Neuronal ceroid lipofuscinosis 3

Summary

Neuronal ceroid lipofuscinosis 3 (MONDO:0008767) is a disease caused by CLN3 (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CLN3 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 276
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		400	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	neuronal ceroid lipofuscinosis 3
Mondo ID	MONDO:0008767
OMIM	204200
Orphanet	228346
DOID	DOID:0110731
NCIT	C61258
UMLS	C0751383
MedGen	155549
GARD	0005897
NORD	843
Is cancer (heuristic)	no

Also known as: ceroid lipofuscinosis, neuronal, 3 · ceroid lipofuscinosis, neuronal, type 3 · CLN3 · CLN3 disease, juvenile · CLN3 neuronal ceroid lipofuscinosis · Juvenile CLN3 Disease · neuronal ceroid lipofuscinosis 3 · neuronal ceroid lipofuscinosis caused by mutation in CLN3 · neuronal ceroid lipofuscinosis type 3 · Spielmeyer Sjogren disease · Vogt Spielmeyer disease

Data availability: 276 ClinVar variants · 6 GenCC gene-disease records · 46 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inherited lipid metabolism disorder › lysosomal lipid storage disorder › neuronal ceroid lipofuscinosis › neuronal ceroid lipofuscinosis 3

Related subtypes (13): ceroid lipofuscinosis, neuronal, 6B (Kufs type), neuronal ceroid lipofuscinosis 2, neuronal ceroid lipofuscinosis 1, neuronal ceroid lipofuscinosis 5, neuronal ceroid lipofuscinosis 8, ceroid lipofuscinosis, neuronal, 6A, neuronal ceroid lipofuscinosis 10, neuronal ceroid lipofuscinosis 7, progressive myoclonic epilepsy type 3, adult neuronal ceroid lipofuscinosis, infantile neuronal ceroid lipofuscinosis, juvenile neuronal ceroid lipofuscinosis, congenital neuronal ceroid lipofuscinosis

Subtypes (2): juvenile neuronal ceroid lipofuscinosis 3, protracted juvenile neuronal ceroid lipofuscinosis 3

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

276 retrieved; paginated sample, class counts are floors:

79 uncertain significance, 64 likely pathogenic, 45 pathogenic/likely pathogenic, 39 pathogenic, 32 conflicting classifications of pathogenicity, 8 likely benign, 7 benign/likely benign, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
100719	NM_001042432.2(CLN3):c.371_372insT (p.Ser125fs)	CLN3	Pathogenic	no assertion criteria provided
1075948	NM_001042432.2(CLN3):c.992_993del (p.Phe331fs)	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1213977	NM_001042432.2(CLN3):c.512C>T (p.Ser171Phe)	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1378760	NM_001042432.2(CLN3):c.639del (p.Leu214fs)	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1685639	NM_001042432.2(CLN3):c.382dup (p.Val128fs)	CLN3	Pathogenic	criteria provided, single submitter
1725180	NM_001042432.2(CLN3):c.610C>T (p.Gln204Ter)	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1908122	NM_001042432.2(CLN3):c.1197+1G>A	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2001596	NM_001042432.2(CLN3):c.18del (p.Ser7fs)	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2012105	NM_001042432.2(CLN3):c.1115_1118dup (p.Val374fs)	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2032700	NM_001042432.2(CLN3):c.552G>A (p.Trp184Ter)	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
205092	NM_001042432.2(CLN3):c.949C>T (p.Gln317Ter)	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
205095	NM_001042432.2(CLN3):c.988G>A (p.Val330Ile)	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2127361	NM_001042432.2(CLN3):c.944_945insGA (p.His315fs)	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2201536	NM_001042432.2(CLN3):c.126G>A (p.Trp42Ter)	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2417180	NM_001042432.2(CLN3):c.551G>A (p.Trp184Ter)	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2431547	NC_000016.10:g.(28485964_28486930)del	CLN3	Pathogenic	criteria provided, single submitter
2435726	NM_001042432.2(CLN3):c.354_355insG (p.Leu119fs)	CLN3	Pathogenic	criteria provided, single submitter
265379	NM_001042432.2(CLN3):c.240del (p.Pro81fs)	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680813	NM_001042432.2(CLN3):c.379dup (p.Arg127fs)	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680817	NM_001042432.2(CLN3):c.849G>A (p.Trp283Ter)	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2769845	NM_001042432.2(CLN3):c.729del (p.Glu244fs)	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280317	NM_001042432.2(CLN3):c.816_817del (p.Glu273fs)	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2920674	GRCh38/hg38 16p12.1(chr16:28485965-28486930)x1	CLN3	Pathogenic	criteria provided, single submitter
3552	NM_001042432.2(CLN3):c.461-280_677+382del	CLN3	Pathogenic	criteria provided, multiple submitters, no conflicts
3553	NG_008654.2:g.(13298_14630)_(15199_19425)del	CLN3	Pathogenic	no assertion criteria provided
3554	NG_008654.2:g.(9848_10812)_(19800_19939)del	CLN3	Pathogenic	no assertion criteria provided
3556	NM_001042432.2(CLN3):c.883G>A (p.Glu295Lys)	CLN3	Pathogenic	criteria provided, multiple submitters, no conflicts
3557	NM_001042432.2(CLN3):c.597C>A (p.Tyr199Ter)	CLN3	Pathogenic	criteria provided, multiple submitters, no conflicts
370455	NM_001042432.2(CLN3):c.906+2T>A	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370667	NM_001042432.2(CLN3):c.963-1G>A	CLN3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CLN3	Definitive	Autosomal recessive	neuronal ceroid lipofuscinosis 3	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CLN3	Orphanet:699780	Juvenile CLN3 disease
CLN3	Orphanet:699796	Protracted juvenile CLN3 disease

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CLN3	HGNC:2074	ENSG00000188603	Q13286	Battenin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CLN3	Battenin	Mediates microtubule-dependent, anterograde transport connecting the Golgi network, endosomes, autophagosomes, lysosomes and plasma membrane, and participates in several cellular processes such as regulation of lysosomal pH, lysosome prote…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CLN3	Transporter	yes		Battenin_disease_Cln3, Battenin_disease_Cln3_subgr, MFS_trans_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
mucosa of transverse colon	1
placenta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CLN3	134	ubiquitous	marker	mucosa of transverse colon, placenta, granulocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CLN3	1,613

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CLN3	Q13286	81.81

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Glycosphingolipid transport	1	1427.5×	7e-04	CLN3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete phagosome-lysosome docking	1	16852.0×	1e-03	CLN3
regulation of cellular response to osmotic stress	1	16852.0×	1e-03	CLN3
regulation of arginine biosynthetic process	1	16852.0×	1e-03	CLN3
renal potassium excretion	1	8426.0×	0.001	CLN3
regulation of phagosome maturation	1	8426.0×	0.001	CLN3
regulation of autophagosome size	1	5617.3×	0.001	CLN3
glycolipid transport	1	5617.3×	0.001	CLN3
regulation of modification of synaptic structure	1	5617.3×	0.001	CLN3
positive regulation of caveolin-mediated endocytosis	1	4213.0×	0.001	CLN3
lysosomal lumen pH elevation	1	3370.4×	0.001	CLN3
positive regulation of pinocytosis	1	3370.4×	0.001	CLN3
positive regulation of Golgi to plasma membrane protein transport	1	2808.7×	0.001	CLN3
plasma membrane raft organization	1	2808.7×	0.001	CLN3
regulation of autophagosome maturation	1	2808.7×	0.001	CLN3
intracellular water homeostasis	1	2407.4×	0.001	CLN3
glycerophospholipid biosynthetic process	1	1872.4×	0.002	CLN3
ceramide transport	1	1532.0×	0.002	CLN3
regulation of protein processing	1	1532.0×	0.002	CLN3
Golgi to lysosome transport	1	1532.0×	0.002	CLN3
blood vessel endothelial cell migration	1	1404.3×	0.002	CLN3
L-arginine transmembrane transport	1	1404.3×	0.002	CLN3
regulation of fibroblast migration	1	1296.3×	0.002	CLN3
ionotropic glutamate receptor signaling pathway	1	1296.3×	0.002	CLN3
phagosome-lysosome fusion	1	1296.3×	0.002	CLN3
amyloid precursor protein catabolic process	1	1203.7×	0.002	CLN3
autophagosome-lysosome fusion	1	1203.7×	0.002	CLN3
regulation of short-term neuronal synaptic plasticity	1	1123.5×	0.002	CLN3
regulation of synaptic transmission, GABAergic	1	1053.2×	0.002	CLN3
regulation of filopodium assembly	1	1053.2×	0.002	CLN3
lysosomal protein catabolic process	1	1053.2×	0.002	CLN3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CLN3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	CLN3
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CLN3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03770572	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Gene Therapy for Children With CLN3 Batten Disease