Late infantile neuronal ceroid lipofuscinosis

Summary

Late infantile neuronal ceroid lipofuscinosis (MONDO:0015674) is a disease with 1 cohort gene and 11 clinical trials. Top therapeutic interventions include cerliponase alfa.

At a glance

• Cohort genes: 1
• ClinVar variants: 167
• Clinical trials: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	late infantile neuronal ceroid lipofuscinosis
Mondo ID	MONDO:0015674
Orphanet	168491
ICD-11	1923920542
SNOMED CT	14637005
UMLS	C0022340
MedGen	9589
GARD	0017032
Is cancer (heuristic)	no

Also known as: Jansky-Bielschowsky disease · late infantile NCL · late-infantile neuronal ceroid lipofuscinosis · LINCL

Data availability: 167 ClinVar variants.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › lysosomal storage disease › late infantile neuronal ceroid lipofuscinosis

Related subtypes (10): lysosomal acid phosphatase deficiency, glycoprotein storage disease, pycnodysostosis, hereditary spastic paraplegia 48, glycoproteinosis, disorder of sialic acid metabolism, lysosomal glycogen storage disease, lysosomal lipid storage disorder, inborn disorder of lysosomal amino acid transport, mucopolysaccharidosis

Subtypes (3): neuronal ceroid lipofuscinosis 5, ceroid lipofuscinosis, neuronal, 6A, neuronal ceroid lipofuscinosis 7

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

167 retrieved; paginated sample, class counts are floors:

95 uncertain significance, 18 pathogenic/likely pathogenic, 14 conflicting classifications of pathogenicity, 12 likely benign, 11 likely pathogenic, 8 pathogenic, 5 benign/likely benign, 4 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1003	NM_001371596.2(MFSD8):c.894T>G (p.Tyr298Ter)	MFSD8	Pathogenic	criteria provided, multiple submitters, no conflicts
1005	NM_001371596.2(MFSD8):c.1235C>T (p.Pro412Leu)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1006	NM_001371596.2(MFSD8):c.881C>A (p.Thr294Lys)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1067690	NM_001371596.2(MFSD8):c.864-1G>A	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074727	NM_001371596.2(MFSD8):c.1325C>A (p.Ser442Ter)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1418701	NM_001371596.2(MFSD8):c.1158_1167del (p.Trp387fs)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454727	NM_001371596.2(MFSD8):c.531_537del (p.Gly179fs)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
162379	NM_001371596.2(MFSD8):c.1141G>T (p.Glu381Ter)	MFSD8	Pathogenic	criteria provided, multiple submitters, no conflicts
162382	NM_001371596.2(MFSD8):c.1444C>T (p.Arg482Ter)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2005771	NM_001371596.2(MFSD8):c.1412del (p.Phe471fs)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2012597	NM_001371596.2(MFSD8):c.1337del (p.Gly446fs)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
206149	NM_001371596.2(MFSD8):c.599G>A (p.Trp200Ter)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
206175	NM_001371596.2(MFSD8):c.217dup (p.Thr73fs)	MFSD8	Pathogenic	criteria provided, multiple submitters, no conflicts
2068020	NM_001371596.2(MFSD8):c.1102+2T>C	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2627614	NM_001371596.2(MFSD8):c.979del (p.Val327fs)	MFSD8	Pathogenic	criteria provided, multiple submitters, no conflicts
418295	NM_001371596.2(MFSD8):c.1361T>C (p.Met454Thr)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
464776	NM_001371596.2(MFSD8):c.1036del (p.Val346fs)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
504888	NM_001371596.2(MFSD8):c.863+1G>A	MFSD8	Pathogenic	criteria provided, multiple submitters, no conflicts
574492	NM_001371596.2(MFSD8):c.64G>T (p.Glu22Ter)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
589240	NM_001371596.2(MFSD8):c.754+1G>T	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
65897	NM_001371596.2(MFSD8):c.754+2T>A	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
802090	NM_001371596.2(MFSD8):c.63-1G>A	MFSD8	Pathogenic	criteria provided, multiple submitters, no conflicts
846459	NM_001371596.2(MFSD8):c.103C>T (p.Arg35Ter)	MFSD8	Pathogenic	criteria provided, multiple submitters, no conflicts
871428	NM_001371596.2(MFSD8):c.754+1G>C	MFSD8	Pathogenic	criteria provided, multiple submitters, no conflicts
872266	NM_001371596.2(MFSD8):c.754+1G>A	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
985208	NM_001371596.2(MFSD8):c.63-2A>G	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2029708	NM_001371596.2(MFSD8):c.439+2T>A	MFSD8	Likely pathogenic	criteria provided, multiple submitters, no conflicts
206150	NM_001371596.2(MFSD8):c.442A>G (p.Asn148Asp)	MFSD8	Likely pathogenic	criteria provided, single submitter
2151748	NM_001371596.2(MFSD8):c.1390G>A (p.Ala464Thr)	MFSD8	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2734673	NM_001371596.2(MFSD8):c.2T>C (p.Met1Thr)	MFSD8	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MFSD8	Orphanet:1872	Cone rod dystrophy
MFSD8	Orphanet:228366	CLN7 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
MFSD8	HGNC:28486	ENSG00000164073	Q8NHS3	Major facilitator superfamily domain-containing protein 8	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MFSD8	Major facilitator superfamily domain-containing protein 8	Outward-rectifying chloride channel involved in endolysosomal chloride homeostasis, membrane fusion and function.

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)
MFSD8	Transporter	yes		MFS, MFS_dom, 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
adrenal tissue	1
calcaneal tendon	1
oviduct epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MFSD8	256	ubiquitous	marker	oviduct epithelium, adrenal tissue, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MFSD8	1,405

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MFSD8	Q8NHS3	83.20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
maintenance of location	1	16852.0×	1e-03	MFSD8
glycolipid metabolic process	1	8426.0×	1e-03	MFSD8
inclusion body assembly	1	8426.0×	1e-03	MFSD8
regulation of lysosomal protein catabolic process	1	5617.3×	0.001	MFSD8
microglia differentiation	1	1532.0×	0.003	MFSD8
glycoprotein metabolic process	1	1123.5×	0.003	MFSD8
lysosomal protein catabolic process	1	1053.2×	0.003	MFSD8
TORC1 signaling	1	802.5×	0.004	MFSD8
astrocyte differentiation	1	766.0×	0.004	MFSD8
motor behavior	1	561.7×	0.004	MFSD8
neuromuscular process	1	526.6×	0.004	MFSD8
reactive oxygen species metabolic process	1	468.1×	0.004	MFSD8
determination of adult lifespan	1	432.1×	0.004	MFSD8
glycolytic process	1	383.0×	0.005	MFSD8
autophagosome maturation	1	351.1×	0.005	MFSD8
lysosome organization	1	306.4×	0.005	MFSD8
neuron development	1	255.3×	0.005	MFSD8
retina development in camera-type eye	1	255.3×	0.005	MFSD8
regulation of autophagy	1	240.7×	0.005	MFSD8
neuron apoptotic process	1	185.2×	0.007	MFSD8
mitochondrion organization	1	151.8×	0.008	MFSD8
multicellular organism growth	1	137.0×	0.008	MFSD8
negative regulation of neuron apoptotic process	1	110.9×	0.010	MFSD8
gene expression	1	79.9×	0.013	MFSD8
protein stabilization	1	66.9×	0.015	MFSD8

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
MFSD8	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	MFSD8
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)
MFSD8	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 11.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5
PHASE1/PHASE2	3
PHASE1	2
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01414985	PHASE1/PHASE2	COMPLETED	AAVRh.10 Administered to Children With Late Infantile Neuronal Ceroid Lipofuscinosis
NCT01907087	PHASE1/PHASE2	COMPLETED	A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Intracerebroventricular BMN 190 in Patients With Late-Infantile Neuronal Ceroid Lipofuscinosis (CLN2) Disease
NCT02485899	PHASE1/PHASE2	COMPLETED	An Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 190 in Patients With CLN2 Disease
NCT02678689	PHASE2	COMPLETED	A Safety, Tolerability, and Efficacy Study of BMN 190 in Pediatric Patients < 18 Years of Age With CLN2 Disease
NCT00151216	PHASE1	COMPLETED	Safety Study of a Gene Transfer Vector for Children With Late Infantile Neuronal Ceroid Lipofuscinosis
NCT01161576	PHASE1	COMPLETED	Safety Study of a Gene Transfer Vector (Rh.10) for Children With Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL)
NCT04476862	Not specified	ACTIVE_NOT_RECRUITING	Cerliponase Alfa Observational Study in the US
NCT01035424	Not specified	COMPLETED	Genotype-Phenotype Correlations of Late Infantile Neuronal Ceroid Lipofuscinosis
NCT01698229	Not specified	TERMINATED	Collection of Cerebrospinal Fluid in Healthy Children
NCT04480476	Not specified	WITHDRAWN	A Retrospective, Natural History Study in Children With CLN2
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CERLIPONASE ALFA	4	3