Neuronal ceroid lipofuscinosis 5

Summary

Neuronal ceroid lipofuscinosis 5 (MONDO:0009745) is a disease caused by CLN5 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CLN5 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 232

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		85	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	neuronal ceroid lipofuscinosis 5
Mondo ID	MONDO:0009745
MeSH	C575534
OMIM	256731
Orphanet	228360
DOID	DOID:0110728
UMLS	C1850442
MedGen	376792
GARD	0001223
Is cancer (heuristic)	no

Also known as: ceroid lipofuscinosis, neuronal, 5 · ceroid lipofuscinosis, neuronal, type 5 · CLN5 · CLN5 disease, adult · CLN5 disease, juvenile · CLN5 disease, late infantile (subtype) · CLN5 neuronal ceroid lipofuscinosis · neuronal ceroid lipofuscinosis caused by mutation in CLN5 · neuronal ceroid lipofuscinosis Finnish variant · neuronal ceroid lipofuscinosis type 5

Data availability: 232 ClinVar variants · 6 GenCC gene-disease records · 5 cell lines.

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 › neuronal ceroid lipofuscinosis 5

Related subtypes (2): ceroid lipofuscinosis, neuronal, 6A, neuronal ceroid lipofuscinosis 7

Subtypes (3): late infantile neuronal ceroid lipofuscinosis 5, juvenile neuronal ceroid lipofuscinosis 5, 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

232 retrieved; paginated sample, class counts are floors:

73 uncertain significance, 47 likely pathogenic, 35 conflicting classifications of pathogenicity, 30 pathogenic/likely pathogenic, 25 pathogenic, 12 benign/likely benign, 6 likely benign, 4 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1072711	NM_006493.4(CLN5):c.990G>A (p.Trp330Ter)	CLN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073281	NM_006493.4(CLN5):c.812del (p.Asn271fs)	CLN5	Pathogenic	criteria provided, multiple submitters, no conflicts
1075607	NM_006493.4(CLN5):c.580C>T (p.Gln194Ter)	CLN5	Pathogenic	criteria provided, multiple submitters, no conflicts
1075843	NM_006493.4(CLN5):c.207_213del (p.Pro68_Tyr69insTer)	CLN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
128784	NM_006493.4(CLN5):c.525del (p.His174_Trp175insTer)	CLN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1425365	NM_006493.4(CLN5):c.404G>A (p.Trp135Ter)	CLN5	Pathogenic	criteria provided, multiple submitters, no conflicts
1454025	NM_006493.4(CLN5):c.987T>G (p.Tyr329Ter)	CLN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455869	NM_006493.4(CLN5):c.913_914del (p.Leu305fs)	CLN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1459372	NM_006493.4(CLN5):c.982G>T (p.Glu328Ter)	CLN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1691798	NM_006493.4(CLN5):c.594G>A (p.Trp198Ter)	CLN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189038	NM_006493.4(CLN5):c.777_778del (p.Phe260fs)	CLN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
205144	NM_006493.4(CLN5):c.448C>T (p.Arg150Ter)	CLN5	Pathogenic	criteria provided, multiple submitters, no conflicts
224505	NM_006493.4(CLN5):c.547C>T (p.Gln183Ter)	CLN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2435733	NM_006493.4(CLN5):c.639_640insTT (p.Val214fs)	CLN5	Pathogenic	criteria provided, single submitter
2564	NM_006493.4(CLN5):c.1028_1029del (p.Thr342_Tyr343insTer)	CLN5	Pathogenic	criteria provided, multiple submitters, no conflicts
2565	NM_006493.4(CLN5):c.78G>A (p.Trp26Ter)	CLN5	Pathogenic	criteria provided, multiple submitters, no conflicts
2567	NM_006493.4(CLN5):c.188G>A (p.Arg63His)	CLN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2568	NM_006493.4(CLN5):c.907G>T (p.Glu303Ter)	CLN5	Pathogenic	criteria provided, multiple submitters, no conflicts
2571	NM_006493.4(CLN5):c.566-42_*46del	CLN5	Pathogenic	no assertion criteria provided
2680828	NM_006493.4(CLN5):c.717dup (p.Asn240Ter)	CLN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680836	NM_006493.4(CLN5):c.431_432del (p.Cys144fs)	CLN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2866615	NM_006493.4(CLN5):c.441_442dup (p.His148fs)	CLN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3242448	NM_006493.4(CLN5):c.339+2T>A	CLN5	Pathogenic	no assertion criteria provided
3362324	NM_006493.4(CLN5):c.429del (p.Cys144fs)	CLN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370765	NM_006493.4(CLN5):c.958C>T (p.Gln320Ter)	CLN5	Pathogenic	criteria provided, multiple submitters, no conflicts
371261	NM_006493.4(CLN5):c.155_167del (p.His52fs)	CLN5	Pathogenic	criteria provided, multiple submitters, no conflicts
371570	NM_006493.4(CLN5):c.793G>T (p.Glu265Ter)	CLN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
434793	NM_006493.4(CLN5):c.510_514dup (p.Asp172fs)	CLN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
451600	NM_006493.4(CLN5):c.84G>A (p.Trp28Ter)	CLN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
522601	NM_006493.4(CLN5):c.675G>A (p.Trp225Ter)	CLN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
CLN5	Definitive	Autosomal recessive	neuronal ceroid lipofuscinosis 5	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CLN5	Orphanet:699802	Late infantile CLN5 disease
CLN5	Orphanet:699807	Juvenile CLN5 disease
CLN5	Orphanet:699812	Adult CLN5 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
CLN5	HGNC:2076	ENSG00000102805	O75503	Bis(monoacylglycero)phosphate synthase CLN5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CLN5	Bis(monoacylglycero)phosphate synthase CLN5	Catalyzes the synthesis of bis(monoacylglycero)phosphate (BMP) via transacylation of 2 molecules of lysophosphatidylglycerol (LPG).

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)
CLN5	Other/Unknown	no		CLN5

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
left lobe of thyroid gland	1
right lobe of thyroid gland	1
thyroid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CLN5	271	ubiquitous	marker	left lobe of thyroid gland, right lobe of thyroid gland, thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CLN5	1,033

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CLN5	O75503	1

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
positive regulation of GTP binding	1	16852.0×	6e-04	CLN5
obsolete signal peptide processing	1	1404.3×	0.004	CLN5
neuron maturation	1	802.5×	0.004	CLN5
lysosomal lumen acidification	1	674.1×	0.004	CLN5
lysosome organization	1	306.4×	0.006	CLN5
protein catabolic process	1	237.3×	0.006	CLN5
neurogenesis	1	208.1×	0.006	CLN5
retrograde transport, endosome to Golgi	1	205.5×	0.006	CLN5
brain development	1	79.5×	0.013	CLN5
visual perception	1	79.5×	0.013	CLN5

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
CLN5	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	0
E	Difficult family or no structure, no drug	1	CLN5

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)
CLN5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.