Neuronal ceroid lipofuscinosis 10

Summary

Neuronal ceroid lipofuscinosis 10 (MONDO:0012414) is a disease caused by CTSD (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CTSD (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 99

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		11	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	neuronal ceroid lipofuscinosis 10
Mondo ID	MONDO:0012414
MeSH	C566438
OMIM	610127
Orphanet	228337
DOID	DOID:0110725
SNOMED CT	720831008
UMLS	C1864669
MedGen	350481
GARD	0001218
Is cancer (heuristic)	no

Also known as: ceroid lipofuscinosis neuronal Cathepsin D-deficient · ceroid lipofuscinosis, neuronal, 10 · ceroid lipofuscinosis, neuronal, type 10 · CLN10 · CLN10 disease, adult (subtype) · CLN10 disease, congenital (subtype) · CLN10 disease, juvenile (subtype) · CLN10 disease, late infantile (subtype) · CLN10-NCL · CTSD neuronal ceroid lipofuscinosis · neuronal ceroid lipofuscinosis caused by mutation in CTSD · neuronal ceroid lipofuscinosis due to cathepsin D deficiency · neuronal ceroid lipofuscinosis type 10

Data availability: 99 ClinVar variants · 4 GenCC gene-disease records.

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 › inherited lipid metabolism disorder › lysosomal lipid storage disorder › neuronal ceroid lipofuscinosis › neuronal ceroid lipofuscinosis 10

Related subtypes (13): neuronal ceroid lipofuscinosis 3, 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 7, progressive myoclonic epilepsy type 3, adult neuronal ceroid lipofuscinosis, infantile neuronal ceroid lipofuscinosis, juvenile neuronal ceroid lipofuscinosis, congenital neuronal ceroid lipofuscinosis

Subtypes (3): congenital neuronal ceroid lipofuscinosis 10, late infantile neuronal ceroid lipofuscinosis 10, juvenile neuronal ceroid lipofuscinosis 10

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

99 retrieved; paginated sample, class counts are floors:

48 uncertain significance, 19 conflicting classifications of pathogenicity, 10 benign, 10 benign/likely benign, 6 pathogenic, 3 likely benign, 3 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
100733	NM_001909.4:c.486-12G>A	CTSD	Pathogenic	no assertion criteria provided
1322174	NM_001909.5(CTSD):c.17_30dup (p.Leu11fs)	CTSD	Pathogenic	criteria provided, multiple submitters, no conflicts
17573	NM_001909.5(CTSD):c.685T>A (p.Phe229Ile)	CTSD	Pathogenic	no assertion criteria provided
17574	NM_001909.5(CTSD):c.1149G>C (p.Trp383Cys)	CTSD	Pathogenic	no assertion criteria provided
17575	NM_001909.5(CTSD):c.764dup (p.Tyr255Ter)	CTSD	Pathogenic	no assertion criteria provided
430138	NM_001909.5(CTSD):c.268dup (p.Gln90fs)	CTSD	Pathogenic	criteria provided, multiple submitters, no conflicts
208848	NM_001909.5(CTSD):c.446G>T (p.Gly149Val)	CTSD	Likely pathogenic	criteria provided, single submitter
3599443	NM_001909.5(CTSD):c.1083del (p.Lys363fs)	CTSD	Likely pathogenic	criteria provided, single submitter
3599444	NM_001909.5(CTSD):c.268C>T (p.Gln90Ter)	CTSD	Likely pathogenic	criteria provided, single submitter
137040	NM_001909.5(CTSD):c.912G>A (p.Pro304=)	CTSD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
137042	NM_001909.5(CTSD):c.1071+7G>A	CTSD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
137043	NM_001909.5(CTSD):c.1071+12A>G	CTSD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
137050	NM_001909.5(CTSD):c.240C>T (p.Tyr80=)	CTSD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
137060	NM_001909.5(CTSD):c.639C>G (p.Pro213=)	CTSD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
137062	NM_001909.5(CTSD):c.827+13T>C	CTSD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205335	NM_001909.5(CTSD):c.154G>A (p.Val52Ile)	CTSD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205353	NM_001909.5(CTSD):c.8C>T (p.Pro3Leu)	CTSD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205360	NM_001909.5(CTSD):c.926G>A (p.Arg309His)	CTSD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
282729	NM_001909.5(CTSD):c.1009G>A (p.Ala337Thr)	CTSD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
303835	NM_001909.5(CTSD):c.973-8C>A	CTSD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
303841	NM_001909.5(CTSD):c.90G>A (p.Thr30=)	CTSD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
303843	NM_001909.5(CTSD):c.-37G>A	CTSD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
375630	NM_001909.5(CTSD):c.683TCT[1] (p.Phe229del)	CTSD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
877669	NM_001909.5(CTSD):c.999C>A (p.Ser333=)	CTSD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
879287	NM_001909.5(CTSD):c.315C>A (p.Val105=)	CTSD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
879288	NM_001909.5(CTSD):c.285C>T (p.Val95=)	CTSD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
137059	NM_001909.5(CTSD):c.-24C>T	LOC130005119	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
303840	NM_001909.5(CTSD):c.111G>C (p.Ser37=)	PRADX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
100732	NM_001909.5(CTSD):c.470C>T (p.Ser157Leu)	CTSD	Uncertain significance	criteria provided, multiple submitters, no conflicts
205341	NM_001909.5(CTSD):c.928G>A (p.Glu310Lys)	CTSD	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 3 · 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
CTSD	Definitive	Autosomal recessive	neuronal ceroid lipofuscinosis	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CTSD	Orphanet:700487	Congenital CLN10 disease
CTSD	Orphanet:700492	Late infantile CLN10 disease
CTSD	Orphanet:700497	Juvenile CLN10 disease

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CTSD	HGNC:2529	ENSG00000117984	P07339	Cathepsin D	gencc,clinvar
PRADX	HGNC:40168	ENSG00000235027		PRC2 and DDX5 associated lncRNA	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CTSD	Cathepsin D	Acid protease active in intracellular protein breakdown.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Protease	1	18.3×	0.108
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CTSD	Protease	yes	3.4.23.5	Aspartic_peptidase_A1, Aspartic_peptidase_AS, Aspartic_peptidase_N
PRADX	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1
blood	1
bone marrow	1
bone marrow cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CTSD	290	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland
PRADX	128		marker	blood, bone marrow, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTSD	4,280
PRADX	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTSD	P07339	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 2 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
Signaling by Insulin receptor	1	878.5×	0.014	CTSD
Metabolism of Angiotensinogen to Angiotensins	1	634.4×	0.014	CTSD
Insulin receptor recycling	1	380.7×	0.016	CTSD
Peptide hormone metabolism	1	271.9×	0.017	CTSD
Collagen degradation	1	175.7×	0.020	CTSD
ESR-mediated signaling	1	128.3×	0.022	CTSD
Degradation of the extracellular matrix	1	117.7×	0.022	CTSD
Signaling by Nuclear Receptors	1	102.0×	0.022	CTSD
MHC class II antigen presentation	1	89.2×	0.022	CTSD
Estrogen-dependent gene expression	1	75.6×	0.024	CTSD
Extracellular matrix organization	1	63.1×	0.026	CTSD
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.029	CTSD
Adaptive Immune System	1	29.8×	0.046	CTSD
Innate Immune System	1	25.5×	0.050	CTSD
Neutrophil degranulation	1	23.1×	0.052	CTSD
Immune System	1	13.0×	0.086	CTSD
Metabolism of proteins	1	12.4×	0.086	CTSD
Signal Transduction	1	10.2×	0.098	CTSD

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
insulin receptor recycling	1	4213.0×	9e-04	CTSD
insulin catabolic process	1	4213.0×	9e-04	CTSD
lipoprotein catabolic process	1	2407.4×	9e-04	CTSD
regulation of establishment of protein localization	1	2407.4×	9e-04	CTSD
execution phase of apoptosis	1	766.0×	0.002	CTSD
antigen processing and presentation of exogenous peptide antigen via MHC class II	1	543.6×	0.003	CTSD
autophagosome assembly	1	224.7×	0.006	CTSD
positive regulation of apoptotic process	1	56.7×	0.020	CTSD
proteolysis	1	34.2×	0.029	CTSD

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CTSD	AMPRENAVIR

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CTSD	8	4
PRADX	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AMPRENAVIR	4	CTSD
TIPRANAVIR	4	CTSD
MOLIBRESIB	2	CTSD
URSOLIC ACID	2	CTSD
PEPSTATIN	2	CTSD
BALICATIB	2	CTSD
PIPERINE	2	CTSD
LY-2811376	1	CTSD

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CTSD	352	Binding:331, ADMET:15, Toxicity:3, Functional:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CTSD	3.4.23.5	cathepsin D

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CTSD	352

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

8 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.

Compound	Max phase	Cohort target (bioactivity)
AMPRENAVIR	4	CTSD
TIPRANAVIR	4	CTSD
MOLIBRESIB	2	CTSD
URSOLIC ACID	2	CTSD
PEPSTATIN	2	CTSD
BALICATIB	2	CTSD
PIPERINE	2	CTSD
LY-2811376	1	CTSD

Druggability pyramid

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

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

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)
PRADX	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.