BMPR1A

Summary

BMPR1A (bone morphogenetic protein receptor type 1A, HGNC:1076) is a protein-coding gene on chromosome 10q23.2, encoding Bone morphogenetic protein receptor type-1A (P36894). On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. It is a selective cancer dependency (DepMap: 13.8% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

The bone morphogenetic protein (BMP) receptors are a family of transmembrane serine/threonine kinases that include the type I receptors BMPR1A and BMPR1B and the type II receptor BMPR2. These receptors are also closely related to the activin receptors, ACVR1 and ACVR2. The ligands of these receptors are members of the TGF-beta superfamily. TGF-betas and activins transduce their signals through the formation of heteromeric complexes with 2 different types of serine (threonine) kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 70-80 kD. Type II receptors bind ligands in the absence of type I receptors, but they require their respective type I receptors for signaling, whereas type I receptors require their respective type II receptors for ligand binding.

Source: NCBI Gene 657 — RefSeq curated summary.

At a glance

• Gene–disease (curated): juvenile polyposis syndrome (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 2,790 total — 235 pathogenic, 69 likely-pathogenic
• Phenotypes (HPO): 117
• Druggable target: yes — 11 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 13.8% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004329

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1076
Approved symbol	BMPR1A
Name	bone morphogenetic protein receptor type 1A
Location	10q23.2
Locus type	gene with protein product
Status	Approved
Aliases	ALK3, CD292
Ensembl gene	ENSG00000107779
Ensembl biotype	protein_coding
OMIM	601299
Entrez	657

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 36 protein_coding, 5 nonsense_mediated_decay

ENST00000372037, ENST00000480152, ENST00000635816, ENST00000636056, ENST00000638429, ENST00000713669, ENST00000713670, ENST00000713671, ENST00000713672, ENST00000713673, ENST00000713674, ENST00000713675, ENST00000883496, ENST00000883497, ENST00000883498, ENST00000883499, ENST00000883500, ENST00000883501, ENST00000883502, ENST00000883503, ENST00000926283, ENST00000926284, ENST00000926285, ENST00000926286, ENST00000926287, ENST00000926288, ENST00000926289, ENST00000926290, ENST00000926291, ENST00000926292, ENST00000926293, ENST00000943087, ENST00000943088, ENST00000943089, ENST00000943090, ENST00000943091, ENST00000943092, ENST00000943093, ENST00000943094, ENST00000943095, ENST00000943096

RefSeq mRNA: 32 — MANE Select: NM_004329 NM_001406559, NM_001406560, NM_001406561, NM_001406562, NM_001406563, NM_001406564, NM_001406565, NM_001406566, NM_001406567, NM_001406568, NM_001406569, NM_001406570, NM_001406571, NM_001406572, NM_001406573, NM_001406574, NM_001406575, NM_001406576, NM_001406577, NM_001406578, NM_001406579, NM_001406580, NM_001406581, NM_001406582, NM_001406583, NM_001406584, NM_001406585, NM_001406586, NM_001406587, NM_001406588, NM_001406589, NM_004329

CCDS: CCDS7378

Canonical transcript exons

ENST00000372037 — 13 exons

Exon	Start	End
ENSE00000711713	86890062	86890224
ENSE00000711717	86892127	86892229
ENSE00000711722	86899794	86899890
ENSE00000711728	86900027	86900126
ENSE00000711732	86912240	86912384
ENSE00000711742	86919172	86919469
ENSE00000830582	86923376	86923506
ENSE00002457271	86921520	86921695
ENSE00003723566	86875867	86876085
ENSE00003800973	86838865	86838979
ENSE00004020647	86923594	86927969
ENSE00004020658	86917134	86917326
ENSE00004020659	86756619	86756919

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 96.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.7576 / max 78.1240, expressed in 1579 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105995	5.9354	1515
105996	1.5585	735
105994	0.7484	467
105997	0.5153	292

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.14	gold quality
calcaneal tendon	UBERON:0003701	94.65	gold quality
saphenous vein	UBERON:0007318	94.01	gold quality
parotid gland	UBERON:0001831	93.57	gold quality
cauda epididymis	UBERON:0004360	93.09	gold quality
biceps brachii	UBERON:0001507	92.26	gold quality
oocyte	CL:0000023	92.12	gold quality
seminal vesicle	UBERON:0000998	91.99	gold quality
popliteal artery	UBERON:0002250	91.91	gold quality
tibial artery	UBERON:0007610	91.90	gold quality
blood vessel layer	UBERON:0004797	91.84	gold quality
urethra	UBERON:0000057	91.55	gold quality
hair follicle	UBERON:0002073	91.32	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.23	gold quality
adrenal tissue	UBERON:0018303	90.88	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.85	gold quality
aorta	UBERON:0000947	90.81	gold quality
tibia	UBERON:0000979	90.71	gold quality
endothelial cell	CL:0000115	90.61	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.58	gold quality
caput epididymis	UBERON:0004358	90.55	gold quality
descending thoracic aorta	UBERON:0002345	90.13	gold quality
heart right ventricle	UBERON:0002080	89.91	gold quality
myocardium	UBERON:0002349	89.77	gold quality
synovial joint	UBERON:0002217	89.60	gold quality
ventricular zone	UBERON:0003053	89.46	gold quality
thoracic aorta	UBERON:0001515	89.30	gold quality
ascending aorta	UBERON:0001496	89.13	gold quality
cardiac muscle of right atrium	UBERON:0003379	88.96	gold quality
choroid plexus epithelium	UBERON:0003911	88.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.46

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
BMP10	Repression
HAMP	Activation
ID1	Activation
MMP2	Activation
MMP9	Activation
NPPA	Repression
POSTN	Activation

Upstream regulators (CollecTRI, top): HFE, SP1

miRNA regulators (miRDB)

185 targeting BMPR1A, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-493-5P	99.96	72.47	2382

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 13.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Germline mutations in BMPR1A cause a subset of juvenile polyposis syndrome and Cowden syndrome cases. (PMID:11536076)
• BMPR1A can act as a minor susceptibility gene for PTEN mutation negative Cowden syndrome (PMID:12620973)
• BMPR-IA may interact with and modulate the activity of a developmentally relevant splicing factor (PMID:15351706)
• A defect in BMPRIA internalization and increased activation of downstream signaling, suggesting that altered BMP receptor trafficking underlies ectopic bone formation in fibrodysplasia ossificans progressiva. (PMID:15940369)
• BMPR1A is a promising marker for evaluating ganglion cells in the enteric nervous system. (PMID:16226113)
• Human granulosa-like tumor cell line KGN expressed BMP type I (BMPR1A and BMPR1B) and type II receptors (BMPR2) and the BMP signaling molecules SMADs (SMAD1 and SMAD5). (PMID:16436528)
• BMPR1A mutation accounts for hereditary mixed polyposis syndrome and inactivating this gene can initiate colorectal tumourigenesis (PMID:16525031)
• structure of the ternary complex representing the signaling competent complex of BMP-2 bound to the entire extracellular domains of both its type I receptor, BMPR-Ia, & its type II receptor, ActRII, at a resolution of 2.2 angstroms (PMID:16672363)
• Cooperation between this gene and PTEN gene is deleted on chromoome 10 in juvenile polyposis coli. (PMID:17101085)
• SF3b4, known to be localized in the nucleus and involved in RNA splicing, binds BMPR-IA and specifically inhibits BMP-mediated osteochondral cell differentiation (PMID:17513295)
• Linkage analysis suggested a cryptic BMPR1A mutation or the presence of another gene in close proximity to the BMPR1A locus. (PMID:17573831)
• Expression of BMP-4 and BMP-7 and their receptors in human ovaries from fetuses as well as adults. (PMID:17624341)
• 5 nonsense, 2 frameshift, 4 missense and 2 splice site mutations were associated with juvenile polyposis syndrome. A 65-BP deletion in intron 4 included -2 of the splice acceptor side of exon 5. (PMID:17873119)
• inactivating BMPR-IA and causing a loss of the BMP-2 tumor suppressor function in colon epithelial cells. (PMID:18160401)
• Large genomic deletions of SMAD4, BMPR1A and PTEN are a common cause of JPS. (PMID:18178612)
• Germline mutation of BMPR1A in a family with juvenile polyposis and colon cancer (PMID:18262054)
• patients with 10q23 microdeletions involving the PTEN and BMPR1A genes have variable clinical phenotypes, which cannot be explained merely by the deletion sizes, and are not restricted to severe infantile juvenile polyposis (PMID:18510548)
• Loss of Bmpr1a, by decreasing MMP2 and/or MMP9 activity, can account for vascular dilatation and persistence of brain microvessels, leading to the impaired organogenesis documented in the brain. (PMID:18667463)
• The overall prevalence of SMAD4 and BMPR1A point mutations and deletions in JPS was 45% in the largest series of patients to date (PMID:18823382)
• The solution structure of BMPR-IA reveals a local disorder-to-order transition upon BMP-2 binding. (PMID:18937504)
• 5-HT transactivates the serine kinase receptor, BMPR 1A, to activate Smads 1/5/8 via Rho and Rho kinase in in bovine and human pulmonary artery smooth muscle cells (PMID:19244313)
• we describe the significance of a bone morphogenetic protein receptor type 1A gene mutation in an Irish family with hereditary mixed polyposis syndrome. (PMID:19438883)
• The prevalence of germline mutations of BMPR1A and SMAD4 are about 20% each in the patient with JPS. (PMID:19463221)
• genetic variation in the BMPR1A may play a role in the pathophysiology of human obesity, possibly mediated through effects on mRNA expression (PMID:19502417)
• Germline BMPR1A defect is the disease-causing mutation in 50% of the HMPS families. (PMID:19773747)
• Low BMP2 is associated with epithelial ovarian cancer. (PMID:20587070)
• Data show that blocking both endogenous BMPR1A and BMPR1B almost offset the effect of BMP7 on the proliferation of NCI-H460 cell completely. (PMID:20673479)
• Crystals BMP receptor type IA bound to the antibody Fab fragment belonged to the monoclinic space group P2(1), with unit-cell parameters a=89.32, b=129.25, c=100.24 A, beta=92.27 degrees (PMID:20693682)
• identified the promoter for BMPR1A, in which mutations may be responsible for as many as 10% of juvenile polyposis cases with unknown mutations (PMID:20843829)
• The crystal structure of the complex of the BMPR-IA bound to the Fab AbD1556 revealed that the contact surface of BMPR-IA overlaps extensively with the contact surface for BMP-2 interaction. (PMID:20927405)
• BMPR1A were detected in the human retina and retinoblastoma cell lines. (PMID:21152263)
• 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)
• Juvenile polyps with a SMAD4 germline mutation were predominantly type B, whereas type A was more common among juvenile polyps with a BMPR1A germline mutation. (PMID:21412070)
• Crystals of GDF5 and BMP receptor IA complex belonged to a monoclinic space group: either I2, with unit-cell parameters a = 63.81, b = 62.85, c = 124.99 A, beta = 95.9 degrees , or C2, with unit-cell parameters a = 132.17, b = 62.78, c = 63.53 A, beta = 112.8 degrees (PMID:21543859)
• Letter: Report the phenotypic spectrum of BMPR1A mutations in hereditary nonpolyposis colorectal cancer without mismatch repair deficiency. (PMID:21640116)
• Sp1 was found to be a candidate factor that likely plays a role in the transcriptional regulation of BMPR1A. (PMID:21872883)
• Results suggest that BMPRIA expression identifies thymic NK cell precursors and that BMP signaling is relevant for NK cell differentiation in the thymus. (PMID:22210872)
• generation of TGF-beta and BMP receptor homo- and hetero-oligomers and its roles as a mechanism capable of fast regulation of signaling by these crucial cytokines [review] (PMID:22293501)
• These data support the role of BMPR-1A as an indicator ofosteoarthritis progression in human knees with circumscribed cartilage lesions. (PMID:22519633)
• analysis of promiscuity and specificity in BMP receptor activation [review] (PMID:22710174)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bmpr1aa	ENSDARG00000019728
danio_rerio	bmpr1ab	ENSDARG00000105045
mus_musculus	Bmpr1a	ENSMUSG00000021796
rattus_norvegicus	Bmpr1a	ENSRNOG00000052469

Paralogs (11): TGFBR1 (ENSG00000106799), ACVR2B (ENSG00000114739), ACVR1 (ENSG00000115170), ACVR2A (ENSG00000121989), ACVR1C (ENSG00000123612), AMHR2 (ENSG00000135409), ACVR1B (ENSG00000135503), BMPR1B (ENSG00000138696), ACVRL1 (ENSG00000139567), TGFBR2 (ENSG00000163513), BMPR2 (ENSG00000204217)

Protein

Protein identifiers

Bone morphogenetic protein receptor type-1A — P36894 (reviewed: P36894)

Alternative names: Activin receptor-like kinase 3, Serine/threonine-protein kinase receptor R5

All UniProt accessions (7): P36894, A0A087X0P8, A0AAQ5BGL1, A0AAQ5BGL8, A0AAQ5BGM0, A0AAQ5BGM8, A0AAQ5BGQ2

UniProt curated annotations — full annotation on UniProt →

Function. On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for BMP2, BMP4, GDF5 and GDF6. Positively regulates chondrocyte differentiation through GDF5 interaction. Mediates induction of adipogenesis by GDF6. May promote the expression of HAMP, potentially via its interaction with BMP2.

Subunit / interactions. Interacts with low affinity with GDF5; positively regulates chondrocyte differentiation. Interacts with BMP4. Interacts with SCUBE3. Interacts with TSC22D1/TSC-22. Interacts with BMP2; the interaction may induce HAMP expression. Interacts with BMP6. Interacts with heterodimers composed of BMP2 and BMP6 in vitro; the interaction may induce HAMP expression. Interacts with TGFBR3.

Subcellular location. Cell membrane. Cell surface.

Tissue specificity. Highly expressed in skeletal muscle.

Post-translational modifications. Glycosylated.

Disease relevance. Juvenile polyposis syndrome (JPS) [MIM:174900] Autosomal dominant gastrointestinal hamartomatous polyposis syndrome in which patients are at risk for developing gastrointestinal cancers. The lesions are typified by a smooth histological appearance, predominant stroma, cystic spaces and lack of a smooth muscle core. Multiple juvenile polyps usually occur in a number of Mendelian disorders. Sometimes, these polyps occur without associated features as in JPS; here, polyps tend to occur in the large bowel and are associated with an increased risk of colon and other gastrointestinal cancers. The disease is caused by variants affecting the gene represented in this entry. Polyposis syndrome, mixed hereditary 2 (HMPS2) [MIM:610069] A disease is characterized by atypical juvenile polyps, colonic adenomas, and colorectal carcinomas. The disease is caused by variants affecting the gene represented in this entry. A microdeletion of chromosome 10q23 involving BMPR1A and PTEN is a cause of chromosome 10q23 deletion syndrome, which shows overlapping features of the following three disorders: Bannayan-Zonana syndrome, Cowden disease and juvenile polyposis syndrome.

Similarity. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.

RefSeq proteins (32): NP_001393488, NP_001393489, NP_001393490, NP_001393491, NP_001393492, NP_001393493, NP_001393494, NP_001393495, NP_001393496, NP_001393497, NP_001393498, NP_001393499, NP_001393500, NP_001393501, NP_001393502, NP_001393503, NP_001393504, NP_001393505, NP_001393506, NP_001393507, NP_001393508, NP_001393509, NP_001393510, NP_001393511, NP_001393512, NP_001393513, NP_001393514, NP_001393515, NP_001393516, NP_001393517, NP_001393518, NP_004320* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000333	TGFB_receptor	Family
IPR000472	Activin_recp	Domain
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR003605	GS_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR045860	Snake_toxin-like_sf	Homologous_superfamily

Pfam: PF01064, PF07714, PF08515

Enzyme classification (BRENDA):

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl-[receptor-protein] + ADP + H(+) (RHEA:18673)
• L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor-protein] + ADP + H(+) (RHEA:44880)

UniProt features (40 total): sequence variant 13, strand 7, disulfide bond 5, binding site 2, topological domain 2, helix 2, domain 2, signal peptide 1, chain 1, glycosylation site 1, transmembrane region 1, mutagenesis site 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
2H62	X-RAY DIFFRACTION	1.85
1REW	X-RAY DIFFRACTION	1.86
2H64	X-RAY DIFFRACTION	1.92
2GOO	X-RAY DIFFRACTION	2.2
3QB4	X-RAY DIFFRACTION	2.28
2QJ9	X-RAY DIFFRACTION	2.44
2QJB	X-RAY DIFFRACTION	2.5
2QJA	X-RAY DIFFRACTION	2.6
3NH7	X-RAY DIFFRACTION	2.7
1ES7	X-RAY DIFFRACTION	2.9
2K3G	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P36894-F1	82.86	0.54

Antibody-complex structures (SAbDab): 1 — 3NH7

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): 362 (proton acceptor)

Ligand- & substrate-binding residues (2): 261; 240–248

Disulfide bonds (5): 61–82, 63–67, 76–100, 110–124, 125–130

Glycosylation sites (1): 73

Mutagenesis-validated functional residues (1):

Position	Phenotype
107–109	affinity for bmp2 decreased by over 200-fold.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-201451	Signaling by BMP
R-HSA-162582	Signal Transduction
R-HSA-9006936	Signaling by TGFB family members

MSigDB gene sets: 746 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_DENDRITE_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_AXIS_SPECIFICATION, GOBP_OUTFLOW_TRACT_SEPTUM_MORPHOGENESIS, GOBP_VENTRICULAR_SEPTUM_MORPHOGENESIS, GOBP_CARTILAGE_DEVELOPMENT, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, GOBP_HEART_TRABECULA_MORPHOGENESIS

GO Biological Process (90): MAPK cascade (GO:0000165), angiogenesis (GO:0001525), osteoblast differentiation (GO:0001649), in utero embryonic development (GO:0001701), mesoderm formation (GO:0001707), somitogenesis (GO:0001756), Mullerian duct regression (GO:0001880), positive regulation of mesenchymal cell proliferation (GO:0002053), chondrocyte differentiation (GO:0002062), outflow tract septum morphogenesis (GO:0003148), outflow tract morphogenesis (GO:0003151), cardiac conduction system development (GO:0003161), atrioventricular valve development (GO:0003171), mitral valve morphogenesis (GO:0003183), tricuspid valve morphogenesis (GO:0003186), endocardial cushion morphogenesis (GO:0003203), cardiac right ventricle morphogenesis (GO:0003215), ventricular trabecula myocardium morphogenesis (GO:0003222), ventricular compact myocardium morphogenesis (GO:0003223), endocardial cushion formation (GO:0003272), protein import into nucleus (GO:0006606), immune response (GO:0006955), transforming growth factor beta receptor signaling pathway (GO:0007179), ectoderm development (GO:0007398), dorsal/ventral axis specification (GO:0009950), dorsal/ventral pattern formation (GO:0009953), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), neural crest cell development (GO:0014032), negative regulation of smooth muscle cell migration (GO:0014912), central nervous system neuron differentiation (GO:0021953), pituitary gland development (GO:0021983), neural plate mediolateral regionalization (GO:0021998), cell differentiation (GO:0030154), lung development (GO:0030324), positive regulation of bone mineralization (GO:0030501), BMP signaling pathway (GO:0030509), positive regulation of transforming growth factor beta2 production (GO:0032915), somatic stem cell population maintenance (GO:0035019), hindlimb morphogenesis (GO:0035137)

GO Molecular Function (14): protein serine/threonine kinase activity (GO:0004674), transmembrane receptor protein serine/threonine kinase activity (GO:0004675), transforming growth factor beta receptor activity, type I (GO:0005025), ATP binding (GO:0005524), BMP binding (GO:0036122), protein homodimerization activity (GO:0042803), SMAD binding (GO:0046332), metal ion binding (GO:0046872), BMP receptor activity (GO:0098821), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (9): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020), dendrite (GO:0030425), neuronal cell body (GO:0043025), signaling receptor complex (GO:0043235), HFE-transferrin receptor complex (GO:1990712), caveola (GO:0005901), cell surface (GO:0009986)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by TGFB family members	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure formation involved in morphogenesis	3
cell differentiation	2
chordate embryonic development	2
heart morphogenesis	2
atrioventricular valve morphogenesis	2
ventricular cardiac muscle tissue morphogenesis	2
cellular anatomical structure	2
intracellular signaling cassette	1
blood vessel morphogenesis	1
ossification	1
formation of primary germ layer	1
mesoderm morphogenesis	1
anterior/posterior pattern specification	1
segmentation	1
somite development	1
developmental process involved in reproduction	1
male sex differentiation	1
anatomical structure regression	1
positive regulation of cell population proliferation	1
mesenchymal cell proliferation	1
regulation of mesenchymal cell proliferation	1
cartilage development	1
outflow tract morphogenesis	1
cardiac septum morphogenesis	1
anatomical structure morphogenesis	1
cardiac muscle tissue development	1
heart valve development	1
mitral valve development	1
tricuspid valve development	1
endocardial cushion development	1
mesenchyme morphogenesis	1
cardiac ventricle morphogenesis	1
heart trabecula morphogenesis	1
endocardial cushion morphogenesis	1
protein kinase activity	1
protein serine/threonine kinase activity	1
cell surface receptor protein serine/threonine kinase signaling pathway	1
transmembrane receptor protein kinase activity	1
transforming growth factor beta receptor activity	1
adenyl ribonucleotide binding	1

Protein interactions and networks

STRING

2800 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BMPR1A	BMP4	P12644	998
BMPR1A	BMP2	P12643	998
BMPR1A	BMP7	P18075	996
BMPR1A	BMP6	P22004	991
BMPR1A	BMPR2	Q13873	986
BMPR1A	ACVR1	Q04771	978
BMPR1A	BMPR1B	P78366	964
BMPR1A	SMAD4	Q13485	912
BMPR1A	BMP5	P22003	903
BMPR1A	GDF5	P43026	901
BMPR1A	GDF2	Q9UK05	893
BMPR1A	ACVR2A	P27037	872
BMPR1A	SMAD5	Q99717	872
BMPR1A	NOG	Q13253	856
BMPR1A	ACVR2B	Q13705	840

IntAct

191 interactions, top by confidence:

A	B	Type	Score
BMP2	BMPR1A	psi-mi:“MI:0407”(direct interaction)	0.970
BMPR1A	BMP2	psi-mi:“MI:0407”(direct interaction)	0.970
BMP2	BMPR1A	psi-mi:“MI:0915”(physical association)	0.970
BMPR1A	BMP2	psi-mi:“MI:0915”(physical association)	0.970
GDF5	BMPR1A	psi-mi:“MI:0407”(direct interaction)	0.730
BMPR1A	GDF5	psi-mi:“MI:0407”(direct interaction)	0.730
SLC20A1	LIN7A	psi-mi:“MI:0914”(association)	0.640
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
BMPR1A	BMP4	psi-mi:“MI:0915”(physical association)	0.610
BMP4	BMPR1A	psi-mi:“MI:0407”(direct interaction)	0.610
Acvr2a	BMP2	psi-mi:“MI:0915”(physical association)	0.540
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530

BioGRID (325): BMPR1A (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), OTUB1 (Biochemical Activity), SF3B4 (Two-hybrid), BMPR1A (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), BMPR1A (Affinity Capture-MS)

ESM2 similar proteins: O00238, O08680, O42127, O42422, O46680, O73875, P09759, P22182, P29318, P29319, P29320, P29323, P36894, P36895, P36896, P36897, P36898, P37023, P37172, P54755, P54756, P54757, P54758, P54759, P54762, P70539, P80201, P80202, P80203, P80204, Q04771, Q05438, Q09488, Q15375, Q28041, Q5CD18, Q5RAN0, Q60629, Q61271, Q61288

Diamond homologs: A0A0P0XII1, A0A0R0HPY5, A7J1T2, C0LGD6, C0LGD8, C0LGD9, C0LGG3, C0LGR6, C0LGV0, O00238, O00506, O04086, O35607, O46680, O64556, O65440, P04627, P09560, P0C5E2, P10398, P10533, P14056, P15056, P18161, P20792, P27037, P27038, P27039, P27040, P27041, P27966, P28028, P34908, P36894, P36895, P36896, P36897, P36898, P37023, P37172

SIGNOR signaling

42 interactions.

A	Effect	B	Mechanism
BMP10	up-regulates	BMPR1A	binding
GDF6	up-regulates	BMPR1A	binding
CTDNEP1	up-regulates	BMPR1A	binding
SMURF1	down-regulates	BMPR1A	ubiquitination
BMPR2	up-regulates	BMPR1A	phosphorylation
BMPR1A	up-regulates	SMAD1	phosphorylation
BMPR1A	up-regulates	SMAD5	phosphorylation
BMPR1A	up-regulates	SOST
NOG	“down-regulates activity”	BMPR1A	binding
SMURF2	down-regulates	BMPR1A	ubiquitination
4-[6-[4-(1-piperazinyl)phenyl]-3-pyrazolo[1,5-a]pyrimidinyl]quinoline	down-regulates	BMPR1A	“chemical inhibition”
AXIN1	down-regulates	BMPR1A	ubiquitination
BMPR1A	“form complex”	BMPR1A/1B/2	binding
BMPR1A	“up-regulates activity”	SMAD5	phosphorylation
BMPR1A	“up-regulates activity”	SMAD1	phosphorylation
BMPR1A	“up-regulates activity”	SMAD9	phosphorylation
BMPR1A	“up-regulates activity”	SMAD1/4	phosphorylation
BMPR1A	“up-regulates activity”	SMAD5/SMAD4	phosphorylation
BMPR1A	“up-regulates activity”	SMAD1/5/8	phosphorylation
BMPR1A	“up-regulates activity”	FAM83G	phosphorylation
SMURF	down-regulates	BMPR1A	ubiquitination
BMPR1A	up-regulates	BMPR1B	binding
BMPR1A	up-regulates	SMAD5
SMAD6	down-regulates	BMPR1A
BMPR2	“up-regulates activity”	BMPR1A	binding
BMPR1A	“up-regulates activity”	MAPK14
BMPR1A	“up-regulates activity”	SMAD8/SMAD4	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 190 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
Gluconeogenesis	5	18.8×	1e-03
Signaling by BMP	6	18.3×	6e-04
Downstream signal transduction	5	16.3×	1e-03
Signaling by SCF-KIT	5	10.6×	7e-03
Constitutive Signaling by Aberrant PI3K in Cancer	8	8.7×	9e-04
Signaling by TGFB family members	8	7.9×	1e-03
Potential therapeutics for SARS	7	6.8×	5e-03
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	8	6.6×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of SMAD protein signal transduction	7	16.6×	1e-04
ureteric bud development	5	14.1×	3e-03
peptidyl-tyrosine phosphorylation	5	13.0×	3e-03
positive regulation of bone mineralization	5	12.1×	4e-03
cellular response to growth factor stimulus	6	11.8×	2e-03
BMP signaling pathway	9	11.2×	1e-04
chondrocyte differentiation	6	11.2×	2e-03
odontogenesis of dentin-containing tooth	6	11.2×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — STAD.

Clinical variants and AI predictions

ClinVar

2790 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	235
Likely pathogenic	69
Uncertain significance	1240
Likely benign	587
Benign	146

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1018119	NM_004329.3(BMPR1A):c.1473+2T>C	Pathogenic
1068878	NC_000010.10:g.(?88651874)(88651996_?)del	Pathogenic
1068880	NC_000010.10:g.(?_88669791)_88681457del	Pathogenic
1071410	NM_004329.3(BMPR1A):c.156_165del (p.Glu53fs)	Pathogenic
1072349	NM_004329.3(BMPR1A):c.1119dup (p.Gly374fs)	Pathogenic
1073369	NM_004329.3(BMPR1A):c.394C>T (p.Gln132Ter)	Pathogenic
1075137	NM_004329.3(BMPR1A):c.1151dup (p.Val385fs)	Pathogenic
1075317	NM_004329.3(BMPR1A):c.813del (p.Trp271fs)	Pathogenic
1075769	NM_004329.3(BMPR1A):c.127_137del (p.Lys43fs)	Pathogenic
1076984	NC_000010.10:g.(?88598623)(88635852_?)del	Pathogenic
1076985	NC_000010.10:g.(?88598623)(88659889_?)del	Pathogenic
127901	NM_004329.3(BMPR1A):c.369del (p.Glu123fs)	Pathogenic
1353523	NM_004329.3(BMPR1A):c.530+3A>G	Pathogenic
1375333	NM_004329.3(BMPR1A):c.1255A>T (p.Lys419Ter)	Pathogenic
1393823	NM_004329.3(BMPR1A):c.1101_1102dup (p.Ile368fs)	Pathogenic
1416153	NM_004329.3(BMPR1A):c.357_360del (p.Arg120fs)	Pathogenic
141674	NM_004329.3(BMPR1A):c.826_827del (p.Glu276fs)	Pathogenic
142351	NM_004329.3(BMPR1A):c.817C>T (p.Arg273Ter)	Pathogenic
142735	NM_004329.3(BMPR1A):c.682C>T (p.Arg228Ter)	Pathogenic
1435228	NM_004329.3(BMPR1A):c.1372dup (p.Tyr458fs)	Pathogenic
1437360	NM_004329.3(BMPR1A):c.1022del (p.Gly341fs)	Pathogenic
1446949	NM_004329.3(BMPR1A):c.97dup (p.Thr33fs)	Pathogenic
1452517	NM_004329.3(BMPR1A):c.1064del (p.Lys355fs)	Pathogenic
1452995	NM_004329.3(BMPR1A):c.1193dup (p.Leu398fs)	Pathogenic
1455939	NC_000010.10:g.(?88678919)(88679236_?)del	Pathogenic
1456917	NM_004329.3(BMPR1A):c.924del (p.Thr309fs)	Pathogenic
1457449	NM_004329.3(BMPR1A):c.1461G>A (p.Trp487Ter)	Pathogenic
1457588	NM_004329.3(BMPR1A):c.1057C>T (p.Gln353Ter)	Pathogenic
1458755	NM_004329.3(BMPR1A):c.829del (p.Ile277fs)	Pathogenic
1459799	NM_004329.3(BMPR1A):c.497del (p.Ala166fs)	Pathogenic

SpliceAI

2928 predictions. Top by Δscore:

Variant	Effect	Δscore
10:86838863:A:AG	acceptor_gain	1.0000
10:86838864:G:GG	acceptor_gain	1.0000
10:86890061:GGACA:G	acceptor_gain	1.0000
10:86890220:TGCAT:T	donor_gain	1.0000
10:86890221:GCAT:G	donor_gain	1.0000
10:86890221:GCATG:G	donor_gain	1.0000
10:86890222:CAT:C	donor_gain	1.0000
10:86890225:G:GG	donor_gain	1.0000
10:86892123:TTAGA:T	acceptor_loss	1.0000
10:86892124:TA:T	acceptor_loss	1.0000
10:86892125:A:AC	acceptor_loss	1.0000
10:86892125:A:AG	acceptor_gain	1.0000
10:86892126:G:A	acceptor_loss	1.0000
10:86892126:G:GA	acceptor_gain	1.0000
10:86892126:GA:G	acceptor_gain	1.0000
10:86892126:GAA:G	acceptor_gain	1.0000
10:86892191:GGGT:G	donor_gain	1.0000
10:86892192:GGTG:G	donor_gain	1.0000
10:86892230:G:GG	donor_gain	1.0000
10:86899788:TTTTA:T	acceptor_loss	1.0000
10:86899789:TTTA:T	acceptor_loss	1.0000
10:86899791:TAGG:T	acceptor_loss	1.0000
10:86899792:A:AG	acceptor_gain	1.0000
10:86899792:A:T	acceptor_loss	1.0000
10:86899792:AG:A	acceptor_gain	1.0000
10:86899793:G:GG	acceptor_gain	1.0000
10:86899793:GG:G	acceptor_gain	1.0000
10:86900127:G:GG	donor_gain	1.0000
10:86912235:A:AG	acceptor_gain	1.0000
10:86912236:A:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000008617 (10:86916303 G>C), RS1000009341 (10:86792785 C>G,T), RS1000020271 (10:86809397 C>T), RS1000055855 (10:86768402 G>A,C), RS1000076134 (10:86785221 G>A), RS1000088553 (10:86857934 A>C), RS1000095877 (10:86826946 C>T), RS1000103588 (10:86774917 A>T), RS1000128161 (10:86784809 A>T), RS1000159933 (10:86897629 CAG>C), RS1000161852 (10:86828402 G>A), RS1000168965 (10:86810018 T>C), RS1000191699 (10:86846323 C>T), RS1000198008 (10:86809821 C>G,T), RS1000200490 (10:86887269 C>T)

Disease associations

OMIM: gene MIM:601299 | disease phenotypes: MIM:174900, MIM:610069, MIM:167000, MIM:607174

GenCC curated gene-disease

Disease	Classification	Inheritance
generalized juvenile polyposis/juvenile polyposis coli	Definitive	Autosomal dominant
juvenile polyposis syndrome	Definitive	Autosomal dominant
polyposis syndrome, hereditary mixed, 2	Strong	Autosomal dominant
primary ovarian failure	Moderate	Autosomal dominant
hereditary mixed polyposis syndrome	Supportive	Autosomal dominant
congenital heart defects, multiple types	Limited	Autosomal dominant
pulmonary arterial hypertension	Disputed Evidence	Unknown

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
juvenile polyposis syndrome	Definitive	AD
pulmonary arterial hypertension	Disputed	UD

Mondo (14): hereditary neoplastic syndrome (MONDO:0015356), juvenile polyposis syndrome (MONDO:0017380), generalized juvenile polyposis/juvenile polyposis coli (MONDO:0008276), polyposis syndrome, hereditary mixed, 2 (MONDO:0012405), pulmonary arterial hypertension (MONDO:0015924), colon carcinoma (MONDO:0002032), ovarian cancer (MONDO:0008170), BMPR1A-related juvenile polyposis syndrome (MONDO:0700348), familial meningioma (MONDO:0011789), familial colorectal cancer type X (MONDO:0018604), breast cancer (MONDO:0007254), congenital heart defects, multiple types (MONDO:0000119), hereditary mixed polyposis syndrome (MONDO:0011023), primary ovarian failure (MONDO:0005387)

Orphanet (11): Inherited cancer-predisposing syndrome (Orphanet:140162), Juvenile polyposis syndrome (Orphanet:2929), Generalized juvenile polyposis/juvenile polyposis coli (Orphanet:329971), Hereditary mixed polyposis syndrome (Orphanet:157794), Pulmonary arterial hypertension (Orphanet:182090), Idiopathic/heritable pulmonary arterial hypertension (Orphanet:422), Pulmonary arterial hypertension associated with another disease (Orphanet:275791), Pulmonary arterial hypertension associated with congenital heart disease (Orphanet:275803), Rare ovarian cancer (Orphanet:213500), Familial multiple meningioma (Orphanet:263662), Familial colorectal cancer Type X (Orphanet:440437)

HPO phenotypes

117 total (30 of 117 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000160	Narrow mouth
HP:0000256	Macrocephaly
HP:0000316	Hypertelorism
HP:0000331	Short chin
HP:0000369	Low-set ears
HP:0000494	Downslanted palpebral fissures
HP:0000505	Visual impairment
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0000737	Irritability
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000969	Edema
HP:0001017	Anemic pallor
HP:0001028	Hemangioma
HP:0001031	Subcutaneous lipoma
HP:0001123	Visual field defect
HP:0001217	Clubbing
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001260	Dysarthria
HP:0001270	Motor delay
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001371	Flexion contracture
HP:0001402	Hepatocellular carcinoma

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST010002_294	Refractive error	3.000000e-08
GCST010241_221	Apolipoprotein A1 levels	2.000000e-09
GCST010242_86	HDL cholesterol levels	3.000000e-08
GCST012490_598	Femur bone mineral density x serum urate levels interaction	2.000000e-10
GCST90002407_303	White blood cell count	7.000000e-09
GCST90020029_134	Waist circumference adjusted for body mass index	7.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004531	urate measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
D000081029	Pulmonary Arterial Hypertension	C08.381.423.847
C537443	Meningioma, familial (supp.)
C563365	Polyposis Syndrome, Hereditary Mixed, 1 (supp.)
C566451	Polyposis Syndrome, Hereditary Mixed, 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5275 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

11 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 14,194 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL5416410	DASATINIB	4	655
CHEMBL217092	SARACATINIB	3	3,982
CHEMBL603469	LESTAURTINIB	3
CHEMBL495727	AT-9283	2	1,376
CHEMBL5314579	ZILURGISERTIB	2	26
CHEMBL5956963	KER-047	2	16
CHEMBL1908397	KW-2449	1	622
CHEMBL3545085	XL-228	1	936
CHEMBL571948	Y-39983	1	705

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Type I receptor serine/threonine kinases

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
compound 13d [PMID: 23639540]	Inhibition	8.3	pIC50
compound 13r [PMID: 23639540]	Inhibition	8.3	pIC50
compound 13a [PMID: 23639540]	Inhibition	7.98	pIC50
K02288	Inhibition	7.46	pIC50
zilurgisertib	Inhibition	6.04	pIC50
LDN-214117	Inhibition	5.93	pIC50
ML347	Inhibition	4.97	pIC50

Binding affinities (BindingDB)

65 measured of 91 human assays (91 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
4-[6-[4-[(2R,6S)-2,6-dimethylpiperazin-1-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-2-methylquinoline	IC50	7.7 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[4-[(2S,6R)-2,6-dimethylpiperazin-1-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	8 nM	US-9682983: BMP inhibitors and methods of use thereof
Momelotinib	IC50	8 nM	US-9469613: (N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide
4-[6-[4-[(2S,6R)-2,6-dimethylpiperazin-1-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	10 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-[4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	12 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(3-fluoro-4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	15 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(5-piperazin-1-yl-2-pyridinyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	16 nM	US-9682983: BMP inhibitors and methods of use thereof
5-piperazin-1-yl-2-(3-quinolin-4-ylpyrazolo[1,5-a]pyrimidin-6-yl)-1,3-thiazole	IC50	19 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-[6-[(2S,6R)-2,6-dimethylpiperazin-1-yl]-3-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	22 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	23 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-4-[6-(4-piperidin-4-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	23 nM	US-9682983: BMP inhibitors and methods of use thereof
2-chloro-4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	24 nM	US-9682983: BMP inhibitors and methods of use thereof
2-piperazin-1-yl-5-(3-quinolin-4-ylpyrazolo[1,5-a]pyrimidin-6-yl)benzonitrile	IC50	24 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline-8-carboxamide	IC50	26 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(6-piperazin-1-yl-3-pyridinyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	29 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(3-chloro-4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	30 nM	US-9682983: BMP inhibitors and methods of use thereof
US10017516, Compound 28	IC50	31 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-(3-fluoro-4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	32 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[4-[(2R,6S)-2,6-dimethylpiperazin-1-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-2-methylquinoline	IC50	32 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[5-[(3S)-pyrrolidin-3-yl]oxy-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	34 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	38 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-(5-piperidin-4-yloxy-2-pyridinyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	41 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-4-[6-(6-piperazin-1-yl-3-pyridinyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	43 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[5-(1-methylpiperidin-4-yl)oxy-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	43 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinolin-7-amine	IC50	44 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[5-[(3R)-pyrrolidin-3-yl]oxy-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	45 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-(3-chloro-4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	46 nM	US-9682983: BMP inhibitors and methods of use thereof
2-piperazin-1-yl-5-(3-quinolin-5-ylpyrazolo[1,5-a]pyrimidin-6-yl)benzonitrile	IC50	47 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[6-[(2R,6S)-2,6-dimethylpiperazin-1-yl]-3-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	56 nM	US-9682983: BMP inhibitors and methods of use thereof
[4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinolin-8-yl]methanol	IC50	62 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(3-piperazin-1-ylprop-1-ynyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	68 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-(6-piperazin-1-yl-3-pyridinyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	84 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-5-[6-[5-(2-piperidin-1-ylethoxy)-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	85 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline-8-carboxylic acid	IC50	88 nM	US-9682983: BMP inhibitors and methods of use thereof
[4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinolin-7-yl]methanol	IC50	102 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(2-piperazin-1-ylpyrimidin-5-yl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	103 nM	US-9682983: BMP inhibitors and methods of use thereof
N-[4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinolin-7-yl]acetamide	IC50	105 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[4-(2-methyl-1-piperidin-1-ylpropan-2-yl)oxyphenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	106 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[2-[[6-(3-quinolin-5-ylpyrazolo[1,5-a]pyrimidin-6-yl)-3-pyridinyl]oxy]ethyl]morpholine	IC50	120 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[6-(2-piperidin-1-ylethoxy)-3-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	127 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[5-[2-(4-methylpiperazin-1-yl)ethoxy]-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	151 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-5-[6-[5-(1-methylpiperidin-4-yl)oxy-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	155 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[5-(2-piperidin-1-ylethoxy)-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	157 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[5-(2-piperazin-1-ylethoxy)-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	157 nM	US-10017516: BMP inhibitors and methods of use thereof
2-methyl-5-[6-(5-piperidin-4-yloxy-2-pyridinyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	180 nM	US-9682983: BMP inhibitors and methods of use thereof
N,N-dimethyl-1-[4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinolin-7-yl]methanamine	IC50	407 nM	US-9682983: BMP inhibitors and methods of use thereof
[4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinolin-8-yl]methanamine	IC50	482 nM	US-9682983: BMP inhibitors and methods of use thereof
2-[[4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinolin-7-yl]methylamino]ethanol	IC50	517 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[2-[[6-[3-(2-methylquinolin-5-yl)pyrazolo[1,5-a]pyrimidin-6-yl]-3-pyridinyl]oxy]ethyl]morpholine	IC50	562 nM	US-9682983: BMP inhibitors and methods of use thereof

ChEMBL bioactivities

417 potent at pChembl≥5 of 450 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.67	IC50	2.15	nM	CHEMBL513147
8.62	IC50	2.4	nM	CHEMBL3818173
8.19	IC50	6.5	nM	CHEMBL5922955
8.19	IC50	6.5	nM	CHEMBL4280599
8.17	IC50	6.78	nM	CHEMBL511563
8.15	IC50	7	nM	CHEMBL4280599
8.04	IC50	9.1	nM	CHEMBL4280599
8.04	IC50	9.2	nM	CHEMBL5989551
7.98	IC50	10.4	nM	CHEMBL2385579
7.72	IC50	19	nM	CHEMBL513147
7.63	IC50	23.4	nM	CHEMBL513147
7.54	IC50	29	nM	CHEMBL6027076
7.46	IC50	34.3	nM	CHEMBL1230714
7.39	IC50	41	nM	CHEMBL2385600
7.32	EC50	48	nM	CHEMBL513147
7.27	IC50	54	nM	CHEMBL5791901
7.26	IC50	55	nM	CHEMBL2385586
7.25	IC50	55.6	nM	CHEMBL5591770
7.24	IC50	57	nM	CHEMBL5924325
7.22	Kd	60	nM	SARACATINIB
7.21	IC50	62	nM	CHEMBL5954063
7.19	Kd	64	nM	CHEMBL1241674
7.17	IC50	68	nM	CHEMBL5590317
7.11	IC50	78	nM	CHEMBL6033935
7.05	IC50	89	nM	CHEMBL5769647
7.04	IC50	92	nM	CHEMBL5989551
7.02	IC50	95	nM	DORSOMORPHIN
6.92	Kd	121	nM	GILTERITINIB
6.89	IC50	129	nM	CHEMBL5189688
6.89	IC50	129	nM	CHEMBL5178564
6.86	IC50	138	nM	CHEMBL6054748
6.84	IC50	146	nM	CHEMBL5856926
6.82	IC50	151	nM	CHEMBL5189461
6.82	IC50	153	nM	CHEMBL5827469
6.79	IC50	161	nM	CHEMBL5183080
6.79	IC50	161	nM	CHEMBL5200241
6.78	IC50	168	nM	CHEMBL4548795
6.77	IC50	171	nM	CHEMBL5186575
6.77	Kd	170	nM	CHEMBL386051
6.77	Kd	170	nM	TAE-684
6.75	IC50	180	nM	CHEMBL5990093
6.75	IC50	180	nM	CHEMBL5879231
6.73	IC50	186	nM	CHEMBL5205781
6.72	IC50	189	nM	CHEMBL6052309
6.72	IC50	190	nM	CHEMBL5795612
6.71	IC50	193	nM	CHEMBL5207070
6.69	Kd	203	nM	XL-228
6.69	IC50	206	nM	CHEMBL5749457
6.67	IC50	212	nM	CHEMBL5945070
6.65	IC50	225	nM	CHEMBL5892456

PubChem BioAssay actives

95 with measured affinity, of 638 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
4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	1431744: Inhibition of human ALK3 using casein as substrate in presence of 10 uM ATP by radiometric kinase assay	ic50	0.0022	uM
6,8-difluoro-2-methyl-4-[7-(4-piperazin-1-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722084: Inhibition of human ALK3 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0050	uM
6-fluoro-2-methyl-4-[7-(4-piperazin-1-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722084: Inhibition of human ALK3 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0050	uM
2-methyl-4-[7-(4-piperazin-1-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722084: Inhibition of human ALK3 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0050	uM
6,8-difluoro-2-methyl-4-[7-(4-piperazin-2-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722084: Inhibition of human ALK3 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0050	uM
2-methyl-4-[7-(4-piperazin-2-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722084: Inhibition of human ALK3 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0050	uM
4-[6-(4-propan-2-yloxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	750131: Inhibition of ALK3 (unknown origin)	ic50	0.0050	uM
4-[6-[4-(4-methylpiperazin-1-yl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	750131: Inhibition of ALK3 (unknown origin)	ic50	0.0050	uM
4-[4-(3-quinolin-4-ylpyrazolo[1,5-a]pyrimidin-6-yl)phenyl]morpholine	750131: Inhibition of ALK3 (unknown origin)	ic50	0.0050	uM
4-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	750131: Inhibition of ALK3 (unknown origin)	ic50	0.0068	uM
4-[6-[4-[(2S,6R)-2,6-dimethylpiperazin-1-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	1417554: Inhibition of ALK3 (unknown origin) using Ulight topo IIa (Thr 1342) peptide as substrate preincubated for 10 mins followed by substrate addition and measured after 1 hr by TR-FRET analysis	ic50	0.0070	uM
4-[4-[3-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]phenyl]morpholine	750131: Inhibition of ALK3 (unknown origin)	ic50	0.0104	uM
3-[6-amino-5-(3,4,5-trimethoxyphenyl)-3-pyridinyl]phenol	1877424: Inhibition of GST-tagged human recombinant ALK3 expressed in insect cells using casein as substrate in presence of [gamma-32P]ATP incubated for 45 mins by Microscint-20 scintillation counting analysis	ic50	0.0343	uM
6-(4-methoxyphenyl)-3-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine	750131: Inhibition of ALK3 (unknown origin)	ic50	0.0410	uM
6-(4-piperazin-1-ylphenyl)-3-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine	750131: Inhibition of ALK3 (unknown origin)	ic50	0.0550	uM
5-(4-acetyl-1H-pyrrol-2-yl)-2-[cyclopropyl-[1-(3-methoxy-4-pyridinyl)pyrazol-4-yl]amino]-1,3-thiazole-4-carboxamide	2112253: Inhibition of ALK3 (unknown origin) by TR-FRET assay	ic50	0.0556	uM
N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(oxan-4-yloxy)quinazolin-4-amine	1424921: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0600	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624945: Binding constant for BMPR1A kinase domain	kd	0.0640	uM
6-[4-(4-methylpiperazin-1-yl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)furo[3,2-b]pyridine	2113166: Inhibition of human ALK3 using casein as substrate in presence of [gamma-33P]ATP and 10 uM ATP by radiometric assay	ic50	0.0680	uM
6-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidine	1948596: Inhibition of ALK3 (unknown origin)	ic50	0.0950	uM
Gilteritinib	1424921: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1210	uM
5-[1-(1-acetylpiperidin-4-yl)pyrazol-4-yl]-8-amino-2-cyclohexyl-3,4-dihydro-2,7-naphthyridin-1-one	1877429: Inhibition of ALK3 (unknown origin)	ic50	0.1290	uM
8-amino-2-cyclohexyl-5-(1-cyclopentylpyrazol-4-yl)-3,4-dihydro-2,7-naphthyridin-1-one	1877429: Inhibition of ALK3 (unknown origin)	ic50	0.1290	uM
8-amino-2-cyclohexyl-5-[1-(piperidin-4-ylmethyl)pyrazol-4-yl]-3,4-dihydro-2,7-naphthyridin-1-one	1877429: Inhibition of ALK3 (unknown origin)	ic50	0.1510	uM
8-amino-2-cyclohexyl-5-(1-propan-2-ylpyrazol-4-yl)-3,4-dihydro-2,7-naphthyridin-1-one	1877429: Inhibition of ALK3 (unknown origin)	ic50	0.1610	uM
8-amino-2-cyclohexyl-5-[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]-3,4-dihydro-2,7-naphthyridin-1-one	1877429: Inhibition of ALK3 (unknown origin)	ic50	0.1610	uM
2-fluoro-6-methoxy-4-[4-methyl-5-[4-(4-propan-2-ylpiperazin-1-yl)phenyl]-3-pyridinyl]benzamide	2113166: Inhibition of human ALK3 using casein as substrate in presence of [gamma-33P]ATP and 10 uM ATP by radiometric assay	ic50	0.1680	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624945: Binding constant for BMPR1A kinase domain	kd	0.1700	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624945: Binding constant for BMPR1A kinase domain	kd	0.1700	uM
8-amino-2-cyclohexyl-5-(1-piperidin-4-ylpyrazol-4-yl)-3,4-dihydro-2,7-naphthyridin-1-one	1877429: Inhibition of ALK3 (unknown origin)	ic50	0.1710	uM
8-amino-2-cyclohexyl-5-(1-piperidin-3-ylpyrazol-4-yl)-3,4-dihydro-2,7-naphthyridin-1-one	1877429: Inhibition of ALK3 (unknown origin)	ic50	0.1860	uM
8-amino-2-cyclohexyl-5-[1-(oxetan-3-yl)pyrazol-4-yl]-3,4-dihydro-2,7-naphthyridin-1-one	1877429: Inhibition of ALK3 (unknown origin)	ic50	0.1930	uM
4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine	1424921: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.2030	uM
methyl (3R,5S)-3,5-dimethyl-4-[3-[6-[(3R)-3-methylpiperazin-1-yl]-3-pyridinyl]-1H-pyrazolo[4,3-d]pyrimidin-5-yl]piperazine-1-carboxylate	1870522: Inhibition of recombinant human N-terminal GST-tagged ALK3 (187 to 532 residues) expressed in baculovirus assessed as loss of peptide phosphorylation activity using peptide substrate in presence of ATP and measured after 1 hrs by HTRF assay	ic50	0.2510	uM
8-amino-2-cyclohexyl-5-[1-(piperidin-3-ylmethyl)pyrazol-4-yl]-3,4-dihydro-2,7-naphthyridin-1-one	1877429: Inhibition of ALK3 (unknown origin)	ic50	0.2740	uM
3-amino-6-[2-chloro-4-[(4-morpholin-4-ylpiperidin-1-yl)methyl]phenyl]-N-(4-hydroxy-1-bicyclo[2.2.2]octanyl)pyrazine-2-carboxamide	1866688: Inhibition of wild type ALK3 (unknown origin) assessed as enzymatic activity using chemiluminescent substrate by ADP-Glo assay	ic50	0.2800	uM
8-amino-2-cyclohexyl-5-(1-methylpyrazol-4-yl)-3,4-dihydro-2,7-naphthyridin-1-one	1877429: Inhibition of ALK3 (unknown origin)	ic50	0.3370	uM
4-[(1R)-1-aminoethyl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzamide	1424921: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.3400	uM
methyl (3S,5R)-3,5-dimethyl-4-[3-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]-1H-pyrazolo[4,3-d]pyrimidin-5-yl]piperazine-1-carboxylate	1870522: Inhibition of recombinant human N-terminal GST-tagged ALK3 (187 to 532 residues) expressed in baculovirus assessed as loss of peptide phosphorylation activity using peptide substrate in presence of ATP and measured after 1 hrs by HTRF assay	ic50	0.3830	uM
1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea	1424921: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.3880	uM
2-(2-adamantyl)-8-amino-5-(1-piperidin-4-ylpyrazol-4-yl)-3,4-dihydro-2,7-naphthyridin-1-one	1877429: Inhibition of ALK3 (unknown origin)	ic50	0.4000	uM
6-(4-piperazin-1-ylphenyl)-3-quinolin-4-ylfuro[3,2-b]pyridine	2113166: Inhibition of human ALK3 using casein as substrate in presence of [gamma-33P]ATP and 10 uM ATP by radiometric assay	ic50	0.4250	uM
1-[4-[4-methyl-5-(3,4,5-trimethoxyphenyl)-3-pyridinyl]phenyl]piperazine	1665328: Inhibition of human ALK3 using casein as substrate in presence of [gamma-33P]-ATP by radiometric hotspot assay	ic50	0.4280	uM
5-[6-[4-[(2S,6R)-2,6-dimethylpiperazin-1-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]naphthalene-1-sulfonamide	1417554: Inhibition of ALK3 (unknown origin) using Ulight topo IIa (Thr 1342) peptide as substrate preincubated for 10 mins followed by substrate addition and measured after 1 hr by TR-FRET analysis	ic50	0.4440	uM
4-[6-(4-piperazin-1-ylphenyl)furo[3,2-b]pyridin-3-yl]pyridin-2-amine	2113166: Inhibition of human ALK3 using casein as substrate in presence of [gamma-33P]ATP and 10 uM ATP by radiometric assay	ic50	0.4570	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147949: Binding affinity to human BMPR1A incubated for 45 mins by Kinobead based pull down assay	kd	0.5229	uM
[(3S,5R)-3,5-dimethyl-4-[3-[6-[(3R)-3-methylpiperazin-1-yl]-3-pyridinyl]-1H-pyrazolo[4,3-d]pyrimidin-5-yl]piperazin-1-yl]-pyrrolidin-1-ylmethanone	1870522: Inhibition of recombinant human N-terminal GST-tagged ALK3 (187 to 532 residues) expressed in baculovirus assessed as loss of peptide phosphorylation activity using peptide substrate in presence of ATP and measured after 1 hrs by HTRF assay	ic50	0.5380	uM
5-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	750131: Inhibition of ALK3 (unknown origin)	ic50	0.5390	uM
2-amino-5-[3-fluoro-4-[[(2R)-2-methylpyrrolidin-1-yl]methyl]phenyl]-N-(4-hydroxy-4-methylcyclohexyl)pyridine-3-carboxamide	1877427: Inhibition of human recombinant ALK3 (198 to 525 residues) expressed in baculovirus-infected insect cells by ADP-Glo kinase assay	ic50	0.5600	uM
3-(4-morpholin-4-ylphenyl)-6-quinolin-4-ylquinazolin-4-one	1399004: Binding affinity to human ALK3 by KdELECT assay	kd	0.6100	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression, increases methylation, decreases reaction (+2 more)	3
Arsenic	affects expression, affects methylation, affects cotreatment, decreases expression, increases abundance	3
Benzo(a)pyrene	affects methylation	2
Valproic Acid	affects expression, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
ginger extract	decreases expression, decreases reaction, increases abundance	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
cadmium acetate	decreases expression	1
rutecarpine	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Glyphosate	decreases expression	1
Adenosine	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Apomorphine	decreases expression	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Dust	increases expression	1
Heparin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1

ChEMBL screening assays

169 unique, capped per target: 166 binding, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1032260	Binding	Inhibition of BMPR1A at 3 uM	Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. — J Med Chem
CHEMBL3998814	ADMET	Inhibition of human ALK3 using casein as substrate in presence of 10 uM ATP by radiometric kinase assay	Identification of the First Selective Activin Receptor-Like Kinase 1 Inhibitor, a Reversible Version of L-783277. — J Med Chem

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1LE	Abcam HeLa BMPR1A KO	Cancer cell line	Female
CVCL_B8C2	Abcam HCT 116 BMPR1A KO	Cancer cell line	Male
CVCL_B8T0	Abcam MCF-7 BMPR1A KO	Cancer cell line	Female
CVCL_B9E8	Abcam A-549 BMPR1A KO	Cancer cell line	Male
CVCL_D9A6	Ubigene HEK293 BMPR1A KO	Transformed cell line	Female
CVCL_EI56	C078	Cancer cell line	Sex unspecified
CVCL_SF38	HAP1 BMPR1A (-) 1	Cancer cell line	Male
CVCL_SF39	HAP1 BMPR1A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00058929	PHASE4	COMPLETED	A Transition Study From Flolan® to Remodulin® in Patients With Pulmonary Arterial Hypertension
NCT00303459	PHASE4	COMPLETED	Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH)
NCT00323297	PHASE4	COMPLETED	Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension
NCT00367770	PHASE4	COMPLETED	BREATHE 5-OL: Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology
NCT00403650	PHASE4	COMPLETED	Inhaled Iloprost for Sarcoidosis-associated Pulmonary Hypertension
NCT00430716	PHASE4	TERMINATED	To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.
NCT00433329	PHASE4	COMPLETED	Combination Therapy in Pulmonary Arterial Hypertension
NCT00439946	PHASE4	TERMINATED	Safety, Efficacy, and Treatment Satisfaction Switching From Flolan to Remodulin Using the Crono Five Ambulatory Pump in Patients With PAH
NCT00483626	PHASE4	UNKNOWN	Hemodynamic Response After Six Months of Sildenafil
NCT00494533	PHASE4	TERMINATED	Study of Intravenous Remodulin in Patients in India With Pulmonary Arterial Hypertension
NCT00617305	PHASE4	COMPLETED	Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)
NCT00625079	PHASE4	WITHDRAWN	Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil
NCT00625469	PHASE4	WITHDRAWN	Pulmonary Arterial Hypertension Secondary to Idiopathic Pulmonary Fibrosis and Treatment With Bosentan
NCT00705588	PHASE4	UNKNOWN	Long Acting Phosphodiesterase 5 Inhibitors as Add-on Therapy for Patients With Pulmonary Hypertension Treated With Prostanoids.
NCT00741819	PHASE4	COMPLETED	Safety Evaluation of Inhaled Treprostinil Administration Following Transition From Inhaled Ventavis in Pulmonary Arterial Hypertension (PAH) Subjects
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT01105091	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension
NCT01105117	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension - Extension of AC-066A401
NCT01268553	PHASE4	COMPLETED	Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication
NCT01302444	PHASE4	TERMINATED	Treprostinil Combined With Tadalafil for Pulmonary Hypertension
NCT01330108	PHASE4	COMPLETED	Safely Change From Bosentan to Ambrisentan in Pulmonary Hypertension
NCT01433328	PHASE4	TERMINATED	Lidocaine Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01508780	PHASE4	WITHDRAWN	Combined Use of Angiography, Optical Coherence Tomography and Intravascular Ultrasound in Evaluation of Pulmonary Vascular Structure and Function in Patients With Pulmonary Arterial Hypertension Treated With Oral Bosentan
NCT01615627	PHASE4	WITHDRAWN	Hypotonic Treprostinil Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01642407	PHASE4	COMPLETED	Safety And Efficacy Of Sildenafil In Children With Pulmonary Arterial Hypertension
NCT01649739	PHASE4	UNKNOWN	Vardenafil as add-on Therapy for Patients With Pulmonary Hypertension Treated With Inhaled Iloprost
NCT02060487	PHASE4	TERMINATED	Effects of Oral Sildenafil on Mortality in Adults With PAH
NCT02253394	PHASE4	TERMINATED	The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study
NCT02284737	PHASE4	TERMINATED	A Study to Investigate the Efficacy of PADN to Improved Functional Capacity and Hemodynamics in Patients With PAH
NCT02310672	PHASE4	COMPLETED	REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension
NCT02847260	PHASE4	COMPLETED	Safety and Tolerability of Rapid Dose Titration of Subcutaneous Remodulin® Therapy in PAH Subjects (RAPID)
NCT02882126	PHASE4	WITHDRAWN	An Open Label Extension Study to Evaluate the Safety of Continued Therapy of Subcutanous Remodulin® in Pulmonary Arterial Hypertension
NCT02885012	PHASE4	TERMINATED	Crossover Study From Macitentan or Bosentan Over to Ambrisentan
NCT02891850	PHASE4	COMPLETED	Riociguat rEplacing PDE-5i Therapy evaLuated Against Continued PDE-5i thErapy
NCT02893995	PHASE4	WITHDRAWN	Safety, Tolerability, Pharmacokinetics and Efficacy of Two Different Rates of Subcutanous Remodulin® Dose Titration in Pulmonary Arterial Hypertension
NCT02968901	PHASE4	TERMINATED	Clinical Study Evaluating the Effects of First-line Oral cOmbination theraPy of maciTentan and tadalafIl in Patients With Newly Diagnosed pulMonary Arterial Hypertension (OPTIMA)
NCT03055221	PHASE4	COMPLETED	TRUST-2: Safety and Efficacy of Intravenous Remodulin® in Patients in India With Pulmonary Arterial Hypertension (PAH)
NCT03078907	PHASE4	COMPLETED	Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension.
NCT03236818	PHASE4	UNKNOWN	Goal Oriented Strategy to Preserve Ejection Fraction Trial
NCT03344159	PHASE4	COMPLETED	Spironolactone Therapy in Chronic Stable Right HF Trial