated record

Documented in OMIA (Online Mendelian Inheritance in Animals). This describes the disease as recorded in the published literature, not a prediction for any individual dog. As of 2026-06-03.

Summary

X-linked nephritis is caused by mutations in the alpha 5 chain of collagen type IV (COL4A5), a key structural component of the glomerular basement membrane. Affected males have severely reduced COL4A5 levels and early-onset renal failure. For other types of hereditary nephritis see also: 'OMIA:002618-9615 Nephropathy, COL4A4 related '; 'OMIA:001114-9615 Nephritis, autosomal dominant'; OMIA:000708-9615: Nephritis' and 'OMIA:000413-9615 Glomerulonephritis'.

Clinical features

Affected males exhibit proteinuria and develop rapidly progressive renal failure, which is usually fatal before 1 year of age in the Samoyed and 18 months of age in the Navasota mixed breed model. Heterozygous female Samoyeds may present with a wide range of renal function, from normal to initially having proteinuria and occasionally microscopic hematuria, but most were healthy until 5 years of age (Baumal et al., 1991). With age, approximately 31% of carrier female Samoyeds developed mild renal disease, and 38% progressed to end-stage renal disease. Possible clinical features may also include hearing loss (Harvey et al., 2001) and and anterior lenticonus (Kashtan, 2002). [IT thanks DVM student Muhammad Elsayed for contributions to this entry in April 2022]

Molecular genetics

The causative mutation in the Samoyed is a G to T substitution in exon 35 of COL4A5, which generates a premature stop codon (Zheng et al., 1994). The causative mutation in the Navasota mixed breed model is a 10 base pair deletion in exon 9 of COL4A5, which generates a premature stop codon. In the Navasota model, the mutant genotype at this locus has no apparent effect on X inactivation in females (Bell et al., 2008).

Pathology

Collagen type IV is an important contributor to basement membrane structural integrity. Affected males have approximately 10% of normal levels of the alpha 5 chain of collagen type IV, as well as decreased levels of the alpha 3 and alpha 4 chains (Thorner et al., 1996). Multilaminar splitting of glomerular basement membranes is found by electron microscopy (Baumal et al., 1991). The thinning and thickening of the glomerular basement membrane appears as “basket weave” patterns under electron microscopy (Clark et al., 2016). Areas of focal segmental glomerulosclerosis are found by light microscopy (Baumal et al., 1991). These basement membrane changes are also indicated to cause decreased strength of the lens capsule preventing maintenance of normal lens shape (Kashtan, 2002). Alport syndrome also weakens the interaction between the extracellular matrix in the ear resulting in reduced tension on the basement membrane and an inability to respond to high frequency sounds (Harvey et al., 2001). [IT thanks DVM students Muhammad Elsayed and Ji Youn Lee for contributions to this entry in April 2022]

Control

Males with signs of renal disease should be tested for the causative mutation. As it is an X-linked trait, the dam of affected males is an obligate carrier. Male siblings of affected dogs should be free of the mutation, but female siblings should be tested. Breeding of affected or carrier dogs is not recommended.

Genetic testing

There are tests available to detect the known causative mutations.

Human analog

OMIA links this condition to its human counterpart in OMIM (Mendelian Inheritance in Man), the place to read across to the deeper human literature for the same biology.

Disease · OMIM 301050 Gene · OMIM 303630

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001112-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

Signs & cross-references

How it presents

Catalogued in the Mondo disease ontology (the cross-species disease identity used by the Monarch Initiative) as X-linked Alport syndrome (MONDO:0010520).

Phenotype terms: Human Phenotype Ontology + Mammalian Phenotype Ontology; disease terms: Mondo (Monarch Initiative). Cross-references curated by OMIA (doi:10.25910/2AMR-PV70, CC-BY 4.0).

The evidence

Published references

The peer-reviewed papers behind this disease, curated by OMIA. Starred entries are OMIA-designated landmark papers. Showing 6 of 33.

  2. Genotype-based molecular mechanisms in Alport syndrome. · J Am Soc Nephrol · 2025 · PMID 39899372

References curated by OMIA (Nicholas, Tammen & the Sydney Informatics Hub), doi:10.25910/2AMR-PV70 (CC-BY 4.0). Full list at the OMIA entry.

Your breed

See what X-Linked Hereditary Nephropathy (Discovered in the Samoyed; XLHN) looks like in your dog's breed.
Variant frequency by breed

Observed only in small-sample breeds

Maximum variant frequency per breed across variants in the Donner 2023 cohort, with . The list below is split into well-sampled breeds (n ≥ 50 tested) and small-sample breeds (n < 50, where the Wilson CI typically spans more than 20 percentage points and frequencies should not be compared directly to the well-sampled entries). Frequencies are population-level, not per-litter or per-line.

Scope of this record

Scope

This record carries the breed-level carrier frequencies from the Donner 2023 cohort. Penetrance data (the fraction of at-risk dogs that develop the phenotype) is not yet quantified for this disease in the Sniff Atlas v1.0.1. The OMIA entry is the authoritative reference for the clinical phenotype, inheritance pattern, and gene assignment.

Predicted disease relevance at the per-dog level is UNPROVEN. The variant frequency is measured; phenotype outcome depends on penetrance, environment, and modifier loci. Consult a veterinarian for clinical interpretation.

How to cite this record

Citations

If you use this record in published work, cite the Sniff Atlas (the published dataset that carries the breed-level carrier frequencies) and the upstream sources:

  • Sniff Atlas v1.0.1 for the per-breed carrier frequencies:

    Gehring, M. (2026). Sniff Atlas v1.0.1. Zenodo. https://doi.org/10.5281/zenodo.20566358. CC-BY 4.0.

  • OMIA for the disease definition, inheritance, and gene assignment:

    Nicholas, F. W., & Tammen, I. (2024). OMIA. Sydney Informatics Hub, The University of Sydney. https://doi.org/10.25910/2AMR-PV70. Entry: OMIA:001112-9615.

  • Donner et al. 2023 for the breed × variant carrier-frequency cohort:

    Donner, J., Freyer, J., Davison, S., Anderson, H., Blades, M., Honkanen, L., et al. (2023). Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLOS Genetics, 19(2), e1010651. https://doi.org/10.1371/journal.pgen.1010651.

Full citation formats (BibTeX, RIS, CITATION.cff) at sniff.world/cite.

Related

Related

Last updated
Sources: Sniff Atlas v1.0.1 · OMIA OMIA:001112-9615 · Donner et al. 2023 · ClinVar (Landrum 2018)