CLN6

Chr 15AR

CLN6 transmembrane ER protein

Also known as: CLN4A, CLN6A, HsT18960, nclf

This gene is one of eight which have been associated with neuronal ceroid lipofuscinoses (NCL). Also referred to as Batten disease, NCL comprises a class of autosomal recessive, neurodegenerative disorders affecting children. The genes responsible likely encode proteins involved in the degradation of post-translationally modified proteins in lysosomes. The primary defect in NCL disorders is thought to be associated with lysosomal storage function. [provided by RefSeq, Oct 2008]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Ceroid lipofuscinosis, neuronal, 6AMIM #601780
AR
Ceroid lipofuscinosis, neuronal, 6B (Kufs type)MIM #204300
AR

Clinical highlights

Gene-disease validity (ClinGen)
neuronal ceroid lipofuscinosis · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
4
Active trials
14
Pubs (1 yr)
P/LP submissions
P/LP missense
1.13
LOEUF
LOF
Mechanism· G2P
📖
GeneReview available — CLN6
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.13LOEUF
pLI 0.000
Z-score 1.23
OE 0.63 (0.371.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.01Z-score
OE missense 1.00 (0.891.14)
176 obs / 175.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.63 (0.371.13)
00.351.4
Missense OE?1.00 (0.891.14)
00.61.4
Synonymous OE?1.37
01.21.6
LoF obs/exp: 8 / 12.7Missense obs/exp: 176 / 175.7Syn Z: -2.53

ClinVar Variant Classifications

0 submitted variants 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.