Lysosomal storage disease

Summary

Lysosomal storage disease (MONDO:0002561) is a disease (an umbrella term covering 11 Mondo subtypes) with 6 cohort genes and 38 clinical trials. The dominant Reactome pathway is Glycosphingolipid metabolism (4 cohort genes). Top therapeutic interventions include laronidase, atidarsagene autotemcel, and rituximab.

At a glance

• Umbrella term: 11 Mondo subtypes
• Cohort genes: 6
• ClinVar variants: 11
• Clinical trials: 38

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lysosomal storage disease
Mondo ID	MONDO:0002561
MeSH	D016464
Orphanet	68366
DOID	DOID:3211
ICD-11	656131403
NCIT	C61250
SNOMED CT	23585005, 28821000119102
UMLS	C0085078
MedGen	43098
GARD	0018884
Is cancer (heuristic)	no

Also known as: disorder of lysosomal enzymes · lysosomal disease · lysosomal disorder · lysosomal storage disorder · lysosome disease · lysosome disorder

Data availability: 11 ClinVar variants.

Disease family

An umbrella term covering 11 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

Related subtypes (92): thiopurine metabolic disease, hypercalcemia, infantile, hypermanganesemia with dystonia, abdominal obesity-metabolic syndrome, plasma protein metabolism disease, inherited lipid metabolism disorder, striatonigral degeneration, inborn metal metabolism disorder, inborn vitamin metabolic disorder, chondrocalcinosis 2, Ehlers-Danlos syndrome, spondylodysplastic type, fish eye disease, aromatase excess syndrome, spondyloepiphyseal dysplasia with congenital joint dislocations, hypertriglyceridemia 1, autosomal dominant myoglobinuria, diastrophic dysplasia, hemolytic anemia due to diphosphoglycerate mutase deficiency, multiple epiphyseal dysplasia type 4, atelosteogenesis type II, inherited threoninemia, inborn glycerol kinase deficiency, achondrogenesis type IB, diabetes mellitus, noninsulin-dependent, 1, diabetes mellitus, noninsulin-dependent, 2, renal tubular acidosis, distal, 3, with or without sensorineural hearing loss, diabetes mellitus, noninsulin-dependent, 3, hypercholesterolemia, familial, 4, hypoalphalipoproteinemia, primary, 1, autosomal recessive proximal renal tubular acidosis, diabetes mellitus, noninsulin-dependent, 4, normophosphatemic familial tumoral calcinosis, apolipoprotein c-III deficiency, hypotonia-failure to thrive-microcephaly syndrome, chondrodysplasia with joint dislocations, gPAPP type, gluthathione peroxidase deficiency, congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome, diabetes mellitus, noninsulin-dependent, 5, congenital disorder of glycosylation, monogenic diabetes, 2-hydroxyglutaric aciduria, familial hypoparathyroidism, familial intrahepatic cholestasis, inborn aminoacylase deficiency, disorder of lysosomal-related organelles, inborn disorder of porphyrin metabolism, disorder of metabolite absorption and transport, autosomal dominant proximal renal tubular acidosis, neurodegeneration with brain iron accumulation, ferro-cerebro-cutaneous syndrome, familial hypocalciuric hypercalcemia, hypophosphatasia, hereditary amyloidosis, peroxisomal disease, inborn disorder of amino acid and other organic acid metabolism, inborn carbohydrate metabolic disorder, inborn disorder of energy metabolism, inborn disorder of biogenic amine metabolism and transport, inborn disorder of purine or pyrimidine metabolism, spondyloepimetaphyseal dysplasia, PAPSS2 type, hereditary lipodystrophy, hereditary recurrent myoglobinuria, DNA repair disease, 4-hydroxyphenylacetic aciduria, 5-nucleotidase syndrome, antigen-peptide-transporter 2 deficiency, APO A-i deficiency, cardiomyopathy hypogonadism metabolic anomalies, deficiency of coenzyme q cytochrome c reductase, defective apolipoprotein b-100, sulfide quinone oxidoreductase deficiency, congenital disorder of deglycosylation, hypoalphalipoproteinemia, primary, 2, uridine-cytidineuria, NAD(P)HX dehydratase deficiency, inborn disorder of aspartate family metabolism, weinstein kliman scully syndrome, glycoprotein metabolism disease, inherited thyroid metabolism disease, tumoral calcinosis, hyperphosphatemic, familial, 2, tumoral calcinosis, hyperphosphatemic, familial, 3, combined ApoA-I and ApoC-III deficiency, familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome, tumoral calcinosis, hyperphosphatemic, familial, 1, Waldenstrom macroglobulinemia, mucopolysaccharidosis or mucopolysaccharidosis-like disorder, disorder of peptide and amine metabolism, CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis, Lane Hamilton syndrome, SQSTM1-related multisystem proteinopathy, hypertriglyceridemia 2, autosomal dominant dopa-responsive dystonia

Subtypes (11): lysosomal acid phosphatase deficiency, glycoprotein storage disease, pycnodysostosis, hereditary spastic paraplegia 48, late infantile neuronal ceroid lipofuscinosis, glycoproteinosis, disorder of sialic acid metabolism, lysosomal glycogen storage disease, lysosomal lipid storage disorder, inborn disorder of lysosomal amino acid transport, mucopolysaccharidosis

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

11 retrieved; paginated sample, class counts are floors:

4 pathogenic/likely pathogenic, 4 pathogenic, 3 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2705278	NM_000487.6(ARSA):c.868_873del (p.Arg290_Met291del)	ARSA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066585	NM_000404.4(GLB1):c.557A>C (p.Glu186Ala)	GLB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
372371	NM_000404.4(GLB1):c.841C>T (p.His281Tyr)	GLB1	Pathogenic	criteria provided, multiple submitters, no conflicts
550413	NM_000404.4(GLB1):c.1634dup (p.Asn545fs)	GLB1	Pathogenic	criteria provided, multiple submitters, no conflicts
807421	NM_000404.4(GLB1):c.716C>T (p.Thr239Met)	GLB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1562	NM_000263.4(NAGLU):c.889C>T (p.Arg297Ter)	NAGLU	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
430342	NM_000434.4(NEU1):c.679G>A (p.Gly227Arg)	NEU1	Pathogenic	criteria provided, multiple submitters, no conflicts
2967	NM_000271.5(NPC1):c.3182T>C (p.Ile1061Thr)	NPC1	Pathogenic	criteria provided, multiple submitters, no conflicts
4813362	NM_000487.6(ARSA):c.811_816del (p.Gly271_Leu272del)	ARSA	Likely pathogenic	criteria provided, single submitter
4819979	NM_000404.4(GLB1):c.1265T>G (p.Leu422Arg)	GLB1	Likely pathogenic	criteria provided, single submitter
1347154	NM_000543.5(SMPD1):c.1132C>T (p.Arg378Cys)	SMPD1	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 19 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMPD1	Orphanet:77292	Infantile neurovisceral acid sphingomyelinase deficiency
SMPD1	Orphanet:77293	Chronic visceral acid sphingomyelinase deficiency
GLB1	Orphanet:309310	Mucopolysaccharidosis type 4B
GLB1	Orphanet:79255	GM1 gangliosidosis type 1
GLB1	Orphanet:79256	GM1 gangliosidosis type 2
GLB1	Orphanet:79257	GM1 gangliosidosis type 3
ARSA	Orphanet:309256	Metachromatic leukodystrophy, late infantile form
ARSA	Orphanet:309263	Metachromatic leukodystrophy, juvenile form
ARSA	Orphanet:309271	Metachromatic leukodystrophy, adult form
NAGLU	Orphanet:447964	Autosomal dominant Charcot-Marie-Tooth disease type 2V
NAGLU	Orphanet:79270	Sanfilippo syndrome type B
NEU1	Orphanet:812	Sialidosis type 1
NEU1	Orphanet:93399	Juvenile sialidosis type 2
NEU1	Orphanet:93400	Congenital sialidosis type 2
NPC1	Orphanet:216972	Niemann-Pick disease type C, severe perinatal form
NPC1	Orphanet:216975	Niemann-Pick disease type C, severe early infantile neurologic onset
NPC1	Orphanet:216978	Niemann-Pick disease type C, late infantile neurologic onset
NPC1	Orphanet:216981	Niemann-Pick disease type C, juvenile neurologic onset
NPC1	Orphanet:216986	Niemann-Pick disease type C, adult neurologic onset

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
SMPD1	HGNC:11120	ENSG00000166311	P17405	Sphingomyelin phosphodiesterase	clinvar
GLB1	HGNC:4298	ENSG00000170266	P16278	Beta-galactosidase	clinvar
ARSA	HGNC:713	ENSG00000100299	P15289	Arylsulfatase A	clinvar
NAGLU	HGNC:7632	ENSG00000108784	P54802	Alpha-N-acetylglucosaminidase	clinvar
NEU1	HGNC:7758	ENSG00000204386	Q99519	Sialidase-1	clinvar
NPC1	HGNC:7897	ENSG00000141458	O15118	NPC intracellular cholesterol transporter 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMPD1	Sphingomyelin phosphodiesterase	Converts sphingomyelin to ceramide.
GLB1	Beta-galactosidase	Cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans.
ARSA	Arylsulfatase A	Hydrolyzes cerebroside sulfate.
NAGLU	Alpha-N-acetylglucosaminidase	Involved in the degradation of heparan sulfate.
NEU1	Sialidase-1	Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moieties from glycoproteins and glycolipids.
NPC1	NPC intracellular cholesterol transporter 1	Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment.

Protein-family classification

Druggable: 4 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.67

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
Enzyme (other)	3	6.0×	0.029
Phosphatase	1	14.0×	0.104
Other/Unknown	2	0.6×	0.936

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SMPD1	Enzyme (other)	yes	3.1.4.12	Calcineurin-like_PHP, SaposinB_dom, Saposin-like
GLB1	Other/Unknown	no		Glycoside_Hdrlase_35, Galactose-bd-like_sf, GH_hydrolase_sf
ARSA	Phosphatase	yes		Sulfatase_N, Alkaline_phosphatase_core_sf, Sulfatase_CS
NAGLU	Enzyme (other)	yes	3.2.1.50	NAGLU, GH_hydrolase_sf, NAGLU_N
NEU1	Enzyme (other)	yes	3.2.1.18	Sialidase, Sialidase_fam, Sialidase_sf
NPC1	Other/Unknown	no		SSD, NPC1-like, NPC1_N

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
stromal cell of endometrium	3
islet of Langerhans	2
type B pancreatic cell	1
monocyte	1
mononuclear cell	1
granulocyte	1
right testis	1
right uterine tube	1
body of pancreas	1
mucosa of stomach	1
right adrenal gland	1
right adrenal gland cortex	1
adrenal tissue	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMPD1	262	ubiquitous	marker	type B pancreatic cell, stromal cell of endometrium, islet of Langerhans
GLB1	258	ubiquitous	marker	monocyte, mononuclear cell, stromal cell of endometrium
ARSA	177	ubiquitous	marker	right uterine tube, right testis, granulocyte
NAGLU	268	ubiquitous	marker	stromal cell of endometrium, body of pancreas, mucosa of stomach
NEU1	132	ubiquitous	marker	islet of Langerhans, right adrenal gland cortex, right adrenal gland
NPC1	292	ubiquitous	marker	secondary oocyte, oocyte, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NPC1	2,648
SMPD1	1,729
GLB1	1,578
ARSA	1,356
NAGLU	1,200
NEU1	794

Intra-cohort edges

A	B	Sources
ARSA	GLB1	string_interaction
ARSA	SMPD1	string_interaction
GLB1	NAGLU	string_interaction
GLB1	NEU1	biogrid_interaction, intact, string_interaction

Structural data

PDB: 5 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NPC1	O15118	20
ARSA	P15289	10
GLB1	P16278	8
SMPD1	P17405	4
NAGLU	P54802	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NEU1	Q99519	89.12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 35. Enrichment computed across 6 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Glycosphingolipid metabolism	4	200.3×	3e-08	SMPD1, GLB1, ARSA, NEU1
Glycosphingolipid catabolism	4	195.2×	3e-08	SMPD1, GLB1, ARSA, NEU1
Sphingolipid metabolism	4	112.0×	2e-07	SMPD1, GLB1, ARSA, NEU1
Defective NEU1 causes sialidosis	2	951.7×	1e-05	GLB1, NEU1
Mucopolysaccharidoses	2	634.4×	2e-05	GLB1, NAGLU
Metabolism of lipids	4	21.0×	8e-05	SMPD1, GLB1, ARSA, NEU1
Diseases of carbohydrate metabolism	2	271.9×	1e-04	GLB1, NAGLU
Metabolism	5	9.7×	1e-04	SMPD1, GLB1, ARSA, NAGLU, NEU1
Diseases associated with N-glycosylation of proteins	2	211.5×	1e-04	GLB1, NEU1
Diseases of metabolism	3	40.2×	1e-04	GLB1, NAGLU, NEU1
Heparan sulfate/heparin (HS-GAG) metabolism	2	181.3×	2e-04	GLB1, NAGLU
HS-GAG degradation	2	165.5×	2e-04	GLB1, NAGLU
Sialic acid metabolism	2	108.8×	4e-04	GLB1, NEU1
Synthesis of substrates in N-glycan biosythesis	2	97.6×	4e-04	GLB1, NEU1
Glycosaminoglycan metabolism	2	73.2×	7e-04	GLB1, NAGLU
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	2	69.2×	7e-04	GLB1, NEU1
MPS IIIB - Sanfilippo syndrome B	1	1903.3×	0.001	NAGLU
Diseases of glycosylation	2	43.8×	0.002	GLB1, NEU1
MPS IV - Morquio syndrome B (Keratin metabolism)	1	951.7×	0.002	GLB1
MPS IV - Morquio syndrome B (CS/DS degradation)	1	951.7×	0.002	GLB1
Metabolism of carbohydrates and carbohydrate derivatives	2	40.1×	0.002	GLB1, NAGLU
Innate Immune System	3	12.8×	0.002	GLB1, ARSA, NEU1
Neutrophil degranulation	3	11.5×	0.002	GLB1, ARSA, NEU1
Post-translational protein modification	3	9.6×	0.004	GLB1, ARSA, NEU1
Asparagine N-linked glycosylation	2	20.0×	0.006	GLB1, NEU1
The activation of arylsulfatases	1	146.4×	0.009	ARSA
Disease	3	6.5×	0.010	GLB1, NAGLU, NEU1
Immune System	3	6.5×	0.010	GLB1, ARSA, NEU1
Keratan sulfate degradation	1	119.0×	0.010	GLB1
Metabolism of proteins	3	6.2×	0.010	GLB1, ARSA, NEU1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
ganglioside catabolic process	2	624.1×	4e-04	GLB1, NEU1
symbiont entry into host cell	2	133.8×	0.005	SMPD1, NPC1
response to disaccharide	1	2808.7×	0.007	NAGLU
cyclodextrin metabolic process	1	2808.7×	0.007	NPC1
liver development	2	73.9×	0.007	NAGLU, NPC1
cholesterol metabolic process	2	65.3×	0.007	SMPD1, NPC1
response to cortisone	1	1404.3×	0.010	GLB1
rod bipolar cell differentiation	1	1404.3×	0.010	NAGLU
termination of signal transduction	1	936.2×	0.010	SMPD1
intracellular lipid transport	1	936.2×	0.010	NPC1
keratan sulfate proteoglycan catabolic process	1	936.2×	0.010	GLB1
response to Thyroglobulin triiodothyronine	1	936.2×	0.010	GLB1
ganglioside metabolic process	1	702.2×	0.010	NAGLU
left ventricular cardiac muscle tissue morphogenesis	1	702.2×	0.010	NAGLU
cone retinal bipolar cell differentiation	1	702.2×	0.010	NAGLU
autophagy	2	36.7×	0.010	NAGLU, NPC1
sphingomyelin metabolic process	1	561.7×	0.010	SMPD1
sphingomyelin catabolic process	1	561.7×	0.010	SMPD1
membrane raft organization	1	561.7×	0.010	NPC1
cytoplasm organization	1	468.1×	0.010	NAGLU
sterol transport	1	468.1×	0.010	NPC1
galactose catabolic process	1	468.1×	0.010	GLB1
heparin proteoglycan metabolic process	1	468.1×	0.010	NAGLU
cholesterol storage	1	401.2×	0.010	NPC1
glycosaminoglycan metabolic process	1	401.2×	0.010	NAGLU
inner ear receptor cell development	1	401.2×	0.010	NAGLU
heparan sulfate proteoglycan catabolic process	1	312.1×	0.011	NAGLU
response to type I interferon	1	312.1×	0.011	SMPD1
establishment of protein localization to membrane	1	312.1×	0.011	NPC1
response to xenobiotic stimulus	2	23.0×	0.011	SMPD1, NPC1

Therapeutics

Drug target analysis

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

Druggability breadth: 6 of 6 evidence-associated genes (100%) 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
SMPD1	IMIPRAMINE
GLB1	MIGALASTAT
NPC1	NABUMETONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NPC1	90	4
SMPD1	3	4
GLB1	1	4
ARSA	0	0
NAGLU	0	0
NEU1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IMIPRAMINE	4	SMPD1
CHLORPROMAZINE	4	SMPD1
MIGALASTAT	4	GLB1
NABUMETONE	4	NPC1
PHENELZINE	4	NPC1
AMLEXANOX	4	NPC1
IDARUBICIN	4	NPC1
RABEPRAZOLE SODIUM	4	NPC1
NITAZOXANIDE	4	NPC1
NICLOSAMIDE	4	NPC1
NITROXOLINE	4	NPC1
NICARDIPINE	4	NPC1
DAUNORUBICIN HYDROCHLORIDE	4	NPC1
INDOPROFEN	4	NPC1
CYCLOSPORINE	4	NPC1
TERFENADINE	4	NPC1
DIGOXIN	4	NPC1
PRAZOSIN	4	NPC1
MAPROTILINE	4	NPC1
DIGITOXIN	4	NPC1
HYDRALAZINE	4	NPC1
EBASTINE	4	NPC1
DEQUALINIUM	4	NPC1
DOXORUBICIN HYDROCHLORIDE	4	NPC1
VINBLASTINE SULFATE	4	NPC1
FLUOXETINE	4	NPC1
DITHIAZANINE IODIDE	4	NPC1
TRIFLUOPERAZINE	4	NPC1
PACLITAXEL	4	NPC1
NORTRIPTYLINE	4	NPC1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
GLB1	124	Binding:123, ADMET:1
SMPD1	42	Binding:40, Functional:2
NEU1	27	Binding:27
NPC1	18	Binding:13, Functional:5
ARSA	4	Binding:3, Functional:1
NAGLU	4	Binding:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SMPD1	3.1.4.12	sphingomyelin phosphodiesterase
NAGLU	3.2.1.50	alpha-N-acetylglucosaminidase
NEU1	3.2.1.18	exo-alpha-sialidase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
GLB1	124

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)
IMIPRAMINE	4	SMPD1
CHLORPROMAZINE	4	SMPD1
MIGALASTAT	4	GLB1
NABUMETONE	4	NPC1
PHENELZINE	4	NPC1
AMLEXANOX	4	NPC1
IDARUBICIN	4	NPC1
RABEPRAZOLE SODIUM	4	NPC1
NITAZOXANIDE	4	NPC1
NICLOSAMIDE	4	NPC1
NITROXOLINE	4	NPC1
NICARDIPINE	4	NPC1
DAUNORUBICIN HYDROCHLORIDE	4	NPC1
INDOPROFEN	4	NPC1
CYCLOSPORINE	4	NPC1
TERFENADINE	4	NPC1
DIGOXIN	4	NPC1
PRAZOSIN	4	NPC1
MAPROTILINE	4	NPC1
DIGITOXIN	4	NPC1
HYDRALAZINE	4	NPC1
EBASTINE	4	NPC1
DEQUALINIUM	4	NPC1
DOXORUBICIN HYDROCHLORIDE	4	NPC1
VINBLASTINE SULFATE	4	NPC1
FLUOXETINE	4	NPC1
DITHIAZANINE IODIDE	4	NPC1
TRIFLUOPERAZINE	4	NPC1
PACLITAXEL	4	NPC1
NORTRIPTYLINE	4	NPC1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	SMPD1, GLB1, NPC1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	ARSA, NAGLU
D	Druggable family + AlphaFold only, no drug	1	NEU1
E	Difficult family or no structure, no drug	0

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)
NEU1	27	GLB1
ARSA	4	—
NAGLU	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 38.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	24
PHASE1/PHASE2	6
PHASE1	4
PHASE3	2
PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04283227	PHASE3	ACTIVE_NOT_RECRUITING	OTL-200 in Patients With Late Juvenile Metachromatic Leukodystrophy (MLD)
NCT00654433	PHASE3	TERMINATED	ALD-101 Adjuvant Therapy of Unrelated Umbilical Cord Blood Transfusion (UCBT) in Patients With Inherited Metabolic Diseases
NCT03952637	PHASE1/PHASE2	RECRUITING	A Phase 1/2 Study of Intravenous Gene Transfer With an AAV9 Vector Expressing Human Beta-galactosidase in Type I and Type II GM1 Gangliosidosis
NCT04093349	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Gene Transfer Study for Late-Onset Pompe Disease (RESOLUTE)
NCT01560182	PHASE1/PHASE2	COMPLETED	Gene Therapy for Metachromatic Leukodystrophy (MLD)
NCT03392987	PHASE2	COMPLETED	A Safety and Efficacy Study of Cryopreserved OTL-200 for Treatment of Metachromatic Leukodystrophy (MLD)
NCT03897361	PHASE1/PHASE2	COMPLETED	Stem Cell Gene Therapy for Cystinosis
NCT04040049	PHASE1/PHASE2	TERMINATED	A Fabry Disease Gene Therapy Study
NCT04455230	PHASE1/PHASE2	COMPLETED	A Long Term Follow-Up Study of Fabry Disease Subjects Treated With FLT190
NCT06130228	PHASE2	UNKNOWN	Nutritional Therapy in Late-onset Pompe Disease
NCT00215527	PHASE1	TERMINATED	Intrathecal Enzyme Replacement Therapy for Spinal Cord Compression in Mucopolysaccharidosis (MPS) I
NCT00744692	PHASE1	COMPLETED	Reduced Intensity Conditioning for Umbilical Cord Blood Transplant in Pediatric Patients With Non-Malignant Disorders
NCT00786968	PHASE1	TERMINATED	Extension Study of Intrathecal Enzyme Replacement Therapy for MPS I
NCT01003912	PHASE1	WITHDRAWN	Fetal Umbilical Cord Blood (UCB) Transplant for Lysosomal Storage Diseases
NCT00001215	Not specified	ENROLLING_BY_INVITATION	Genetic Studies of Lysosomal Storage Disorders
NCT03333200	Not specified	RECRUITING	Longitudinal Study of Neurodegenerative Disorders
NCT04393701	Not specified	RECRUITING	A Pilot Study for Systematic Neonatal Screening for Lysosomal Storage Diseases Using Tandem Mass Spectrometry
NCT04943991	Not specified	ACTIVE_NOT_RECRUITING	Fabry Disease in High-risk Patients With Left Ventricular Hypertrophy: Prevalence and Implementation of a Clinical Score
NCT07494058	Not specified	ACTIVE_NOT_RECRUITING	A Study of Home vs Hospital Treatment in People With Fabry, Gaucher or Hunter Conditions in Mexico
NCT00001671	Not specified	COMPLETED	The Classification and Cause of Leukodystrophies of Unknown Cause
NCT00001780	Not specified	COMPLETED	Magnetic Stimulation of the Human Nervous System
NCT00046202	Not specified	COMPLETED	Study of Inborn Errors of Cholesterol Synthesis and Related Disorders
NCT00852358	Not specified	COMPLETED	A Study of Intrathecal Enzyme Therapy for Cognitive Decline in MPS I
NCT01458613	Not specified	WITHDRAWN	Biomarker for Maroteaux-Lamy Disease (BioMaroteaux)
NCT01626092	Not specified	COMPLETED	Reduced-Intensity Hematopoietic Stem Cell Transplant for High Risk Lysosomal and Peroxisomal Disorders
NCT01963650	Not specified	TERMINATED	Natural History Study of Children With Metachromatic Leukodystrophy
NCT02000310	Not specified	UNKNOWN	Molecular and Cellular Mechanisms of Lysosomal Storage Diseases
NCT02120235	Not specified	UNKNOWN	Investigating Lysosomal Storage Diseases in Minority Groups
NCT02363153	Not specified	COMPLETED	Diet and Exercise in Pompe Disease
NCT02416661	Not specified	COMPLETED	Lyso-Gb1 as a Long-term Prognostic Biomarker in Gaucher Disease
NCT03639844	Not specified	NO_LONGER_AVAILABLE	BPX-501 T Cells Infused Post Stem Cell Transplant in Pediatrics With Non-Malignant Disorders Ineligible for BPU004 Study
NCT03812042	Not specified	UNKNOWN	Screening of Lysosomal Storage Disorders Diseases in Minority Groups
NCT03812055	Not specified	UNKNOWN	Cellular Pharmacodynamics of Small Molecules in Lysosomal Storage Disorders
NCT03853876	Not specified	TERMINATED	A Natural History Study of Aspartylglucosaminuria
NCT03893240	Not specified	COMPLETED	Neutralizing Antibody Seroprevalence Study With a Retrospective Component in Participants With Late-Onset Pompe Disease
NCT04189601	Not specified	WITHDRAWN	Complement Activation in the Lysosomal Storage Disorders
NCT04399694	Not specified	COMPLETED	Identification and Characterization of Novel Non-Coding Variants That Contribute to Genetic Disorders
NCT05431127	Not specified	COMPLETED	High Dose Inspiratory Muscle Training in LOPD

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LARONIDASE	4	3
ATIDARSAGENE AUTOTEMCEL	4	2
RITUXIMAB	4	1
RIMIDUCID	2	1
RIVOGENLECLEUCEL	2	1
BOMTABEGAGENE BAVOPARVOVEC	1	1
VANGLUSAGENE ENSIPARVOVEC	1	1