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Canine Mendelian disease record

Cystinuria Type I-A (SLC3A1 p.I192V)

Cystinuria Type I-A (SLC3A1 p.I192V). Autosomal recessive. Observed in 50 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:000256-9615
Autosomal recessive
Linked gene
SLC3A1
Human counterpart
In humans, this gene is SLC3A1. OMIM 104614
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human cystinuria

Dogs with this condition carry a change in SLC3A1. In people, changes in the same gene cause cystinuria. 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: Cystinuria is a renal tubular amino acid transport disorder characterized by recurrent formation of kidneys cystine stones.

In humans it is also called: CSNU, cystinuria (disease), cystinuria, type non-I, cystinuria-lysinuria, cystinuria-lysinuria syndrome.

MONDO:0009067 OMIM 220100

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

Cystinuria, type 1 - A is an inherited defect that causes failure of reabsorption of cystine in the proximal renal tubule, leading to cystine precipitation in the urine. Formation of crystals and calculi lead to urolithiasis and urinary tract obstruction. The disorder is inherited as an autosomal recessive trait and it is caused by a mutation in SLC3A1. Edited by Dr. Paula Henthorn (modified by IT 23/5/2022 and 29/3/2023)

Clinical features

Presenting signs include recurrent cystitis, hematuria, and stranguria. Calculi may become lodged in the urinary bladder, urethra, or kidney, causing partial or complete urinary blockage, which can result in renal failure (Brons et al., 2013). A relatively earlier age of onset has been identified in Newfoundlands compared to other breeds that develop cystinuria. Diagnosis is achieved by identifying characteristically hexagonal cystine crystals in urine sediment, or cystine calculi in stone analysis. Metabolic screening tests on urine (cyanide nitroprusside test, amino acid chromatography or amino acid quantification) can detect cystinuria before or after clinical onset. Since cystine easily precipitates in acidic urine to form uroliths, treatment includes alkalinization of the urine, high fluid intake, and drugs that increase cystine solubility (Harnevik et al., 2006). As summarised by Brons et al. (2013), Cystinuria type I - A is characterised by: occurs in males and females; not androgen-dependent; COLA [μmol/g creatinine (normal ≤500)] ≥8,000 in homozygotes and ≤500 in heterozygotes.

Molecular genetics

By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Henthorn et al., 2000 reported the causative mutation in Newfoundlands is a C to T substitution in exon 2 [c.586C>T) of solute carrier family 3 member one (SLC3A1), which introduces a stop codon [p.Arg196*] and leads to translation of a truncated protein. Cystinuric dogs of other breeds do not have this mutation (Henthorn et al., 2000; Harvenik et al 2006). Harnevik et al. (2006): "Mutation analysis of the two cystinuria disease genes revealed one SLC7A9 mutation (A217T) and two SLC3A1 mutations (I192V and S698G) in French and English Bulldogs." The SLC3A1 variants have been suggested to be associated with cystinuria in English Bulldog by Ruggerone et al., (2016) and Fitzwilliams et al. (2023). Brons et al. (2013) reported a single bp deletion (c.350delG; p.Gly117Alafs*41) in the same gene as a causal mutation in Labradors.

Pathology

Cystinuria is caused by a defect in amino acid transport in epithelial cells of the proximal tubule of the nephron and gastrointestinal epithelium. The relevant amino acids (cystine, ornithine, lysine, and arginine) are transported by a heteromeric amino acid transporter encoded by the genes SLC3A1 and SLC7A9. Clinical signs are caused by failure of reabsorption of these amino acids, leading to precipitation in the urine. In the case of cystine, it readily reaches saturation concentration in urine, which can be exacerbated by a low urinary pH. Formation of crystals and calculi lead to urolithiasis, recurrent cystitis and urinary tract obstruction. Although the transport defect also occurs in the intestine, there is no associated nutritional deficiency.

Prevalence

Cystinuria is most commonly identified in male dogs, and rarely seen in female dogs. In at least one breed, this is due to the differences in the anatomy of the urethra in males and females. Cystinuria has been most extensively studied in Newfoundlands (Henthorn et al., 2000), but various forms of cystinuria have been recognized in over 60 breeds (Osborne et al., 1999).

Inheritance

The mode of inheritance in Newfoundlands is autosomal recessive (Casal et al., 1995). The Labrador genotyping results of Brons et al. (2013) implied autosomal recessive inheritance in that breed. Genotyping results in English Bulldogs also suggest a recessive mode of inheritance (Harnevik et al. 2006; Ruggerone et al., 2016; Fitzwilliams et al., 2023).

Control

Affected Newfoundlands are homozygous for the c.586C>T mutation, but homozygous females may be undetected clinically. Heterozygous Newfoundlands are unaffected carriers. All progeny of affected male and female Newfoundlands are carriers. It is recommended to avoid breeding that may result in affected dogs. Should carriers be bred to noncarriers, all offspring should be tested. Fitzwilliams et al. (2023) identified allele frequencies of 0.40 and 0.40 in English bulldogs from Denmark for the c.574A>G and c.2092A>G variants, respectively. The authors state: “Due to high allele frequencies, limited genetic diversity, continued uncertainty about the genetic background of cystinuria, and more severe health problems in the [English bulldog] breed, selection based on genetic testing for the mutations in SLC3A1 cannot be recommended in the Danish population of English bulldogs. However, results of the genetic test may be used as a guide to recommend prophylactic treatment.”

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 220100 Gene · OMIM 104614

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:000256-9615, 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 19.

  4. Cystinuria in dogs and cats: What do we know after almost 200 years? · Animals (Basel) · 2021 · PMID 34438894

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 Cystinuria Type I-A (SLC3A1 p.I192V) and see the odds for their puppies. Single recessive variant, exact Mendelian math.

Parent A
Parent B
NNClear
NmCarrier
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 Cystinuria Type I-A (SLC3A1 p.I192V) looks like in your dog's breed.
Carrier frequency by breed

Top 25 well-sampled breeds (n ≥ 50)

Maximum 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.

0%25%50%
Bulldog Standard39.4% · n 4,816
French Bulldog23.6% · n 13,114
Boerboel19.1% · n 165
Kooikerhondje16.5% · n 200
Akita15.2% · n 992
Mastiff14.1% · n 767
Dogue De Bordeaux7.0% · n 199
Newfoundland6.7% · n 463
Chow Chow6.5% · n 643
Rhodesian Ridgeback5.9% · n 323
American Staffordshire Terrier3.6% · n 42,793
Presa Canario3.1% · n 64
Boston Terrier3.0% · n 3,702
Catahoula Leopard Dog2.3% · n 154
Bullmastiff1.9% · n 209
n = 68,604 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 Cystinuria Type I-A (SLC3A1 p.I192V) is measured; phenotype outcome depends on penetrance and modifiers.
▸ Full table with Wilson 95% confidence intervals
Breed Carrier frequency n tested
Bulldog Standard 39.4% 4,816
French Bulldog 23.6% 13,114
Boerboel 19.1% 165
Kooikerhondje 16.5% 200
Akita 15.2% 992
Mastiff 14.1% 767
Dogue De Bordeaux 7.0% 199
Newfoundland 6.7% 463
Chow Chow 6.5% 643
Rhodesian Ridgeback 5.9% 323
American Staffordshire Terrier 3.6% 42,793
Presa Canario 3.1% 64
Boston Terrier 3.0% 3,702
Catahoula Leopard Dog 2.3% 154
Bullmastiff 1.9% 209
Spanish Water Dog 1.6% 96
Bulldog American 1.4% 540
Australian Cattle Dog 1.3% 982
Chinese Shar Pei 0.88% 400
Maltese 0.56% 2,413
Neapolitan Mastiff 0.56% 90
Soft Coated Wheaten Terrier 0.49% 607
Boxer 0.48% 4,557
Miniature Pinscher 0.30% 658
Chihuahua 0.26% 4,273

Top 25 of 42 well-sampled breeds with at least one observed carrier shown.

▸ Also observed in 8 small-sample breeds (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 n tested
Shikoku Ken 75.0% 6
Dingo 62.5% 12
Eurasier 36.8% 19
Lakeland Terrier 31.3% 8
Norwegian Buhund 25.0% 2
Coyote 11.1% 9
Fox Terrier Toy 5.2% 48
Tibetan Mastiff 3.1% 32

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

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 carrier 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:000256-9615.

  • 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:000256-9615 · Donner et al. 2023