What is the human equivalent of Xanthinuria, Type II (Discovered in the Cavalier King Charles Spaniel)?

OMIA links Xanthinuria, Type II (Discovered in the Cavalier King Charles Spaniel) to its human counterpart in OMIM (OMIM 603592), the bridge to the deeper human-medicine literature for the same underlying biology.

Canine Mendelian disease record

Xanthinuria, Type II (Discovered in the Cavalier King Charles Spaniel)

Q: How well studied is Xanthinuria, Type II (Discovered in the Cavalier King Charles Spaniel) in dogs?

OMIA curates 9 peer-reviewed references for Xanthinuria, Type II (Discovered in the Cavalier King Charles Spaniel). The full, linked citation list is on this page.

Xanthinuria, Type II (Discovered in the Cavalier King Charles Spaniel). Autosomal recessive. Observed in 4 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,665 dogs (Donner 2023). Per-dog phenotype outcome depends on penetrance, modifiers, and environment; the carrier frequencies below describe variant prevalence, not disease incidence.

OMIA identifier: OMIA:001819-9615
Inheritance: Autosomal recessive
Source dataset: Sniff Atlas v1.0.1 / DOI

The human connection

A model of human xanthinuria type II

This is the canine counterpart of xanthinuria type II in people. 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: Type II xanthinuria, a type of classical xanthinuria, is a rare autosomal recessive disorder of purine metabolism characterized by the deficiency of both xanthine dehydrogenase and aldehyde oxidase, leading to the formation of urinary xanthine urolithiasis and leading, in some patients, to kidney failure. Other less common manifestations include arthropathy, myopathy and duodenal ulcer, while some patients remain asymptomatic.

In humans it is also called: XAN2, type 2 xanthinuria, type II xanthinuria, xanthinuria type 2, XDH and AOX dual deficiency.

MONDO:0011346 OMIM 603592

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

Animals with hereditary xanthinuria (excretion of large amounts of xanthine in the urine) may be asymptomatic, may have subclinical uroliths (xanthine stones), or present with clinical signs of urolithiasis. Urolith formation can be influenced by other biologic and environmental factors such as sex, diet and urine properties. Xanthinuria, type I (OMIA:002445) is caused by variation in the XDH gene and xanthinuria, type II (OMIA:001819) is caused by variation in the MOCOS gene. Information relating to xanthinuria without identified causal variants is listed under xanthinuria, generic (OMIA:001283).

Clinical features

In affected dogs with MOCOS deficiency excess xanthine builds up in the urine, a product which has a low solubility and readily precipitates out of urine, creating xanthine calculi (Furrow et al., 2016). These calculi act similar to most uroliths, creating partial or complete urethral obstruction, resulting in intermittent or consistent stranguria and dysuria, and may result in secondary renal damage (Furrow et al., 2016). In the dogs investigated by Tate et al. (2021) "age at first diagnosis ranged from 7 weeks to 4 years." IT thanks DVM student Cameron Stuart, who provided the basis of this contribution in May 2023.

Molecular genetics

Furrow et al. (2016) reported in a conference abstract the identification of three likely disease-causing mutations for xanthine urolithiasis. Affected Cavalier King Charles Spaniels had a mutation resulting in a premature stop codon in the molybdenum cofactor sulfurase gene (MOCOS), affected Toy Manchester Terriers had a splice site mutation in MOCOS, and an affected mixed breed dog had a splice site mutation in the xanthine dehydrogenase (XDH) gene. These findings were included in the publication by Tate et al. (2021). Tate et al. (2021): "The aim of this study was to uncover variants underlying risk for xanthinuria in dogs. Affected dogs included two Manchester Terriers, three Cavalier King Charles Spaniels, an English Cocker Spaniel, a Dachshund, and a mixed-breed dog. ...Sanger sequencing of [candidate genes] XDH and MOCOS identified four putative causal variants ... : an XDH c.654G > A splice site variant that results in skipping of exon 8 (mixed-breed dog), a MOCOS c.232G > T splice site variant that results in skipping of exon 2 (Manchester Terriers), a MOCOS p.Leu46Pro missense variant (Dachshund), and a MOCOS p.Ala128Glyfs*30 frameshift variant that results in a premature stop codon (Cavalier King Charles Spaniels and English Cocker Spaniel). ... All variants were found in a homozygous state in the affected dogs, consistent with an autosomal recessive mode of inheritance."

Prevalence

The allele frequency of the MOCOS c.232G > T (p.Gly78Cys) variant was 0,13 and 0,10 in 386 Manchester Terriers and 285 English Toy Terriers, respectively. The allele frequency of the MOCOS c.383delC variant was 0.03 and 0 in 109 Cavalier King Charles Spaniels and 42 English Cocker Spaniels, respectively. The MOCOS c.137 T > C variant was absent from a population of 116 Dachshunds. (Tate et al., 2021)

Inheritance

Tate et al. (2021) conducted pedigree analysis in Manchester Terriers and their findings were consistent with autosomal recessive inheritance.

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 603592 Gene · OMIM 613274

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001819-9615, 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 xanthinuria type II (MONDO:0011346).

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 9.

Multiple variants in XDH and MOCOS underlie xanthine urolithiasis in dogs. · Mol Genet Metab Rep · 2021 · PMID 34584846
2016 ACVIM Forum Research Report Program: Three diverse mutations underlying canine xanthine urolithiasis. · J Vet Intern Med · 2016
Urine concentrations of xanthine, hypoxanthine and uric acid in UK Cavalier King Charles spaniels. · J Small Anim Pract · 2013 · PMID 23859747
Xanthine urolithiasis in a Cavalier King Charles spaniel. · Vet Rec · 2011 · PMID 21742684
Xanthine urolithiasis in a dachshund · Vet Rec · 1998 · PMID 9807792
Bilateral xanthine nephrolithiasis in a dog · J Small Anim Pract · 1997 · PMID 9239633

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.

Predict a litter

Set each parent's status for Xanthinuria, Type II (Discovered in the Cavalier King Charles Spaniel) and see the odds for their puppies. Single recessive variant, exact Mendelian math.

Parent A

Parent B

NNClear

NmCarrier

mmAffected

Clear25%

Carrier50%

Affected25%

These are the genetic odds for one known variant, not a promise: a real litter varies around them, and penetrance or other genes can change whether the condition ever appears. Use it to avoid pairing two carriers and to keep a line healthy, not to engineer a dog. Inheritance mode per OMIA.

Your breed

See what Xanthinuria, Type II (Discovered in the Cavalier King Charles Spaniel) looks like in your dog's breed.

Carrier frequency by breed

Top 3 well-sampled breeds (n ≥ 50)

Maximum carrier frequency per breed across variants in the Donner 2023 cohort, with Wilson 95% confidence intervals. 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.

0%3%5%

Cavalier King Charles Spaniel2.0% · n 2,243

2.0%n 2,243

English Cocker Spaniel0.52% · n 580

0.52%n 580

Cocker Spaniel<0.1% · n 1,881

<0.1%n 1,881

n = 4,704 dogs · Donner et al. 2023 carrier-screening cohort · Sniff Atlas

Each bar is one well-sampled breed; the whisker is its Wilson 95% CI, and fainter bars have wider intervals. Frequencies are population-level, not per-litter. Carrier status for Xanthinuria, Type II (Discovered in the Cavalier King Charles Spaniel) is measured; phenotype outcome depends on penetrance and modifiers.

▸ Full table with Wilson 95% confidence intervals

Breed	Carrier frequency	Wilson 95% CI	n tested
Cavalier King Charles Spaniel	2.0%	[1.5%, 2.7%]	2,243
English Cocker Spaniel	0.52%	[0.2%, 1.5%]	580
Cocker Spaniel	<0.1%	[0.0%, 0.3%]	1,881

▸ Also observed in 1 small-sample breed (n < 50)

Frequencies in this section are statistical estimates with wide Wilson 95% confidence intervals (typically >20 percentage points). Treat these as "carriers observed but the true population frequency is not yet measurable" rather than as comparable to the well-sampled entries above.

Breed	Estimate	Wilson 95% CI	n tested
Manchester Terrier Toy	4.2%	[0.4%, 30.1%]	12

262 additional breeds in the Donner 2023 cohort were tested but showed no carriers.

Scope of this record

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 carrier frequency is measured; phenotype outcome depends on penetrance, environment, and modifier loci. Consult a veterinarian for clinical interpretation.

How to cite this record

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:001819-9615.
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.

Sniff Atlas v1.0.1, the source dataset for these frequencies.
Browse breeds, per-breed Mendelian profiles, including this disease in context.
OMIA entry OMIA:001819-9615, authoritative clinical reference.
About OMIA, the catalogue this record comes from, and how Sniff uses it.

Last updated June 20, 2026

Sources: Sniff Atlas v1.0.1 · OMIA OMIA:001819-9615 · Donner et al. 2023