Neuronal ceroid lipofuscinosis 13

Summary

Neuronal ceroid lipofuscinosis 13 (MONDO:0014147) is a disease caused by CTSF (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CTSF (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 156

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		6	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	neuronal ceroid lipofuscinosis 13
Mondo ID	MONDO:0014147
OMIM	615362
Orphanet	352709
DOID	DOID:0110727
UMLS	C3715049
MedGen	811566
GARD	0017527
Is cancer (heuristic)	no

Also known as: ceroid lipofuscinosis, neuronal, 13 · ceroid lipofuscinosis, neuronal, 13 (Kufs type) · ceroid lipofuscinosis, neuronal, type 13 · CLN13 · CTSF neuronal ceroid lipofuscinosis · neuronal ceroid lipofuscinosis caused by mutation in CTSF · neuronal ceroid lipofuscinosis type 13

Data availability: 156 ClinVar variants · 5 GenCC gene-disease records.

Disease family

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 › adult neuronal ceroid lipofuscinosis › neuronal ceroid lipofuscinosis 13

Related subtypes (4): ceroid lipofuscinosis, neuronal, 4 (Kufs type), neuronal ceroid lipofuscinosis 11, adult neuronal ceroid lipofuscinosis 1, adult neuronal ceroid lipofuscinosis 5

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

156 retrieved; paginated sample, class counts are floors:

66 likely benign, 37 uncertain significance, 13 conflicting classifications of pathogenicity, 13 pathogenic, 9 benign/likely benign, 9 likely pathogenic, 8 benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
208844	NM_003793.4(CTSF):c.213+1G>C	CTSF	Pathogenic	no assertion criteria provided
2417211	NM_003793.4(CTSF):c.594T>A (p.Tyr198Ter)	CTSF	Pathogenic	criteria provided, single submitter
2857442	NM_003793.4(CTSF):c.992del (p.Lys331fs)	CTSF	Pathogenic	criteria provided, single submitter
3018158	NM_003793.4(CTSF):c.664C>T (p.Gln222Ter)	CTSF	Pathogenic	criteria provided, single submitter
3711871	NM_003793.4(CTSF):c.329_347del (p.Val110fs)	CTSF	Pathogenic	criteria provided, single submitter
4293328	NM_003793.4(CTSF):c.416C>A (p.Ser139Ter)	CTSF	Pathogenic	criteria provided, single submitter
434869	NM_003793.4(CTSF):c.843_844del (p.Ala282fs)	CTSF	Pathogenic	criteria provided, single submitter
4724736	NM_003793.4(CTSF):c.375_382del (p.Pro126fs)	CTSF	Pathogenic	criteria provided, single submitter
4765938	NM_003793.4(CTSF):c.871_872del (p.Met291fs)	CTSF	Pathogenic	criteria provided, single submitter
60675	NM_003793.4(CTSF):c.962A>G (p.Gln321Arg)	CTSF	Pathogenic	criteria provided, single submitter
60676	NM_003793.4(CTSF):c.1373G>C (p.Gly458Ala)	CTSF	Pathogenic	no assertion criteria provided
60679	NM_003793.4(CTSF):c.954del (p.Ser319fs)	CTSF	Pathogenic	no assertion criteria provided
807589	NM_003793.4(CTSF):c.1247T>C (p.Ile416Thr)	CTSF	Pathogenic	criteria provided, single submitter
1324192	NM_003793.4(CTSF):c.1045+1G>T	CTSF	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324193	NM_003793.4(CTSF):c.530_531+11del	CTSF	Likely pathogenic	criteria provided, single submitter
2572494	NM_003793.4(CTSF):c.965-1G>A	CTSF	Likely pathogenic	criteria provided, single submitter
3373769	NM_003793.4(CTSF):c.971T>C (p.Leu324Ser)	CTSF	Likely pathogenic	criteria provided, single submitter
3393247	NM_003793.4(CTSF):c.1316del (p.Gly439fs)	CTSF	Likely pathogenic	criteria provided, single submitter
3600133	NM_003793.4(CTSF):c.1267_1277dup (p.Trp427fs)	CTSF	Likely pathogenic	criteria provided, single submitter
3600135	NM_003793.4(CTSF):c.1165+2T>G	CTSF	Likely pathogenic	criteria provided, single submitter
3600137	NM_003793.4(CTSF):c.934C>T (p.Gln312Ter)	CTSF	Likely pathogenic	criteria provided, single submitter
3691050	NM_003793.4(CTSF):c.213+2T>A	CTSF	Likely pathogenic	criteria provided, single submitter
1305235	NM_003793.4(CTSF):c.1100A>G (p.Asn367Ser)	CTSF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1382735	NM_003793.4(CTSF):c.160C>A (p.Arg54=)	CTSF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
265519	NM_003793.4(CTSF):c.1046-2A>C	CTSF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3600134	NM_003793.4(CTSF):c.1171del (p.Ala391fs)	CTSF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
424983	NM_003793.4(CTSF):c.683C>G (p.Thr228Arg)	CTSF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
587775	NM_003793.4(CTSF):c.1253G>A (p.Arg418His)	CTSF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
588044	NM_003793.4(CTSF):c.200_205dup (p.Gly67_Arg68dup)	CTSF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
588058	NM_003793.4(CTSF):c.676C>T (p.Arg226Cys)	CTSF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
CTSF	Definitive	Autosomal recessive	neuronal ceroid lipofuscinosis 13	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CTSF	Orphanet:352709	CLN13 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
CTSF	HGNC:2531	ENSG00000174080	Q9UBX1	Cathepsin F	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CTSF	Cathepsin F	Thiol protease which is believed to participate in intracellular degradation and turnover of proteins.

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CTSF	Protease	yes	3.4.22.41	Pept_cys_AS, Peptidase_C1A_C, Peptidase_C1A

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CTSF	293	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTSF	1,402

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTSF	Q9UBX1	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
MHC class II antigen presentation	1	89.2×	0.034	CTSF
Adaptive Immune System	1	29.8×	0.050	CTSF
Immune System	1	13.0×	0.077	CTSF

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
antigen processing and presentation of exogenous peptide antigen via MHC class II	1	543.6×	0.003	CTSF
obsolete proteolysis involved in protein catabolic process	1	526.6×	0.003	CTSF
proteolysis	1	34.2×	0.029	CTSF

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
CTSF	BOCEPREVIR

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CTSF	3	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BOCEPREVIR	4	CTSF
ODANACATIB	3	CTSF
ATUZAGINSTAT	2	CTSF

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CTSF	18	Binding:17, Toxicity:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CTSF	3.4.22.41	cathepsin F

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

3 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)
BOCEPREVIR	4	CTSF
ODANACATIB	3	CTSF
ATUZAGINSTAT	2	CTSF

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CTSF
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.