SGPL1

Summary

SGPL1 (sphingosine-1-phosphate lyase 1, HGNC:10817) is a protein-coding gene on chromosome 10q22.1, encoding Sphingosine-1-phosphate lyase 1 (O95470). Cleaves phosphorylated sphingoid bases (PSBs), such as sphingosine-1-phosphate, into fatty aldehydes and phosphoethanolamine.

Enables sphinganine-1-phosphate aldolase activity. Involved in apoptotic signaling pathway; fatty acid metabolic process; and sphingolipid metabolic process. Located in endoplasmic reticulum. Implicated in nephrotic syndrome type 14.

Source: NCBI Gene 8879 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nephrotic syndrome 14 (Definitive, ClinGen)
• GWAS associations: 7
• Clinical variants (ClinVar): 377 total — 20 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 36
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003901

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10817
Approved symbol	SGPL1
Name	sphingosine-1-phosphate lyase 1
Location	10q22.1
Locus type	gene with protein product
Status	Approved
Aliases	SPL
Ensembl gene	ENSG00000166224
Ensembl biotype	protein_coding
OMIM	603729
Entrez	8879

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 11 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000299297, ENST00000373202, ENST00000409118, ENST00000486993, ENST00000611290, ENST00000613857, ENST00000620724, ENST00000697924, ENST00000697925, ENST00000697926, ENST00000697927, ENST00000697928, ENST00000697929, ENST00000697930, ENST00000697931, ENST00000697932, ENST00000697988, ENST00000697989, ENST00000697990

RefSeq mRNA: 1 — MANE Select: NM_003901 NM_003901

CCDS: CCDS31216

Canonical transcript exons

ENST00000373202 — 15 exons

Exon	Start	End
ENSE00003972214	70868345	70868433
ENSE00003972217	70869792	70869897
ENSE00003972220	70873351	70873589
ENSE00003972223	70844473	70844638
ENSE00003972226	70851143	70851210
ENSE00003972228	70857614	70857690
ENSE00003972232	70876541	70876661
ENSE00003972233	70815948	70816126
ENSE00003972236	70859371	70859499
ENSE00003972238	70854708	70854855
ENSE00003972240	70871837	70871986
ENSE00003972242	70875402	70875548
ENSE00003972243	70816811	70816880
ENSE00003972244	70871048	70871146
ENSE00003972594	70877195	70881184

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 96.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.5280 / max 283.5309, expressed in 1797 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105400	17.0327	1794
105401	0.2612	96
105404	0.2342	109

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	96.47	gold quality
epithelium of esophagus	UBERON:0001976	95.64	gold quality
upper leg skin	UBERON:0004262	94.14	gold quality
squamous epithelium	UBERON:0006914	93.72	gold quality
lower esophagus mucosa	UBERON:0035834	93.33	gold quality
gingival epithelium	UBERON:0001949	93.08	gold quality
sural nerve	UBERON:0015488	92.44	gold quality
gingiva	UBERON:0001828	92.28	gold quality
ventricular zone	UBERON:0003053	92.23	gold quality
upper arm skin	UBERON:0004263	92.07	gold quality
germinal epithelium of ovary	UBERON:0001304	91.91	gold quality
islet of Langerhans	UBERON:0000006	91.83	gold quality
secondary oocyte	CL:0000655	91.45	gold quality
epithelium of nasopharynx	UBERON:0001951	91.29	gold quality
nasopharynx	UBERON:0001728	91.28	gold quality
skin of leg	UBERON:0001511	91.19	gold quality
adrenal tissue	UBERON:0018303	91.09	gold quality
ganglionic eminence	UBERON:0004023	90.96	gold quality
zone of skin	UBERON:0000014	90.85	gold quality
skin of abdomen	UBERON:0001416	90.75	gold quality
jejunal mucosa	UBERON:0000399	90.46	gold quality
esophagus mucosa	UBERON:0002469	90.45	gold quality
oocyte	CL:0000023	90.40	gold quality
nasal cavity epithelium	UBERON:0005384	90.14	gold quality
ileal mucosa	UBERON:0000331	89.99	gold quality
endometrium	UBERON:0001295	89.82	gold quality
bronchial epithelial cell	CL:0002328	89.76	gold quality
pancreas	UBERON:0001264	89.67	gold quality
palpebral conjunctiva	UBERON:0001812	89.62	gold quality
urinary bladder	UBERON:0001255	89.55	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7381	yes	632.50
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, GATA4, POU3F2, POU4F1, SP1, TFE3

miRNA regulators (miRDB)

146 targeting SGPL1, 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-8485	100.00	77.57	4731
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354

Literature-anchored findings (GeneRIF, showing 39)

• sphingosine-1-phosphate lyase is a dual modulator of sphingosine 1-phosphate and ceramide metabolism as well as a regulator of cell fate decisions (PMID:14570870)
• genetic or epigenetic changes affecting intestinal sphingosine-1-phosphate metabolism may correlate with and potentially contribute to carcinogenesis (PMID:17090686)
• extracellular S1P is dephosphorylated and subsequently converted by cells, which appears to be important for clearance of the signaling molecule S1P in the local tissue environment after infections or injuries (PMID:18172856)
• Data suggest that lymphocyte trafficking is particularly sensitive to variations in sphingosine 1-phosphate lyase (S1PL) activity and suggest that there is a window in which partial inhibition of S1PL could produce therapeutic levels of immunosuppression. (PMID:19119317)
• Overexpression of sphingosine 1-phosphate lyase (SPL), which induces the degradation of sphingosine 1-phosphate, interfered with the amplification of infectious influenza virus. (PMID:20519401)
• high SPL transcription of H1155 cells was regulated by Sp1 and GATA-4/Sp1 complex formation, both of which bind to Sp1 sites of the 5’-SPL promoter. (PMID:21184844)
• S1P(ext) mediated endothelial cell motility is dependent on intracellular S1P production, which is regulated, in part, by SphK1 and S1PL. (PMID:21304987)
• S1P lyase regulates DNA damage responses through a sphingolipid feedback mechanism. (PMID:21368890)
• SPL expression and activity are downregulated in cancerous tissues, there is a relationship between loss of SPL expression and prostate cancer aggressiveness. (PMID:22784711)
• Data show that a easy assay for 2-hydroxyacyl-CoA lyase (HACL1) and sphingosine-1-phosphate lyase (SGPL1) activities was developed. (PMID:24323699)
• results highlight the importance of S1P in AD suggesting the existence of a global deregulation of S1P signaling in this disease from its synthesis by SphK1 and degradation by SPL to its signaling by the S1P1 receptor. (PMID:24468113)
• S1P lyase - by facilitating S1P1 receptor recycling - is essential for S1P-mediated sustained signaling (PMID:24704119)
• The cells expressing SGPL1 in the parenchyma were CD68(+) APCs. (PMID:24825162)
• Sphingosine-1-phosphate lyase downregulation promotes colon carcinogenesis through STAT3-activated microRNAs. (PMID:25347472)
• Results show that dissociation of SHP-1 from spinophilin is followed by an increase in the binding of spinophilin to PP1. (PMID:25785436)
• SPHK1:SGPL1 ratio correlated with increased cellular sphingosine-1-phosphate (S1P), and S1P correlated with drug resistance (IC50). (PMID:26493335)
• increased SK and SPL mRNA expression along with reduced sphingosine 1-phosphate levels were more commonly observed in hepatocellular carcinoma tissues. (PMID:26886371)
• Data show that sphingosine kinase 1 (SPHK1) was significantly upregulated in oral squamous cell carcinoma (OSCC) tissues and low levels of sphingosine-1-phosphate lyase 1 (SGPL1) mRNA correlated with a worse overall survival, and that sphingosine-1-phosphate receptor 2 (S1PR2) is over-expressed in a subset of tumours, which in part mediates sphingosine 1-phosphate (S1P)-induced migration of OSCC cells. (PMID:27160553)
• Overexpression of sphingosine-1-phosphate lyase 1 (SGPL1), reverse the interleukin-8 (IL-8) secretion enhancing effect of microRNA miR-125b in trophoblast cell line HTR8/SVneo cells. (PMID:27935985)
• Report a candidate gene (SGPL1) for autosomal recessive Charcot-Marie-Tooth disease with atypical disease course. Studies in patient-derived biosamples suggested that this phenotype is due to partial loss of SGPL1 function. Neuron-specific downregulation of the Drosophila orthologue impaired the morphology of the neuromuscular junction and caused progressive neurodegeneration (PMID:28077491)
• Exposure to the combination of 100 muM genistein and 10 nM calcitriol reduced the number of proliferative cells to control levels, increased ERb and VDR expression, and reduced extracellular acidification (40%) as well as respiratory activity (70%), primarily in MG-63 cells..strong overexpression SGPL1, which irreversibly degrades sphingosine-1-phosphate thereby, generating ethanolamine (PMID:28125641)
• Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency (PMID:28165339)
• Sphingosine-1-phosphate lyase mutations cause primary adrenal insufficiency and steroid-resistant nephrotic syndrome. (PMID:28165343)
• Loss of SGPL1 function is associated with congenital nephrotic syndrome (CNS), adrenal calcifications, and hypogonadism. (PMID:28181337)
• results demonstrate that Sphingosine 1-phosphate lyase (SPL) is a host factor that augments type I IFN responses during influenza A virus infection; study delineates the relationship between IKKepsilon and SPL, which provides a mechanistic understanding of the pro-IFN activity of SPL (PMID:28600291)
• High SGPL1 expression is associated with Huntington’s disease. (PMID:28706199)
• Study verifies the role of a high-ranked gene in dysregulation of sphingolipid metabolism in the disease and demonstrate that inhibiting the enzyme, sphingosine-1-phosphate lyase 1 (SPL), has neuroprotective effects in Huntington’s disease models. (PMID:28931805)
• describe the sequential expression and localization of the endogenous S1P regulators SGPP-1 and SGPL-1 and highlight their contribution to the sphingolipid rheostat in inflammation. (PMID:29375197)
• SGPL1 Deficiency is associated with Primary Adrenal Insufficiency. (PMID:30517686)
• SGPL1321 mutation: one main trigger for invasiveness of pediatric alveolar rhabdomyosarcoma. (PMID:31455837)
• Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1. (PMID:32630435)
• S1P Lyase siRNA Dampens Malignancy of DLD-1 Colorectal Cancer Cells. (PMID:32971566)
• Neurodegeneration Caused by S1P-Lyase Deficiency Involves Calcium-Dependent Tau Pathology and Abnormal Histone Acetylation. (PMID:32998447)
• Influenza A virus NS1 induces degradation of sphingosine 1-phosphate lyase to obstruct the host innate immune response. (PMID:33730651)
• S1P Lyase Regulates Intestinal Stem Cell Quiescence via Ki-67 and FOXO3. (PMID:34073605)
• Nuclear Sphingosine-1-phosphate Lyase Generated 2-hexadecenal is A Regulator of HDAC Activity and Chromatin Remodeling in Lung Epithelial Cells. (PMID:34085165)
• A rare cause of nephrotic syndrome-sphingosine-1-phosphate lyase (SGPL1) deficiency: 6 cases and a review of the literature. (PMID:35748945)
• SGPL1 Deficiency: Nephrotic Syndrome with Lymphopenia. (PMID:36050428)
• Loss of S1P Lyase Expression in Human Podocytes Causes a Reduction in Nephrin Expression That Involves PKCdelta Activation. (PMID:36834691)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	sgpl1	ENSDARG00000061375
mus_musculus	Sgpl1	ENSMUSG00000020097
rattus_norvegicus	Sgpl1	ENSRNOG00000000565
drosophila_melanogaster	Sply	FBGN0010591
caenorhabditis_elegans		WBGENE00006418
caenorhabditis_elegans		WBGENE00022427

Paralogs (7): GAD1 (ENSG00000128683), DDC (ENSG00000132437), GAD2 (ENSG00000136750), CSAD (ENSG00000139631), HDC (ENSG00000140287), GADL1 (ENSG00000144644), PDXDC1 (ENSG00000179889)

Protein

Protein identifiers

Sphingosine-1-phosphate lyase 1 — O95470 (reviewed: O95470)

Alternative names: Sphingosine-1-phosphate aldolase

All UniProt accessions (7): A0A8V8TLB6, A0A8V8TLU3, A0A8V8TLU8, A0A8V8TN35, A0A8V8TN38, O95470, H7BXL7

UniProt curated annotations — full annotation on UniProt →

Function. Cleaves phosphorylated sphingoid bases (PSBs), such as sphingosine-1-phosphate, into fatty aldehydes and phosphoethanolamine. Elevates stress-induced ceramide production and apoptosis. Required for global lipid homeostasis in liver and cholesterol homeostasis in fibroblasts. Involved in the regulation of pro-inflammatory response and neutrophil trafficking. Modulates neuronal autophagy via phosphoethanolamine production which regulates accumulation of aggregate-prone proteins such as APP. Seems to play a role in establishing neuronal contact sites and axonal maintenance.

Subunit / interactions. Homodimer.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Ubiquitously expressed. Expressed in fetal and adult adrenal gland (at protein level).

Disease relevance. RENI syndrome (RENI) [MIM:617575] An autosomal recessive, steroid-resistant nephrotic syndrome that manifests in infancy or early childhood, and progresses to end-stage renal failure within a few years. Additional clinical features include ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects. In rare cases, patients present with isolated primary adrenal insufficiency. Some patients present in utero with fetal hydrops and fetal demise. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Lipid metabolism; sphingolipid metabolism.

Similarity. Belongs to the group II decarboxylase family. Sphingosine-1-phosphate lyase subfamily.

RefSeq proteins (1): NP_003892* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002129	PyrdxlP-dep_de-COase	Domain
IPR015421	PyrdxlP-dep_Trfase_major	Homologous_superfamily
IPR015422	PyrdxlP-dep_Trfase_small	Homologous_superfamily
IPR015424	PyrdxlP-dep_Trfase	Homologous_superfamily
IPR050477	GrpII_AminoAcid_Decarb	Family

Pfam: PF00282

Enzyme classification (BRENDA):

• EC 4.1.2.27 — sphinganine-1-phosphate aldolase (BRENDA: 26 organisms, 58 substrates, 129 inhibitors, 13 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
SPHINGANINE 1-PHOSPHATE	0.016–0.11	3
SPHINGOSINE 1-PHOSPHATE	0.0057–0.0146	2
(2E)-HEXADECENAL	0.0194	1
4,4-DIFLUORO-4-BORA-3A,4A-DIAZA-S-INDACENE-LABEL	0.035	1
C17-SPHINGANINE-1-PHOSPHATE	0.006	1
D-(+)-ERYTHRO-DIHYDROSPHINGOSINE 1-PHOSPHATE	0.009	1
DEOXYSPHINGANINE 1-PHOSPHONATE	0.016	1
DIHYDROSPHINGOSINE 1-PHOSPHONATE	0.0201	1
SPHINGANINE-PHOSPHATE	0.11	1

Catalyzed reactions (Rhea), 2 shown:

• sphinganine 1-phosphate = hexadecanal + phosphoethanolamine (RHEA:18593)
• sphing-4-enine 1-phosphate = (2E)-hexadecenal + phosphoethanolamine (RHEA:33507)

UniProt features (64 total): helix 18, strand 15, sequence variant 10, turn 7, modified residue 5, mutagenesis site 4, topological domain 2, chain 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8AYF	X-RAY DIFFRACTION	1.84
4Q6R	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95470-F1	92.07	0.74

Functional residue map

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

Post-translational modifications (5): 353, 353, 356, 366, 564

Mutagenesis-validated functional residues (4):

Position	Phenotype
132	no effect on the sphinganine-1-phosphate aldolase activity; no effect on protein abundance.
218	loss of sphinganine-1-phosphate aldolase activity.
317	almost no sphinganine-1-phosphate aldolase activity.
353	loss of sphinganine-1-phosphate aldolase activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9845614	Sphingolipid catabolism
R-HSA-1430728	Metabolism
R-HSA-428157	Sphingolipid metabolism
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 364 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, AAGCAAT_MIR137, GOBP_BODY_MORPHOGENESIS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_GROWTH, DITTMER_PTHLH_TARGETS_UP, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_MALE_GAMETE_GENERATION, RAMJAUN_APOPTOSIS_BY_TGFB1_VIA_MAPK1_DN, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_MEMBRANE_LIPID_CATABOLIC_PROCESS, MORF_RAD51L3

GO Biological Process (24): luteinization (GO:0001553), vasculogenesis (GO:0001570), kidney development (GO:0001822), fatty acid metabolic process (GO:0006631), ceramide metabolic process (GO:0006672), spermatogenesis (GO:0007283), androgen metabolic process (GO:0008209), estrogen metabolic process (GO:0008210), post-embryonic development (GO:0009791), fibroblast migration (GO:0010761), hemopoiesis (GO:0030097), sphingolipid catabolic process (GO:0030149), Leydig cell differentiation (GO:0033327), regulation of multicellular organism growth (GO:0040014), platelet-derived growth factor receptor signaling pathway (GO:0048008), skeletal system morphogenesis (GO:0048705), roof of mouth development (GO:0060021), face morphogenesis (GO:0060325), apoptotic signaling pathway (GO:0097190), lipid metabolic process (GO:0006629), sphingolipid metabolic process (GO:0006665), apoptotic process (GO:0006915), female gonad development (GO:0008585), carboxylic acid metabolic process (GO:0019752)

GO Molecular Function (5): sphinganine-1-phosphate aldolase activity (GO:0008117), pyridoxal phosphate binding (GO:0030170), protein binding (GO:0005515), lyase activity (GO:0016829), carbon-carbon lyase activity (GO:0016830)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Sphingolipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	2
sphingolipid metabolic process	2
developmental process involved in reproduction	2
steroid metabolic process	2
hormone metabolic process	2
female gonad development	1
ovulation cycle process	1
blood vessel morphogenesis	1
animal organ development	1
renal system development	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
male gamete generation	1
multicellular organism development	1
multicellular organismal process	1
ameboidal-type cell migration	1
cell development	1
lipid catabolic process	1
male gonad development	1
multicellular organism growth	1
regulation of developmental growth	1
regulation of multicellular organismal process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
skeletal system development	1
animal organ morphogenesis	1
anatomical structure development	1
anatomical structure morphogenesis	1
head morphogenesis	1
face development	1
apoptotic process	1
signal transduction	1
primary metabolic process	1
aldehyde-lyase activity	1
anion binding	1
vitamin B6 binding	1
binding	1
catalytic activity	1
lyase activity	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

2313 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SGPL1	SPHK2	Q9NRA0	915
SGPL1	SPHK1	Q9NYA1	914
SGPL1	ADAMTS14	Q8WXS8	836
SGPL1	SGPP1	Q9BX95	790
SGPL1	SGPP2	Q8IWX5	751
SGPL1	S1PR2	O95136	738
SGPL1	CERS6	Q6ZMG9	699
SGPL1	SPTLC1	O15269	690
SGPL1	CERS4	Q9HA82	676
SGPL1	SPTLC2	O15270	656
SGPL1	CERS5	Q8N5B7	652
SGPL1	EIF4EBP2	Q13542	647
SGPL1	SPTLC3	Q9NUV7	629
SGPL1	S1PR3	Q99500	585
SGPL1	SPNS2	Q8IVW8	583

IntAct

276 interactions, top by confidence:

A	B	Type	Score
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
CDH1	CTNND1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SGPL1	PAQR5	psi-mi:“MI:0915”(physical association)	0.560
ERG28	SGPL1	psi-mi:“MI:0915”(physical association)	0.560
MFSD6	SGPL1	psi-mi:“MI:0915”(physical association)	0.560
RTP2	SGPL1	psi-mi:“MI:0915”(physical association)	0.560
TMEM97	SGPL1	psi-mi:“MI:0915”(physical association)	0.560
TUSC5	SGPL1	psi-mi:“MI:0915”(physical association)	0.560
AQP9	SGPL1	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	SGPL1	psi-mi:“MI:0915”(physical association)	0.560
UNC50	SGPL1	psi-mi:“MI:0915”(physical association)	0.560
STATH	SGPL1	psi-mi:“MI:0915”(physical association)	0.560
PAQR5	SGPL1	psi-mi:“MI:0915”(physical association)	0.560
STX8	SGPL1	psi-mi:“MI:0915”(physical association)	0.560
HMOX2	SGPL1	psi-mi:“MI:0915”(physical association)	0.560
SGPL1	PLPP4	psi-mi:“MI:0915”(physical association)	0.560
SLC30A3	SGPL1	psi-mi:“MI:0915”(physical association)	0.560
SGPL1	MIP	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (310): SGPL1 (Affinity Capture-MS), SGPL1 (Affinity Capture-MS), SGPL1 (Affinity Capture-MS), SGPL1 (Affinity Capture-MS), SGPL1 (Affinity Capture-MS), SGPL1 (Affinity Capture-MS), SGPL1 (Affinity Capture-MS), ATP5L (Co-fractionation), SGPL1 (Co-fractionation), SGPL1 (Co-fractionation), SGPL1 (Co-fractionation), SGPL1 (Co-fractionation), SGPL1 (Co-fractionation), SGPL1 (Co-fractionation), SGPL1 (Co-fractionation)

ESM2 similar proteins: A2AV36, A2VD33, A4QN59, A4QP75, A6QQV6, B0WSX1, B3MZN7, B4PYH5, B8A5G9, D3ZG52, D9IVE5, E1BMP7, F1QCV2, O95470, P51530, Q14CH1, Q16GH0, Q16P90, Q28CZ7, Q2VPA6, Q32PX9, Q3T0H0, Q3TZM9, Q4KLT3, Q4V7D6, Q502I6, Q58E95, Q5U4E8, Q5U534, Q5ZIB9, Q5ZKG3, Q655R6, Q6NTR1, Q6P4Z6, Q6PCI6, Q6ZQJ5, Q8AWD2, Q8BIP0, Q8GWT4, Q8LGM7

Diamond homologs: A0B9M9, A2STQ3, A3CWM4, A4G060, A5ULW4, A6URB4, A6UVR4, A6VIC0, A7IAB9, B0R349, B8GDM7, C5A2X8, I0DFJ0, O27188, O28275, O58679, O95470, P31672, P48320, P48321, Q05683, Q0W498, Q12VA2, Q2FSD2, Q2NHY7, Q3IT46, Q46DU3, Q4PRC2, Q5JJ82, Q5R4G0, Q5V1B4, Q60358, Q6M0Y7, Q8PXA5, Q8TUQ9, Q8TV92, Q8U1P6, Q9HSA3, Q9UZD5, Q9V7Y2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	8
Uncertain significance	135
Likely benign	160
Benign	25

Top pathogenic / likely-pathogenic (28)

Variant ID	HGVS	Classification
1173092	NM_003901.4(SGPL1):c.1483C>T (p.Arg495Ter)	Pathogenic
1445356	NM_003901.4(SGPL1):c.993C>G (p.Tyr331Ter)	Pathogenic
2030611	NM_003901.4(SGPL1):c.134G>A (p.Trp45Ter)	Pathogenic
2050780	NM_003901.4(SGPL1):c.1266_1267del (p.Gln422fs)	Pathogenic
2076836	NM_003901.4(SGPL1):c.165G>A (p.Trp55Ter)	Pathogenic
2577413	NM_003901.4(SGPL1):c.1298+6T>C	Pathogenic
2771802	NM_003901.4(SGPL1):c.397_401del (p.Tyr133fs)	Pathogenic
2779742	NM_003901.4(SGPL1):c.166G>T (p.Gly56Ter)	Pathogenic
2792254	NM_003901.4(SGPL1):c.517dup (p.Leu173fs)	Pathogenic
3254596	NM_003901.4(SGPL1):c.423del (p.Glu142fs)	Pathogenic
3617997	NM_003901.4(SGPL1):c.184del (p.Gln62fs)	Pathogenic
430861	NM_003901.4(SGPL1):c.665G>A (p.Arg222Gln)	Pathogenic
430862	NM_003901.4(SGPL1):c.1632CTT[1] (p.Phe545del)	Pathogenic
430863	NM_003901.4(SGPL1):c.261+1G>A	Pathogenic
430864	NM_003901.4(SGPL1):c.7dup (p.Ser3fs)	Pathogenic
430865	NM_003901.4(SGPL1):c.664C>T (p.Arg222Trp)	Pathogenic
430867	NM_003901.4(SGPL1):c.1513C>T (p.Arg505Ter)	Pathogenic
430868	NM_003901.4(SGPL1):c.934del (p.Leu312fs)	Pathogenic
4709730	NM_003901.4(SGPL1):c.395A>G (p.Glu132Gly)	Pathogenic
4809576	NM_003901.4(SGPL1):c.924C>A (p.Tyr308Ter)	Pathogenic
1942047	NM_003901.4(SGPL1):c.705-1G>A	Likely pathogenic
2571782	NM_003901.4(SGPL1):c.868T>C (p.Phe290Leu)	Likely pathogenic
3064759	NM_003901.4(SGPL1):c.1588dup (p.Gln530fs)	Likely pathogenic
3317940	NM_003901.4(SGPL1):c.146G>A (p.Trp49Ter)	Likely pathogenic
3661600	NM_003901.4(SGPL1):c.616-1G>A	Likely pathogenic
3780599	NM_003901.4(SGPL1):c.991_1001del (p.Tyr331fs)	Likely pathogenic
599179	NM_003901.4(SGPL1):c.87del (p.Asn28_Tyr29insTer)	Likely pathogenic
851784	NM_003901.4(SGPL1):c.1247A>G (p.Tyr416Cys)	Likely pathogenic

SpliceAI

4096 predictions. Top by Δscore:

Variant	Effect	Δscore
10:70816066:G:GT	donor_gain	1.0000
10:70816093:G:T	donor_gain	1.0000
10:70816104:G:GT	donor_gain	1.0000
10:70816124:G:GT	donor_gain	1.0000
10:70844459:A:AG	acceptor_gain	1.0000
10:70844472:GAA:G	acceptor_gain	1.0000
10:70844634:AGAGA:A	donor_gain	1.0000
10:70844635:GAGA:G	donor_gain	1.0000
10:70844635:GAGAG:G	donor_gain	1.0000
10:70844636:AGA:A	donor_gain	1.0000
10:70844636:AGAG:A	donor_loss	1.0000
10:70844637:GA:G	donor_gain	1.0000
10:70844637:GAG:G	donor_gain	1.0000
10:70844637:GAGTA:G	donor_loss	1.0000
10:70844639:G:GG	donor_gain	1.0000
10:70844640:T:A	donor_loss	1.0000
10:70851208:AAGG:A	donor_loss	1.0000
10:70851211:GTA:G	donor_loss	1.0000
10:70854675:ATCT:A	acceptor_gain	1.0000
10:70854703:T:TA	acceptor_gain	1.0000
10:70854779:G:GG	donor_gain	1.0000
10:70856944:ACACT:A	acceptor_gain	1.0000
10:70856946:A:AG	acceptor_gain	1.0000
10:70856946:ACT:A	acceptor_gain	1.0000
10:70856946:ACTG:A	acceptor_gain	1.0000
10:70856946:ACTGG:A	acceptor_gain	1.0000
10:70856948:T:A	acceptor_gain	1.0000
10:70857612:A:AG	acceptor_gain	1.0000
10:70857613:G:GG	acceptor_gain	1.0000
10:70857689:AGGTG:A	donor_loss	1.0000

AlphaMissense

3740 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:70868394:G:C	R222P	0.999
10:70871963:A:C	S346R	0.999
10:70871965:C:A	S346R	0.999
10:70871965:C:G	S346R	0.999
10:70868366:A:C	S213R	0.998
10:70868368:C:A	S213R	0.998
10:70868368:C:G	S213R	0.998
10:70869828:A:C	K247N	0.998
10:70869828:A:T	K247N	0.998
10:70875517:T:A	W472R	0.997
10:70875517:T:C	W472R	0.997
10:70859397:C:A	N171K	0.995
10:70859397:C:G	N171K	0.995
10:70869826:A:G	K247E	0.995
10:70871975:G:C	D350H	0.995
10:70844581:A:C	S46R	0.994
10:70844583:T:A	S46R	0.994
10:70844583:T:G	S46R	0.994
10:70859495:G:A	G204E	0.994
10:70868361:C:T	T211I	0.994
10:70869827:A:T	K247I	0.994
10:70869829:G:C	A248P	0.994
10:70869830:C:A	A248E	0.994
10:70871878:T:G	C317W	0.994
10:70873375:T:C	S362P	0.994
10:70873478:G:C	R396P	0.994
10:70871105:T:C	F290L	0.993
10:70871107:T:A	F290L	0.993
10:70871107:T:G	F290L	0.993
10:70871976:A:T	D350V	0.993

dbSNP variants (sampled 300 via entrez): RS1000073729 (10:70857438 T>C), RS1000079217 (10:70862185 C>T), RS1000109426 (10:70847244 T>C), RS1000114428 (10:70880734 G>T), RS1000208100 (10:70837595 A>G), RS1000302938 (10:70837244 A>G), RS1000424815 (10:70843794 T>C), RS1000533189 (10:70818319 C>A,T), RS1000567583 (10:70842513 A>G), RS1000568557 (10:70823247 C>G), RS1000594889 (10:70823087 G>A), RS1000611686 (10:70881550 G>A), RS1000640385 (10:70838755 A>G), RS1000709712 (10:70845730 G>C), RS1000894591 (10:70818043 A>G)

Disease associations

OMIM: gene MIM:603729 | disease phenotypes: MIM:617575

GenCC curated gene-disease

Disease	Classification	Inheritance
nephrotic syndrome 14	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
nephrotic syndrome 14	Definitive	AR

Mondo (2): nephrotic syndrome 14 (MONDO:0033203), nephrotic syndrome (MONDO:0005377)

Orphanet (1): Familial steroid-resistant nephrotic syndrome with adrenal insufficiency (Orphanet:506334)

HPO phenotypes

36 total (30 of 36 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000100	Nephrotic syndrome
HP:0000135	Hypogonadism
HP:0000252	Microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000821	Hypothyroidism
HP:0000846	Adrenal insufficiency
HP:0000953	Hyperpigmentation of the skin
HP:0000969	Edema
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001268	Mental deterioration
HP:0001290	Generalized hypotonia
HP:0001888	Decreased total lymphocyte count
HP:0001943	Hypoglycemia
HP:0001967	Diffuse mesangial sclerosis
HP:0002155	Hypertriglyceridemia
HP:0002376	Developmental regression
HP:0003073	Hypoalbuminemia
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0003676	Progressive
HP:0003774	Stage 5 chronic kidney disease

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003253_5	Microalbuminuria	4.000000e-06
GCST009391_810	Metabolite levels	9.000000e-06
GCST90002385_483	High light scatter reticulocyte count	9.000000e-14
GCST90002386_404	High light scatter reticulocyte percentage of red cells	2.000000e-14
GCST90002387_360	Immature fraction of reticulocytes	2.000000e-14
GCST90002404_491	Red cell distribution width	2.000000e-09
GCST90002406_302	Reticulocyte fraction of red cells	2.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010396	sphingomyelin 22:1 measurement
EFO:0007986	reticulocyte count
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3286061 (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: 16,015 (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
CHEMBL314854	FINGOLIMOD	4	16,015

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Sphingosine 1-phosphate lyase

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 31 [PMID: 24809814]	Inhibition	6.68	pIC50
LX2931	Inhibition	4.0	pIC50

Binding affinities (BindingDB)

101 measured of 228 human assays (228 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[(1R,3S)-1-amino-3-[(6R)-6-(2,2-dimethylpropylsulfanylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-(6-heptoxy-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(Z)-hex-2-enoxy]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6S)-6-(phenylmethoxymethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6S)-6-(decoxymethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-(4,4,4-trifluorobutoxymethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-(3-methylbut-2-enoxymethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-(pent-4-enoxymethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-(3-methylbutoxymethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-(3-methoxypropoxymethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6S)-6-(phenoxymethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-(3,3-dimethylbutoxymethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6S)-6-[(4-methylphenoxy)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(4-methylphenoxy)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6S)-6-[(2-methylphenoxy)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(2-methylphenoxy)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(3-methylphenoxy)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(1-methylpyrazol-4-yl)methoxymethyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-(thiophen-3-ylmethoxymethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(4-methylphenyl)methoxymethyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(2-methoxyphenoxy)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(4-methoxyphenoxy)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(5-methoxy-3-pyridinyl)oxymethyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(3-propan-2-ylphenoxy)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(4-propan-2-ylphenoxy)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(4-methoxyphenyl)methoxymethyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(4,5-dimethylthiophen-2-yl)methoxymethyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(5-ethylthiophen-2-yl)methoxymethyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[[3-[(dimethylamino)methyl]phenoxy]methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(3,4-dimethoxyphenoxy)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(2,3-difluoro-4-methoxyphenoxy)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[[3-(dimethylcarbamoyl)phenoxy]methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[[5-(trifluoromethyl)thiophen-2-yl]methoxymethyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6S)-6-(propylsulfanylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-(2-methylpropylsulfanylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6S)-6-(2-methylpropylsulfanylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-(3-methylbutylsulfanylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6S)-6-(3-methylbutylsulfanylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6S)-6-(pentylsulfanylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-(pentylsulfanylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6S)-6-(2,2-dimethylpropylsulfanylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-(pyridin-3-ylsulfanylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-(pyridin-4-ylsulfanylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(2-methylphenyl)sulfanylmethyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6S)-6-(2-phenylethylsulfanylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-(2-phenylethylsulfanylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(2,6-dimethylphenyl)sulfanylmethyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-(2-pyridin-4-ylethylsulfanylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6S)-6-(2-pyrazin-2-ylethylsulfanylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds
[(1R,3S)-1-amino-3-[(6R)-6-[(3-methoxyphenyl)sulfanylmethyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	55 nM	US-9522888: Substituted bicyclic compounds

ChEMBL bioactivities

409 potent at pChembl≥5 of 439 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.22	EC50	0.6	nM	CHEMBL5756629
8.92	EC50	1.2	nM	CHEMBL6009182
8.77	IC50	1.7	nM	CHEMBL5971641
8.64	IC50	2.3	nM	CHEMBL5910640
8.52	IC50	3	nM	CHEMBL5806105
8.36	EC50	4.4	nM	CHEMBL5910640
8.28	IC50	5.2	nM	CHEMBL5973530
8.24	EC50	5.7	nM	CHEMBL5971641
8.05	EC50	8.9	nM	CHEMBL5756629
7.72	EC50	19.2	nM	CHEMBL5973530
7.67	EC50	21.4	nM	CHEMBL5806105
7.62	IC50	24	nM	CHEMBL3290335
7.41	EC50	38.6	nM	CHEMBL5869099
7.31	IC50	48.7	nM	CHEMBL5795098
7.31	EC50	49	nM	CHEMBL5974391
7.26	EC50	55	nM	CHEMBL5829968
7.26	IC50	55	nM	CHEMBL5829968
7.26	IC50	55	nM	CHEMBL5971013
7.26	EC50	55	nM	CHEMBL5900398
7.26	IC50	55	nM	CHEMBL5900398
7.26	EC50	55	nM	CHEMBL5745795
7.26	IC50	55	nM	CHEMBL5745795
7.26	IC50	55	nM	CHEMBL5806008
7.26	IC50	55	nM	CHEMBL5978452
7.26	EC50	55	nM	CHEMBL5960338
7.26	IC50	55	nM	CHEMBL6051593
7.26	EC50	55	nM	CHEMBL6051593
7.26	IC50	55	nM	CHEMBL6007008
7.26	EC50	55	nM	CHEMBL5945812
7.26	IC50	55	nM	CHEMBL5917708
7.26	EC50	55	nM	CHEMBL5917708
7.26	IC50	55	nM	CHEMBL5763507
7.26	EC50	55	nM	CHEMBL5772576
7.26	EC50	55	nM	CHEMBL6036256
7.26	EC50	55	nM	CHEMBL5784922
7.26	IC50	55	nM	CHEMBL5902237
7.26	IC50	55	nM	CHEMBL5906247
7.26	EC50	55	nM	CHEMBL5906247
7.26	IC50	55	nM	CHEMBL5753737
7.26	EC50	55	nM	CHEMBL5912810
7.26	EC50	55	nM	CHEMBL5891107
7.26	EC50	55	nM	CHEMBL5763201
7.26	IC50	55	nM	CHEMBL5744419
7.26	EC50	55	nM	CHEMBL5744419
7.26	EC50	55	nM	CHEMBL6015584
7.26	IC50	55	nM	CHEMBL6027474
7.26	EC50	55	nM	CHEMBL5800686
7.26	EC50	55	nM	CHEMBL5753277
7.26	EC50	55	nM	CHEMBL5849716
7.26	EC50	55	nM	CHEMBL6025881

PubChem BioAssay actives

44 with measured affinity, of 95 total; 32 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
1-benzyl-4-[(3R)-4-(5-cyano-2-pyridinyl)-3-methylpiperazin-1-yl]phthalazine-6-carbonitrile	1152735: Inhibition of human recombinant S1PL (62 to 568) expressed in Sf9 insect cells using S1P as substrate after 1 hr	ic50	0.0240	uM
6-[(2R)-4-[4-benzyl-7-(trifluoromethyl)phthalazin-1-yl]-2-methylpiperazin-1-yl]pyridine-3-carbonitrile	1152735: Inhibition of human recombinant S1PL (62 to 568) expressed in Sf9 insect cells using S1P as substrate after 1 hr	ic50	0.1000	uM
N-[2-[(4-butoxy-2,5-dimethylphenyl)methylamino]-1-phenylethyl]-5-methyl-1,2-oxazole-3-carboxamide	1297353: Inhibition of human sphingosine 1-phosphate lyase after 22 hrs by umbelliferone fluorescence analysis	ic50	0.1170	uM
N-[1-[4-(4-amino-4-oxobutyl)phenyl]-2-[(4-methoxy-2,5-dimethylphenyl)methylamino]ethyl]-5-methyl-1,2-oxazole-3-carboxamide	1297353: Inhibition of human sphingosine 1-phosphate lyase after 22 hrs by umbelliferone fluorescence analysis	ic50	0.1500	uM
N-[1-[4-(3-hydroxyprop-1-ynyl)phenyl]-2-[(4-methoxy-2,5-dimethylphenyl)methylamino]ethyl]-5-methyl-1,2-oxazole-3-carboxamide	1297353: Inhibition of human sphingosine 1-phosphate lyase after 22 hrs by umbelliferone fluorescence analysis	ic50	0.1500	uM
6-[(2R)-4-(4-benzyl-7-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl]pyridine-3-carbonitrile	1152735: Inhibition of human recombinant S1PL (62 to 568) expressed in Sf9 insect cells using S1P as substrate after 1 hr	ic50	0.2100	uM
N-[2-[[2,5-dimethyl-4-(2,2,2-trifluoroethoxy)phenyl]methylamino]-1-phenylethyl]-5-methyl-1,2-oxazole-3-carboxamide	1297354: Inhibition of wild-type full-length human sphingosine 1-phosphate lyase transfected in HEK293-H cells preincubated for 30 mins followed by addition of NBD-sphingosine for 3 hrs by fluorescence analysis	ic50	0.2400	uM
N-[2-[(4-ethoxy-2,5-dimethylphenyl)methylamino]-1-phenylethyl]-5-methyl-1,2-oxazole-3-carboxamide	1297353: Inhibition of human sphingosine 1-phosphate lyase after 22 hrs by umbelliferone fluorescence analysis	ic50	0.2600	uM
N-[(1S)-2-[(4-methoxy-2,5-dimethylphenyl)methylamino]-1-phenylethyl]-5-methyl-1,2-oxazole-3-carboxamide	1297353: Inhibition of human sphingosine 1-phosphate lyase after 22 hrs by umbelliferone fluorescence analysis	ic50	0.4850	uM
N-[1-(4-fluorophenyl)-2-[(4-methoxy-2,5-dimethylphenyl)methylamino]ethyl]-5-methyl-1,2-oxazole-3-carboxamide	1297353: Inhibition of human sphingosine 1-phosphate lyase after 22 hrs by umbelliferone fluorescence analysis	ic50	0.7200	uM
5-cyclopropyl-N-[2-[(4-methoxy-2,5-dimethylphenyl)methylamino]-1-phenylethyl]-1,2-oxazole-3-carboxamide	1297353: Inhibition of human sphingosine 1-phosphate lyase after 22 hrs by umbelliferone fluorescence analysis	ic50	0.7300	uM
1-benzyl-4-[(3R)-3-methyl-4-(5-nitro-2-pyridinyl)piperazin-1-yl]phthalazine	1152735: Inhibition of human recombinant S1PL (62 to 568) expressed in Sf9 insect cells using S1P as substrate after 1 hr	ic50	0.7400	uM
N-[2-[(4-methoxy-2,5-dimethylphenyl)methylamino]-1-pyridin-4-ylethyl]-5-methyl-1,2-oxazole-3-carboxamide	1297353: Inhibition of human sphingosine 1-phosphate lyase after 22 hrs by umbelliferone fluorescence analysis	ic50	0.8500	uM
N-[2-[[2,5-dimethyl-4-(pyridin-4-ylmethoxy)phenyl]methylamino]-1-phenylethyl]-5-methyl-1,2-oxazole-3-carboxamide	1297353: Inhibition of human sphingosine 1-phosphate lyase after 22 hrs by umbelliferone fluorescence analysis	ic50	1.0000	uM
N-[2-[(4-methoxy-2,5-dimethylphenyl)methylamino]-1-phenylethyl]-5-methyl-1,2-oxazole-3-carboxamide	1297353: Inhibition of human sphingosine 1-phosphate lyase after 22 hrs by umbelliferone fluorescence analysis	ic50	1.0000	uM
N-[2-[[4-methoxy-2-methyl-5-(trifluoromethyl)phenyl]methylamino]-1-phenylethyl]-5-methyl-1,2-oxazole-3-carboxamide	1297353: Inhibition of human sphingosine 1-phosphate lyase after 22 hrs by umbelliferone fluorescence analysis	ic50	1.2000	uM
4-benzyl-1-[(3R)-4-(5-cyano-2-pyridinyl)-3-methylpiperazin-1-yl]phthalazine-6-carbonitrile	1152735: Inhibition of human recombinant S1PL (62 to 568) expressed in Sf9 insect cells using S1P as substrate after 1 hr	ic50	1.3000	uM
6-[(2R)-4-(4-benzylphthalazin-1-yl)-2-ethylpiperazin-1-yl]pyridine-3-carbonitrile	1152735: Inhibition of human recombinant S1PL (62 to 568) expressed in Sf9 insect cells using S1P as substrate after 1 hr	ic50	1.7000	uM
6-[(2R)-4-(4-benzyl-6-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl]pyridine-3-carbonitrile	1152735: Inhibition of human recombinant S1PL (62 to 568) expressed in Sf9 insect cells using S1P as substrate after 1 hr	ic50	2.3000	uM
6-[(2R)-4-(4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]pyridine-3-carbonitrile	1152735: Inhibition of human recombinant S1PL (62 to 568) expressed in Sf9 insect cells using S1P as substrate after 1 hr	ic50	2.4000	uM
6-[(2R)-4-(4-benzylphthalazin-1-yl)-2-propan-2-ylpiperazin-1-yl]pyridine-3-carbonitrile	1152735: Inhibition of human recombinant S1PL (62 to 568) expressed in Sf9 insect cells using S1P as substrate after 1 hr	ic50	2.5000	uM
ethyl 6-[(2R)-4-(4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]pyridine-3-carboxylate	1152735: Inhibition of human recombinant S1PL (62 to 568) expressed in Sf9 insect cells using S1P as substrate after 1 hr	ic50	3.4000	uM
N-[2-[(4-methoxy-2,5-dimethylphenyl)methylamino]-1-phenylethyl]-3-methyl-1,2-oxazole-5-carboxamide	1297353: Inhibition of human sphingosine 1-phosphate lyase after 22 hrs by umbelliferone fluorescence analysis	ic50	3.8000	uM
5-cyclopropyl-N-[2-[(4-ethoxy-2,5-dimethylphenyl)methylamino]-1-(4-fluorophenyl)ethyl]-1,2-oxazole-3-carboxamide	1297353: Inhibition of human sphingosine 1-phosphate lyase after 22 hrs by umbelliferone fluorescence analysis	ic50	4.6000	uM
N-[2-[(4-methoxy-2,5-dimethylphenyl)methylamino]-1-(4-methoxyphenyl)ethyl]-5-methyl-1,2-oxazole-3-carboxamide	1297353: Inhibition of human sphingosine 1-phosphate lyase after 22 hrs by umbelliferone fluorescence analysis	ic50	5.0000	uM
[(E,2R,3S)-2-azido-3-hydroxyoctadec-4-enyl] dihydrogen phosphate	1713365: Inhibition of recombinant human S1PL using RBM13 as fluorogenic substrate incubated for 1 hr	ic50	5.2000	uM
[(2R,3S)-2-azido-3-hydroxyoctadecyl] dihydrogen phosphate	1713366: Competitive inhibition of human S1PL using varying levels of RBM13 as substrate by Lineweaver-Burk plot analysis	ki	6.3000	uM
N-[2-[(4-methoxy-2,5-dimethylphenyl)methylamino]-1-phenylethyl]-1,2-oxazole-3-carboxamide	1297353: Inhibition of human sphingosine 1-phosphate lyase after 22 hrs by umbelliferone fluorescence analysis	ic50	6.4000	uM
N-[2-[(4-methoxy-2,5-dimethylphenyl)methylamino]-1-(3-methoxyphenyl)ethyl]-5-methyl-1,2-oxazole-3-carboxamide	1297353: Inhibition of human sphingosine 1-phosphate lyase after 22 hrs by umbelliferone fluorescence analysis	ic50	7.3000	uM
[(E,2S,3R)-2-azido-3-hydroxyoctadec-4-enyl] dihydrogen phosphate	1713366: Competitive inhibition of human S1PL using varying levels of RBM13 as substrate by Lineweaver-Burk plot analysis	ki	9.1000	uM
5-methoxy-N-[2-[(4-methoxy-2,5-dimethylphenyl)methylamino]-1-phenylethyl]-1,2-oxazole-3-carboxamide	1297353: Inhibition of human sphingosine 1-phosphate lyase after 22 hrs by umbelliferone fluorescence analysis	ic50	9.2000	uM
N-[1-[3-(4-amino-4-oxobutyl)phenyl]-2-[(4-methoxy-2,5-dimethylphenyl)methylamino]ethyl]-5-methyl-1,2-oxazole-3-carboxamide	1297353: Inhibition of human sphingosine 1-phosphate lyase after 22 hrs by umbelliferone fluorescence analysis	ic50	9.6000	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, decreases expression	3
perfluoro-n-nonanoic acid	decreases expression, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
beta-lapachone	increases expression	1
sodium bichromate	decreases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	decreases expression	1
3,3’-dichlorobiphenyl	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Oxygen	decreases expression	1
Plant Extracts	increases expression, affects cotreatment	1
Smoke	increases abundance, increases expression	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

19 unique, capped per target: 19 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3293780	Binding	Inhibition of S1PL (unknown origin)	Orally active 7-substituted (4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitriles as active-site inhibitors of sphingosine 1-phosphate lyase for the treatment of multiple sclerosis. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0ND	Ubigene HeLa SGPL1 KO	Cancer cell line	Female
CVCL_TK93	HAP1 SGPL1 (-) 1	Cancer cell line	Male
CVCL_XS71	HAP1 SGPL1 (-) 2	Cancer cell line	Male
CVCL_XS72	HAP1 SGPL1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00308321	PHASE4	UNKNOWN	Long Term Tapering or Standard Steroids for Nephrotic Syndrome
NCT01021540	PHASE4	COMPLETED	Prospective Study Evaluating the Effect of Repository Corticotropin in the Treatment of Various Nephrotic Syndromes
NCT01028287	PHASE4	COMPLETED	Adrenocorticotropic Hormone (ACTH) Treatment of Nephrotic Range Proteinuria in Diabetic Nephropathy (NRDN)
NCT01162005	PHASE4	COMPLETED	Therapeutic Effect of Tacrolimus on Primary Nephrotic Syndrome in Children
NCT01895894	PHASE4	COMPLETED	Mycophenolate Mofetil in Pediatric Steroid Dependent Nephrotic Syndrome
NCT02238418	PHASE4	COMPLETED	Efficacy of Usual Vitamin D Supplementation and Its Impact on Children and Adolescents Calciuria.
NCT02382575	PHASE4	UNKNOWN	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Resistant Nephrotic Syndrome
NCT02427880	PHASE4	COMPLETED	Role of Acetazolamide and Hydrochlorothiazide Followed by Furosemide in Treating Nephrotic Edema
NCT03210688	PHASE4	COMPLETED	Active Vitamin D And Reduced Dose Prednisolone for Treatment in Minimal Change Nephropathy
NCT03347357	PHASE4	COMPLETED	Pharmacokinetics of Tacrolimus in Children
NCT05696977	PHASE4	UNKNOWN	Effect of Obesity on Cyclosporine Blood Trough Level in Nephrotic Syndrome Patients
NCT05966818	PHASE4	UNKNOWN	Effect of Dapagliflozin in Non-Diabetic Patients With Nephrotic Syndrome.
NCT06026787	PHASE4	COMPLETED	Clinical Value of Adding Dapagliflozin in Patients With Nephrotic Syndrome
NCT00354731	PHASE3	COMPLETED	Efficacy of Pentoxifylline on Primary Nephrotic Syndrome
NCT00615667	PHASE3	COMPLETED	Prospective, Multicenter Study of the Efficacy and Tolerance of Tacrolimus on Refractory Nephrotic Syndrome (RNS)
NCT00981838	PHASE3	COMPLETED	Rituximab in Multirelapsing Minimal Change Disease (MCD) or Focal Segmental Glomerulosclerosis (FSGS)
NCT01197040	PHASE3	COMPLETED	Evaluation of Low Dose Corticosteroids Efficiency, Associated With Myfortic ® in the Treatment of Nephrotic Syndrome
NCT01309477	PHASE3	COMPLETED	The Efficacy and Tolerance of Tacrolimus Sustained-release Capsules on Refractory Nephrotic Syndrome (RNS)
NCT02132195	PHASE3	COMPLETED	Adrenocorticotropic Hormone (ACTH) for Frequently Relapsing and Steroid Dependent Nephrotic Syndrome
NCT02257697	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mizoribine in the Treatment of Refractory Nephrotic Syndrome
NCT02438982	PHASE3	COMPLETED	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Dependent Nephrotic Syndrome
NCT03141970	PHASE3	COMPLETED	Prednisolone Trial in Children Younger Than 4 Years
NCT03501459	PHASE3	UNKNOWN	Lymphocyte Markers As Predictors Of Responsiveness To Rituximab Among Patients With Idiopathic Nephrotic Syndrome
NCT05079789	PHASE3	TERMINATED	Amiloride in Nephrotic Syndrome
NCT05716880	PHASE3	RECRUITING	Ketoanalogues for Muscle Mass Loss in Nephrotic Syndrome
NCT06635720	PHASE3	ACTIVE_NOT_RECRUITING	REduced-dose Steroid PrOtocol for Childhood Nephrotic SyndromE (RESPONSE)
NCT00001212	PHASE2	COMPLETED	Drug Therapy in Lupus Nephropathy
NCT00001959	PHASE2	COMPLETED	Pirfenidone to Treat Kidney Disease (Focal Segmental Glomerulosclerosis)
NCT00004466	PHASE2	TERMINATED	Pilot Study of Atorvastatin in Children With Chronic Hyperlipidemia Secondary to Nephrotic Syndrome
NCT00004990	PHASE2	COMPLETED	Once-A-Month Steroid Treatment for Patients With Focal Segmental Glomerulosclerosis
NCT00977977	PHASE2	RECRUITING	Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy
NCT02394106	PHASE2	TERMINATED	Ofatumumab in Children With Drug Resistant Idiopathic Nephrotic Syndrome
NCT02394119	PHASE2	COMPLETED	Ofatumumab Versus Rituximab in Children With Steroid and Calcineurin Inhibitor Dependent Idiopathic Nephrotic Syndrome
NCT02592798	PHASE2	COMPLETED	Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Adults and Children 6 Years and Older With Excessive Loss of Protein in the Urine Due to Either Focal Segmental Glomerulosclerosis (FSGS) or Minimal Change Disease (MCD)
NCT02966717	PHASE2	UNKNOWN	Rituximab Combined With MSCs in the Treatment of PNS (3-4 Stage of CKD)
NCT03004001	PHASE2	TERMINATED	Effect of PCSK9-Antibody (Alirocumab) on Dyslipidemia Secondary to Nephrotic Syndrome
NCT03949855	PHASE2	RECRUITING	Belimumab With Rituximab for Primary Membranous Nephropathy
NCT05599815	PHASE2	WITHDRAWN	Part 1 - A Clinical Trial in Patients With Frequently Relapsing and Steroid-Dependent Nephrotic Syndrome
NCT05704400	PHASE2	UNKNOWN	Efficacy of Anti-CD20 Ab Associated With Anti-CD38 in the Childhood Multidrug Dependent and Resistant Nephrotic Syndrome
NCT06983028	PHASE2	RECRUITING	Atacicept in Multiple Glomerular Diseases