MBTPS1

Summary

MBTPS1 (membrane bound transcription factor peptidase, site 1, HGNC:15456) is a protein-coding gene on chromosome 16q23.3-q24.1, encoding Membrane-bound transcription factor site-1 protease (Q14703). Serine protease that cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4: known substrates include SREBF1/SREBP1, SREBF2/SREBP2, BDNF, GNPTAB, ATF6, ATF6B and FAM20C. It is a selective cancer dependency (DepMap: 59.4% of cell lines).

This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER and sorts to the cis/medial-Golgi where a second autocatalytic event takes place and the catalytic activity is acquired. It encodes a type 1 membrane bound protease which is ubiquitously expressed and regulates cholesterol or lipid homeostasis via cleavage of substrates at non-basic residues. Mutations in this gene may be associated with lysosomal dysfunction.

Source: NCBI Gene 8720 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spondyloepiphyseal dysplasia, kondo-fu type (Definitive, ClinGen)
• GWAS associations: 2
• Clinical variants (ClinVar): 586 total — 21 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 36
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 59.4% of screened cell lines
• MANE Select transcript: NM_003791

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15456
Approved symbol	MBTPS1
Name	membrane bound transcription factor peptidase, site 1
Location	16q23.3-q24.1
Locus type	gene with protein product
Status	Approved
Aliases	S1P, KIAA0091, SKI-1, PCSK8
Ensembl gene	ENSG00000140943
Ensembl biotype	protein_coding
OMIM	603355
Entrez	8720

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 6 retained_intron, 5 protein_coding, 5 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000343411, ENST00000561936, ENST00000562788, ENST00000562886, ENST00000562906, ENST00000563231, ENST00000564049, ENST00000564444, ENST00000564643, ENST00000565863, ENST00000567557, ENST00000568051, ENST00000569770, ENST00000569907, ENST00000570012, ENST00000570064, ENST00000851026

RefSeq mRNA: 1 — MANE Select: NM_003791 NM_003791

CCDS: CCDS10941

Canonical transcript exons

ENST00000343411 — 23 exons

Exon	Start	End
ENSE00002216003	84101621	84102107
ENSE00002266120	84095602	84095805
ENSE00002281114	84099053	84099310
ENSE00002284824	84093711	84093821
ENSE00003462167	84056005	84056135
ENSE00003463128	84063305	84063445
ENSE00003491734	84067667	84067823
ENSE00003502718	84081747	84081908
ENSE00003518868	84069866	84070038
ENSE00003519805	84087358	84087460
ENSE00003533286	84091732	84091848
ENSE00003541264	84074597	84074741
ENSE00003564284	84090875	84090942
ENSE00003567133	84084983	84085134
ENSE00003589283	84093188	84093297
ENSE00003616795	84053763	84054645
ENSE00003617442	84070588	84070776
ENSE00003635336	84059302	84059428
ENSE00003635729	84065690	84065767
ENSE00003636561	84068339	84068454
ENSE00003651284	84066489	84066613
ENSE00003683220	84060682	84060813
ENSE00004283437	84116735	84116942

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 97.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 44.4919 / max 284.3093, expressed in 1822 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158332	23.9999	1816
158334	18.2916	1804
158331	0.9991	648
158333	0.7076	426
158330	0.4936	228

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	97.35	gold quality
endometrium epithelium	UBERON:0004811	96.76	gold quality
pituitary gland	UBERON:0000007	96.02	gold quality
left ovary	UBERON:0002119	95.88	gold quality
adenohypophysis	UBERON:0002196	95.83	gold quality
cerebellar hemisphere	UBERON:0002245	95.79	gold quality
cerebellar cortex	UBERON:0002129	95.74	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.66	gold quality
right ovary	UBERON:0002118	95.49	gold quality
islet of Langerhans	UBERON:0000006	95.48	gold quality
right uterine tube	UBERON:0001302	95.26	gold quality
right lobe of thyroid gland	UBERON:0001119	95.17	gold quality
left lobe of thyroid gland	UBERON:0001120	95.03	gold quality
cerebellum	UBERON:0002037	94.99	gold quality
body of uterus	UBERON:0009853	94.98	gold quality
thyroid gland	UBERON:0002046	94.96	gold quality
adrenal tissue	UBERON:0018303	94.88	gold quality
right atrium auricular region	UBERON:0006631	94.83	gold quality
smooth muscle tissue	UBERON:0001135	94.81	gold quality
endocervix	UBERON:0000458	94.76	gold quality
right coronary artery	UBERON:0001625	94.66	gold quality
gall bladder	UBERON:0002110	94.64	gold quality
left uterine tube	UBERON:0001303	94.53	gold quality
cardiac atrium	UBERON:0002081	94.42	gold quality
right lung	UBERON:0002167	94.40	gold quality
popliteal artery	UBERON:0002250	94.37	gold quality
descending thoracic aorta	UBERON:0002345	94.36	gold quality
tibial artery	UBERON:0007610	94.36	gold quality
ganglionic eminence	UBERON:0004023	94.26	gold quality
aorta	UBERON:0000947	94.25	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF6, ESR1, NFKB1

miRNA regulators (miRDB)

49 targeting MBTPS1, 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-9-5P	100.00	72.28	2361
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-217-5P	99.49	69.93	1419

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 59.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 27)

• S1P has a role in reducing the size of the luminal domain to prepare ATF6 to be an optimal S2P substrate (PMID:15299016)
• enzymatic activity of S1P is not calcium dependent, but can be modulated by a variety of mono- and divalent cations. S1P displayed pronounced positive cooperativity with a substrate derived from the viral coat glycoprotein of the lassa virus. (PMID:16973377)
• SKI-1/S1P inhibition resulted in reduced cholesterol synthesis and mRNA levels of the rate-limiting enzymes, HMG-CoA reductase and squalene epoxidase, in the cholesterol synthetic pathway. (PMID:17867930)
• Complementation of SKI-1/S1P-deficient cells with a SKI-1/S1P expression vector restored release of infectious Crimean-Congo hemorrhagic fever virus (>106 PFU/ml), confirming that SKI-1/S1P processing is required for incorporation of viral glycoproteins. (PMID:17898072)
• Site 1 protease is required for proteolytic processing of the glycoproteins of the South American hemorrhagic fever viruses Junin, Machupo, and Guanarito. (PMID:18400865)
• The role of MBTPS1 (SKI-1/S1P) peptides in cancer and approaches used to inhibit SKI-1/S1P were studied. (PMID:21568902)
• study found that the N-acetylglucosamine-1-phosphotransferase alpha/beta-subunit precursor is cleaved by S1P that activates sterol regulatory element-binding proteins in response to cholesterol deprivation; S1P functions in the biogenesis of lysosomes (PMID:21719679)
• Diabetic high-density lipoprotein carries higher levels of S1P compared with normal high-density lipoprotein. (PMID:23360427)
• Y285 of SKI-1 is crucial for the efficient processing of envelope glycoproteins from Old World and clade C New World arenavirus. (PMID:23536681)
• We show that SKI-1 is constitutively expressed in human pigment cells with higher SKI activity in seven out of eight melanoma cell lines compared with normal melanocytes. (PMID:23884247)
• The interaction between S1P and C5a plays an important role in neutrophils for antineutrophil cytoplasmic antibody -mediated activation (PMID:25000985)
• Incompletely matured forms of SKI-1/S1P further process cellular and viral substrates in distinct subcellular compartments. (PMID:25378398)
• S1P substrate-dependent regulatory mechanisms for lipid synthesis and biogenesis of lysosomes are different (PMID:26108224)
• primordial SKI-1/S1P likely contained a simpler prodomain consisting of the highly conserved AB fragment that represents an independent folding unit (PMID:26645686)
• Results suggest that (pro)renin receptor (s(P)RR) is generated by sequential processing by site-1 protease (S1P) and furin protein. (PMID:28013223)
• In the absence of S1P, the catalytically inactive alpha/beta-subunit precursor of GlcNAc-1-phosphotransferase fails to be activated and results in missorting of newly synthesized lysosomal enzymes, and lysosomal accumulation of non-degraded material, which are biochemical features of defective GlcNAc-1-phosphotransferase subunits and the associated pediatric lysosomal diseases mucolipidosis type II and III. (PMID:28693924)
• rs11642644 associated with facial profile (PMID:29301965)
• Site-1 protease function is essential for the generation of antibody secreting cells and reprogramming for secretory activity (PMID:30254311)
• Spondyloepimetaphyseal dysplasia with elevated plasma lysosomal enzymes caused by homozygous variant in MBTPS1. (PMID:32420688)
• Cleavage of the soluble (pro)renin receptor (sATP6AP2) in the placenta. (PMID:32920451)
• Proteolytic processing of secretory pathway kinase Fam20C by site-1 protease promotes biomineralization. (PMID:34349020)
• Sphingosine 1-phosphate alleviates radiation-induced ferroptosis in ovarian granulosa cells by upregulating glutathione peroxidase 4. (PMID:36503164)
• Targeting SPHK1/S1PR3-regulated S-1-P metabolic disorder triggers autophagic cell death in pulmonary lymphangiomyomatosis (LAM). (PMID:36543771)
• Enhancing Spns2/S1P in macrophages alleviates hyperinflammation and prevents immunosuppression in sepsis. (PMID:37358015)
• Targeting the SphK1/S1P/PFKFB3 axis suppresses hepatocellular carcinoma progression by disrupting glycolytic energy supply that drives tumor angiogenesis. (PMID:38200582)
• The Inhibition of the Membrane-Bound Transcription Factor Site-1 Protease (MBTP1) Alleviates the p.Phe508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Defects in Cystic Fibrosis Cells. (PMID:38247876)
• Hepatic glycogenesis antagonizes lipogenesis by blocking S1P via UDPG. (PMID:38359126)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mbtps1	ENSDARG00000014634
mus_musculus	Mbtps1	ENSMUSG00000031835
rattus_norvegicus	Mbtps1	ENSRNOG00000015173
drosophila_melanogaster	S1P	FBGN0037105

Paralogs (9): PCSK5 (ENSG00000099139), PCSK4 (ENSG00000115257), PCSK2 (ENSG00000125851), TPP2 (ENSG00000134900), PCSK6 (ENSG00000140479), FURIN (ENSG00000140564), PCSK7 (ENSG00000160613), PCSK9 (ENSG00000169174), PCSK1 (ENSG00000175426)

Protein

Protein identifiers

Membrane-bound transcription factor site-1 protease — Q14703 (reviewed: Q14703)

Alternative names: Endopeptidase S1P, Subtilisin/kexin-isozyme 1

All UniProt accessions (5): Q14703, A0A087WXJ6, H3BS61, H3BU75, H3BV53

UniProt curated annotations — full annotation on UniProt →

Function. Serine protease that cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4: known substrates include SREBF1/SREBP1, SREBF2/SREBP2, BDNF, GNPTAB, ATF6, ATF6B and FAM20C. Cleaves substrates after Arg-Ser-Val-Leu (SREBP2), Arg-His-Leu-Leu (ATF6), Arg-Gly-Leu-Thr (BDNF) and its own propeptide after Arg-Arg-Leu-Leu. Catalyzes the first step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2. Also mediates the first step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B). Mediates the protein cleavage of GNPTAB into subunit alpha and beta, thereby participating in biogenesis of lysosomes. Cleaves the propeptide from FAM20C which is required for FAM20C secretion from the Golgi apparatus membrane and for enhancement of FAM20C kinase activity, promoting osteoblast differentiation and biomineralization. Involved in the regulation of M6P-dependent Golgi-to-lysosome trafficking of lysosomal enzymes. It is required for the activation of CREB3L2/BBF2H7, a transcriptional activator of MIA3/TANGO and other genes controlling mega vesicle formation. Therefore, it plays a key role in the regulation of mega vesicle-mediated collagen trafficking. Promotes FAD binding to the ETFA/ETFB complex and is therefore involved in mitochondrial respiratory chain regulation. In astrocytes and osteoblasts, upon DNA damage and ER stress, mediates the first step of the regulated intramembrane proteolytic activation of the transcription factor CREB3L1, leading to the inhibition of cell-cycle progression.

Subunit / interactions. Interacts with LYSET; this interaction bridges GNPTAB to MBTPS1. Forms a complex with ETFA and ETFB; the interaction stabilizes the ETFA/ETFB heterodimer, promotes FAD binding to ETFA/ETFB and is independent of MBTPS1 proteolytic activity.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus membrane. Secreted. Mitochondrion.

Tissue specificity. Widely expressed.

Post-translational modifications. The 148 kDa zymogen is processed progressively into two membrane-bound 120 and 106 kDa forms in the endoplasmic reticulum, and into a secreted 98 kDa form. The propeptide is autocatalytically removed through an intramolecular cleavage after Leu-186. Further cleavage generates 14, 10, and 8 kDa intermediates.

Disease relevance. Spondyloepiphyseal dysplasia, Kondo-Fu type (SEDKF) [MIM:618392] A disorder characterized by severely retarded growth, spondyloepiphyseal dysplasia, reduced bone mineral density, and markedly elevated plasma levels of various lysosomal enzymes. Additional features include pectus carinatum, kyphosis, a waddling gait, brachydactyly and dysmorphic facial features. SEDKF transmission pattern is consistent with autosomal recessive inheritance. The disease is caused by variants affecting the gene represented in this entry. Cataract, alopecia, oral mucosal disorder, and psoriasis-like syndrome (CAOP) [MIM:621252] An autosomal recessive disorder characterized by early-onset bilateral lens cataract, generalized non-scarring alopecia, oral mucosal disorder, and severe psoriasiform skin lesions affecting the scalp, facial, inguinal region, buttocks, and lower extremities. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by divalent copper and zinc ions, but not by nickel or cobalt. Inhibited by its prosegment, but not smaller fragments. Inhibited by 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), a serine protease inhibitor.

Induction. Down-regulated by sterols.

Similarity. Belongs to the peptidase S8 family.

RefSeq proteins (1): NP_003782* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000209	Peptidase_S8/S53_dom	Domain
IPR015500	Peptidase_S8_subtilisin-rel	Family
IPR022398	Peptidase_S8_His-AS	Active_site
IPR023828	Peptidase_S8_Ser-AS	Active_site
IPR034185	Site-1_peptidase_cat_dom	Domain
IPR036852	Peptidase_S8/S53_dom_sf	Homologous_superfamily
IPR050131	Peptidase_S8_subtilisin-like	Family
IPR055143	MBTP1_N	Domain
IPR057032	MBTPS1_4th	Domain
IPR057060	MBTPS1_3rd	Domain

Pfam: PF00082, PF23001, PF23090, PF23094

Enzyme classification (BRENDA):

• EC 3.4.21.112 — site-1 protease (BRENDA: 9 organisms, 92 substrates, 74 inhibitors, 37 Km, 3 kcat entries)

Substrate kinetics (BRENDA)

23 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
AC-YISRRLL-7-AMIDO-4-METHYLCOUMARIN	0.0028–0.0057	4
AC-AISRRLL-7-AMIDO-4-METHYLCOUMARIN	0.0504–0.067	2
AC-FISRRLL-7-AMIDO-4-METHYLCOUMARIN	0.0123–0.015	2
AC-IAVGRTLK-7-AMIDO-4-METHYLCOUMARIN	0.0226–0.0846	2
AC-IYISRRLL-7-AMIDO-4-METHYLCOUMARIN	0.0047–0.0074	2
AC-QKSIAVGRTLK-7-AMIDO-4-METHYLCOUMARIN	0.0025–0.0156	2
AC-RKLL-7-AMIDO-4-METHYLCOUMARIN	0.0274–0.0564	2
AC-RRLL-7-AMIDO-4-METHYLCOUMARIN	0.0153–0.0228	2
AC-RRLQ-7-AMIDO-4-METHYLCOUMARIN	0.0971–0.2263	2
AC-RTLK-7-AMIDO-4-METHYLCOUMARIN	0.0967–0.2167	2
AC-SFITRRLQ-7-AMIDO-4-METHYLCOUMARIN	0.0443–0.0784	2
AC-YSSVSRKLL-7-AMIDO-4-METHYLCOUMARIN	0.0212–0.0281	2
2-AMINOBENZOIC ACID-SSGSRRLLSEESY(NO2)-ALA-NH2	0.0051	1
2-AMINOBENZOYL-ARG-ASN-THR-PRO-ARG-ARG-GLU-ARG-A	0.028	1
2-AMINOBENZOYL-ARG-HIS-SER-SER-ARG-ARG-LEU-LEU-A	0.02	1

UniProt features (111 total): strand 46, helix 24, turn 12, glycosylation site 5, sequence variant 5, active site 3, compositionally biased region 2, mutagenesis site 2, topological domain 2, region of interest 2, signal peptide 1, propeptide 1, site 1, modified residue 1, chain 1, sequence conflict 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8UWC	ELECTRON MICROSCOPY	2.27
8UW8	ELECTRON MICROSCOPY	2.3
9CSD	ELECTRON MICROSCOPY	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14703-F1	80.39	0.54

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 (4): 218 (charge relay system); 249 (charge relay system); 414 (charge relay system); 186–187 (cleavage; by autolysis)

Post-translational modifications (1): 168

Glycosylation sites (5): 236, 305, 515, 728, 939

Mutagenesis-validated functional residues (2):

Position	Phenotype
249	abolishes serine protease activity.
414	abolishes serine protease activity. does not promote fam20c kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-1655829	Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-381033	ATF6 (ATF6-alpha) activates chaperones
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8874177	ATF6B (ATF6-beta) activates chaperones
R-HSA-8874211	CREB3 factors activate genes
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-8963889	Assembly of active LPL and LIPC lipase complexes
R-HSA-1430728	Metabolism
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-2262752	Cellular responses to stress
R-HSA-381119	Unfolded Protein Response (UPR)
R-HSA-382551	Transport of small molecules
R-HSA-392499	Metabolism of proteins
R-HSA-556833	Metabolism of lipids
R-HSA-597592	Post-translational protein modification
R-HSA-8953897	Cellular responses to stimuli
R-HSA-8957322	Metabolism of steroids
R-HSA-8963899	Plasma lipoprotein remodeling

MSigDB gene sets: 289 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOBP_VACUOLE_ORGANIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MITOTIC_G2_M_TRANSITION_CHECKPOINT, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP

GO Biological Process (17): proteolysis (GO:0006508), protein import into nucleus (GO:0006606), lysosome organization (GO:0007040), mitotic G2 DNA damage checkpoint signaling (GO:0007095), cholesterol metabolic process (GO:0008203), protein processing (GO:0016485), endoplasmic reticulum unfolded protein response (GO:0030968), membrane protein intracellular domain proteolysis (GO:0031293), response to endoplasmic reticulum stress (GO:0034976), ATF6-mediated unfolded protein response (GO:0036500), regulation of cholesterol biosynthetic process (GO:0045540), protein maturation (GO:0051604), regulation of vesicle-mediated transport (GO:0060627), NLS-bearing protein import into nucleus (GO:0006607), lipid metabolic process (GO:0006629), steroid metabolic process (GO:0008202), positive regulation of cholesterol biosynthetic process (GO:0045542)

GO Molecular Function (5): serine-type endopeptidase activity (GO:0004252), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (8): Golgi membrane (GO:0000139), mitochondrion (GO:0005739), endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), Golgi stack (GO:0005795), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Unfolded Protein Response (UPR)	3
Metabolism of proteins	2
Metabolism of steroids	1
Post-translational protein modification	1
Plasma lipoprotein remodeling	1
Transport of small molecules	1
Cellular responses to stimuli	1
Cellular responses to stress	1
Metabolism	1
Metabolism of lipids	1
Plasma lipoprotein assembly, remodeling, and clearance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
intracellular membrane-bounded organelle	3
protein metabolic process	2
cholesterol biosynthetic process	2
endomembrane system	2
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
lytic vacuole organization	1
mitotic G2 phase	1
mitotic DNA damage checkpoint signaling	1
mitotic G2/M transition checkpoint	1
sterol metabolic process	1
secondary alcohol metabolic process	1
proteolysis	1
protein maturation	1
cellular response to unfolded protein	1
response to endoplasmic reticulum stress	1
intracellular signal transduction	1
membrane protein proteolysis	1
cellular response to stress	1
ER-nucleus signaling pathway	1
endoplasmic reticulum unfolded protein response	1
regulation of cholesterol metabolic process	1
regulation of sterol biosynthetic process	1
regulation of alcohol biosynthetic process	1
gene expression	1
vesicle-mediated transport	1
regulation of cellular process	1
regulation of transport	1
protein import into nucleus	1
primary metabolic process	1
lipid metabolic process	1
regulation of cholesterol biosynthetic process	1
positive regulation of cholesterol metabolic process	1
positive regulation of sterol biosynthetic process	1
positive regulation of alcohol biosynthetic process	1
endopeptidase activity	1
serine-type peptidase activity	1

Protein interactions and networks

STRING

2074 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MBTPS1	MBTPS2	O43462	978
MBTPS1	SCAP	Q12770	907
MBTPS1	ATF6	P18850	899
MBTPS1	SREBF2	Q12772	838
MBTPS1	PCSK6	P29122	835
MBTPS1	SREBF1	P36956	813
MBTPS1	CREB3L3	Q68CJ9	790
MBTPS1	ATF6B	Q99941	784
MBTPS1	HSPA5	P11021	758
MBTPS1	PCSK5	Q92824	753
MBTPS1	SPRING1	Q9H741	751
MBTPS1	PCSK9	Q8NBP7	728
MBTPS1	GTPBP1	O00178	704
MBTPS1	HMGCS1	Q01581	701
MBTPS1	PCSK7	Q16549	679

IntAct

69 interactions, top by confidence:

A	B	Type	Score
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
MBTPS1	CLGN	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
DNAJC3	DEDD	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
GPIHBP1	ADAM10	psi-mi:“MI:0914”(association)	0.530
MBTPS1	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
FCN1	MBTPS1	psi-mi:“MI:0915”(physical association)	0.370
SMAP	MBTPS1	psi-mi:“MI:0915”(physical association)	0.370
CDK2AP2	MBTPS1	psi-mi:“MI:0915”(physical association)	0.370
FAM200C	MBTPS1	psi-mi:“MI:0915”(physical association)	0.370
MBTPS1	TNFRSF14	psi-mi:“MI:0915”(physical association)	0.370
TNFSF11	MBTPS1	psi-mi:“MI:0915”(physical association)	0.370
TANK	CNOT1	psi-mi:“MI:0914”(association)	0.350
PLAUR	DDX11L8	psi-mi:“MI:0914”(association)	0.350
TAZ	MANBA	psi-mi:“MI:0914”(association)	0.350
SIAE	COCH	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
PAGE1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
LLCFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
CEACAM8	PRRT4	psi-mi:“MI:0914”(association)	0.350
GPIHBP1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
TAFAZZIN	MANBA	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
VEGFD	RPSA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (99): MBTPS1 (Affinity Capture-RNA), MBTPS1 (Affinity Capture-RNA), MBTPS1 (Affinity Capture-MS), MBTPS1 (Affinity Capture-MS), MBTPS1 (Affinity Capture-MS), MBTPS1 (Affinity Capture-MS), MBTPS1 (Affinity Capture-MS), MBTPS1 (Affinity Capture-MS), MBTPS1 (Affinity Capture-MS), MBTPS1 (Affinity Capture-RNA), MBTPS1 (Affinity Capture-RNA), MBTPS1 (Affinity Capture-MS), MBTPS1 (Affinity Capture-RNA), MBTPS1 (Affinity Capture-MS), MBTPS1 (Proximity Label-MS)

ESM2 similar proteins: A0A0N9E2K8, A0A1D5NSK0, A0A8M9PFP2, G5ECS8, G5EFD9, O15072, O18767, O43909, O60882, O62806, O77656, O93470, P07152, P22003, P23097, P28825, P29788, P33435, P49003, P57748, P79287, Q10835, Q11005, Q14703, Q16819, Q16820, Q19791, Q24025, Q3U435, Q568B8, Q61847, Q64230, Q6GQB9, Q6NP60, Q8CGD2, Q8K3F2, Q8N119, Q8R4K8, Q8VDA1, Q90YC2

Diamond homologs: A0A0M3R8G2, A7UKV6, A9JQS7, A9QY38, A9QY39, A9QY40, B8XGQ7, C5FMY5, C5FXZ6, D4AWY5, D4AXW3, D4D6Q4, D4DLA2, E4UN97, E4UWA4, F4HPF1, F4HSQ2, F4HYR6, F4IG09, F4JA91, F4JJH4, F4JJH5, F4JJL8, F4JXC5, F4KEL0, F4KGD4, G7KEU7, I1N462, O23357, O31788, O49607, O64481, O64495, O65351, O82777, P00780, P00781, P00782, P00783, P04189

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MBTPS1	up-regulates	CREB3L1	cleavage
MBTPS1	up-regulates	CREB3L2	cleavage
MBTPS1	“up-regulates activity”	SREBF2	cleavage
MBTPS1	“up-regulates activity”	SREBF1	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neutrophil degranulation	12	5.2×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	7
Uncertain significance	262
Likely benign	213
Benign	32

Top pathogenic / likely-pathogenic (28)

Variant ID	HGVS	Classification
1334154	NM_003791.4(MBTPS1):c.3157T>C (p.Ter1053Arg)	Pathogenic
1334417	NM_003791.4(MBTPS1):c.1064T>G (p.Val355Gly)	Pathogenic
2185994	NM_003791.4(MBTPS1):c.1781_1782del (p.Glu594fs)	Pathogenic
3612404	NM_003791.4(MBTPS1):c.388C>T (p.Arg130Ter)	Pathogenic
3668239	NM_003791.4(MBTPS1):c.1790dup (p.Asn597fs)	Pathogenic
3672072	NM_003791.4(MBTPS1):c.1824del (p.Ile609fs)	Pathogenic
3686776	NM_003791.4(MBTPS1):c.721C>T (p.Arg241Ter)	Pathogenic
3689439	NM_003791.4(MBTPS1):c.1601G>A (p.Trp534Ter)	Pathogenic
3906948	D365*	Pathogenic
3908082	MBTPS1, VAL355GLY	Pathogenic
3908083	*1053R	Pathogenic
3908084	MBTPS1, A-T, NT2072-2	Pathogenic
3908085	*1053C	Pathogenic
4706667	NM_003791.4(MBTPS1):c.1018G>T (p.Gly340Ter)	Pathogenic
4713215	NM_003791.4(MBTPS1):c.393del (p.Val132fs)	Pathogenic
4728103	NM_003791.4(MBTPS1):c.2413_2414del (p.Gln805fs)	Pathogenic
4774885	NM_003791.4(MBTPS1):c.1391dup (p.Lys465fs)	Pathogenic
625457	NM_003791.4(MBTPS1):c.285dup (p.Asp96Ter)	Pathogenic
625458	NM_003791.4(MBTPS1):c.1094A>G (p.Asp365Gly)	Pathogenic
812671	NM_003791.4(MBTPS1):c.2948G>A (p.Trp983Ter)	Pathogenic
976662	NM_003791.4(MBTPS1):c.1995C>G (p.Tyr665Ter)	Pathogenic
1305616	NM_003791.4(MBTPS1):c.1241G>C (p.Ser414Thr)	Likely pathogenic
2576117	NM_003791.4(MBTPS1):c.2567dup (p.Lys857fs)	Likely pathogenic
2582787	NM_003791.4(MBTPS1):c.2255G>T (p.Gly752Val)	Likely pathogenic
3065874	NM_003791.4(MBTPS1):c.2896C>T (p.Arg966Ter)	Likely pathogenic
4734111	NM_003791.4(MBTPS1):c.2432-1G>C	Likely pathogenic
4769493	NM_003791.4(MBTPS1):c.846+1G>A	Likely pathogenic
4849444	NM_003791.4(MBTPS1):c.2781T>A (p.Cys927Ter)	Likely pathogenic

SpliceAI

4910 predictions. Top by Δscore:

Variant	Effect	Δscore
16:84056000:CTCA:C	donor_loss	1.0000
16:84056001:TCACC:T	donor_loss	1.0000
16:84056002:CACCT:C	donor_loss	1.0000
16:84056003:A:T	donor_loss	1.0000
16:84056131:GGTTA:G	acceptor_gain	1.0000
16:84056132:GTTA:G	acceptor_gain	1.0000
16:84056133:TTA:T	acceptor_gain	1.0000
16:84056134:TA:T	acceptor_gain	1.0000
16:84056136:C:CC	acceptor_gain	1.0000
16:84056136:C:CG	acceptor_loss	1.0000
16:84056146:A:AC	acceptor_gain	1.0000
16:84056146:A:C	acceptor_gain	1.0000
16:84056150:A:C	acceptor_gain	1.0000
16:84056151:T:TC	acceptor_gain	1.0000
16:84059440:A:T	acceptor_gain	1.0000
16:84059449:A:T	acceptor_gain	1.0000
16:84063303:AC:A	donor_gain	1.0000
16:84063304:CC:C	donor_gain	1.0000
16:84063304:CCCTT:C	donor_gain	1.0000
16:84063443:ATCC:A	acceptor_loss	1.0000
16:84063444:TC:T	acceptor_gain	1.0000
16:84063445:CC:C	acceptor_gain	1.0000
16:84063445:CCTGA:C	acceptor_loss	1.0000
16:84063446:C:CC	acceptor_gain	1.0000
16:84063446:CTG:C	acceptor_loss	1.0000
16:84063447:T:A	acceptor_loss	1.0000
16:84065684:CTTTA:C	donor_loss	1.0000
16:84065685:TTTA:T	donor_loss	1.0000
16:84065686:TTA:T	donor_loss	1.0000
16:84065687:TAC:T	donor_loss	1.0000

AlphaMissense

6901 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:84054583:C:G	G1009R	1.000
16:84054583:C:T	G1009R	1.000
16:84054591:G:T	A1006D	1.000
16:84063332:A:G	C849R	1.000
16:84063337:G:A	S847F	1.000
16:84065753:C:A	G790W	1.000
16:84066590:C:T	G751E	1.000
16:84066599:G:T	P748Q	1.000
16:84066604:C:A	W746C	1.000
16:84066604:C:G	W746C	1.000
16:84066606:A:G	W746R	1.000
16:84066606:A:T	W746R	1.000
16:84067672:G:C	N741K	1.000
16:84067672:G:T	N741K	1.000
16:84067679:T:A	D739V	1.000
16:84067679:T:G	D739A	1.000
16:84067680:C:G	D739H	1.000
16:84067684:A:C	F737L	1.000
16:84067684:A:T	F737L	1.000
16:84067685:A:C	F737C	1.000
16:84067685:A:G	F737S	1.000
16:84067686:A:G	F737L	1.000
16:84067717:C:A	W726C	1.000
16:84067717:C:G	W726C	1.000
16:84067719:A:G	W726R	1.000
16:84067719:A:T	W726R	1.000
16:84068430:A:C	N660K	1.000
16:84068430:A:T	N660K	1.000
16:84068446:T:A	D655V	1.000
16:84068446:T:G	D655A	1.000

dbSNP variants (sampled 300 via entrez): RS1000056151 (16:84084041 C>A,T), RS1000068018 (16:84086630 G>A), RS1000068969 (16:84057376 C>T), RS1000104133 (16:84115055 A>G,T), RS1000105009 (16:84084247 C>T), RS1000155027 (16:84096334 A>G), RS1000159398 (16:84108991 T>C), RS1000194904 (16:84075303 C>T), RS1000211014 (16:84108773 C>G), RS1000274773 (16:84090465 G>A,C), RS1000284670 (16:84103160 C>G), RS1000410667 (16:84099601 T>C,G), RS1000417686 (16:84075486 G>C), RS1000470942 (16:84078639 G>A), RS1000491273 (16:84070332 G>A)

Disease associations

OMIM: gene MIM:603355 | disease phenotypes: MIM:618392, MIM:621252

GenCC curated gene-disease

Disease	Classification	Inheritance
spondyloepiphyseal dysplasia, kondo-fu type	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
spondyloepiphyseal dysplasia, kondo-fu type	Definitive	AR

Mondo (2): spondyloepiphyseal dysplasia, kondo-fu type (MONDO:0032721), cataract, alopecia, oral mucosal disorder, and psoriasis-like syndrome (MONDO:0979240)

Orphanet (0):

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000230	Gingivitis
HP:0000358	Posteriorly rotated ears
HP:0000400	Macrotia
HP:0000518	Cataract
HP:0000613	Photophobia
HP:0000768	Pectus carinatum
HP:0001156	Brachydactyly
HP:0001216	Delayed ossification of carpal bones
HP:0001263	Global developmental delay
HP:0001298	Encephalopathy
HP:0001324	Muscle weakness
HP:0001518	Small for gestational age
HP:0001596	Alopecia
HP:0001818	Paronychia
HP:0002194	Delayed gross motor development
HP:0002515	Waddling gait
HP:0002655	Spondyloepiphyseal dysplasia
HP:0002808	Kyphosis
HP:0003198	Myopathy
HP:0003388	Easy fatigability
HP:0003593	Infantile onset
HP:0003765	Psoriasiform dermatitis
HP:0004322	Short stature
HP:0004325	Decreased body weight
HP:0004349	Reduced bone mineral density
HP:0007502	Follicular hyperkeratosis
HP:0008064	Ichthyosis
HP:0010280	Stomatitis

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004097_3	Response to platinum-based neoadjuvant chemotherapy in cervical cancer	3.000000e-06
GCST007740_31	Iris color (a* coordinate)	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007943	response to platinum-based neoadjuvant chemotherapy
EFO:0009764	eye colour measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5916 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S8: Subtilisin

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 7b [PMID: 17583500]	Inhibition	8.1	pIC50

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
N-(2-methoxyphenethyl)-4-(6-aza-bicyclo[3.2.1]octan-6-ylmethyl)-N-(pyrrolidin-3-yl)benzamide	IC50	29 nM

ChEMBL bioactivities

21 potent at pChembl≥5 of 23 total, top 21 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.10	IC50	8	nM	CHEMBL391935
7.54	IC50	29	nM	CHEMBL233987
7.43	IC50	37	nM	CHEMBL233799
7.02	IC50	95	nM	CHEMBL233421
7.00	IC50	100	nM	CHEMBL233422
6.85	IC50	140	nM	CHEMBL233609
6.80	IC50	160	nM	CHEMBL233610
6.77	IC50	170	nM	CHEMBL233611
6.60	IC50	250	nM	CHEMBL394028
6.51	IC50	310	nM	CHEMBL393989
6.37	IC50	430	nM	CHEMBL232587
6.29	IC50	510	nM	CHEMBL232777
6.27	IC50	540	nM	CHEMBL231776
6.23	IC50	590	nM	CHEMBL233573
6.08	IC50	840	nM	CHEMBL233572
6.01	IC50	970	nM	CHEMBL394029
5.85	IC50	1400	nM	CHEMBL232577
5.80	IC50	1600	nM	CHEMBL393377
5.43	IC50	3700	nM	CHEMBL232776
5.05	IC50	9000	nM	CHEMBL233165
5.02	IC50	9600	nM	CHEMBL233166

PubChem BioAssay actives

21 with measured affinity, of 35 total; 21 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
N-[2-(2-chlorophenyl)ethyl]-4-[[3-(2-methylphenyl)piperidin-1-yl]methyl]-N-pyrrolidin-3-ylbenzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	0.0080	uM
4-(6-azabicyclo[3.2.1]octan-6-ylmethyl)-N-[2-(2-methoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	0.0290	uM
N-[2-(2-methoxyphenyl)ethyl]-4-[[3-(2-methylphenyl)piperidin-1-yl]methyl]-N-pyrrolidin-3-ylbenzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	0.0370	uM
4-(2-azabicyclo[2.2.1]heptan-2-ylmethyl)-N-[2-(2-methoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	0.0950	uM
4-[[[(1S,2S)-2-hydroxycyclohexyl]amino]methyl]-N-[2-(2-methoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	0.1000	uM
4-[[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]methyl]-N-[2-(2-methoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	0.1400	uM
1-[[4-[2-(2-methoxyphenyl)ethyl-pyrrolidin-3-ylcarbamoyl]phenyl]methyl]piperidine-3-carboxamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	0.1600	uM
4-(diethylaminomethyl)-N-[2-(2-methoxyphenyl)ethyl]-N-[(3R)-pyrrolidin-3-yl]benzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	0.1700	uM
N-[2-(2-methoxyphenyl)ethyl]-4-(piperidin-1-ylmethyl)-N-pyrrolidin-3-ylbenzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	0.2500	uM
N-[2-(2-methoxyphenyl)ethyl]-4-phenylmethoxy-N-pyrrolidin-3-ylbenzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	0.3100	uM
N-[2-(2,6-dichlorophenyl)ethyl]-4-(diethylaminomethyl)-N-pyrrolidin-3-ylbenzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	0.4300	uM
N-[2-(3-chlorophenyl)ethyl]-4-phenylmethoxy-N-pyrrolidin-3-ylbenzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	0.5100	uM
4-(diethylaminomethyl)-N-[2-(2-methoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	0.5400	uM
N-[2-(2-chlorophenyl)ethyl]-4-phenylmethoxy-N-pyrrolidin-3-ylbenzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	0.5900	uM
N-[2-(2-chlorophenyl)ethyl]-4-(diethylaminomethyl)-N-pyrrolidin-3-ylbenzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	0.8400	uM
4-(diethylaminomethyl)-N-[2-(2-methoxyphenyl)ethyl]-N-[(3S)-pyrrolidin-3-yl]benzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	0.9700	uM
N-[2-(2-chlorophenyl)ethyl]-4-propan-2-yloxy-N-pyrrolidin-3-ylbenzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	1.4000	uM
4-(diethylaminomethyl)-N-[2-(2-methylphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	1.6000	uM
N-[2-(4-chlorophenyl)ethyl]-4-(diethylaminomethyl)-N-pyrrolidin-3-ylbenzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	3.7000	uM
N-[2-(2-fluorophenyl)ethyl]-4-propan-2-yloxy-N-pyrrolidin-3-ylbenzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	9.0000	uM
N-[2-(3-chlorophenyl)ethyl]-4-propan-2-yloxy-N-pyrrolidin-3-ylbenzamide	299745: Inhibition of human S1P expressed in CHOK1 cells	ic50	9.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, increases expression, affects cotreatment	5
T-2 Toxin	decreases expression	2
bisphenol F	affects cotreatment, increases expression	1
2,4,6-tribromophenol	decreases expression	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
aflatoxin B2	increases methylation	1
coumarin	increases phosphorylation	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
deguelin	decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
Air Pollutants	increases abundance, affects expression	1
Cisplatin	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ozone	affects expression, increases abundance	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Rotenone	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1175363	Binding	Inhibition of human recombinant soluble Kexin isozyme 1	C(2)-Symmetric azobenzene-amino acid conjugates and their inhibition of Subtilisin Kexin Isozyme-1. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SX53	HAP1 MBTPS1 (-) 1	Cancer cell line	Male
CVCL_SX54	HAP1 MBTPS1 (-) 2	Cancer cell line	Male
CVCL_SX55	HAP1 MBTPS1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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