Neuronal ceroid lipofuscinosis 11

Summary

Neuronal ceroid lipofuscinosis 11 (MONDO:0013866) is a disease caused by GRN (GenCC Strong), with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: GRN (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 611

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		22	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	neuronal ceroid lipofuscinosis 11
Mondo ID	MONDO:0013866
OMIM	614706
Orphanet	314629
DOID	DOID:0110732
UMLS	C3539123
MedGen	761331
GARD	0017426
Is cancer (heuristic)	no

Also known as: ceroid lipofuscinosis, neuronal, 11 · ceroid lipofuscinosis, neuronal, type 11 · CLN11 · GRN neuronal ceroid lipofuscinosis · Grn neuronal ceroid lipofuscinosis · neuronal ceroid lipofuscinosis caused by mutation in GRN · neuronal ceroid lipofuscinosis caused by mutation in Grn · neuronal ceroid lipofuscinosis type 11

Data availability: 611 ClinVar variants · 5 GenCC gene-disease records · 2 cell lines.

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 11

Related subtypes (4): ceroid lipofuscinosis, neuronal, 4 (Kufs type), 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

600 retrieved; paginated sample, class counts are floors:

260 uncertain significance, 208 likely benign, 59 pathogenic, 33 conflicting classifications of pathogenicity, 15 benign/likely benign, 10 benign, 8 likely pathogenic, 7 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
98125	NM_002087.4(GRN):c.102del (p.Gly35fs)	FAM171A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1072132	NM_002087.4(GRN):c.614C>A (p.Ser205Ter)	GRN	Pathogenic	criteria provided, single submitter
1075941	NM_002087.4(GRN):c.299del (p.Pro100fs)	GRN	Pathogenic	criteria provided, single submitter
1352426	NM_002087.4(GRN):c.1A>G (p.Met1Val)	GRN	Pathogenic	criteria provided, single submitter
1371968	NM_002087.4(GRN):c.1153del (p.Glu385fs)	GRN	Pathogenic	criteria provided, single submitter
1453069	NM_002087.4(GRN):c.39dup (p.Leu14fs)	GRN	Pathogenic	criteria provided, single submitter
1455419	NM_002087.4(GRN):c.1216C>T (p.Gln406Ter)	GRN	Pathogenic	criteria provided, single submitter
1457149	NM_002087.4(GRN):c.775_778del (p.Lys259fs)	GRN	Pathogenic	criteria provided, single submitter
1458018	NC_000017.10:g.(?42426434)(42430018_?)del	GRN	Pathogenic	criteria provided, single submitter
16008	NM_002087.4(GRN):c.2T>C (p.Met1Thr)	GRN	Pathogenic	criteria provided, single submitter
16011	NM_002087.4(GRN):c.388_391del (p.Gln130fs)	GRN	Pathogenic	criteria provided, multiple submitters, no conflicts
16013	NM_002087.4(GRN):c.26C>A (p.Ala9Asp)	GRN	Pathogenic	criteria provided, multiple submitters, no conflicts
16014	NM_002087.4(GRN):c.1477C>T (p.Arg493Ter)	GRN	Pathogenic	criteria provided, multiple submitters, no conflicts
16020	NM_002087.4(GRN):c.813_816del (p.Thr272fs)	GRN	Pathogenic	criteria provided, multiple submitters, no conflicts
1922048	NM_002087.4(GRN):c.472_496dup (p.Pro166delinsLeuTer)	GRN	Pathogenic	criteria provided, single submitter
1955531	NM_002087.4(GRN):c.1492_1495del (p.Glu498fs)	GRN	Pathogenic	criteria provided, single submitter
1994860	NM_002087.4(GRN):c.180dup (p.Cys61fs)	GRN	Pathogenic	criteria provided, single submitter
1999202	NM_002087.4(GRN):c.264+1del	GRN	Pathogenic	criteria provided, single submitter
2007840	NM_002087.4(GRN):c.1179+1G>C	GRN	Pathogenic	criteria provided, single submitter
2028731	NM_002087.4(GRN):c.118_121dup (p.Cys41Ter)	GRN	Pathogenic	criteria provided, single submitter
203459	NM_002087.4(GRN):c.87dup (p.Cys30fs)	GRN	Pathogenic	criteria provided, single submitter
203460	NM_002087.4(GRN):c.708+1G>A	GRN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2119142	NM_002087.4(GRN):c.784_787del (p.Ser262fs)	GRN	Pathogenic	criteria provided, single submitter
2127749	NM_002087.4(GRN):c.1158G>A (p.Trp386Ter)	GRN	Pathogenic	criteria provided, single submitter
2127919	NM_002087.4(GRN):c.711del (p.Thr238fs)	GRN	Pathogenic	criteria provided, single submitter
2138053	NM_002087.4(GRN):c.265-2del	GRN	Pathogenic	criteria provided, single submitter
2138054	NM_002087.4(GRN):c.295_308del (p.Cys99fs)	GRN	Pathogenic	criteria provided, single submitter
2175081	NM_002087.4(GRN):c.910_911dup (p.Trp304fs)	GRN	Pathogenic	criteria provided, single submitter
2925624	NM_002087.4(GRN):c.388C>T (p.Gln130Ter)	GRN	Pathogenic	criteria provided, single submitter
2925625	NM_002087.4(GRN):c.1317_1318del (p.Asp441fs)	GRN	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 4 · 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
GRN	Strong	Autosomal recessive	neuronal ceroid lipofuscinosis 11	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GRN	Orphanet:100069	Semantic dementia
GRN	Orphanet:100070	Progressive non-fluent aphasia
GRN	Orphanet:275864	Behavioral variant of frontotemporal dementia
GRN	Orphanet:314629	CLN11 disease

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GRN	HGNC:4601	ENSG00000030582	P28799	Progranulin	gencc,clinvar
ASB16	HGNC:19768	ENSG00000161664	Q96NS5	Ankyrin repeat and SOCS box protein 16	clinvar
FAM171A2	HGNC:30480	ENSG00000161682	A8MVW0	Protein FAM171A2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GRN	Progranulin	Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation.
ASB16	Ankyrin repeat and SOCS box protein 16	May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 2 · 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
Scaffold/PPI	1	5.8×	0.327
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GRN	Other/Unknown	no		Granulin, Granulin_sf, Granulin_fam
ASB16	Scaffold/PPI	no		SOCS_box, Ankyrin_rpt, SOCS_box-like_dom_sf
FAM171A2	Other/Unknown	no		FAM171, FAM171_N, FAM171_C

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
monocyte	1
stromal cell of endometrium	1
gastrocnemius	1
hindlimb stylopod muscle	1
muscle of leg	1
cortical plate	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GRN	301	ubiquitous	marker	monocyte, granulocyte, stromal cell of endometrium
ASB16	156	tissue_specific	yes	hindlimb stylopod muscle, gastrocnemius, muscle of leg
FAM171A2	150	ubiquitous	yes	cortical plate, ganglionic eminence, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GRN	1,490
ASB16	1,063
FAM171A2	744

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GRN	P28799	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ASB16	Q96NS5	88.68
FAM171A2	A8MVW0	59.81

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Class I MHC mediated antigen processing & presentation	1	35.0×	0.132	ASB16
Neddylation	1	23.7×	0.132	ASB16
Antigen processing: Ubiquitination & Proteasome degradation	1	18.6×	0.132	ASB16
Adaptive Immune System	1	14.9×	0.132	ASB16
Neutrophil degranulation	1	11.5×	0.135	GRN
Post-translational protein modification	1	9.6×	0.135	ASB16
Immune System	1	6.5×	0.155	ASB16
Metabolism of proteins	1	6.2×	0.155	ASB16

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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 aspartic-type peptidase activity	1	8426.0×	0.002	GRN
positive regulation of inflammatory response to wounding	1	4213.0×	0.002	GRN
positive regulation of trophectodermal cell proliferation	1	4213.0×	0.002	GRN
positive regulation of protein folding	1	2808.7×	0.002	GRN
astrocyte activation involved in immune response	1	2106.5×	0.002	GRN
positive regulation of lysosome organization	1	2106.5×	0.002	GRN
trophectodermal cell proliferation	1	1685.2×	0.002	GRN
microglial cell activation involved in immune response	1	1685.2×	0.002	GRN
positive regulation of axon regeneration	1	1685.2×	0.002	GRN
negative regulation of respiratory burst involved in inflammatory response	1	1685.2×	0.002	GRN
negative regulation of neutrophil activation	1	1203.7×	0.003	GRN
negative regulation of microglial cell activation	1	1053.2×	0.003	GRN
positive regulation of defense response to bacterium	1	936.2×	0.003	GRN
maintenance of synapse structure	1	766.0×	0.003	GRN
lysosomal protein catabolic process	1	526.6×	0.004	GRN
locomotory exploration behavior	1	495.6×	0.004	GRN
lysosomal transport	1	351.1×	0.006	GRN
lysosomal lumen acidification	1	337.0×	0.006	GRN
blastocyst hatching	1	271.8×	0.007	GRN
embryo implantation	1	175.5×	0.010	GRN
epithelial cell proliferation	1	156.0×	0.010	GRN
lysosome organization	1	153.2×	0.010	GRN
positive regulation of neuron apoptotic process	1	135.9×	0.011	GRN
retina development in camera-type eye	1	127.7×	0.011	GRN
positive regulation of endothelial cell migration	1	125.8×	0.011	GRN
positive regulation of epithelial cell proliferation	1	122.1×	0.011	GRN
regulation of inflammatory response	1	84.3×	0.015	GRN
positive regulation of angiogenesis	1	57.7×	0.021	GRN
negative regulation of neuron apoptotic process	1	55.4×	0.021	GRN
protein stabilization	1	33.4×	0.034	GRN

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GRN	0	0
ASB16	0	0
FAM171A2	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
GRN	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	GRN, ASB16, FAM171A2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GRN	2	—
ASB16	0	—
FAM171A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.