CLN3

Chr 16AR

CLN3 lysosomal/endosomal transmembrane protein, battenin

Also known as: BTN1, BTS, JNCL, RP101, SLC29B1

NCBI Gene: 1201 ENSG00000188603 UniProt: Q13286 OMIM: 607042

The protein mediates microtubule-dependent transport between cellular compartments including the Golgi, endosomes, lysosomes and plasma membrane, and regulates lysosomal pH, autophagy, and synaptic transmission. Mutations cause neuronal ceroid lipofuscinosis type 3 (CLN3 disease), a form of Batten disease characterized by progressive neurodegeneration, through an autosomal recessive inheritance pattern. Disease results from loss-of-function mutations that disrupt the protein's essential roles in intracellular transport and lysosomal function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a protein that is involved in lysosomal function. Mutations in this, as well as other neuronal ceroid-lipofuscinosis (CLN) genes, cause neurodegenerative diseases commonly known as Batten disease or collectively known as neuronal ceroid lipofuscinoses (NCLs). Many alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Ceroid lipofuscinosis, neuronal, 3MIM #204200

Retinitis pigmentosa 101MIM #621548

Clinical highlights

Gene–disease validity (ClinGen · GenCC)

Definitive · neuronal ceroid lipofuscinosis · AR · ClinGen 2023
Definitive · neuronal ceroid lipofuscinosis 3 · AR · Ambry Genetics
Definitive · inherited retinal dystrophy · AR · G2P

Interpreting a novel variant

Loss of function is the established mechanism, 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.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.91

LOEUF

LOF

Mechanism· annotated

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.91LOEUF

pLI 0.000

Z-score 1.93

OE 0.59 (0.39–0.91)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.15Z-score

OE missense 1.03 (0.93–1.14)

255 obs / 248.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.59 (0.39–0.91)

0≤0.351.4

Missense OE?1.03 (0.93–1.14)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 15 / 25.5Missense obs/exp: 255 / 248.5Syn Z: -1.08

Background carrier burden — how many people carry a rare variant somewhere in CLN3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

666 rare PASS variants

Rare truncating (LoF)

1 in 2,000

117 rare PASS variants

Rare synonymous (reference)

1 in 100

291 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CLN3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 100	1 in 3,100
South Asian	~43k	1 in 66	1 in 3,100
Remaining (unassigned)	~30k	1 in 99	1 in 3,400
European (Finnish)	~27k	1 in 480	1 in 680
Admixed American	~22k	1 in 98	1 in 1,200
African / African American	~21k	1 in 80	1 in 1,900
East Asian	~20k	1 in 99	1 in 740
Ashkenazi Jewish	~13k	1 in 570	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 150	1 in 480

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.