CLN6
Chr 15ARCLN6 transmembrane ER protein
Also known as: CLN4A, CLN6A, HsT18960, nclf
The CLN6 protein is an endoplasmic reticulum membrane protein involved in lysosomal degradation of post-translationally modified proteins. Mutations cause neuronal ceroid lipofuscinosis types 6A and 6B (including Kufs type), autosomal recessive neurodegenerative disorders that comprise part of the Batten disease spectrum affecting children. The pathogenic mechanism involves defective lysosomal storage function leading to accumulation of cellular debris.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
346 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 23 | 7 | 11 | 0 | 41 |
Likely Pathogenic | 17 | 9 | 1 | 0 | 27 |
VUS | 1 | 73 | 19 | 0 | 93 |
Likely Benign | 0 | 3 | 61 | 74 | 138 |
Benign | 0 | 0 | 10 | 0 | 10 |
Conflicting | — | 35 | |||
| Total | 41 | 92 | 102 | 74 | 344 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CLN6 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Natural History of Neuronal Ceroid Lipofuscinosis, Batten's CLN6 Diseae
ACTIVE NOT RECRUITINGLong-Term Follow Up of CLN6 Batten Disease Subjects Following Gene Transfer
ACTIVE NOT RECRUITINGNatural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database
RECRUITINGExternal Resources
Links to major genomics databases and tools