CLN3

Chr 16AR

CLN3 lysosomal/endosomal transmembrane protein, battenin

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.913 OMIM phenotypes
Clinical SummaryCLN3
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Gene-Disease Validity (ClinGen)
neuronal ceroid lipofuscinosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
10 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.91LOEUF
pLI 0.000
Z-score 1.93
OE 0.59 (0.390.91)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.15Z-score
OE missense 1.03 (0.931.14)
255 obs / 248.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.59 (0.390.91)
00.351.4
Missense OE1.03 (0.931.14)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 15 / 25.5Missense obs/exp: 255 / 248.5Syn Z: -1.08
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCLN3-related retinal dystrophyOTHERAR
definitiveCLN3-related neuronal ceroid lipofuscinosisLOFAR
Mechanism Note (expert annotation)
LOF

Lysosomal membrane protein. Biallelic LOF causes CLN3 disease (juvenile Batten disease). The common 1-kb deletion accounts for most alleles. This is a classic autosomal recessive LOF gene.

References:PMID:7670472

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.76top 25%
GOF
0.6930th %ile
LOF
0.2288th %ile

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CLN3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

CLN7

Study for the Treatment for CLN7 Disease

ACTIVE NOT RECRUITING
NCT04737460Phase PHASE1Benjamin GreenbergStarted 2021-05-04
AAV9/CLN7
CLN3Batten Disease

Gene Therapy for Children With CLN3 Batten Disease

ACTIVE NOT RECRUITING
NCT03770572Phase PHASE1, PHASE2Alcyone Therapeutics, IncStarted 2018-11-13
Low dose CLN-301High dose CLN-301
Batten DiseaseCLN6

Natural History of Neuronal Ceroid Lipofuscinosis, Batten's CLN6 Diseae

ACTIVE NOT RECRUITING
NCT03285425Emily de los ReyesStarted 2017-01
Natural history
Batten DiseaseCLN2Neuronal Ceroid-Lipofuscinoses

Examining Developmental Outcomes of Children Diagnosed With CLN2 Disease

ENROLLING BY INVITATION
NCT03862274Jessica ScherrStarted 2018-12-01
CLN2 Treatment
CLN6Batten Disease

Long-Term Follow Up of CLN6 Batten Disease Subjects Following Gene Transfer

ACTIVE NOT RECRUITING
NCT04273243Emily de los ReyesStarted 2020-01-24
AT-GTX-501
Neuronal Ceroid LipofuscinosisBatten DiseaseCLN1 Disease

Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database

RECRUITING
NCT04613089Universitätsklinikum Hamburg-EppendorfStarted 2020-04-08
Natural History
Rare DisordersUndiagnosed DisordersDisorders of Unknown Prevalence

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

RECRUITING
NCT01793168Sanford HealthStarted 2010-07
Neuronal Ceroid Lipofuscinosis Type 2

A First-in-Human, Open-Label, Dose-Escalation Study to Evaluate the Safety and Tolerability of Gene Therapy With TTX-381 for the Ocular Manifestations Associated With Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) Disease

RECRUITING
NCT05791864Phase PHASE1, PHASE2Tern Therapeutics, LLCStarted 2023-05-17
TTX-381
Neuronal Ceroid Lipofuscinosis CLN5

Gene Therapy Study for Children With CLN5 Batten Disease

ACTIVE NOT RECRUITING
NCT05228145Phase PHASE1, PHASE2Neurogene Inc.Started 2022-01-31
NGN-101
Eye Diseases HereditaryRetinal DiseaseAchromatopsia

Inherited Retinal Degenerative Disease Registry

RECRUITING
NCT02435940Foundation Fighting BlindnessStarted 2014-06
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
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