Adult neuronal ceroid lipofuscinosis

Summary

Adult neuronal ceroid lipofuscinosis (MONDO:0019260) is a disease (an umbrella term covering 5 Mondo subtypes) with 1 cohort gene.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	adult neuronal ceroid lipofuscinosis
Mondo ID	MONDO:0019260
Orphanet	79262
ICD-11	1460031344
SNOMED CT	62009002
UMLS	C0022797
MedGen	7230
GARD	0010973
NORD	1341
Is cancer (heuristic)	no

Also known as: adult NCL · adult neuronal ceroid lipofuscinosis · ANCL · CLN4 disease, adult autosomal dominant · Kuf’s disease · Kufs disease · neuronal ceroid lipofuscinosis 4 · neuronal ceroid lipofuscinosis of adults

Data availability: 7 ClinVar variants.

Disease family

An umbrella term covering 5 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 › adult neuronal ceroid lipofuscinosis

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 10, neuronal ceroid lipofuscinosis 7, progressive myoclonic epilepsy type 3, infantile neuronal ceroid lipofuscinosis, juvenile neuronal ceroid lipofuscinosis, congenital neuronal ceroid lipofuscinosis

Subtypes (5): ceroid lipofuscinosis, neuronal, 4 (Kufs type), neuronal ceroid lipofuscinosis 11, neuronal ceroid lipofuscinosis 13, 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

7 retrieved; paginated sample, class counts are floors:

3 likely pathogenic, 2 conflicting classifications of pathogenicity, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
984028	NM_017882.3(CLN6):c.499G>T (p.Glu167Ter)	CLN6	Likely pathogenic	criteria provided, single submitter
984029	NM_017882.3(CLN6):c.427C>T (p.Gln143Ter)	CLN6	Likely pathogenic	criteria provided, single submitter
984030	NM_017882.3(CLN6):c.218G>A (p.Trp73Ter)	CLN6	Likely pathogenic	criteria provided, single submitter
193389	NM_017882.3(CLN6):c.53C>T (p.Ala18Val)	CLN6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
198573	NM_017882.3(CLN6):c.923G>C (p.Ser308Thr)	CLN6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
452272	NM_017882.3(CLN6):c.482C>T (p.Thr161Met)	CLN6	Uncertain significance	criteria provided, multiple submitters, no conflicts
579778	NM_017882.3(CLN6):c.41G>A (p.Gly14Asp)	CLN6	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CLN6	Orphanet:700467	Late infantile CLN6 disease
CLN6	Orphanet:700472	Juvenile CLN6 disease
CLN6	Orphanet:700477	Adult CLN6 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
CLN6	HGNC:2077	ENSG00000128973	Q9NWW5	Ceroid-lipofuscinosis neuronal protein 6	clinvar

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CLN6	Other/Unknown	no		CLN6

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
bone marrow	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CLN6	139	ubiquitous	marker	monocyte, leukocyte, bone marrow

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CLN6	1,107

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CLN6	Q9NWW5	85.86

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
ganglioside metabolic process	1	4213.0×	0.001	CLN6
glycosaminoglycan metabolic process	1	2407.4×	0.001	CLN6
locomotion involved in locomotory behavior	1	2407.4×	0.001	CLN6
positive regulation of proteolysis	1	802.5×	0.003	CLN6
lysosomal lumen acidification	1	674.1×	0.003	CLN6
lysosome organization	1	306.4×	0.005	CLN6
protein catabolic process	1	237.3×	0.005	CLN6
cholesterol metabolic process	1	195.9×	0.006	CLN6
visual perception	1	79.5×	0.013	CLN6

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CLN6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CLN6	1	Binding:1

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	0
E	Difficult family or no structure, no drug	1	CLN6

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)
CLN6	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.