BMP1

Summary

BMP1 (bone morphogenetic protein 1, HGNC:1067) is a protein-coding gene on chromosome 8p21.3, encoding Bone morphogenetic protein 1 (P13497). Metalloprotease that plays key roles in regulating the formation of the extracellular matrix (ECM) via processing of various precursor proteins into mature functional enzymes or structural proteins.

This gene encodes a protein that is capable of inducing formation of cartilage in vivo. Although other bone morphogenetic proteins are members of the TGF-beta superfamily, this gene encodes a protein that is not closely related to other known growth factors. This gene is expressed as alternatively spliced variants that share an N-terminal protease domain but differ in their C-terminal region.

Source: NCBI Gene 649 — RefSeq curated summary.

At a glance

• Gene–disease (curated): osteogenesis imperfecta type 13 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 1,075 total — 29 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 40
• Druggable target: yes
• MANE Select transcript: NM_006129

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1067
Approved symbol	BMP1
Name	bone morphogenetic protein 1
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Aliases	BMP-1
Ensembl gene	ENSG00000168487
Ensembl biotype	protein_coding
OMIM	112264
Entrez	649

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 8 nonsense_mediated_decay, 4 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000306349, ENST00000306385, ENST00000354870, ENST00000397814, ENST00000471755, ENST00000483364, ENST00000517324, ENST00000518656, ENST00000518913, ENST00000520626, ENST00000520970, ENST00000520982, ENST00000521385, ENST00000521521, ENST00000522332, ENST00000523457, ENST00000523749, ENST00000523849

RefSeq mRNA: 2 — MANE Select: NM_006129 NM_001199, NM_006129

CCDS: CCDS34856, CCDS6026

Canonical transcript exons

ENST00000306385 — 20 exons

Exon	Start	End
ENSE00001271402	22176961	22177139
ENSE00001686063	22211594	22212326
ENSE00001897101	22165372	22165553
ENSE00003460517	22194058	22194174
ENSE00003461202	22206854	22206981
ENSE00003470238	22180368	22180483
ENSE00003499800	22194445	22194590
ENSE00003561862	22195462	22195587
ENSE00003575235	22207303	22207516
ENSE00003578070	22173602	22173715
ENSE00003584046	22192049	22192151
ENSE00003592494	22201803	22201928
ENSE00003601618	22179705	22179829
ENSE00003619502	22197240	22197420
ENSE00003619716	22196680	22196840
ENSE00003636319	22176533	22176650
ENSE00003650341	22194724	22194919
ENSE00003660493	22176143	22176313
ENSE00003677593	22209445	22209695
ENSE00003680229	22177852	22177957

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 97.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.5807 / max 233.0660, expressed in 1659 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87733	7.3685	1469
87732	4.2317	1268
87731	3.9804	1140

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	97.04	gold quality
left uterine tube	UBERON:0001303	95.67	gold quality
right adrenal gland cortex	UBERON:0035827	94.36	gold quality
left coronary artery	UBERON:0001626	94.16	gold quality
right adrenal gland	UBERON:0001233	93.85	gold quality
olfactory bulb	UBERON:0002264	93.84	gold quality
endocervix	UBERON:0000458	93.81	gold quality
ectocervix	UBERON:0012249	93.74	gold quality
coronary artery	UBERON:0001621	93.72	gold quality
left adrenal gland cortex	UBERON:0035825	93.60	gold quality
right coronary artery	UBERON:0001625	93.55	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.53	gold quality
body of uterus	UBERON:0009853	93.52	gold quality
lower esophagus	UBERON:0013473	93.50	gold quality
mucosa of stomach	UBERON:0001199	93.45	gold quality
ascending aorta	UBERON:0001496	93.27	gold quality
adrenal cortex	UBERON:0001235	93.25	gold quality
thoracic aorta	UBERON:0001515	93.25	gold quality
left adrenal gland	UBERON:0001234	93.24	gold quality
descending thoracic aorta	UBERON:0002345	93.10	gold quality
type B pancreatic cell	CL:0000169	93.05	gold quality
placenta	UBERON:0001987	93.04	gold quality
omental fat pad	UBERON:0010414	92.92	gold quality
peritoneum	UBERON:0002358	92.89	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.66	gold quality
lower esophagus mucosa	UBERON:0035834	92.65	gold quality
tibial nerve	UBERON:0001323	92.34	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.14	gold quality
right lung	UBERON:0002167	92.05	gold quality
aorta	UBERON:0000947	91.98	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	17.67
E-MTAB-5061	yes	11.06
E-MTAB-6678	yes	4.10

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI2, ZNF8

Literature-anchored findings (GeneRIF, showing 40)

• bone morphogenetic protein-1 (BMP-1), which exhibits procollagen C-proteinase activity, cleaves the C-terminal propeptide from human procollagen VII (PMID:11986329)
• Post-translational modification is required for secretion and stability of the protein. (PMID:12218058)
• the minimal domain structure for PCP activity is considerably shorter than expected and comprises the metalloproteinase domain and the CUB1 and CUB2 domains of BMP-1 (PMID:12637537)
• Pro-BMP-1 is cleaved in the trans-Golgi network (PMID:12637569)
• Dermal wound healing in red Duroc pigs show unique mRNA expression of HSP47,BMP-1,TIMP1-3 and hypercontracted,hyperpigmented scars. (PMID:15225209)
• cleaves LG3 from recombinant endorepellin at the physiologically relevant site and cleaves LG3 from endogenous perlecan in cultured mouse and human cells (PMID:15591058)
• chordinase activity of BMP1 is not enhanced by PCPE-1 (PMID:15817489)
• tolloid-like 1 binds procollagen C-proteinase enhancer protein 1 and differs from bone morphogenetic protein 1 in the functional roles of homologous protein domains (PMID:16507574)
• bone morphogenetic protein 1 is inhibited by native and altered forms of alpha2-macroglobulin (PMID:17071617)
• the BMP1 prodomain specifically binds and regulates signaling by BMP2 and BMP4 (PMID:17255107)
• By mutating residues flanking the cleavage site of collagen type V alpha 1, we showed that the aspartate residue at position P2’ is essential for BMP-1 activity. (PMID:17407447)
• data support the concept that the C-terminal domains of BMP1 are important for substrate recognition and for controlling and restricting its proteolytic activity via exosite binding (PMID:17516847)
• BMP1 processes PRL to a 17-kDa anti-angiogenic factor. (PMID:17548836)
• vascular Bmp Msx2 Wnt signaling and oxidative stress have roles in arterial calcification [review] (PMID:18056036)
• Expression of BMP1, BMP6, BMP7, and BMP-receptor 2 was significantly increased in advanced stages of myelofibrosis compared and enhanced levels of BMP6 expression were already evident in prefibrotic stages of primary myelofibrosis. (PMID:18349123)
• The crystal structures of the protease domains of human BMP-1 and the closely related Tolloid-like protease 1 (TLL-1), are reported. (PMID:18824173)
• BMP-1 expression was significantly higher in thyroid tumors with psammoma bodies or with stromal calcification. (PMID:19305382)
• Regulation of alternative splicing of mRNA for procollagen C-endopeptidase in leiomyomas and myometrium depends mainly on the hormonal status of women (PMID:19323056)
• FN binds BMP1-like proteinases in vivo and that FN is an important determinant of the in vivo activity levels of BMP1-like proteinases. (PMID:19617627)
• Data show that only those containing both PCPE1 CUB1 and CUB2 were capable of enhancing BMP-1 activity and binding to a mini-procollagen substrate with nanomolar affinity. (PMID:19801683)
• Three isoforms of BMP1 ranging from the shortest BMP1-5 to the longest (mTLD, inefficient at processing procollagen in vitro) were all shown to be capable of removing the highly conserved propeptides from both proDCN. (PMID:20026052)
• Disruption of BMPR1A-mediated BMP1 signalling during the narrow window of early embryogenesis may interfere with normal VBW formation, causing omphalocele phenotype in the Cd chick model. (PMID:21258932)
• Circulating bone morphogenetic protein 1-3 isoform increases renal fibrosis. (PMID:21415150)
• BMP1-3 is a novel systemic regulator of bone repair. (PMID:21453682)
• Bone morphogenetic protein-1 processes insulin-like growth factor-binding protein 3. (PMID:21697095)
• Excluding anterior cervical fusions, there are no significant differences between spinal fusion procedures with and without BMP-associated overall complications. (PMID:21897187)
• High expression of BMP pathway genes are associated with atypical teratoid/rhabdoid tumors. (PMID:21946044)
• We conclude that BMP1 is an additional gene mutated in autosomal recessive osteogenesis imperfecta (AR-OI). (PMID:22052668)
• The molecular and cellular bases of BMP1-dependent osteogenesis were defined. The importance of BMP1 for bone formation and stability were shown in humans and zebrafish. (PMID:22482805)
• Controlling inhibition of bone morphogenetic protein (BMP1) modulates the number of SOX1 expressing cells, whereas PAX6, another neural precursor marker, remains the same. (PMID:22860217)
• miR-194 suppresses metastasis of non-small cell lung cancer through regulating expression of BMP1 and p27kip1 (PMID:23584484)
• Sequence analysis of BMP1 genes did not reveal any putative mutations for hyperostosis cranialis interna to chromosome 8p21 (PMID:23640157)
• Loss of bone morphogenetic protein is associated with prostate cancer. (PMID:24042462)
• High BMP1 expression is associated with type-1 diabetes. (PMID:24984282)
• mutations of the DSP-PP P4 to P4’ cleavage site can block, impair or accelerate dentin sialoprotein phosphophoryn cleavage, and suggest that its Bone morphogenic protein 1 cleavage site is conserved in order to regulate its cleavage efficiency (PMID:25158199)
• Frequent bone fracture in children is cause by BMP1-1 deficiency. (PMID:25214535)
• Two novel variants in the BMP1 gene: c.808A>G and c.1297G>T care associated with osteogenesis imperfecta. (PMID:25402547)
• study thus highlights the severe and progressive nature of BMP1-associated OI in adults and broadens insights into the functional consequences of BMP1/mTLD-deficiency on ECM organization. (PMID:25656619)
• Data indicate that BMP-1 can simultaneously trigger matrix assembly and boost the synthesis of matrix proteins via a direct effect on growth factors in the contexts of development, growth and tissue repair. [review] (PMID:25701650)
• BMP-1 accelerates the connective tissue growth factor production dependently on cellular internalization in human dental pulp cells, indicating a novel property of BMP-1 which potentially enhances bone-like reparative dentin formation. (PMID:25944709)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bmp1b	ENSDARG00000028053
danio_rerio	bmp1a	ENSDARG00000028071
mus_musculus	Bmp1	ENSMUSG00000022098
rattus_norvegicus	Bmp1	ENSRNOG00000010890

Paralogs (35): NRXN3 (ENSG00000021645), TLL1 (ENSG00000038295), CP (ENSG00000047457), DCBLD2 (ENSG00000057019), HEPH (ENSG00000089472), TLL2 (ENSG00000095587), NRP1 (ENSG00000099250), PCOLCE (ENSG00000106333), CNTNAP3 (ENSG00000106714), CUBN (ENSG00000107611), CNTNAP1 (ENSG00000108797), NRXN2 (ENSG00000110076), MEP1A (ENSG00000112818), NRP2 (ENSG00000118257), CUZD1 (ENSG00000138161), MFGE8 (ENSG00000140545), MEP1B (ENSG00000141434), PDGFC (ENSG00000145431), CNTNAP4 (ENSG00000152910), CNTNAP3B (ENSG00000154529), CNTNAP5 (ENSG00000155052), CDCP2 (ENSG00000157211), PCOLCE2 (ENSG00000163710), EDIL3 (ENSG00000164176), NETO1 (ENSG00000166342), PDGFD (ENSG00000170962), NETO2 (ENSG00000171208), CNTNAP2 (ENSG00000174469), NRXN1 (ENSG00000179915), HEPHL1 (ENSG00000181333), F8 (ENSG00000185010), ASTL (ENSG00000188886), F5 (ENSG00000198734), MFRP (ENSG00000235718), CNTNAP3C (ENSG00000283378)

Protein

Protein identifiers

Bone morphogenetic protein 1 — P13497 (reviewed: P13497)

Alternative names: Mammalian tolloid protein, Procollagen C-proteinase

All UniProt accessions (4): P13497, B7ZKR5, E5RH22, Q3MIM8

UniProt curated annotations — full annotation on UniProt →

Function. Metalloprotease that plays key roles in regulating the formation of the extracellular matrix (ECM) via processing of various precursor proteins into mature functional enzymes or structural proteins. Thereby participates in several developmental and physiological processes such as cartilage and bone formation, muscle growth and homeostasis, wound healing and tissue repair. Roles in ECM formation include cleavage of the C-terminal propeptides from procollagens such as procollagen I, II and III or the proteolytic activation of the enzyme lysyl oxidase LOX, necessary to formation of covalent cross-links in collagen and elastic fibers. Additional substrates include matricellular thrombospondin-1/THBS1 whose cleavage leads to cell adhesion disruption and TGF-beta activation. Plays an important role in bone repair by acting as a coactivator of BMP7.

Subunit / interactions. Interacts with POSTN, the interaction promotes deposition on the extracellular matrix.

Subcellular location. Golgi apparatus. trans-Golgi network. Secreted. Extracellular space. Extracellular matrix. Secreted Secreted.

Tissue specificity. Ubiquitous.

Post-translational modifications. Proteolytically activated in the trans-Golgi network by furin-like/paired basic proprotein convertases, cleavage is not required for secretion.

Disease relevance. Osteogenesis imperfecta 13 (OI13) [MIM:614856] An autosomal recessive form of osteogenesis imperfecta, a disorder of bone formation characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI13 is characterized by normal teeth, faint blue sclerae, severe growth deficiency, severe bone deformity, and recurrent fractures affecting both upper and lower limbs. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activity is increased by the procollagen C-endopeptidase enhancer protein.

Cofactor. Binds 1 zinc ion per subunit.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (7)

UniProt ID	Names	Canonical?
P13497-1	BMP1-3	yes
P13497-2	BMP1-1
P13497-7	BMP1-2
P13497-3	BMP1-4
P13497-4	BMP1-5
P13497-5	BMP1-6
P13497-6	BMP1-7

RefSeq proteins (2): NP_001190, NP_006120* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR000859	CUB_dom	Domain
IPR001506	Peptidase_M12A	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR006026	Peptidase_Metallo	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR015446	BMP_1/tolloid-like	Family
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR034036	ZnMP_TLD/BMP1	Domain
IPR035914	Sperma_CUB_dom_sf	Homologous_superfamily
IPR049883	NOTCH1_EGF-like	Domain

Pfam: PF00431, PF01400, PF07645, PF14670

Enzyme classification (BRENDA):

• EC 2.7.11.4 — [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase (BRENDA: 6 organisms, 32 substrates, 117 inhibitors, 7 Km, 2 kcat entries)
• EC 3.4.24.19 — procollagen C-endopeptidase (BRENDA: 9 organisms, 51 substrates, 208 inhibitors, 6 Km, 5 kcat entries)
• EC 3.4.24.21 — astacin (BRENDA: 25 organisms, 107 substrates, 82 inhibitors, 35 Km, 36 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ATP	0.004–0.025	7
PROCOLLAGEN TYPE I	0.0001–0.0004	5
DANSYL-GLY-LYS-ASN-ALA-PRO-LEU-VAL	0.4–0.52	2
2-AMINOBENZOYL-ARG-GLY-PRO-PHE-SER-PRO-(4-NITRO)	0.327	1
2-AMINOBENZOYL-ARG-HYP-GLY-PHE-SER-PRO-(4-NITRO)	0.044	1
2-AMINOBENZOYL-ARG-PRO-GLY-ALA-SER-PRO-(4-NITRO)	0.154	1
2-AMINOBENZOYL-ARG-PRO-GLY-GLU-SER-PRO-(4-NITRO)	0.954	1
2-AMINOBENZOYL-ARG-PRO-GLY-LYS-SER-PRO-(4-NITRO)	0.281	1
2-AMINOBENZOYL-ARG-PRO-ILE-PHE-SER-PRO-(4-NITRO)	0.029	1
AC-RE(EDANS)-DRNLEVGDDPYK(DABCYL)-NH2	0.034	1
ARG-PRO-PRO-GLY-(4-NITRO)PHE-ALA-PRO-PHE-ARG	0.306	1
ARG-PRO-PRO-GLY-(4-NITRO)PHE-ARG-PRO-PHE-ARG	0.209	1
ARG-PRO-PRO-GLY-(4-NITRO)PHE-LYS-PRO-PHE-ARG	0.116	1
ARG-PRO-PRO-GLY-(4-NITRO)PHE-PHE-PRO-PHE-ARG	0.194	1
ARG-PRO-PRO-GLY-(4-NITRO)PHE-SER-PRO-PHE-ARG	0.085	1

UniProt features (83 total): disulfide bond 19, helix 11, splice variant 10, strand 9, domain 8, glycosylation site 5, sequence variant 5, binding site 3, compositionally biased region 2, modified residue 2, sequence conflict 2, signal peptide 1, propeptide 1, region of interest 1, active site 1, chain 1, mutagenesis site 1, turn 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
3EDH	X-RAY DIFFRACTION	1.25
3EDG	X-RAY DIFFRACTION	1.27
6BSL	X-RAY DIFFRACTION	1.45
6BTQ	X-RAY DIFFRACTION	1.75
6BTP	X-RAY DIFFRACTION	1.93
6BTN	X-RAY DIFFRACTION	2.05
6BTO	X-RAY DIFFRACTION	2.05
6BSM	X-RAY DIFFRACTION	2.33

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13497-F1	81.89	0.45

Functional residue map

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

Catalytic / active sites (1): 214

Ligand- & substrate-binding residues (3): 213; 217; 223

Post-translational modifications (2): 934, 937

Disulfide bonds (19): 163–319, 183–205, 185–186, 322–348, 375–397, 435–461, 488–510, 551–563, 559–572, 574–587, 591–617, 644–666, 707–718, 714–727, 729–742, 747–773, 800–822, 860–890, 917–939

Glycosylation sites (5): 91, 142, 332, 363, 599

Mutagenesis-validated functional residues (1):

Position	Phenotype
119–120	doesn’t abolish secretion.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-1650814	Collagen biosynthesis and modifying enzymes
R-HSA-2214320	Anchoring fibril formation
R-HSA-2243919	Crosslinking of collagen fibrils
R-HSA-8963896	HDL assembly
R-HSA-1474244	Extracellular matrix organization
R-HSA-1474290	Collagen formation
R-HSA-2022090	Assembly of collagen fibrils and other multimeric structures

MSigDB gene sets: 333 (showing top): MODULE_172, TGGTGCT_MIR29A_MIR29B_MIR29C, MODULE_52, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_REGULATION_OF_CARTILAGE_DEVELOPMENT, MODULE_45, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GOMF_GROWTH_FACTOR_ACTIVITY, MODULE_16, CACCAGC_MIR138

GO Biological Process (11): skeletal system development (GO:0001501), cartilage condensation (GO:0001502), ossification (GO:0001503), proteolysis (GO:0006508), dorsal/ventral pattern formation (GO:0009953), protein processing (GO:0016485), cell differentiation (GO:0030154), collagen fibril organization (GO:0030199), positive regulation of cartilage development (GO:0061036), signal transduction (GO:0007165), cartilage development (GO:0051216)

GO Molecular Function (12): metalloendopeptidase activity (GO:0004222), serine-type endopeptidase activity (GO:0004252), cytokine activity (GO:0005125), calcium ion binding (GO:0005509), growth factor activity (GO:0008083), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), Golgi apparatus (GO:0005794), vesicle (GO:0031982)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Extracellular matrix organization	2
Collagen formation	2
Assembly of collagen fibrils and other multimeric structures	2
Plasma lipoprotein assembly	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cartilage development	2
endopeptidase activity	2
receptor ligand activity	2
system development	1
skeletal system morphogenesis	1
cell aggregation	1
multicellular organismal process	1
protein metabolic process	1
regionalization	1
proteolysis	1
protein maturation	1
cellular developmental process	1
extracellular matrix organization	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
regulation of cartilage development	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
skeletal system development	1
animal organ development	1
connective tissue development	1
metallopeptidase activity	1
serine-type peptidase activity	1
metal ion binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
transition metal ion binding	1
protein binding	1
binding	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane-bounded organelle	1

Protein interactions and networks

STRING

1770 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BMP1	POSTN	Q15063	982
BMP1	CHRD	Q9H2X0	933
BMP1	FN1	P02751	886
BMP1	C1R	P00736	865
BMP1	BMP2	P12643	838
BMP1	SFRP2	Q96HF1	757
BMP1	C1S	P09871	753
BMP1	LOXL3	P58215	747
BMP1	LOXL2	Q9Y4K0	735
BMP1	BMP7	P18075	732
BMP1	LOX	P28300	729
BMP1	CRTAP	O75718	717
BMP1	SERPINH1	P29043	705
BMP1	BMPR2	Q13873	687
BMP1	FKBP10	Q96AY3	679

IntAct

99 interactions, top by confidence:

A	B	Type	Score
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
BMP1	MSTN	psi-mi:“MI:0194”(cleavage reaction)	0.710
MSTN	BMP1	psi-mi:“MI:0194”(cleavage reaction)	0.710
BMP1	BMP1	psi-mi:“MI:0407”(direct interaction)	0.640
KLHL22	METTL15	psi-mi:“MI:0914”(association)	0.640
KLHL22	TMEM223	psi-mi:“MI:0914”(association)	0.640
SDF2L1	OLFM2	psi-mi:“MI:0914”(association)	0.640
BMP1	CHRD	psi-mi:“MI:0194”(cleavage reaction)	0.620
BMP1	PCOLCE	psi-mi:“MI:0915”(physical association)	0.610
PCOLCE	BMP1	psi-mi:“MI:0407”(direct interaction)	0.610
BMP1	COL5A1	psi-mi:“MI:0407”(direct interaction)	0.540
BMP1	COL5A1	psi-mi:“MI:0915”(physical association)	0.540
	BMP1	psi-mi:“MI:0407”(direct interaction)	0.540
BMP1	MBL2	psi-mi:“MI:0407”(direct interaction)	0.540
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
BMP1	TLL1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
PON2	NPC1	psi-mi:“MI:0914”(association)	0.530
GREM2	ZZEF1	psi-mi:“MI:0914”(association)	0.530
IGFBP4	MYCBP2	psi-mi:“MI:0914”(association)	0.530
CMA1	MANBA	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530

BioGRID (134): BMP1 (Affinity Capture-MS), TLL2 (Affinity Capture-MS), TLL1 (Affinity Capture-MS), CLIP1 (Affinity Capture-MS), RMND5B (Affinity Capture-MS), NBN (Affinity Capture-MS), GOLGA4 (Affinity Capture-MS), KIF2C (Affinity Capture-MS), GID4 (Affinity Capture-MS), MRE11A (Affinity Capture-MS), CSTF3 (Affinity Capture-MS), MAD1L1 (Affinity Capture-MS), WDR26 (Affinity Capture-MS), ARMC8 (Affinity Capture-MS), RAD50 (Affinity Capture-MS)

ESM2 similar proteins: A5PK46, B3EWZ3, B3EWZ5, B3EWZ6, B8V7S0, B8VIV4, O13065, O18783, O43897, O57382, O57460, O88354, P00591, P00732, P00747, P06867, P06868, P0DJJ2, P12545, P13497, P16233, P19637, P20918, P22894, P27657, P28826, P29183, P33436, P42664, P42674, P50903, P55114, P81139, P98060, P98063, P98068, P98070, Q01177, Q02157, Q11174

Diamond homologs: A0A0C5PRQ1, A0FKN6, A8Q2D1, C9D7R2, C9D7R3, D2KBH9, D5FM34, D5FM37, D5FM38, K7Z9Q9, O16977, O17264, O43897, O57382, O57460, O62243, P07584, P0DM61, P0DM62, P13497, P28825, P28826, P31579, P31580, P31581, P42674, P55112, P55113, P55114, P55115, P84748, P91137, P98060, P98061, P98063, P98068, P98069, P98070, Q16819, Q16820

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
BMP1	“up-regulates quantity”	COL7A1	cleavage
BMP1	“up-regulates activity”	COL5A2	cleavage
BMP1	“up-regulates activity”	COL5A1	cleavage
BMP1	“up-regulates activity”	COL1A1	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 112 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
Initial triggering of complement	5	42.3×	3e-05
Collagen biosynthesis and modifying enzymes	5	12.0×	5e-03
ECM proteoglycans	5	10.6×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
complement activation, classical pathway	5	28.0×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

1075 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	29
Likely pathogenic	19
Uncertain significance	289
Likely benign	608
Benign	66

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1299300	NM_006129.5(BMP1):c.584dup (p.Gln197fs)	Pathogenic
1433797	NM_006129.5(BMP1):c.2T>C (p.Met1Thr)	Pathogenic
190231	NM_006129.5(BMP1):c.2108-359T>C	Pathogenic
190232	NM_006129.5(BMP1):c.2107G>C (p.Asp703His)	Pathogenic
190233	NM_006129.5(BMP1):c.808A>G (p.Met270Val)	Pathogenic
190234	NM_006129.5(BMP1):c.1297G>T (p.Ala433Ser)	Pathogenic
2041847	NM_006129.5(BMP1):c.2431C>T (p.Arg811Ter)	Pathogenic
2735141	NM_001199.4(BMP1):c.2188dup (p.Gln730fs)	Pathogenic
2763843	NM_006129.5(BMP1):c.1841dup (p.Asn614fs)	Pathogenic
2785857	NM_006129.5(BMP1):c.1938C>A (p.Tyr646Ter)	Pathogenic
2789346	NM_006129.5(BMP1):c.2632C>T (p.Gln878Ter)	Pathogenic
2815049	NM_006129.5(BMP1):c.388_389dup (p.Trp130fs)	Pathogenic
2862468	NM_006129.5(BMP1):c.1072del (p.Glu358fs)	Pathogenic
2866182	NC_000008.11:g.22180369_22180385del	Pathogenic
2979051	NM_006129.5(BMP1):c.1833C>A (p.Tyr611Ter)	Pathogenic
2982338	NM_006129.5(BMP1):c.2545C>T (p.Arg849Ter)	Pathogenic
2987540	NM_006129.5(BMP1):c.1A>G (p.Met1Val)	Pathogenic
3004772	NM_001199.4(BMP1):c.2110_2111del (p.Lys704fs)	Pathogenic
3245573	NC_000008.10:g.(?22031095)(22038016_?)del	Pathogenic
3639674	NM_006129.5(BMP1):c.33_44del (p.Gly12_Leu15del)	Pathogenic
3640153	NM_006129.5(BMP1):c.1857G>A (p.Trp619Ter)	Pathogenic
3652773	NM_006129.5(BMP1):c.1838_1872del (p.Pro613fs)	Pathogenic
3668306	NM_006129.5(BMP1):c.1734C>G (p.Tyr578Ter)	Pathogenic
3690564	NM_006129.5(BMP1):c.743del (p.Asn248fs)	Pathogenic
3692495	NM_006129.5(BMP1):c.1A>C (p.Met1Leu)	Pathogenic
3729016	NM_006129.5(BMP1):c.2675G>A (p.Trp892Ter)	Pathogenic
4082206	NM_006129.5(BMP1):c.835A>G (p.Arg279Gly)	Pathogenic
4808167	NM_006129.5(BMP1):c.312dup (p.Gln105fs)	Pathogenic
4847560	NM_006129.5(BMP1):c.1750_1751del (p.Lys584fs)	Pathogenic
1236182	NM_001199.4(BMP1):c.2191T>C (p.Ter731Arg)	Likely pathogenic

SpliceAI

3795 predictions. Top by Δscore:

Variant	Effect	Δscore
8:22165550:GCGG:G	donor_gain	1.0000
8:22165552:GG:G	donor_gain	1.0000
8:22165553:GG:G	donor_gain	1.0000
8:22173597:TTTA:T	acceptor_loss	1.0000
8:22173598:TTA:T	acceptor_loss	1.0000
8:22173599:TAGCT:T	acceptor_loss	1.0000
8:22173600:A:AG	acceptor_gain	1.0000
8:22173600:A:C	acceptor_loss	1.0000
8:22173600:AGCT:A	acceptor_gain	1.0000
8:22173601:G:GG	acceptor_gain	1.0000
8:22173601:GC:G	acceptor_gain	1.0000
8:22173601:GCT:G	acceptor_gain	1.0000
8:22173601:GCTG:G	acceptor_gain	1.0000
8:22173601:GCTGC:G	acceptor_gain	1.0000
8:22173688:GCTC:G	donor_gain	1.0000
8:22173713:CAG:C	donor_loss	1.0000
8:22173714:AG:A	donor_loss	1.0000
8:22173715:GGTA:G	donor_loss	1.0000
8:22173716:GT:G	donor_loss	1.0000
8:22173717:T:G	donor_loss	1.0000
8:22176527:T:TA	acceptor_gain	1.0000
8:22176530:CA:C	acceptor_loss	1.0000
8:22176532:GGTA:G	acceptor_gain	1.0000
8:22176659:G:GT	donor_gain	1.0000
8:22176957:CCAG:C	acceptor_loss	1.0000
8:22176958:CAGGT:C	acceptor_loss	1.0000
8:22177135:GCCAG:G	donor_gain	1.0000
8:22177137:CAG:C	donor_loss	1.0000
8:22177138:AG:A	donor_gain	1.0000
8:22177139:GG:G	donor_gain	1.0000

AlphaMissense

6541 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:22176268:T:A	W130R	1.000
8:22176268:T:C	W130R	1.000
8:22176270:G:C	W130C	1.000
8:22176270:G:T	W130C	1.000
8:22176571:T:A	W158R	1.000
8:22176571:T:C	W158R	1.000
8:22176573:G:C	W158C	1.000
8:22176573:G:T	W158C	1.000
8:22176967:C:G	C186W	1.000
8:22177022:T:A	C205S	1.000
8:22177022:T:C	C205R	1.000
8:22177023:G:A	C205Y	1.000
8:22177023:G:C	C205S	1.000
8:22177023:G:T	C205F	1.000
8:22177024:T:G	C205W	1.000
8:22192094:T:C	C375R	1.000
8:22192095:G:A	C375Y	1.000
8:22192096:C:G	C375W	1.000
8:22192119:G:C	R383P	1.000
8:22194112:T:C	L412P	1.000
8:22194450:T:C	C435R	1.000
8:22194451:G:A	C435Y	1.000
8:22194528:T:A	C461S	1.000
8:22194528:T:C	C461R	1.000
8:22194529:G:A	C461Y	1.000
8:22194529:G:C	C461S	1.000
8:22194529:G:T	C461F	1.000
8:22194530:C:G	C461W	1.000
8:22194534:T:A	W463R	1.000
8:22194534:T:C	W463R	1.000

dbSNP variants (sampled 300 via entrez): RS1000051372 (8:22179370 C>A), RS1000061493 (8:22201352 T>A,G), RS1000156033 (8:22182796 T>C), RS1000209734 (8:22182509 C>T), RS1000223049 (8:22199297 C>T), RS1000282013 (8:22210502 G>A,C), RS1000333750 (8:22210215 G>A), RS1000334919 (8:22206127 A>G), RS1000471047 (8:22192460 C>A), RS1000476157 (8:22184679 G>A,T), RS1000549477 (8:22166254 A>G,T), RS1000587425 (8:22164423 C>T), RS1000633407 (8:22197632 T>A), RS1000703994 (8:22209888 C>T), RS1000802590 (8:22173241 C>T)

Disease associations

OMIM: gene MIM:112264 | disease phenotypes: MIM:614856, MIM:166200, MIM:259420

GenCC curated gene-disease

Disease	Classification	Inheritance
osteogenesis imperfecta type 13	Strong	Autosomal recessive
osteogenesis imperfecta type 3	Supportive	Autosomal dominant
high bone mass osteogenesis imperfecta	Supportive	Autosomal dominant

Mondo (4): osteogenesis imperfecta type 13 (MONDO:0013924), osteogenesis imperfecta (MONDO:0019019), osteogenesis imperfecta type 3 (MONDO:0009804), high bone mass osteogenesis imperfecta (MONDO:0017791)

Orphanet (2): Osteogenesis imperfecta (Orphanet:666), Osteogenesis imperfecta type 3 (Orphanet:216812)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000233	Thin vermilion border
HP:0000325	Triangular face
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000365	Hearing impairment
HP:0000411	Protruding ear
HP:0000527	Long eyelashes
HP:0000592	Blue sclerae
HP:0000637	Long palpebral fissure
HP:0000703	Dentinogenesis imperfecta
HP:0000768	Pectus carinatum
HP:0000926	Platyspondyly
HP:0000939	Osteoporosis
HP:0001166	Arachnodactyly
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001290	Generalized hypotonia
HP:0001382	Joint hypermobility
HP:0001537	Umbilical hernia
HP:0002194	Delayed gross motor development
HP:0002230	Generalized hirsutism
HP:0002645	Wormian bones
HP:0002650	Scoliosis
HP:0002751	Kyphoscoliosis
HP:0002757	Recurrent fractures
HP:0002980	Femoral bowing
HP:0003083	Dislocated radial head
HP:0003183	Wide pubic symphysis
HP:0003202	Skeletal muscle atrophy

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001905_1	Hypertriglyceridemia	7.000000e-06
GCST005194_87	Coronary artery disease	2.000000e-10
GCST005195_63	Coronary artery disease	1.000000e-11
GCST005196_159	Coronary artery disease	2.000000e-11
GCST008159_43	Waist-to-hip ratio adjusted for BMI	2.000000e-06
GCST011365_11	Myocardial infarction	5.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D010013	Osteogenesis Imperfecta	C05.116.099.708.685; C16.320.737; C17.300.200.540
C536044	Osteogenesis imperfecta, type 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3898 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M12: Astacin/Adamalysin

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

Ligand	Action	Affinity	Parameter
compound 2 [PMID: 11934595]	Inhibition	6.7	pIC50

ChEMBL bioactivities

384 potent at pChembl≥5 of 420 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.62	IC50	0.024	nM	CHEMBL21249
10.40	Ki	0.04	nM	CHEMBL4214046
9.70	IC50	0.2	nM	CHEMBL282896
9.00	IC50	1	nM	CHEMBL4204567
9.00	IC50	1	nM	CHEMBL4202714
8.74	IC50	1.8	nM	CHEMBL389491
8.70	IC50	2	nM	CHEMBL226748
8.52	IC50	3	nM	CHEMBL226840
8.52	IC50	3	nM	CHEMBL226777
8.52	IC50	3	nM	CHEMBL226697
8.41	IC50	3.9	nM	CHEMBL279023
8.34	IC50	4.6	nM	CHEMBL282484
8.30	IC50	5	nM	CHEMBL226725
8.22	IC50	6	nM	CHEMBL229814
8.22	IC50	6	nM	CHEMBL229813
8.22	IC50	6	nM	CHEMBL437488
8.22	IC50	6	nM	CHEMBL373953
8.22	IC50	6	nM	CHEMBL226853
8.22	IC50	6	nM	CHEMBL226746
8.22	IC50	6	nM	CHEMBL20787
8.15	IC50	7	nM	CHEMBL439012
8.15	Ki	7	nM	CHEMBL65208
8.10	IC50	8	nM	CHEMBL4207907
8.10	IC50	8	nM	CHEMBL229866
8.10	IC50	8	nM	CHEMBL226957
8.10	Ki	8	nM	CHEMBL292073
8.05	IC50	9	nM	CHEMBL21486
8.03	IC50	9.3	nM	CHEMBL226686
8.00	IC50	10	nM	CHEMBL2204087
8.00	IC50	10	nM	CHEMBL229812
8.00	IC50	10	nM	CHEMBL226852
8.00	IC50	10	nM	CHEMBL226686
8.00	IC50	10	nM	CHEMBL279655
7.96	IC50	11	nM	CHEMBL389020
7.96	Ki	11	nM	CHEMBL389020
7.96	Ki	11	nM	CHEMBL432160
7.89	IC50	13	nM	CHEMBL390931
7.89	IC50	13	nM	CHEMBL373951
7.85	IC50	14	nM	CHEMBL226889
7.85	IC50	14	nM	CHEMBL376115
7.85	IC50	14	nM	CHEMBL226800
7.85	Ki	14	nM	CHEMBL294742
7.85	IC50	14	nM	CHEMBL21237
7.82	IC50	15	nM	CHEMBL227153
7.80	IC50	16	nM	CHEMBL281582
7.77	IC50	17	nM	CHEMBL226890
7.77	IC50	17	nM	CHEMBL226903
7.77	IC50	17	nM	CHEMBL447539
7.77	IC50	17	nM	CHEMBL375964
7.77	IC50	17	nM	CHEMBL482320

PubChem BioAssay actives

390 with measured affinity, of 461 total; 50 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
[3-ethoxy-5-[5-[[[(2R)-2-[(1R)-1-[formyl(hydroxy)amino]propyl]heptanoyl]amino]methylcarbamoyl]furan-2-yl]phenyl]phosphonic acid	1385212: Binding affinity to BMP1 (unknown origin) using ((5-FAM)-ELIDQYDVQRDDSSDGSLED-K(5,6 TAMRA)-CONH2 as substrate preincubated for 3 hrs followed by substrate addition measured for 120 mins by FRET assay	ki	<0.0001	uM
(2S)-2-[[2-ethoxy-4-[5-[[[(2R)-2-[(1R)-1-[formyl(hydroxy)amino]propyl]heptanoyl]amino]methylcarbamoyl]furan-2-yl]benzoyl]amino]butanedioic acid	1385212: Binding affinity to BMP1 (unknown origin) using ((5-FAM)-ELIDQYDVQRDDSSDGSLED-K(5,6 TAMRA)-CONH2 as substrate preincubated for 3 hrs followed by substrate addition measured for 120 mins by FRET assay	ki	<0.0001	uM
9H-fluoren-9-ylmethyl N-[(4R)-2-amino-4-[1,3-benzodioxol-5-ylmethyl-(4-methoxyphenyl)sulfonylamino]-5-(hydroxyamino)-3,5-dioxopentyl]carbamate	161629: Inhibitory activity against Procollagen C-Proteinase (PCP)	ic50	<0.0001	uM
(2R)-2-[1,3-benzodioxol-5-ylmethyl-(4-methoxyphenyl)sulfonylamino]-N-hydroxy-3-thiophen-2-ylpropanamide	161629: Inhibitory activity against Procollagen C-Proteinase (PCP)	ic50	0.0002	uM
[2-ethoxy-4-[5-[[[(2R)-2-[(1R)-1-[formyl(hydroxy)amino]propyl]heptanoyl]amino]methylcarbamoyl]furan-2-yl]phenyl]phosphonic acid	1385188: Inhibition of recombinant human N-terminal 6His/flag-tagged BMP1 (121 to 721 residues) expressed in CHO cells using ((5-FAM)-ELIDQYDVQRDDSSDGSLED-K(5,6 TAMRA)-CONH2) as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins	ic50	0.0010	uM
3-ethoxy-5-[5-[[[(2R)-2-[(1R)-1-[formyl(hydroxy)amino]propyl]heptanoyl]amino]methylcarbamoyl]furan-2-yl]benzoic acid	1385188: Inhibition of recombinant human N-terminal 6His/flag-tagged BMP1 (121 to 721 residues) expressed in CHO cells using ((5-FAM)-ELIDQYDVQRDDSSDGSLED-K(5,6 TAMRA)-CONH2) as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins	ic50	0.0010	uM
5-(3-ethoxyphenyl)-N-[[[(2R)-2-[[formyl(hydroxy)amino]methyl]heptanoyl]amino]methyl]furan-2-carboxamide	1385188: Inhibition of recombinant human N-terminal 6His/flag-tagged BMP1 (121 to 721 residues) expressed in CHO cells using ((5-FAM)-ELIDQYDVQRDDSSDGSLED-K(5,6 TAMRA)-CONH2) as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins	ic50	0.0010	uM
(2S)-2-[[3-ethoxy-5-[5-[[[(2R)-2-[(1R)-1-[formyl(hydroxy)amino]propyl]heptanoyl]amino]methylcarbamoyl]furan-2-yl]benzoyl]amino]butanedioic acid	1385188: Inhibition of recombinant human N-terminal 6His/flag-tagged BMP1 (121 to 721 residues) expressed in CHO cells using ((5-FAM)-ELIDQYDVQRDDSSDGSLED-K(5,6 TAMRA)-CONH2) as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins	ic50	0.0010	uM
4-[5-[[[(2R)-2-[[formyl(hydroxy)amino]methyl]heptanoyl]amino]methylcarbamoyl]furan-2-yl]benzoic acid	1385188: Inhibition of recombinant human N-terminal 6His/flag-tagged BMP1 (121 to 721 residues) expressed in CHO cells using ((5-FAM)-ELIDQYDVQRDDSSDGSLED-K(5,6 TAMRA)-CONH2) as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins	ic50	0.0010	uM
2-ethoxy-4-[5-[[[(2R)-2-[(1R)-1-[formyl(hydroxy)amino]propyl]heptanoyl]amino]methylcarbamoyl]furan-2-yl]benzoic acid	1385188: Inhibition of recombinant human N-terminal 6His/flag-tagged BMP1 (121 to 721 residues) expressed in CHO cells using ((5-FAM)-ELIDQYDVQRDDSSDGSLED-K(5,6 TAMRA)-CONH2) as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins	ic50	0.0010	uM
5-[(3R)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-N-(3,4-dimethoxyphenyl)sulfonyl-1,2,4-oxadiazole-3-carboxamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0018	uM
(3R)-6-cyclohexyl-N-hydroxy-3-(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)hexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0020	uM
(3R)-3-[3-[[acetyl(methyl)amino]methyl]-1,2,4-oxadiazol-5-yl]-6-cyclohexyl-N-hydroxyhexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0030	uM
(3R)-6-cyclohexyl-N-hydroxy-3-[3-[4-(methanesulfonamido)phenyl]-1,2,4-oxadiazol-5-yl]hexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0030	uM
(3R)-6-cyclohexyl-N-hydroxy-3-[3-[[(1-methylsulfonylpiperidin-4-yl)amino]methyl]-1,2,4-oxadiazol-5-yl]hexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0030	uM
(2-chlorophenyl)methyl N-[(4R)-4-[1,3-benzodioxol-5-ylmethyl-(4-methoxyphenyl)sulfonylamino]-5-(hydroxyamino)-5-oxopentyl]carbamate	161628: Inhibitory activity against procollagen C-Proteinase (PCP).	ic50	0.0039	uM
(2-chlorophenyl)methyl N-[(4R)-2-amino-4-[1,3-benzodioxol-5-ylmethyl-(4-methoxyphenyl)sulfonylamino]-5-(hydroxyamino)-3,5-dioxopentyl]carbamate	161629: Inhibitory activity against Procollagen C-Proteinase (PCP)	ic50	0.0046	uM
(3R)-6-cyclohexyl-N-hydroxy-3-[3-(morpholin-4-ylmethyl)-1,2,4-oxadiazol-5-yl]hexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0050	uM
(3R)-6-cyclohexyl-3-[3-[(cyclopropylamino)methyl]-1,2,4-oxadiazol-5-yl]-N-hydroxyhexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0060	uM
(3R)-6-cyclohexyl-N-hydroxy-3-[3-(pyridin-2-ylmethyl)-1,2,4-oxadiazol-5-yl]hexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0060	uM
(3R)-3-[3-[(cyclobutylamino)methyl]-1,2,4-oxadiazol-5-yl]-6-cyclohexyl-N-hydroxyhexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0060	uM
3-[5-[(3R)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-1,2,4-oxadiazol-3-yl]benzoic acid	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0060	uM
2-[5-[(3R)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-1,2,4-oxadiazol-3-yl]pyridine-4-carboxylic acid	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0060	uM
(3R)-6-cyclohexyl-N-hydroxy-3-[3-(pyridin-3-ylmethyl)-1,2,4-oxadiazol-5-yl]hexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0060	uM
(2R)-N-hydroxy-2-[(4-methoxyphenyl)sulfonyl-[[2-(trifluoromethyl)phenyl]methyl]amino]propanamide	161629: Inhibitory activity against Procollagen C-Proteinase (PCP)	ic50	0.0060	uM
methyl 4-[[(2R)-2-[1,3-benzodioxol-5-ylmethyl-(4-methoxyphenyl)sulfonylamino]-3-(hydroxyamino)-3-oxopropyl]carbamoyl]benzoate	161630: In vitro inhibitory activity against procollagen C-terminal proteinase (PCP) in HT1080 cells using synthetic peptide as substrate	ki	0.0070	uM
N-(benzenesulfonyl)-5-[(3R)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-1,2,4-oxadiazole-3-carboxamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0070	uM
(3R)-6-cyclohexyl-N-hydroxy-3-[3-[[(1-hydroxy-2-methylpropan-2-yl)amino]methyl]-1,2,4-oxadiazol-5-yl]hexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0080	uM
3-[5-[[[(2R)-2-[[formyl(hydroxy)amino]methyl]heptanoyl]amino]methylcarbamoyl]furan-2-yl]benzoic acid	1385188: Inhibition of recombinant human N-terminal 6His/flag-tagged BMP1 (121 to 721 residues) expressed in CHO cells using ((5-FAM)-ELIDQYDVQRDDSSDGSLED-K(5,6 TAMRA)-CONH2) as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins	ic50	0.0080	uM
(3R)-6-cyclohexyl-N-hydroxy-3-[3-(4-methylpiperazin-2-yl)-1,2,4-oxadiazol-5-yl]hexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0080	uM
N-[(2R)-2-[1,3-benzodioxol-5-ylmethyl-(4-methoxyphenyl)sulfonylamino]-3-(hydroxyamino)-3-oxopropyl]-2-pyrrol-1-ylbenzamide	161630: In vitro inhibitory activity against procollagen C-terminal proteinase (PCP) in HT1080 cells using synthetic peptide as substrate	ki	0.0080	uM
benzyl N-[(4R)-4-[1,3-benzodioxol-5-ylmethyl-(4-methoxyphenyl)sulfonylamino]-5-(hydroxyamino)-5-oxopentyl]carbamate	161628: Inhibitory activity against procollagen C-Proteinase (PCP).	ic50	0.0090	uM
5-[(3R)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-N,N-dimethyl-1,2,4-oxadiazole-3-carboxamide	370933: Inhibition of human procollagen C-proteinase assessed as [3H]procollagen turnover by scintillation counting	ic50	0.0093	uM
(3R)-3-[3-[(tert-butylamino)methyl]-1,2,4-oxadiazol-5-yl]-6-cyclohexyl-N-hydroxyhexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0100	uM
(3R)-6-cyclohexyl-3-[3-(2,4-dioxo-1H-pyrimidin-5-yl)-1,2,4-oxadiazol-5-yl]-N-hydroxyhexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0100	uM
(2R)-2-[1,3-benzodioxol-5-ylmethyl-(4-methoxyphenyl)sulfonylamino]pent-4-ynoic acid	161632: Inhibitory activity against procollagen C-proteinase (PCP).	ic50	0.0100	uM
3-[[4-(benzylcarbamoylamino)phenyl]sulfonyl-[2-(4-methoxyphenyl)ethyl]amino]-N-hydroxypropanamide	718936: Inhibition of PCP after 1 hr by fluorescence assay	ic50	0.0100	uM
(3R)-6-cyclohexyl-N-hydroxy-3-[3-(methanesulfonamidomethyl)-1,2,4-oxadiazol-5-yl]hexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0110	uM
(2R)-2-[1,3-benzodioxol-5-ylmethyl-(4-methoxyphenyl)sulfonylamino]-N-hydroxy-N’-[(4-phenylphenyl)methyl]pentanediamide	161636: Ability to inhibit procollagen C-terminal proteinase (PCP) tested in vitro	ki	0.0110	uM
(3R)-6-cyclohexyl-N-hydroxy-3-[3-[(4-hydroxypiperidin-1-yl)methyl]-1,2,4-oxadiazol-5-yl]hexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0130	uM
(3R)-6-cyclohexyl-N-hydroxy-3-[3-[6-(methylamino)-3-pyridinyl]-1,2,4-oxadiazol-5-yl]hexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0130	uM
(3R)-6-cyclohexyl-N-hydroxy-3-(3-pyrimidin-5-yl-1,2,4-oxadiazol-5-yl)hexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0140	uM
5-[(3R)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-N-(4-methylphenyl)sulfonyl-1,2,4-oxadiazole-3-carboxamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0140	uM
N-[(2R)-2-[1,3-benzodioxol-5-ylmethyl-(4-methoxyphenyl)sulfonylamino]-3-(hydroxyamino)-3-oxopropyl]benzamide	161630: In vitro inhibitory activity against procollagen C-terminal proteinase (PCP) in HT1080 cells using synthetic peptide as substrate	ki	0.0140	uM
(3R)-6-cyclohexyl-N-hydroxy-3-(3-pyrazin-2-yl-1,2,4-oxadiazol-5-yl)hexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0140	uM
benzyl N-[(4R)-2-amino-4-[1,3-benzodioxol-5-ylmethyl-(4-methoxyphenyl)sulfonylamino]-5-(hydroxyamino)-3,5-dioxopentyl]carbamate	161629: Inhibitory activity against Procollagen C-Proteinase (PCP)	ic50	0.0140	uM
(3R)-6-cyclohexyl-3-[3-[(1,1-dioxo-1,2-thiazolidin-2-yl)methyl]-1,2,4-oxadiazol-5-yl]-N-hydroxyhexanamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0150	uM
benzyl N-[(5R)-5-[1,3-benzodioxol-5-ylmethyl-(4-methoxyphenyl)sulfonylamino]-6-(hydroxyamino)-6-oxohexyl]carbamate	161629: Inhibitory activity against Procollagen C-Proteinase (PCP)	ic50	0.0160	uM
2-[5-[(3R)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-1,2,4-oxadiazol-3-yl]pyridine-4-carboxamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0170	uM
5-[(3R)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-N-(4-methoxyphenyl)sulfonyl-1,2,4-oxadiazole-3-carboxamide	292110: Inhibition of human procollagen C-proteinase expressed in CHO cells	ic50	0.0170	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	4
Tobacco Smoke Pollution	affects expression, decreases expression	3
graphene oxide	increases expression	2
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	increases expression, increases methylation	2
Ozone	affects cotreatment, increases expression, increases abundance	2
Valproic Acid	increases methylation, decreases expression	2
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
bisphenol A	decreases methylation	1
lead acetate	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects expression	1
beta-lapachone	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
arsenic trichloride	affects binding, decreases reaction	1
seocalcitol	increases expression	1
apatinib	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Aluminum Oxide	increases expression	1
Cacodylic Acid	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diethylhexyl Phthalate	increases expression	1

ChEMBL screening assays

30 unique, capped per target: 29 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2216690	Binding	Inhibition of PCP in HFF cells assessed as inhibition of collagen deposition after 48 hrs by ELISA	Design and synthesis of procollagen C-proteinase inhibitors. — Bioorg Med Chem Lett
CHEMBL4189610	ADMET	Inhibition of human BMP1 expressed in Escherichia coli assessed as residual activity using Abz-YVADAPK(Dnp)G-OH as substrate at 200 uM by fluorescence assay relative to control	Structure-Guided Design, Synthesis, and Characterization of Next-Generation Meprin β Inhibitors. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1S4	HAP1 BMP1 (-) 1	Cancer cell line	Male
CVCL_E1S5	HAP1 BMP1 (-) 2	Cancer cell line	Male
CVCL_E1S6	HAP1 BMP1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00131469	PHASE4	COMPLETED	Study of Teriparatide (FORTEO) to Treat Adults With Osteogenesis Imperfecta
NCT00159419	PHASE4	COMPLETED	Bisphosphonate Therapy for Osteogenesis Imperfecta
NCT01713231	PHASE4	COMPLETED	Effect of High-Dose Vitamin D on Bone Density in Osteogenesis Imperfecta
NCT02303873	PHASE4	COMPLETED	Efficacy and Safety of Alendronate in Chinese Children or Adolescents With Osteogenesis Imperfecta
NCT03735537	PHASE4	COMPLETED	Treatment of Osteogenesis Imperfecta With Parathyroid Hormone and Zoledronic Acid
NCT04152551	PHASE4	RECRUITING	Effects of Bisphosphonates on OI-Related Hearing Loss
NCT00001305	PHASE3	COMPLETED	Growth Hormone Therapy in Osteogenesis Imperfecta
NCT00005901	PHASE3	COMPLETED	Pamidronate to Treat Osteogenesis Imperfecta in Children
NCT00106028	PHASE3	COMPLETED	Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children
NCT00982124	PHASE3	COMPLETED	An Efficacy and Safety Trial of Intravenous Zoledronic Acid in Infants Less Than One Year of Age, With Severe Osteogenesis Imperfecta
NCT02352753	PHASE3	TERMINATED	Multicenter,Single-arm Study to Evaluate Efficacy, Safety, & Pharmacokinetics of Denosumab in Children w/ OI
NCT03638128	PHASE3	TERMINATED	Open-label Extension of Study 20130173 of Denosumab in Children and Young Adults With Osteogenesis Imperfecta
NCT05768854	PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta
NCT05972551	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate Efficacy and Safety of Romosozumab Compared With Bisphosphonates in Children and Adolescents With Osteogenesis Imperfecta
NCT06636071	PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab in Pediatric Japanese Subjects With Osteogenesis Imperfecta
NCT07366086	PHASE3	RECRUITING	Pediatric Safety Follow-up Study of Prior Treatment With Romosozumab for Osteogenesis Imperfecta
NCT03118570	PHASE2	COMPLETED	A Study in Adult Patients With Type I, III or IV Osteogenesis Imperfecta Treated With BPS804
NCT00063479	PHASE2	COMPLETED	Bisphosphonate Treatment of Osteogenesis Imperfecta
NCT00131118	PHASE2	COMPLETED	Zoledronic Acid in Children (1 -17 Years) With Severe Osteogenesis Imperfecta
NCT01417091	PHASE2	COMPLETED	Safety, Pharmacokinetics and Pharmacodynamics of BPS804 in Osteogenesis Imperfecta
NCT01679080	PHASE2	TERMINATED	The Effect of Treatment With Teriparatide and Zoledronic Acid in Patients With Osteogenesis Imperfecta
NCT01799798	PHASE2	COMPLETED	Translational Therapy in Patients With Osteogenesis Imperfecta - A Pilot Trial on Treatment With the Rankl-Antibody Denosumab
NCT03208582	PHASE2	COMPLETED	Do Bisphosphonates Alter the Skeletal Response to Mechanical Stimulation in Children With Osteogenesis Imperfecta?
NCT03216486	PHASE2	WITHDRAWN	An Exploratory Study of BPS804 Treatment in Adult Patients With Type I, III or IV Osteogenesis Imperfecta
NCT05312697	PHASE2	TERMINATED	Long-term Extension Study of Setrusumab in Adults With Type I, III, or IV Osteogenesis Imperfecta
NCT07062588	PHASE2	RECRUITING	Osteogenesis Imperfecta Trial of AGA2115 for ADUlts With COL1A1 and/or COL1A2 GeNetic Variations (IDUN)
NCT07557446	PHASE2	NOT_YET_RECRUITING	A Dose REgimen-Finding Study of AGA2115 in Chinese Patients With Osteogenesis ImpeRfecta (EIR)
NCT01061099	PHASE1	COMPLETED	Repeated Infusions of Mesenchymal Stromal Cells in Children With Osteogenesis Imperfecta
NCT00705120	PHASE1	COMPLETED	Treatment of Severe Osteogenesis Imperfecta by Allogeneic Bone Marrow Transplantation
NCT02172885	PHASE1	COMPLETED	Mesenchymal Stem Cell Based Therapy for the Treatment of Osteogenesis Imperfecta
NCT03064074	PHASE1	COMPLETED	Safety of Fresolimumab in the Treatment of Osteogenesis Imperfecta
NCT04545554	PHASE1	COMPLETED	Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta
NCT05231668	PHASE1	TERMINATED	Single Ascending Dose Study of SAR439459 in Adults With Osteogenesis Imperfecta (OI)
NCT06086613	PHASE1	COMPLETED	A First-in-Human Study Evaluating AGA2115 in Adult Healthy Volunteers
NCT05559801	PHASE1/PHASE2	NOT_YET_RECRUITING	Mesenchymal Cell Therapy in Osteogenesis Imperfecta (OI)
NCT05125809	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab vs Placebo for Osteogenesis Imperfecta
NCT03706482	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Boost Brittle Bones Before Birth
NCT04623606	PHASE1/PHASE2	UNKNOWN	Boost to Brittle Bones - Stem Cell Transplantation for Treatment of Brittle Bones
NCT00001594	Not specified	COMPLETED	Evaluation and Intervention for the Effects of Osteogenesis Imperfecta
NCT00076830	Not specified	COMPLETED	Evaluation and Treatment of Patients With Connective Tissue Disease