CLN3 disease: genes and variants
Explore variant evidence for CLN3 disease across 2 analyzed proteins (CLN3, GRN). Linked ClinVar records include 25 pathogenic or likely pathogenic variants, 468 variants of uncertain significance and 31 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to CLN3 disease
CLN3: Battenin
It participates in lysosomal and endosomal homeostasis, membrane trafficking, and cellular lipid handling, although its complete molecular role remains unresolved. Biallelic loss-of-function variants cause juvenile neuronal ceroid lipofuscinosis, with progressive vision loss, epilepsy, cognitive decline, and motor impairment.
22 ClinVar pathogenic / likely pathogenic and 264 uncertain variants in CLN3 have source records linked to CLN3 disease. Association strength is not clinical gene validity.
GRN: Progranulin
It is secreted and proteolytically processed into granulins and has roles in lysosomal function, inflammation, neuronal survival, and tissue repair. Heterozygous loss-of-function variants cause frontotemporal dementia through progranulin haploinsufficiency, while biallelic loss causes neuronal ceroid lipofuscinosis.
3 ClinVar pathogenic / likely pathogenic and 235 uncertain variants in GRN have source records linked to CLN3 disease. Association strength is not clinical gene validity.
Weakly linked (only a few uncertain records): MEFV.
Where CLN3 disease variants cluster
- CLN3 Transmembrane (positions 152–172): 4 of 22 ClinVar pathogenic / likely pathogenic variants, 3.8× more than its size predicts.
- CLN3 Cytoplasmic (positions 1–37): 4 of 22 ClinVar pathogenic / likely pathogenic variants, 2.1× more than its size predicts.
- CLN3 Lumenal (positions 299–346): 4 of 22 ClinVar pathogenic / likely pathogenic variants, 1.7× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to CLN3 disease
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CLN3 M1V | 1 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| CLN3 M1I | 1 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| CLN3 V330F | 330 | Lumenal | Pathogenic / likely pathogenic (★★) |
| CLN3 R334C | 334 | Lumenal | Pathogenic / likely pathogenic (★★) |
| CLN3 E295K | 295 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| CLN3 V330I | 330 | Lumenal | Pathogenic / likely pathogenic (★★) |
| CLN3 R334H | 334 | Lumenal | Pathogenic / likely pathogenic (★★) |
| CLN3 A5T | 5 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| CLN3 G165R | 165 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| CLN3 S171F | 171 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| CLN3 G189R | 189 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| CLN3 D416G | 416 | Lysosomal targeting motif | Pathogenic / likely pathogenic (★★) |
| CLN3 A59T | 59 | Lumenal | Pathogenic / likely pathogenic (★★) |
| CLN3 V167D | 167 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| CLN3 R405W | 405 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| GRN A9D | 9 | Pathogenic / likely pathogenic (★★) | |
| CLN3 M1L | 1 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| CLN3 E295G | 295 | Transmembrane | Pathogenic / likely pathogenic (★) |
| GRN M1T | 1 | Pathogenic / likely pathogenic (★) | |
| GRN M1V | 1 | Pathogenic / likely pathogenic (★) | |
| CLN3 Q352H | 352 | Transmembrane | Pathogenic / likely pathogenic (★) |
| CLN3 S161L | 161 | Transmembrane | Pathogenic / likely pathogenic (★) |
| CLN3 L422P | 422 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| CLN3 G187A | 187 | Transmembrane | Pathogenic / likely pathogenic |
| CLN3 L101P | 101 | Lumenal | Pathogenic / likely pathogenic |
Uncertain variants prioritized for review in CLN3 disease
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| CLN3 G187E | 187 | Transmembrane | Uncertain (★) | +6: 2 other pathogenic changes within 3 positions; G187A at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.85 |
Which prediction tools work for CLN3 disease
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- phyloP: 97 out of 100
- CADD: 95 out of 100
- CATVariant: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 95 out of 100
- PolyPhen-2: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Diseases related to CLN3 disease
- Retinitis pigmentosa, also linked to CLN3
- Alzheimer disease, also linked to GRN
- Frontotemporal dementia, also linked to GRN
- GRN-related frontotemporal lobar degeneration with Tdp43 inclusions, also linked to GRN
- Dementia, also linked to GRN
Frequently asked questions
Which genes have records linked to CLN3 disease?
This view contains 2 analyzed proteins: CLN3, GRN. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 25 pathogenic or likely pathogenic variants, 468 variants of uncertain significance and 31 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 1 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 590 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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