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Canine Mendelian disease record

Neuronal Ceroid Lipofuscinosis 5 (Discovered in the Border Collie; NCL5)

Neuronal Ceroid Lipofuscinosis 5 (Discovered in the Border Collie; NCL5). Autosomal recessive. Observed in 5 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,658 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:001482-9615
Autosomal recessive
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human neuronal ceroid lipofuscinosis 5

Dogs with this condition carry a change in CLN5. In people, changes in the same gene cause neuronal ceroid lipofuscinosis 5. 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: Neuronal ceroid lipofuscinosis 5 (CLN5-NCL) is a rare condition that affects the nervous system. Signs and symptoms of the condition generally develop between ages 4.5 and 7 years, although later onset cases have been reported. Affected people may experience loss of muscle coordination (ataxia), seizures that do not respond to medications, muscle twitches (myoclonus), visual impairment, and cognitive/motor decline. It occurs predominantly in the Finnish population. CLN5-NCL is caused by changes (mutations) in the CLN5 gene and is inherited in an autosomal recessive manner. Treatment options are limited to therapies that can help relieve some of the symptoms.

In humans it is also called: CLN5, ceroid lipofuscinosis, neuronal, 5, ceroid lipofuscinosis, neuronal, type 5, CLN5 disease, adult, CLN5 disease, juvenile.

MONDO:0009745 OMIM 256731

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.

The signs, in shared terms

What this looks like

The clinical signs of Neuronal Ceroid Lipofuscinosis 5 (Discovered in the Border Collie; NCL5), recorded by OMIA using the human (HP) and mouse (MP) phenotype vocabularies applied to the dog, as the closest shared terms. Each is a model of the canine sign, not a claim the dog has the human condition. This is the phenotype-level bridge to human and mouse medicine, the layer uPheno unifies.

Clinical signs per OMIA (omia_uphenolink), termed in HP / MP / uPheno / NBO and applied to the dog as a model, not identity. See uPheno.

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

The neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal storage diseases characterized by intraneuronal accumulation of fluorescent granules and early neuronal death. Affected Border collies present at 18-24 months of age. There is a genetic test available.

Clinical features

Dogs present at 18-24 months of age with progressive behavioral changes, hyperactivity, dementia, aggression, loss of coordination, ataxia, delayed postural responses, blindness, and slow pupillary light responses (Taylor et al., 1988, Melville et al., 2005). Blind affected dogs have normal retinal structure on fundic and light microscopic examination, but have severe ultrastructural lesions (Taylor et al., 1988). Changes observed by MRI include slightly dilated cerebral sulci and cerebellar fissures, and left ventricular enlargement (Koie et al., 2004).

Molecular genetics

Sequencing of the strong comparative positional candidate gene CLN5 (see Mapping section above) revealed to Melville et al. (2005) that the causative mutation in Border Collies is "a nonsense mutation (Q206X) within exon 4" which "should result in a protein product of a size similar to that of some mutations identified in human CLN5 and therefore the Border collie may make a good model for human NCL". CLN5 encodes a soluble lysosomal glycoprotein, the function of which is unknown, but it interacts with the proteins of TPP1 and CLN3 (Vesa et al., 2002). Melville et al. (2005) report the causative variant as c.619C>T or p.Q206X. This curator (T.L.) thinks that the original protein designation (Melville et al. 2005) is incorrect and should actually read p.Q207X, based on the RefSeq entry NM_001011556.1 of the dog CLN 5 transcript. Small deletion in Golden Retrievers: CLN5:c.934_935delAG; p.E312Vfs*6 (Gilliam et al., 2015), who explain that this mutation is "predicted to produce a frameshift and premature termination codon and encode a protein variant, CLN5:p.E312Vfs*6, which would lack 39 C-terminal amino acids". Kolicheski et al. (2016) reported that affected Australian Cattle Dogs have the same causal mutation as reported by Melville et al. (2005) in Border Collies.

Pathology

There is widespread accumulation of autofluorescent storage granules in the cerebrum, cerebellum, and spinal cord. In the cerebellum there is Purkinje cell depletion, and those remaining contain eosinophilic, autofluorescent granules. Storage also occurs in the ganglion cells of the retina, peribronchial phagocytes, Kupffer cells, macrophages in the spleen, renal tubular epithelium, thyroid epithelial cells, enteric ganglia and submucosal plexus cells (Taylor et al., 1988).

Prevalence

The frequency of the c.619C>T allele is estimated at 3.5% in the Border collie population of Australia (Melville et al., 2005). Mizukami et al. (2016) reported the frequency of the c.619C>T allele as 0.035 in 500 Border collies in Japan. Villani et al. (2019) reported the c.619C>T variant to be homozygous in an affected mixed-breed dog of unknown parentage. They also reported a 87kb haplotype including the variant that is shared by this affected dog and the breeds in which this variant has been previously reported. Villani et al. (2019) concluded "that the NCL in all of these dogs stems from the same founding mutation event that may have predated the establishment of the modern dog breeds. If so, the CLN5 nonsence allele is probably segregating in other, as yet unidentified, breeds. Thus, dogs exhibiting similar NCL-like signs should be screened for this CLN5 nonsense allele regardless of breed."

History

This disorder in dogs was first reported by Taylor and Farrow (1988).

Control

Relatives of affected dogs should be tested. Avoid breeding affected dogs. If a carrier dog is bred with a dog that is DNA tested to not have the disease causing mutation, then all offspring need to be DNA tested to reduce the risk of future carrier by carrier matings.

Genetic testing

A test is available.

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 256731 Gene · OMIM 608102

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001482-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

Signs & cross-references

How it presents

Clinical signs documented for this disease, as standardized phenotype terms. These describe the condition in the literature, not a prediction for any individual dog. Each links to Monarch.

Aggressive behavior Agitation Anxiety Bilateral tonic-clonic seizure Cerebellar atrophy Clumsiness Cognitive regression Compulsive behaviors Focal-onset seizure Global brain atrophy Hyperpigmentation of the fundus Incoordination Mania Motor regression Motor stereotypy Poor gross motor coordination Ventriculomegaly Vertical nystagmus abnormal fear/anxiety-related behavior abnormal learning/memory/conditioning aggression towards inanimate objects ataxia blindness dilated brain ventricle dysphagia excessive vocalization focal seizures impaired limb coordination increased aggression increased aggression towards humans increased anxiety-related response seizures spinning strabismus tonic-clonic seizures weight loss arrested detection of light stimulus involved in visual perception brain atrophy cerebellum atrophy decreased motor coordination decreased qualitatively memory decreased swallowing dilated brain ventricle increased aggressive behavior towards humans increased anxiety-related behavior increased pigmentation in ocular fundus

Catalogued in the Mondo disease ontology (the cross-species disease identity used by the Monarch Initiative) as neuronal ceroid lipofuscinosis 5 (MONDO:0009745).

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 22.

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 Neuronal Ceroid Lipofuscinosis 5 (Discovered in the Border Collie; NCL5) 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 Neuronal Ceroid Lipofuscinosis 5 (Discovered in the Border Collie; NCL5) looks like in your dog's breed.
Carrier frequency by breed

Top 5 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%3%5%
Australian Cattle Dog1.5% · n 982
Border Collie<0.1% · n 6,714
Great Pyrenees<0.1% · n 1,985
German Shepherd<0.1% · n 15,648
Labrador Retriever<0.1% · n 16,856
n = 42,185 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 Neuronal Ceroid Lipofuscinosis 5 (Discovered in the Border Collie; NCL5) is measured; phenotype outcome depends on penetrance and modifiers.
▸ Full table with Wilson 95% confidence intervals
Breed Carrier frequency n tested
Australian Cattle Dog 1.5% 982
Border Collie <0.1% 6,714
Great Pyrenees <0.1% 1,985
German Shepherd <0.1% 15,648
Labrador Retriever <0.1% 16,856

261 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:001482-9615.

  • 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:001482-9615 · Donner et al. 2023