PSAP

Summary

PSAP (prosaposin, HGNC:9498) is a protein-coding gene on chromosome 10q22.1, encoding Prosaposin (P07602). Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46).

This gene encodes a highly conserved preproprotein that is proteolytically processed to generate four main cleavage products including saposins A, B, C, and D. Each domain of the precursor protein is approximately 80 amino acid residues long with nearly identical placement of cysteine residues and glycosylation sites. Saposins A-D localize primarily to the lysosomal compartment where they facilitate the catabolism of glycosphingolipids with short oligosaccharide groups. The precursor protein exists both as a secretory protein and as an integral membrane protein and has neurotrophic activities. Mutations in this gene have been associated with Gaucher disease and metachromatic leukodystrophy. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed.

Source: NCBI Gene 5660 — RefSeq curated summary.

At a glance

• Gene–disease (curated): metachromatic leukodystrophy due to saposin B deficiency (Definitive, ClinGen) — +4 more curated relationships
• Clinical variants (ClinVar): 1,004 total — 42 pathogenic, 48 likely-pathogenic
• Phenotypes (HPO): 180
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002778

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9498
Approved symbol	PSAP
Name	prosaposin
Location	10q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000197746
Ensembl biotype	protein_coding
OMIM	176801
Entrez	5660

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 37 protein_coding, 2 retained_intron

ENST00000394936, ENST00000493143, ENST00000495196, ENST00000633965, ENST00000870500, ENST00000870501, ENST00000870502, ENST00000870503, ENST00000870504, ENST00000870505, ENST00000870506, ENST00000870507, ENST00000870508, ENST00000870509, ENST00000870510, ENST00000870511, ENST00000870512, ENST00000870513, ENST00000870514, ENST00000870515, ENST00000870516, ENST00000870517, ENST00000870518, ENST00000870519, ENST00000931476, ENST00000931477, ENST00000931478, ENST00000931479, ENST00000931480, ENST00000931481, ENST00000931482, ENST00000931483, ENST00000958165, ENST00000958166, ENST00000958167, ENST00000958168, ENST00000958169, ENST00000958170, ENST00000958171

RefSeq mRNA: 3 — MANE Select: NM_002778 NM_001042465, NM_001042466, NM_002778

CCDS: CCDS7311

Canonical transcript exons

ENST00000394936 — 14 exons

Exon	Start	End
ENSE00000987088	71831126	71831251
ENSE00000987090	71828014	71828157
ENSE00000987091	71825837	71825893
ENSE00000987094	71819714	71819900
ENSE00000987095	71819465	71819622
ENSE00000987096	71819031	71819111
ENSE00000987097	71818617	71818724
ENSE00001239711	71821876	71822007
ENSE00001239733	71828877	71829077
ENSE00001239781	71834372	71834505
ENSE00001858117	71851182	71851251
ENSE00001917960	71816298	71817476
ENSE00002498004	71831846	71831920
ENSE00003561267	71820240	71820335

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1027.7168 / max 19321.1976, expressed in 1829 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109942	964.4777	1829
109943	24.3536	1808
109944	23.5349	1789
109945	9.9650	1720
109921	2.7094	1035
109911	1.5272	654
109920	1.1489	540

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.92	gold quality
mononuclear cell	CL:0000842	99.91	gold quality
leukocyte	CL:0000738	99.90	gold quality
tendon of biceps brachii	UBERON:0008188	99.89	gold quality
right adrenal gland cortex	UBERON:0035827	99.87	gold quality
gall bladder	UBERON:0002110	99.86	gold quality
medial globus pallidus	UBERON:0002477	99.85	gold quality
right adrenal gland	UBERON:0001233	99.84	gold quality
stromal cell of endometrium	CL:0002255	99.83	gold quality
tendon	UBERON:0000043	99.83	gold quality
left adrenal gland	UBERON:0001234	99.83	gold quality
visceral pleura	UBERON:0002401	99.83	gold quality
calcaneal tendon	UBERON:0003701	99.83	gold quality
adrenal cortex	UBERON:0001235	99.81	gold quality
left adrenal gland cortex	UBERON:0035825	99.81	gold quality
prefrontal cortex	UBERON:0000451	99.80	gold quality
cranial nerve II	UBERON:0000941	99.80	gold quality
right frontal lobe	UBERON:0002810	99.80	gold quality
globus pallidus	UBERON:0001875	99.79	gold quality
cerebellar cortex	UBERON:0002129	99.79	gold quality
cerebellar hemisphere	UBERON:0002245	99.79	gold quality
adrenal gland	UBERON:0002369	99.79	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.79	gold quality
islet of Langerhans	UBERON:0000006	99.78	gold quality
descending thoracic aorta	UBERON:0002345	99.78	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.78	gold quality
granulocyte	CL:0000094	99.77	gold quality
caudate nucleus	UBERON:0001873	99.77	gold quality
postcentral gyrus	UBERON:0002581	99.77	gold quality
right atrium auricular region	UBERON:0006631	99.77	gold quality

Single-cell (SCXA)

Detected in 40 experiment(s), a significant marker in 33.

Experiment	Marker?	Max mean expression
E-MTAB-7381	yes	7904.40
E-GEOD-150728	yes	7852.12
E-HCAD-13	yes	7247.44
E-MTAB-9801	yes	5336.64
E-CURD-55	yes	5224.86
E-MTAB-8498	yes	4920.19
E-HCAD-15	yes	4741.45
E-MTAB-6701	yes	3736.00
E-MTAB-7407	yes	3623.61
E-MTAB-6653	yes	3308.47
E-CURD-122	yes	3205.03
E-CURD-112	yes	3081.44
E-MTAB-8410	yes	2812.33
E-MTAB-9435	yes	2779.80
E-GEOD-139324	yes	2314.38

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, MYC, NKX2-1, NR1I2, SP1, SP3, STAT5A, STAT5B, USF1

miRNA regulators (miRDB)

59 targeting PSAP, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548G-5P	99.78	71.12	3085

Literature-anchored findings (GeneRIF, showing 40)

• reconstruction of the order of internal duplications that gave rise to the four saposins by using phylogenetic tools (PMID:11734895)
• procathepsin D interacts with prosaposin in human breast and ovarian cancer cells. (PMID:12083803)
• crystal structure reveals a dimeric shell for lipid binding (PMID:12518053)
• data indicate that saposin C is required for acid beta-glucosidase resistance to proteolytic degradation in the cell (PMID:12813057)
• The structure of saposin C compared to other saposin-fold family members provides an explanation for function variability of this protein family. (PMID:14674747)
• model proposed in which saposin C exposes lipid antigens from intralysosomal membranes for loading onto CD1b (PMID:14716313)
• There might be a potential pleuripotent regulatory function for prosaposin in prostate cancer. (PMID:15305334)
• Prosaposin and/or saposin C via modulation of caspases expression/activity and/or PI3K/Akt signaling pathway act as a survival and anti-apoptotic factor for prostate cancer cells. (PMID:15548330)
• Saposin C stimulates prostate cancer and stromal cells growth and invasion and uPA/uPAR expression, and activates p42/44 and SAPK/JNK signaling pathways of MAPK. (PMID:15897971)
• Amplification and overexpression of PSAP was studied in prostatic neoplasms. (PMID:16080200)
• The prosaposin gene is amplified in human metastatic AI PCa cell lines and punch biopsy samples of prostate cancer xenografts and lymph node metastases. (PMID:16080200)
• determination of crystal structure of human saposins A and C to 2.0 Angstroms and 2.4 Angstroms, respectively and both reveal the compact, monomeric saposin fold (PMID:16823039)
• Saposin C or its precursor (PSAP) function as an androgen-agonist and upregulate androgen receptor and prostate-specific antigen expression/activity in androgen-responsive prostate cancer cells LNCaP, TRAMP-C1 and -C2, and CWR 22RV1. (PMID:17044040)
• Prosaposin is an androgen-target gene and its expression in androgen-responsive prostate cancer cells can be upregulated by male hormones. (PMID:17171640)
• FSAP (Factor VII-activating protease) can cleave and inactivate PDGF-BB (platelet-derived growth factor-BB) and thereby inhibits VSMC (vascular smooth-muscle cell) proliferation. (PMID:17300216)
• saposin B may facilitate lipid binding to CD1d molecules throughout the endocytic pathway (PMID:17372201)
• an unglycosylated Sap-B variant, Asn215His, which causes a fatal sphingolipid storage disease, lost the ability to extract membrane lipids at acidic pH in the presence of BMP (PMID:17561962)
• Expression of saposin C-originated saposin C may upregulate AR gene expression and activate the androgen receptor transcriptional function in an androgen-independent manner in prostate cancer cells. (PMID:17712477)
• These data for the first time demonstrate that not only saposin C or PSAP regulates AR expression/activity, but also function as an androgen-regulated gene in prostate stromal cells. (PMID:18481277)
• findings point to the role of lipid rafts in the prosaposin-triggered signalling pathway, thus supporting a role for this factor as a new component of the multimolecular signalling complex involved in the neurotrophic response. (PMID:18761669)
• Saposin B(Sap B) is not a limiting factor of the coupled Sap B-arylsulfatase A reaction in mouse kidney cells even if sulfatide has accumulated to unphysiologically high levels (PMID:19224915)
• two new patients with PSAP gene defects; one, with pSap-d, who had a severe neurovisceral dystrophy and died as a neonate, and the other with SapB-d, who presented with a metachromatic leukodystrophy-like disorder but had normal arylsulfatase activity (PMID:19267410)
• Report the up-regulation of prosaposin in the senescent fibroblasts and endothelial cells. (PMID:19471889)
• Prosaposin functions in a paracrine and endocrine fashion by stimulating the expression of thrombospondin-1 (Tsp-1) in fibroblasts present in both primary tumors and distant organs, doing so in a p53-dependent manner. (PMID:19581582)
• PSAP is involved in prostate cancer invasion. (PMID:20132547)
• The biological properties of cells from four recently described Gaucher disease patients carrying mutations in the Sap C domain of the PSAP gene have been characterized. (PMID:20484222)
• saposin C caused stimulation of androgen receptor expression and activity by associations with Src kinases (PMID:21328455)
• PSAP is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• novel esophageal squamous cell carcinoma marker PSAP was identified by mass spectrometry and immunohistochemical analysis (PMID:21743296)
• PSAP is a novel TFPI-2-interacting protein and that the binding sites are the KD2 of TFPI-2 and the C-terminus of PSAP. (PMID:21943334)
• These findings suggested that prosaposin might enhance estrogen receptor alpha-mediated signaling axis and play a role in breast cancer development and progression. (PMID:22738294)
• Urine of patients with early prostate cancer contains lower levels of light chain fragments of inter-alpha-trypsin inhibitor and prosaposin fragment or saposin B. (PMID:23417432)
• Saposin C protects glucocerebrosidase against alpha-synuclein inhibition. (PMID:24070323)
• Of the 2575 proteins identified, proteins upregulated in gallbladder cancer included several lysosomal proteins such as prosaposin, cathepsin Z and cathepsin H. (PMID:24657443)
• Mesotrypsin generated saposins A-D from prosaposin, and mature caspase-14 contributed to this process by activating mesotrypsinogen to mesotrypsin. Knockdown of these proteases markedly down-regulated saposin A synthesis in skin equivalent models. (PMID:24872419)
• findings support a lung metastasis-promoting function of the miR-23b/27b/24 cluster of miRNAs, which functions in part through the direct inhibition of PSAP in breast cancer (PMID:24966325)
• Our findings suggest a novel pharmacological approach to Sap C deficiency directed to treat major secondary pathological aspects in this disorder. (PMID:25926625)
• Data suggested that the abundance of Psap in sperm sample may be a sensitive endpoint to predict PCB exposure. (PMID:26045750)
• PSAP is a secreted biomarker. (PMID:26341737)
• Prosaposin facilitates sortilin-independent lysosomal trafficking of progranulin. (PMID:26370502)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	psap	ENSDARG00000013968
mus_musculus	Psap	ENSMUSG00000004207
rattus_norvegicus	Psap	ENSRNOG00000000571

Paralogs (2): SFTPB (ENSG00000168878), PSAPL1 (ENSG00000178597)

Protein

Protein identifiers

Prosaposin — P07602 (reviewed: P07602)

Alternative names: Proactivator polypeptide

All UniProt accessions (2): A0A0J9YXB8, P07602

UniProt curated annotations — full annotation on UniProt →

Function. Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently acts by combining with the enzyme and acidic lipid to form an activated complex, rather than by solubilizing the substrate. Saposin-B stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases. Saposin-D is a specific sphingomyelin phosphodiesterase activator (EC 3.1.4.12). Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosphorylation signaling. Saposins are specific low-molecular mass non-enzymic proteins, they participate in the lysosomal degradation of sphingolipids, which takes place by the sequential action of specific hydrolases.

Subunit / interactions. Saposin-B is a homodimer. Prosaposin exists as a roughly half-half mixture of monomers and disulfide-linked dimers. Monomeric prosaposin interacts (via C-terminus) with sortilin/SORT1, the interaction is required for targeting to lysosomes. Interacts with GRN; facilitates lysosomal delivery of progranulin from the extracellular space and the biosynthetic pathway.

Subcellular location. Lysosome Secreted.

Post-translational modifications. The lysosomal precursor is proteolytically processed to 4 small peptides, which are similar to each other and are sphingolipid hydrolase activator proteins. N-linked glycans show a high degree of microheterogeneity. The one residue extended Saposin-B-Val is only found in 5% of the chains.

Disease relevance. Combined saposin deficiency (PSAPD) [MIM:611721] An autosomal recessive storage disorder characterized by hepatosplenomegaly and severe neurologic disease, due to absence of all saposins. PSAPD has a fatal outcome in infancy. The disease is caused by variants affecting the gene represented in this entry. Metachromatic leukodystrophy due to saposin B deficiency (MLDSAPB) [MIM:249900] A form of metachromatic leukodystrophy biochemically characterized by tissue accumulation of cerebroside-3-sulfate, saposin B deficiency, and normal arylsulfatase A activity. Clinical manifestations include periventricular white matter abnormalities, demyelination, and peripheral neuropathy. Additional neurological features include dysarthria, ataxic gait, psychomotor regression, seizures, cognitive decline and spastic quadriparesis. The disease is caused by variants affecting the gene represented in this entry. Gaucher disease, atypical, due to saposin C deficiency (GDSAPC) [MIM:610539] A disease characterized by marked glucosylceramide accumulation in the spleen without having a deficiency of glucosylceramide-beta glucosidase characteristic of classic Gaucher disease. Gaucher disease is a lysosomal storage disorder characterized by skeletal deterioration, hepatosplenomegaly, and organ dysfunction. There are several subtypes based on the presence and severity of neurological involvement. The disease is caused by variants affecting the gene represented in this entry. Krabbe disease, atypical, due to saposin A deficiency (KRBSAPA) [MIM:611722] An autosomal recessive disorder of galactosylceramide metabolism. Clinical features include neurologic regression around age 3 months, loss of spontaneous movements, hyporeflexia, generalized brain atrophy, and diffuse white matter dysmyelination. The disease is caused by variants affecting the gene represented in this entry. Defects in PSAP saposin-D region are found in a variant of Tay-Sachs disease (GM2-gangliosidosis). Parkinson disease 24, autosomal dominant (PARK24) [MIM:619491] An autosomal dominant form of Parkinson disease, a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. PARK24 shows incomplete penetrance. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Miscellaneous. Saposin-B co-purifies with 1 molecule of phosphatidylethanolamine.

Isoforms (3)

UniProt ID	Names	Canonical?
P07602-1	Sap-mu-0	yes
P07602-2	Sap-mu-6
P07602-3	Sap-mu-9

RefSeq proteins (3): NP_001035930, NP_001035931, NP_002769* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003119	SAP_A	Domain
IPR007856	SapB_1	Domain
IPR008138	SapB_2	Domain
IPR008139	SaposinB_dom	Domain
IPR008373	Saposin	Family
IPR011001	Saposin-like	Homologous_superfamily
IPR021165	Saposin_chordata	Family
IPR051428	Sphingo_Act-Surfact_Prot	Family

Pfam: PF02199, PF03489, PF05184

UniProt features (71 total): helix 20, disulfide bond 12, sequence variant 9, chain 6, domain 6, propeptide 5, glycosylation site 5, splice variant 2, signal peptide 1, site 1, mutagenesis site 1, sequence conflict 1, strand 1, turn 1

Structure

Experimental structures (PDB)

20 structures.

PDB	Method	Resolution (Å)
3BQP	X-RAY DIFFRACTION	1.3
9I63	X-RAY DIFFRACTION	1.65
4UEX	X-RAY DIFFRACTION	1.8
4DDJ	X-RAY DIFFRACTION	1.9
2DOB	X-RAY DIFFRACTION	2
3BQQ	X-RAY DIFFRACTION	2
2RB3	X-RAY DIFFRACTION	2.1
4V2O	X-RAY DIFFRACTION	2.13
1N69	X-RAY DIFFRACTION	2.2
6SLR	X-RAY DIFFRACTION	2.38
2GTG	X-RAY DIFFRACTION	2.4
2QYP	X-RAY DIFFRACTION	2.45
2R0R	X-RAY DIFFRACTION	2.5
2R1Q	X-RAY DIFFRACTION	2.5
2Z9A	X-RAY DIFFRACTION	2.5
9AXG	X-RAY DIFFRACTION	2.68
8EQU	ELECTRON MICROSCOPY	2.8
9AVS	X-RAY DIFFRACTION	3.53
1M12	SOLUTION NMR
1SN6	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07602-F1	73.90	0.17

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 215 (not glycosylated; in variant mldsapb ile-217)

Disulfide bonds (12): 63–138, 66–132, 94–106, 198–271, 201–265, 230–241, 315–388, 318–382, 346–357, 409–482, 412–476, 440–451

Glycosylation sites (5): 80, 101, 215, 332, 426

Mutagenesis-validated functional residues (1):

Position	Phenotype
240	strongly decreases stimulation of cerebroside sulfate hydrolysis.

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-418594	G alpha (i) signalling events
R-HSA-6798695	Neutrophil degranulation
R-HSA-9840310	Glycosphingolipid catabolism
R-HSA-109582	Hemostasis
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-1660662	Glycosphingolipid metabolism
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-428157	Sphingolipid metabolism
R-HSA-500792	GPCR ligand binding
R-HSA-556833	Metabolism of lipids
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+

MSigDB gene sets: 685 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_LYSOSOMAL_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_GROWTH, HSIAO_HOUSEKEEPING_GENES, GOBP_VACUOLAR_TRANSPORT, KEGG_LYSOSOME, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, MARTINEZ_RB1_TARGETS_UP

GO Biological Process (11): sphingolipid metabolic process (GO:0006665), lysosomal transport (GO:0007041), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), gene expression (GO:0010467), regulation of autophagy (GO:0010506), regulation of lipid metabolic process (GO:0019216), prostate gland growth (GO:0060736), epithelial cell differentiation involved in prostate gland development (GO:0060742), ganglioside GM1 transport to membrane (GO:1905572), lipid metabolic process (GO:0006629), positive regulation of beta-galactosidase activity (GO:1903771)

GO Molecular Function (13): protease binding (GO:0002020), phospholipid binding (GO:0005543), enzyme activator activity (GO:0008047), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), scaffold protein binding (GO:0097110), ganglioside GM1 binding (GO:1905573), ganglioside GM2 binding (GO:1905574), ganglioside GM3 binding (GO:1905575), ganglioside GT1b binding (GO:1905576), ganglioside GP1c binding (GO:1905577), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (10): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), lysosome (GO:0005764), lysosomal membrane (GO:0005765), late endosome (GO:0005770), plasma membrane (GO:0005886), azurophil granule membrane (GO:0035577), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Signaling by GPCR	2
Response to elevated platelet cytosolic Ca2+	1
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
Innate Immune System	1
Glycosphingolipid metabolism	1
Sphingolipid metabolism	1
Immune System	1
Signal Transduction	1
GPCR ligand binding	1
Metabolism of lipids	1
Metabolism	1
Hemostasis	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ganglioside binding	5
carboxylic acid binding	4
lipid metabolic process	2
developmental process involved in reproduction	2
prostate gland development	2
protein binding	2
binding	2
cellular anatomical structure	2
lysosome	2
vacuolar transport	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
macromolecule biosynthetic process	1
autophagy	1
regulation of catabolic process	1
regulation of primary metabolic process	1
organ growth	1
epithelial cell differentiation	1
ceramide transport	1
glycolipid transport	1
carboxylic acid transport	1
localization within membrane	1
primary metabolic process	1
beta-galactosidase activity	1
positive regulation of hydrolase activity	1
enzyme binding	1
lipid binding	1
catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
identical protein binding	1
protein dimerization activity	1
monocarboxylic acid binding	1
lytic vacuole	1
lytic vacuole membrane	1
endosome	1
membrane	1
cell periphery	1
lysosomal membrane	1
secretory granule membrane	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

70 interactions, top by confidence:

A	B	Type	Score
GRN	PSAP	psi-mi:“MI:0915”(physical association)	0.700
GRN	PSAP	psi-mi:“MI:0407”(direct interaction)	0.700
GRN	PSAP	psi-mi:“MI:0403”(colocalization)	0.700
PSAP	GRN	psi-mi:“MI:0403”(colocalization)	0.700
ZBED1	PSAP	psi-mi:“MI:0915”(physical association)	0.670
FGL1	LCMT2	psi-mi:“MI:0914”(association)	0.640
PSAP	PEX5	psi-mi:“MI:0915”(physical association)	0.560
PSAP	APPBP2	psi-mi:“MI:0915”(physical association)	0.560
PSAP	CSNK1D	psi-mi:“MI:0915”(physical association)	0.560
PSAP	LYN	psi-mi:“MI:0915”(physical association)	0.560
APP	PSAP	psi-mi:“MI:0915”(physical association)	0.560
GPIHBP1	ADAM10	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
CASP14	PSAP	psi-mi:“MI:0915”(physical association)	0.470
CASP14	PSAP	psi-mi:“MI:2364”(proximity)	0.470
PSAP	SMAD2	psi-mi:“MI:0915”(physical association)	0.370
PSAP	SMAD9	psi-mi:“MI:0915”(physical association)	0.370
PSAP	UBE3A	psi-mi:“MI:0915”(physical association)	0.370
ERBB2	PSAP	psi-mi:“MI:0915”(physical association)	0.370
CFTR	SNHG32	psi-mi:“MI:0914”(association)	0.350
SOD1	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
GRN	OPA1	psi-mi:“MI:0914”(association)	0.350
PSAP	Otud4	psi-mi:“MI:0914”(association)	0.350

BioGRID (147): PSAP (Two-hybrid), PSAP (Two-hybrid), PSAP (Affinity Capture-MS), PSAP (Two-hybrid), PSAP (Affinity Capture-MS), AK2 (Co-fractionation), AK4 (Co-fractionation), C21orf33 (Co-fractionation), FXN (Co-fractionation), GABARAPL2 (Co-fractionation), GLRX5 (Co-fractionation), GUK1 (Co-fractionation), HINT1 (Co-fractionation), ISCA2 (Co-fractionation), MSRB3 (Co-fractionation)

ESM2 similar proteins: F1R520, O13035, O18823, O35298, O70367, O75829, O77770, O94985, P02771, P02774, P04276, P05067, P07602, P08592, P0C5H9, P0C5I0, P10960, P12023, P17129, P17404, P20097, P21614, P26779, P28039, P28050, P49066, P53601, P53789, P55145, P79307, P80513, P81405, Q02391, Q28789, Q3SZ57, Q49AH0, Q5IS80, Q60495, Q61207, Q61543

Diamond homologs: O13035, P07602, P07988, P10960, P20097, P26779, P81405, Q61207, Q6NUJ1, Q8C1C1, O65390, P40782, P42210, P15285, P15781, P15782, P17129, P22355, P50405, O04057, P42211, Q42456, Q8VYL3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TFEB	“up-regulates quantity by expression”	PSAP	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

1004 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	42
Likely pathogenic	48
Uncertain significance	297
Likely benign	472
Benign	49

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070932	NM_002778.4(PSAP):c.1120del (p.Glu374fs)	Pathogenic
1300259	NM_002778.4(PSAP):c.209T>G (p.Val70Gly)	Pathogenic
13364	NM_002778.4(PSAP):c.1145G>T (p.Cys382Phe)	Pathogenic
13365	NM_002778.4(PSAP):c.1A>T (p.Met1Leu)	Pathogenic
13366	NM_002778.4(PSAP):c.577-1G>T	Pathogenic
13368	NM_002778.4(PSAP):c.794del (p.Cys265fs)	Pathogenic
13370	NM_002778.4(PSAP):c.1144T>G (p.Cys382Gly)	Pathogenic
13371	NM_002778.4(PSAP):c.1288C>T (p.Gln430Ter)	Pathogenic
13374	NM_002778.4(PSAP):c.577-2A>G	Pathogenic
1366889	NC_000010.10:g.(?73587761)(73588844_?)del	Pathogenic
1382238	NM_002778.4(PSAP):c.83del (p.Gly28fs)	Pathogenic
1399943	NM_002778.4(PSAP):c.299_315del (p.Pro100fs)	Pathogenic
1412783	NC_000010.10:g.(?73610929)(73610988_?)del	Pathogenic
1438752	NM_002778.4(PSAP):c.670G>T (p.Glu224Ter)	Pathogenic
1455040	NM_002778.4(PSAP):c.889G>T (p.Glu297Ter)	Pathogenic
1455762	NM_002778.4(PSAP):c.1204C>T (p.Gln402Ter)	Pathogenic
1676842	NM_002778.4(PSAP):c.721T>G (p.Cys241Gly)	Pathogenic
1989545	NM_002778.4(PSAP):c.1050dup (p.Lys351fs)	Pathogenic
1993070	NM_002778.4(PSAP):c.527dup (p.Leu177fs)	Pathogenic
2005872	NM_002778.4(PSAP):c.1340dup (p.Tyr447Ter)	Pathogenic
2007832	NM_002778.4(PSAP):c.555_556dup (p.Arg186fs)	Pathogenic
2026090	NM_002778.4(PSAP):c.457C>T (p.Gln153Ter)	Pathogenic
2122068	NM_002778.4(PSAP):c.723_726del (p.Ile240_Cys241insTer)	Pathogenic
2126174	NM_002778.4(PSAP):c.100del (p.Gln34fs)	Pathogenic
2424541	NC_000010.10:g.(?73578585)(73581640_?)del	Pathogenic
2582396	NM_002778.4(PSAP):c.1192+1G>A	Pathogenic
2694009	NM_002778.4(PSAP):c.785_788del (p.Lys262fs)	Pathogenic
2709568	NM_002778.4(PSAP):c.202del (p.Asp68fs)	Pathogenic
2735420	NM_002778.4(PSAP):c.148C>T (p.Gln50Ter)	Pathogenic
2763225	NM_002778.4(PSAP):c.1402del (p.Glu468fs)	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3471 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:71818648:C:G	C503S	0.997
10:71818649:A:T	C503S	0.997
10:71834387:C:A	W53C	0.997
10:71834387:C:G	W53C	0.997
10:71817463:C:G	C518S	0.996
10:71817464:A:T	C518S	0.996
10:71818621:C:G	C512S	0.996
10:71818622:A:T	C512S	0.996
10:71817447:C:A	W523C	0.995
10:71817447:C:G	W523C	0.995
10:71817462:G:C	C518W	0.995
10:71817463:C:T	C518Y	0.995
10:71819580:C:T	C412Y	0.994
10:71831220:C:T	C94Y	0.994
10:71834402:G:C	C48W	0.994
10:71834403:C:G	C48S	0.994
10:71834404:A:T	C48S	0.994
10:71834448:C:G	C33S	0.994
10:71834449:A:T	C33S	0.994
10:71818650:C:A	W502C	0.993
10:71818650:C:G	W502C	0.993
10:71819036:A:G	C476R	0.993
10:71819496:C:G	C440S	0.993
10:71819497:A:T	C440S	0.993
10:71819581:A:G	C412R	0.993
10:71821991:C:T	C265Y	0.993
10:71821992:A:G	C265R	0.993
10:71817463:C:A	C518F	0.992
10:71818622:A:G	C512R	0.992
10:71819035:C:G	C476S	0.992

dbSNP variants (sampled 300 via entrez): RS1000104926 (10:71827135 G>A), RS1000205470 (10:71827446 G>A), RS1000259446 (10:71820824 C>A), RS1000358595 (10:71852596 T>C), RS1000394728 (10:71843054 C>T), RS1000507265 (10:71817032 C>A,G), RS1000539973 (10:71849868 A>C), RS1000677901 (10:71844482 A>G), RS1000684719 (10:71842033 C>T), RS1000685192 (10:71849247 T>C), RS1000729927 (10:71844208 A>C,T), RS1000736608 (10:71842237 C>G), RS1000871253 (10:71833148 G>C,T), RS1000894483 (10:71836257 T>G), RS1000909848 (10:71850127 C>T)

Disease associations

OMIM: gene MIM:176801 | disease phenotypes: MIM:249900, MIM:611721, MIM:619491, MIM:611722, MIM:610539, MIM:245200, MIM:168600

GenCC curated gene-disease

Disease	Classification	Inheritance
Krabbe disease due to saposin A deficiency	Definitive	Autosomal recessive
metachromatic leukodystrophy due to saposin B deficiency	Strong	Autosomal recessive
Gaucher disease due to saposin C deficiency	Strong	Autosomal recessive
combined PSAP deficiency	Strong	Autosomal recessive
Parkinson disease 24, autosomal dominant, susceptibility to	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (4)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
metachromatic leukodystrophy due to saposin B deficiency	Definitive	AR
Krabbe disease due to saposin A deficiency	Moderate	AR
Gaucher disease due to saposin C deficiency	Definitive	AR
combined PSAP deficiency	Definitive	AR

Mondo (9): metachromatic leukodystrophy due to saposin B deficiency (MONDO:0009590), metachromatic leukodystrophy (MONDO:0018868), combined PSAP deficiency (MONDO:0012719), Parkinson disease 24, autosomal dominant, susceptibility to (MONDO:0859183), Krabbe disease due to saposin A deficiency (MONDO:0012720), Gaucher disease due to saposin C deficiency (MONDO:0012517), Krabbe disease (MONDO:0009499), neuromuscular disease (MONDO:0019056), late-onset Parkinson disease (MONDO:0008199)

Orphanet (7): Metachromatic leukodystrophy (Orphanet:512), Encephalopathy due to prosaposin deficiency (Orphanet:139406), Krabbe disease (Orphanet:487), Atypical Gaucher disease due to saposin C deficiency (Orphanet:309252), Gaucher disease (Orphanet:355), Neuromuscular disease (Orphanet:68381), Hereditary late-onset Parkinson disease (Orphanet:411602)

HPO phenotypes

180 total (30 of 180 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000365	Hearing impairment
HP:0000467	Neck muscle weakness
HP:0000496	Abnormality of eye movement
HP:0000508	Ptosis
HP:0000545	Myopia
HP:0000572	Visual loss
HP:0000602	Ophthalmoplegia
HP:0000605	Supranuclear gaze palsy
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000648	Optic atrophy
HP:0000649	Abnormality of visual evoked potentials
HP:0000666	Horizontal nystagmus
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000726	Dementia
HP:0000736	Short attention span
HP:0000737	Irritability
HP:0000738	Hallucinations
HP:0000746	Delusion
HP:0000762	Decreased nerve conduction velocity
HP:0000938	Osteopenia
HP:0001053	Hypopigmented skin patches
HP:0001082	Cholecystitis
HP:0001188	Hand clenching

GWAS associations

0 associations (top):

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D007965	Leukodystrophy, Globoid Cell	C10.228.140.163.100.362.500; C10.228.140.163.100.435.825.590; C10.228.140.695.625.500; C10.314.400.500; C16.320.565.189.362.500; C16.320.565.189.435.825.590; C16.320.565.398.641.803.585; C16.320.565.595.554.825.590; C18.452.132.100.362.500; C18.452.132.100.435.825.590; C18.452.584.563.641.803.585; C18.452.648.189.362.500; C18.452.648.189.435.825.590; C18.452.648.398.641.803.585; C18.452.648.595.554.825.590
D007966	Leukodystrophy, Metachromatic	C10.228.140.163.100.362.550; C10.228.140.163.100.435.825.850.500; C10.228.140.695.625.550; C10.314.400.550; C16.320.565.189.362.550; C16.320.565.189.435.825.850.500; C16.320.565.398.641.803.925.500; C16.320.565.595.554.825.850.500; C18.452.132.100.362.550; C18.452.132.100.435.825.850.500; C18.452.584.563.641.803.925.500; C18.452.648.189.362.550; C18.452.648.189.435.825.850.500; C18.452.648.398.641.803.925.500; C18.452.648.595.554.825.850.500
D009468	Neuromuscular Diseases	C10.668
C567125	Combined Saposin Deficiency (supp.)
C566435	Gaucher Disease, Atypical, Due To Saposin C Deficiency (supp.)
C567097	Krabbe Disease, Atypical, due to Saposin A Deficiency (supp.)
C562609	Metachromatic Leukodystrophy due to Saposin B Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3580523 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 23,935 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL7301	FENRETINIDE	3	23,935

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.16	Kd	6900	nM	FENRETINIDE

PubChem BioAssay actives

2 with measured affinity, of 8 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2E,4E,6E,8E)-N-(4-hydroxyphenyl)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenamide	1695703: Binding affinity to human saposin D (1 to 81 residues) expressed in Escherichia coli at 25 degree C by electronic absorption spectroscopy	kd	6.9000	uM

CTD chemical–gene interactions

66 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment, increases abundance, affects expression, decreases expression	4
Valproic Acid	affects expression, increases expression	4
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance	2
Acetaminophen	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression	2
ginger extract	affects cotreatment, affects expression, increases abundance	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
glycidyl methacrylate	decreases expression	1
sodium arsenate	decreases expression	1
titanium dioxide	affects binding, increases expression	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	increases expression	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
tetrabromobisphenol A	increases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
octa-2,4,6-trienoic acid	increases expression	1
yessotoxin	increases expression	1
chloropicrin	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
LG 100815	increases expression	1

ChEMBL screening assays

12 unique, capped per target: 8 binding, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3585104	ADMET	Binding affinity to human saposin B expressed in Escherichia coli BL21 Gold (DE3) at 120 uM using 15 uM sapB and 50 mM MES and 4% THF at pH 5.5 and 25 degC by ITC method	The antimalarial drug atovaquone binds to saposin B with comparable affinity to coenzyme Q10 — Medchemcomm
CHEMBL4700523	Binding	Binding affinity to human saposin D (1 to 81 residues) expressed in Escherichia coli assessed as decrease in BODIPY-TR labeled ceramide solubilization in sodium phosphate buffer measured after 30 mins by fluorescence assay	Fenretinide binding to the lysosomal protein saposin D alters ceramide solubilization and hydrolysis — RSC Med Chem

Cellosaurus cell lines

6 cell lines: 4 cancer cell line, 1 transformed cell line, 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2CB	Abcam HeLa PSAP KO	Cancer cell line	Female
CVCL_D5F6	HeLa::TMEM192-3xHA PSAP KO	Cancer cell line	Female
CVCL_D9PW	Ubigene HEK293 PSAP KO	Transformed cell line	Female
CVCL_E2I1	HAP1 PSAP (-) 1	Cancer cell line	Male
CVCL_E2I2	HAP1 PSAP (-) 2	Cancer cell line	Male
CVCL_F0Q2	H9 AAVS1-TRE3G-NGN2 TMEM192-3xHA (heterozygous) PSAP-/-	Embryonic stem cell	Female

Clinical trials (associated diseases)

243 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00331656	PHASE4	UNKNOWN	Comparative Study of Non-Invasive Mask Ventilation vs Cuirass Ventilation in Patients With Acute Respiratory Failure.
NCT00994552	PHASE4	UNKNOWN	Comparison of Pressure Support and Pressure Control Ventilation in Chronic Respiratory Failure
NCT04283227	PHASE3	ACTIVE_NOT_RECRUITING	OTL-200 in Patients With Late Juvenile Metachromatic Leukodystrophy (MLD)
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00942227	PHASE3	COMPLETED	The Value of Traction in Treatment of Lumbar Radiculopathy
NCT00979108	PHASE3	COMPLETED	The Value of Traction in the Treatment of Cervical Radiculopathy
NCT01826487	PHASE3	COMPLETED	Phase 3 Study of Ataluren in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)
NCT02090959	PHASE3	TERMINATED	An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy
NCT02436096	PHASE3	COMPLETED	A Study to Evaluate eFFIcacy and Safety of Sublingual TNX-102 SL Tablet Taken at Bedtime in Patients With fibRoMyalgia
NCT02829814	PHASE3	TERMINATED	Repeat of: A Study to Evaluate Efficacy and Safety of Sublingual TNX-102 SL Tablet Taken at Bedtime in Patients With Fibromyalgia
NCT03179631	PHASE3	COMPLETED	Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy
NCT05126758	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Deramiocel (CAP-1002) in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT05156320	PHASE3	COMPLETED	Efficacy and Safety of Apitegromab in Patients With Later-Onset Spinal Muscular Atrophy Treated With Nusinersen or Risdiplam
NCT05337553	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy
NCT05626855	PHASE3	ACTIVE_NOT_RECRUITING	Long-Term Safety & Efficacy of Apitegromab in Patients With SMA Who Completed Previous Trials of Apitegromab
NCT06672237	PHASE3	RECRUITING	A Phase 3 Study of NTLA-2001 in ATTRv-PN
NCT00383448	PHASE2	COMPLETED	HSCT for High Risk Inherited Inborn Errors
NCT01043640	PHASE2	COMPLETED	Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders
NCT01303146	PHASE2	COMPLETED	Efficacy METAZYM for the Treatment Metachromatic Leukodystrophy Treated With Hematopoietic Stem Cell Transplantation
NCT02171104	PHASE2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT03392987	PHASE2	COMPLETED	A Safety and Efficacy Study of Cryopreserved OTL-200 for Treatment of Metachromatic Leukodystrophy (MLD)
NCT03771898	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Intrathecal SHP611 in Children With Metachromatic Leukodystrophy
NCT00668564	PHASE2	TERMINATED	Hematopoietic Stem Cell Transplantation (HCT) for Inborn Errors of Metabolism
NCT01074359	PHASE2	TERMINATED	Safety and Efficacy Study of A0001 in Patients With the A3243G Mitochondrial DNA Point Mutation
NCT01371149	PHASE2	COMPLETED	Patient -Ventilator Interaction in Chronic Respiratory Failure
NCT02022072	PHASE2	TERMINATED	Evaluation of Vital Capacity
NCT03127514	PHASE2	COMPLETED	AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT03406780	PHASE2	COMPLETED	A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT03921528	PHASE2	COMPLETED	An Active Treatment Study of SRK-015 in Patients With Type 2 or Type 3 Spinal Muscular Atrophy
NCT05479981	PHASE2	COMPLETED	Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients
NCT06339580	PHASE2	RECRUITING	Assessment of Volume-targeted Ventilation in Patients With Neuromuscular Disease
NCT07071935	PHASE2	NOT_YET_RECRUITING	A Clinical Trial of Early Ventilation in Amyotrophic Lateral Sclerosis (EVENT ALS)
NCT07287189	PHASE2	RECRUITING	Phase 2 Study of SAT-3247 in Pediatric Ambulatory Patients
NCT00418561	PHASE1	COMPLETED	Metazym for the Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD)
NCT01586455	PHASE1	COMPLETED	Human Placental-Derived Stem Cell Transplantation
NCT00252252	PHASE1	COMPLETED	AutoVPAP Versus VPAP; Assessment of Sleep and Ventilation
NCT01560741	PHASE1	UNKNOWN	Telemedicine and Ventilator Titration in Chronic Respiratory Patients Initiating Non-invasive Ventilation
NCT01621984	PHASE1	COMPLETED	Therapeutic Riding and Neuromuscular Disease
NCT01758510	PHASE1	COMPLETED	Safety Study of HLA-haplo Matched Allogenic Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral Sclerosis
NCT03440034	PHASE1	COMPLETED	Study of Pioglitazone in Sporadic Inclusion Body Myositis