ceroid lipofuscinosis, neuronal, 6B (Kufs type)

Summary

ceroid lipofuscinosis, neuronal, 6B (Kufs type) (MONDO:0008768) is a disease caused by CLN6 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CLN6 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 62

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ceroid lipofuscinosis, neuronal, 6B (Kufs type)
Mondo ID	MONDO:0008768
OMIM	204300
Orphanet	228340, 700477
DOID	DOID:0110730
UMLS	C5561927
MedGen	1794137
GARD	0006845
Is cancer (heuristic)	no

Also known as: adult neuronal ceroid lipofuscinosis 4A · ceroid lipofuscinosis, neuronal, 4A, autosomal recessive · CLN4A · CLN6 neuronal ceroid lipofuscinosis · Kuf’s disease type A · Kuf’s disease, autosomal recessive · neuronal ceroid lipofuscinosis caused by mutation in CLN6 · neuronal ceroid lipofuscinosis type 4A

Data availability: 62 ClinVar variants · 3 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 › ceroid lipofuscinosis, neuronal, 6B (Kufs type)

Related subtypes (13): neuronal ceroid lipofuscinosis 3, 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

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

62 retrieved; paginated sample, class counts are floors:

20 conflicting classifications of pathogenicity, 12 pathogenic/likely pathogenic, 12 likely pathogenic, 8 pathogenic, 7 uncertain significance, 2 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1017289	NM_017882.3(CLN6):c.3G>A (p.Met1Ile)	CLN6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072427	NM_017882.3(CLN6):c.768C>G (p.Asp256Glu)	CLN6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072428	NM_017882.3(CLN6):c.712_713delinsAC (p.Phe238Thr)	CLN6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1180629	NM_017882.3(CLN6):c.396dup (p.Val133fs)	CLN6	Pathogenic	criteria provided, multiple submitters, no conflicts
1326899	NM_017882.3(CLN6):c.350T>G (p.Ile117Ser)	CLN6	Pathogenic	no assertion criteria provided
1449558	NM_017882.3(CLN6):c.358_366del (p.Phe120_Met122del)	CLN6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1990218	NM_017882.3(CLN6):c.827G>A (p.Trp276Ter)	CLN6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2583179	NM_017882.3(CLN6):c.195dup (p.Met66fs)	CLN6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30599	NM_017882.3(CLN6):c.200T>C (p.Leu67Pro)	CLN6	Pathogenic	no assertion criteria provided
30600	NM_017882.3(CLN6):c.308G>A (p.Arg103Gln)	CLN6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30602	NM_017882.3(CLN6):c.17G>C (p.Arg6Thr)	CLN6	Pathogenic	no assertion criteria provided
3577615	NM_017882.3(CLN6):c.516T>A (p.Tyr172Ter)	CLN6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4077	NM_017882.3(CLN6):c.214G>T (p.Glu72Ter)	CLN6	Pathogenic	criteria provided, multiple submitters, no conflicts
4081	NM_017882.3(CLN6):c.316dup (p.Arg106fs)	CLN6	Pathogenic	criteria provided, multiple submitters, no conflicts
4082	NM_017882.3(CLN6):c.395_396del (p.Ser132fs)	CLN6	Pathogenic	criteria provided, multiple submitters, no conflicts
4083	NC_000015.9:g.68504037_68504039delGAT	CLN6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
424086	NM_017882.3(CLN6):c.84-1G>A	CLN6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
522639	NM_017882.3(CLN6):c.476C>T (p.Pro159Leu)	CLN6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
550973	NM_017882.3(CLN6):c.896C>T (p.Pro299Leu)	CLN6	Pathogenic	criteria provided, multiple submitters, no conflicts
557725	NM_017882.3(CLN6):c.498dup (p.Glu167Ter)	CLN6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1027501	NM_017882.3(CLN6):c.665+1G>T	CLN6	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1724445	NM_017882.3(CLN6):c.377_378delinsG (p.Ile126fs)	CLN6	Likely pathogenic	criteria provided, single submitter
1724835	NM_017882.3(CLN6):c.385dup (p.Val129fs)	CLN6	Likely pathogenic	criteria provided, single submitter
1726067	NM_017882.3(CLN6):c.322del (p.Leu108fs)	CLN6	Likely pathogenic	criteria provided, single submitter
3577614	NM_017882.3(CLN6):c.543-1G>A	CLN6	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3577617	NM_017882.3(CLN6):c.199-1G>A	CLN6	Likely pathogenic	criteria provided, single submitter
3577618	NM_017882.3(CLN6):c.171del (p.Leu58fs)	CLN6	Likely pathogenic	criteria provided, single submitter
3577619	NM_017882.3(CLN6):c.95_96del (p.Val32fs)	CLN6	Likely pathogenic	criteria provided, single submitter
4533291	NM_017882.3(CLN6):c.85del (p.His29fs)	CLN6	Likely pathogenic	criteria provided, single submitter
457972	NM_017882.3(CLN6):c.445C>T (p.Arg149Cys)	CLN6	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · 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
CLN6	Definitive	Autosomal recessive	neuronal ceroid lipofuscinosis	10

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	gencc,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.