Neuronal ceroid lipofuscinosis 7

Summary

Neuronal ceroid lipofuscinosis 7 (MONDO:0012588) is a disease caused by MFSD8 (GenCC Definitive), with 6 cohort genes and 2 clinical trials.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: MFSD8 (GenCC Definitive)
• Cohort genes: 6
• ClinVar variants: 888
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		70	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	neuronal ceroid lipofuscinosis 7
Mondo ID	MONDO:0012588
MeSH	C563989
OMIM	610951
Orphanet	228366
DOID	DOID:0110722
UMLS	C1838571
MedGen	325457
GARD	0001220
Is cancer (heuristic)	no

Also known as: ceroid lipofuscinosis, neuronal, 7 · ceroid lipofuscinosis, neuronal, type 7 · CLN7 · CLN7 disease · CLN7 disease, late infantile · MFSD8 neuronal ceroid lipofuscinosis · neuronal ceroid lipofuscinosis 7 · neuronal ceroid lipofuscinosis caused by mutation in MFSD8 · neuronal ceroid lipofuscinosis type 7

Data availability: 888 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 › lysosomal storage disease › late infantile neuronal ceroid lipofuscinosis › neuronal ceroid lipofuscinosis 7

Related subtypes (2): neuronal ceroid lipofuscinosis 5, ceroid lipofuscinosis, neuronal, 6A

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:

265 likely benign, 202 uncertain significance, 60 pathogenic, 24 likely pathogenic, 19 conflicting classifications of pathogenicity, 14 pathogenic/likely pathogenic, 8 benign, 8 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069575	NC_000004.11:g.(?128544537)(129131208_?)del	INTU	Pathogenic	criteria provided, single submitter
1002	NM_001371596.2(MFSD8):c.1286G>A (p.Gly429Asp)	MFSD8	Pathogenic	no assertion criteria provided
1003	NM_001371596.2(MFSD8):c.894T>G (p.Tyr298Ter)	MFSD8	Pathogenic	criteria provided, multiple submitters, no conflicts
1005	NM_001371596.2(MFSD8):c.1235C>T (p.Pro412Leu)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1006	NM_001371596.2(MFSD8):c.881C>A (p.Thr294Lys)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1007	NM_001371596.2(MFSD8):c.468_469delinsCC (p.Ala157Pro)	MFSD8	Pathogenic	no assertion criteria provided
1050805	NM_001371596.2(MFSD8):c.1437G>A (p.Trp479Ter)	MFSD8	Pathogenic	criteria provided, multiple submitters, no conflicts
1067690	NM_001371596.2(MFSD8):c.864-1G>A	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069576	NC_000004.11:g.(?128886217)(128886288_?)del	MFSD8	Pathogenic	criteria provided, single submitter
1069577	NC_000004.11:g.(?128841785)(128843128_?)del	MFSD8	Pathogenic	criteria provided, single submitter
1073057	NM_001371596.2(MFSD8):c.878del (p.Pro292_Leu293insTer)	MFSD8	Pathogenic	criteria provided, single submitter
1073549	NM_001371596.2(MFSD8):c.1113del (p.Asn371fs)	MFSD8	Pathogenic	criteria provided, single submitter
1073899	NM_001371596.2(MFSD8):c.1120del (p.Ile374fs)	MFSD8	Pathogenic	criteria provided, single submitter
1074190	NM_001371596.2(MFSD8):c.1316_1322del (p.Thr439fs)	MFSD8	Pathogenic	criteria provided, single submitter
1074681	NM_001371596.2(MFSD8):c.1217_1218dup (p.Trp407fs)	MFSD8	Pathogenic	criteria provided, single submitter
1074727	NM_001371596.2(MFSD8):c.1325C>A (p.Ser442Ter)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075481	NM_001371596.2(MFSD8):c.136_137del (p.Met46fs)	MFSD8	Pathogenic	criteria provided, single submitter
1206979	NM_001371596.2(MFSD8):c.259C>T (p.Gln87Ter)	MFSD8	Pathogenic	criteria provided, multiple submitters, no conflicts
1252058	NM_001371596.2(MFSD8):c.1354_1369del (p.Gly451_Val452insTer)	MFSD8	Pathogenic	no assertion criteria provided
1339217	NM_001371596.2(MFSD8):c.198+2T>C	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1356532	NM_001371596.2(MFSD8):c.1064T>G (p.Leu355Ter)	MFSD8	Pathogenic	criteria provided, multiple submitters, no conflicts
1373124	NM_001371596.2(MFSD8):c.77T>G (p.Leu26Ter)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1394953	NM_001371596.2(MFSD8):c.690dup (p.Ile231fs)	MFSD8	Pathogenic	criteria provided, single submitter
1418701	NM_001371596.2(MFSD8):c.1158_1167del (p.Trp387fs)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453415	NM_001371596.2(MFSD8):c.65_66del (p.Glu22fs)	MFSD8	Pathogenic	criteria provided, single submitter
1454619	NM_001371596.2(MFSD8):c.593_594del (p.Val198fs)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454727	NM_001371596.2(MFSD8):c.531_537del (p.Gly179fs)	MFSD8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455411	NM_001371596.2(MFSD8):c.1090del (p.Ile364fs)	MFSD8	Pathogenic	criteria provided, single submitter
1456161	NM_001371596.2(MFSD8):c.1229dup (p.Tyr410Ter)	MFSD8	Pathogenic	criteria provided, single submitter
1458681	NC_000004.11:g.(?128864897)(128886298_?)del	MFSD8	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
MFSD8	Definitive	Autosomal recessive	neuronal ceroid lipofuscinosis	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MFSD8	Orphanet:1872	Cone rod dystrophy
MFSD8	Orphanet:228366	CLN7 disease
PLK4	Orphanet:2518	Autosomal recessive chorioretinopathy-microcephaly syndrome
PLK4	Orphanet:808	Seckel syndrome

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MFSD8	HGNC:28486	ENSG00000164073	Q8NHS3	Major facilitator superfamily domain-containing protein 8	gencc,clinvar
PLK4	HGNC:11397	ENSG00000142731	O00444	Serine/threonine-protein kinase PLK4	clinvar
LARP1B	HGNC:24704	ENSG00000138709	Q659C4	La-related protein 1B	clinvar
SLC25A31	HGNC:25319	ENSG00000151475	Q9H0C2	ADP/ATP translocase 4	clinvar
ABHD18	HGNC:26111	ENSG00000164074	Q0P651	Protein ABHD18	clinvar
INTU	HGNC:29239	ENSG00000164066	Q9ULD6	Protein inturned	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MFSD8	Major facilitator superfamily domain-containing protein 8	Outward-rectifying chloride channel involved in endolysosomal chloride homeostasis, membrane fusion and function.
PLK4	Serine/threonine-protein kinase PLK4	Serine/threonine-protein kinase that plays a central role in centriole duplication.
SLC25A31	ADP/ATP translocase 4	ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell.
INTU	Protein inturned	Plays a key role in ciliogenesis and embryonic development.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.33

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
Transporter	1	13.0×	0.299
Kinase	1	4.6×	0.396
Scaffold/PPI	1	2.9×	0.401
Other/Unknown	3	0.9×	0.758

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MFSD8	Transporter	yes		MFS, MFS_dom, MFS_trans_sf
PLK4	Kinase	yes	2.7.11.21	Prot_kinase_dom, POLO_box_dom, Tyr_kinase_AS
LARP1B	Other/Unknown	no		DM15, La_HTH, WH-like_DNA-bd_sf
SLC25A31	Other/Unknown	no		MCP, ADT_euk_type, MCP_transmembrane
ABHD18	Other/Unknown	no		ABHD18, AB_hydrolase_fold
INTU	Scaffold/PPI	no		PDZ, PDZ_sf, INTU

Expression context

Cohort genes with no expression data: 0.

6 cohort genes 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
adrenal tissue	1
calcaneal tendon	1
oviduct epithelium	1
ganglionic eminence	1
primordial germ cell in gonad	1
body of pancreas	1
secondary oocyte	1
sperm	1
adult organism	1
left testis	1
right testis	1
buccal mucosa cell	1
jejunal mucosa	1
jejunum	1
bronchial epithelial cell	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MFSD8	256	ubiquitous	marker	oviduct epithelium, adrenal tissue, calcaneal tendon
PLK4	201	ubiquitous	marker	ventricular zone, ganglionic eminence, primordial germ cell in gonad
LARP1B	252	ubiquitous	marker	secondary oocyte, sperm, body of pancreas
SLC25A31	27	tissue_specific	marker	adult organism, right testis, left testis
ABHD18	263	ubiquitous	marker	buccal mucosa cell, jejunal mucosa, jejunum
INTU	226	ubiquitous	marker	right uterine tube, bronchial epithelial cell, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PLK4	3,694
INTU	2,947
LARP1B	1,823
SLC25A31	1,662
MFSD8	1,405
ABHD18	405

Intra-cohort edges

A	B	Sources
ABHD18	LARP1B	string_interaction
ABHD18	MFSD8	string_interaction
INTU	MFSD8	string_interaction
INTU	SLC25A31	string_interaction
LARP1B	SLC25A31	string_interaction
MFSD8	SLC25A31	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PLK4	O00444	19
INTU	Q9ULD6	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC25A31	Q9H0C2	89.97
MFSD8	Q8NHS3	83.20
ABHD18	Q0P651	80.82
LARP1B	Q659C4	56.94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 6 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
Signaling by Hedgehog	1	92.1×	0.020	INTU
Hedgehog ‘off’ state	1	89.2×	0.020	INTU
Loss of Nlp from mitotic centrosomes	1	79.3×	0.020	PLK4
Loss of proteins required for interphase microtubule organization from the centrosome	1	79.3×	0.020	PLK4
AURKA Activation by TPX2	1	76.1×	0.020	PLK4
Recruitment of mitotic centrosome proteins and complexes	1	68.0×	0.020	PLK4
Regulation of PLK1 Activity at G2/M Transition	1	63.4×	0.020	PLK4
Recruitment of NuMA to mitotic centrosomes	1	58.3×	0.020	PLK4
Anchoring of the basal body to the plasma membrane	1	56.5×	0.020	PLK4
Signal Transduction	1	5.1×	0.187	INTU

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
maintenance of location	1	3370.4×	0.011	MFSD8
glycolipid metabolic process	1	1685.2×	0.011	MFSD8
inclusion body assembly	1	1685.2×	0.011	MFSD8
regulation of lysosomal protein catabolic process	1	1123.5×	0.011	MFSD8
tongue morphogenesis	1	674.1×	0.011	INTU
positive regulation of centriole replication	1	674.1×	0.011	PLK4
de novo centriole assembly involved in multi-ciliated epithelial cell differentiation	1	674.1×	0.011	PLK4
mitochondrial ADP transmembrane transport	1	674.1×	0.011	SLC25A31
cilium assembly	2	29.4×	0.012	PLK4, INTU
negative regulation of cell division	1	481.5×	0.013	INTU
spinal cord dorsal/ventral patterning	1	421.3×	0.013	INTU
mitochondrial ATP transmembrane transport	1	374.5×	0.014	SLC25A31
microglia differentiation	1	306.4×	0.015	MFSD8
regulation of mitochondrial membrane permeability	1	280.9×	0.015	SLC25A31
regulation of ossification	1	240.7×	0.015	INTU
trophoblast giant cell differentiation	1	240.7×	0.015	PLK4
glycoprotein metabolic process	1	224.7×	0.015	MFSD8
establishment of planar polarity	1	210.7×	0.015	INTU
negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway	1	210.7×	0.015	SLC25A31
lysosomal protein catabolic process	1	210.7×	0.015	MFSD8
TORC1 signaling	1	160.5×	0.018	MFSD8
astrocyte differentiation	1	153.2×	0.018	MFSD8
centriole replication	1	146.5×	0.018	PLK4
negative regulation of keratinocyte proliferation	1	140.4×	0.018	INTU
regulation of smoothened signaling pathway	1	124.8×	0.018	INTU
regulation of cilium assembly	1	120.4×	0.018	INTU
male meiosis I	1	116.2×	0.018	SLC25A31
motile cilium assembly	1	116.2×	0.018	INTU
intraciliary transport	1	112.3×	0.018	INTU
motor behavior	1	112.3×	0.018	MFSD8

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 5

Druggability breadth: 1 of 6 evidence-associated genes (17%) 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
PLK4	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PLK4	65	4
MFSD8	0	0
LARP1B	0	0
SLC25A31	0	0
ABHD18	0	0
INTU	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	PLK4
FEDRATINIB	4	PLK4
AXITINIB	4	PLK4
SORAFENIB	4	PLK4
RUXOLITINIB	4	PLK4
ENTRECTINIB	4	PLK4
DABRAFENIB	4	PLK4
FOSTAMATINIB	4	PLK4
CERITINIB	4	PLK4
VANDETANIB	4	PLK4
GILTERITINIB	4	PLK4
PAZOPANIB	4	PLK4
NINTEDANIB	4	PLK4
SUNITINIB	4	PLK4
DASATINIB	4	PLK4
ERLOTINIB	4	PLK4
CRIZOTINIB	4	PLK4
MIDOSTAURIN	4	PLK4
IMATINIB	4	PLK4
LINIFANIB	3	PLK4
RIPASUDIL	3	PLK4
ALVOCIDIB	3	PLK4
ALISERTIB	3	PLK4
CEDIRANIB	3	PLK4
DOVITINIB	3	PLK4
LESTAURTINIB	3	PLK4
RUBOXISTAURIN	3	PLK4
FORETINIB	2	PLK4
AZD-1480	2	PLK4
TANDUTINIB	2	PLK4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PLK4	303	Binding:293, Functional:10

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PLK4	2.7.11.21	polo kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
PLK4	303

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 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)
MOMELOTINIB	4	PLK4
FEDRATINIB	4	PLK4
AXITINIB	4	PLK4
SORAFENIB	4	PLK4
RUXOLITINIB	4	PLK4
ENTRECTINIB	4	PLK4
DABRAFENIB	4	PLK4
FOSTAMATINIB	4	PLK4
CERITINIB	4	PLK4
VANDETANIB	4	PLK4
GILTERITINIB	4	PLK4
PAZOPANIB	4	PLK4
NINTEDANIB	4	PLK4
SUNITINIB	4	PLK4
DASATINIB	4	PLK4
ERLOTINIB	4	PLK4
CRIZOTINIB	4	PLK4
MIDOSTAURIN	4	PLK4
IMATINIB	4	PLK4
LINIFANIB	3	PLK4
RIPASUDIL	3	PLK4
ALVOCIDIB	3	PLK4
ALISERTIB	3	PLK4
CEDIRANIB	3	PLK4
DOVITINIB	3	PLK4
LESTAURTINIB	3	PLK4
RUBOXISTAURIN	3	PLK4
FORETINIB	2	PLK4
AZD-1480	2	PLK4
TANDUTINIB	2	PLK4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PLK4
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	MFSD8
E	Difficult family or no structure, no drug	4	LARP1B, SLC25A31, ABHD18, INTU

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MFSD8	0	—
LARP1B	0	—
SLC25A31	0	—
ABHD18	0	—
INTU	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04737460	PHASE1	ACTIVE_NOT_RECRUITING	Study for the Treatment for CLN7 Disease
NCT04613089	Not specified	RECRUITING	Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database