BMP4

Summary

BMP4 (bone morphogenetic protein 4, HGNC:1071) is a protein-coding gene on chromosome 14q22.2, encoding Bone morphogenetic protein 4 (P12644). Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including neurogenesis, vascular development, angiogenesis and osteogenesis. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein regulates heart development and adipogenesis. Mutations in this gene are associated with orofacial cleft and microphthalmia in human patients. The encoded protein may also be involved in the pathology of multiple cardiovascular diseases and human cancers.

Source: NCBI Gene 652 — RefSeq curated summary.

At a glance

• Gene–disease (curated): BMP4-related ocular growth disorder (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 41
• Clinical variants (ClinVar): 307 total — 13 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 157
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 13 downstream targets (CollecTRI)
• MANE Select transcript: NM_001202

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1071
Approved symbol	BMP4
Name	bone morphogenetic protein 4
Location	14q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000125378
Ensembl biotype	protein_coding
OMIM	112262
Entrez	652

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 23 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000245451, ENST00000417573, ENST00000558489, ENST00000558961, ENST00000558984, ENST00000559087, ENST00000559501, ENST00000559642, ENST00000609748, ENST00000890805, ENST00000890806, ENST00000890807, ENST00000890808, ENST00000890809, ENST00000890810, ENST00000890811, ENST00000890812, ENST00000939836, ENST00000939837, ENST00000939838, ENST00000939839, ENST00000939840, ENST00000939841, ENST00000951376

RefSeq mRNA: 9 — MANE Select: NM_001202 NM_001202, NM_001347912, NM_001347913, NM_001347914, NM_001347915, NM_001347916, NM_001347917, NM_130850, NM_130851

CCDS: CCDS9715

Canonical transcript exons

ENST00000245451 — 4 exons

Exon	Start	End
ENSE00000854771	53951853	53952229
ENSE00001002754	53953276	53953400
ENSE00001164752	53956550	53956825
ENSE00001818483	53949736	53950888

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 97.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.1691 / max 271.1054, expressed in 1047 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143298	3.2583	699
143305	3.0034	521
143294	1.5824	407
143299	1.5303	456
143304	1.3312	504
143300	0.6323	249
143303	0.3375	185
143295	0.1848	91
143297	0.1473	63
143296	0.1109	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	97.30	gold quality
retina	UBERON:0000966	97.27	gold quality
rectum	UBERON:0001052	90.18	gold quality
mucosa of transverse colon	UBERON:0004991	89.03	gold quality
right coronary artery	UBERON:0001625	88.72	gold quality
apex of heart	UBERON:0002098	87.51	gold quality
mucosa of stomach	UBERON:0001199	87.42	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.69	gold quality
gall bladder	UBERON:0002110	85.06	gold quality
fundus of stomach	UBERON:0001160	84.72	gold quality
body of stomach	UBERON:0001161	84.55	gold quality
transverse colon	UBERON:0001157	84.52	gold quality
stomach	UBERON:0000945	84.47	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.35	gold quality
ascending aorta	UBERON:0001496	84.19	gold quality
thoracic aorta	UBERON:0001515	84.12	gold quality
left coronary artery	UBERON:0001626	83.99	gold quality
descending thoracic aorta	UBERON:0002345	83.80	gold quality
coronary artery	UBERON:0001621	83.40	gold quality
muscle layer of sigmoid colon	UBERON:0035805	83.37	gold quality
skin of leg	UBERON:0001511	83.33	gold quality
aorta	UBERON:0000947	83.29	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.88	gold quality
left ovary	UBERON:0002119	82.87	gold quality
popliteal artery	UBERON:0002250	82.84	gold quality
lower esophagus	UBERON:0013473	82.81	gold quality
tibial artery	UBERON:0007610	82.80	gold quality
small intestine	UBERON:0002108	82.77	gold quality
sigmoid colon	UBERON:0001159	82.69	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-11	yes	1531.44
E-MTAB-9906	yes	838.53
E-MTAB-9154	yes	378.99
E-MTAB-6108	yes	249.68
E-HCAD-10	yes	19.12
E-MTAB-8271	yes	7.82
E-MTAB-10137	no	4.66
E-MTAB-5061	no	3.18
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

13 targets.

Target	Regulation
ALPL	Activation
BMP2	Activation
BMP7	Repression
BMPER	Activation
FGF2	Activation
HAMP	Activation
HAND1	Activation
HAND2	Activation
PITX2	Activation
RUNX2	Activation
SEMA3C	Activation
SPP1	Activation
THBS1	Repression

Upstream regulators (CollecTRI, top): AP1, AR, BARX1, CDX2, CTNNB1, DLX3, DLX4, DLX5, E2F1, ETS1, EVX2, FOS, FOXL1, FOXO1, FOXO3, FOXQ1, GATA2, GATA5, GATA6, GBX2, GLI2, GSC, HAND2, HIF1A, HLX, HOXA13, HOXA2, HOXD13, ID1, ID2, ID3, JUN, KAT5, KDM5A, LEF1, LHX8, MEF2C, MEGF8, MSX1, MSX2

miRNA regulators (miRDB)

30 targeting BMP4, 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-6867-5P	100.00	82.21	3464
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-4274	98.59	66.10	630
HSA-MIR-147A	98.33	66.40	795
HSA-MIR-3650	97.88	64.89	693
HSA-MIR-6782-3P	97.60	67.75	931
HSA-MIR-101-5P	96.84	65.66	649
HSA-MIR-1292-5P	96.74	62.14	238
HSA-MIR-3974	96.56	66.22	928
HSA-MIR-6082	96.40	70.86	216
HSA-MIR-644A	96.02	66.52	786
HSA-MIR-1277-3P	93.47	68.97	156

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• The expression signals of BMP-4 mRNA in malignant schwannoma were relatively lower than in benign lesions (PMID:11642720)
• BMP4 reached criteria of suggestive evidence of linkage in candidate genes of ossification of the posterior longitudinal ligament of the spine. (PMID:11771659)
• Bmp-4 only activates Dkk-1 when it concomitantly induces apoptosis. Implanted recombinant human Bmp-4 beads abolish Dkk-1 transcription in chick limb buds and mouse embryo cells. (PMID:11867524)
• Oncogenic beta-catenin is required for bone morphogenetic protein 4 expression in human cancer cells. (PMID:12019147)
• Dissection of promoter control modules that direct Bmp4 expression in the epithelium-derived components of hair follicles. (PMID:12054672)
• directs Smad5 activation in human hematopoietic cells, resulting in significantly increased proliferation of erythroid progenitors and formation of glycophorin-A+ cells. (PMID:12064918)
• Transgenic expression of human Bmp4 driven by the mouse Msx1 promoter in the Msx1(-/-) palatal mesenchyme rescued the cleft palate phenotype and neonatal lethality (PMID:12163415)
• Data show that VEGF plays a role in bone formation elicited by bone morphogenetic protein 4, and can significantly enhance BMP4-elicited bone formation and regeneration. (PMID:12235106)
• Mutations act together with other gene variants in unlinked loci as susceptibility factors in spina bifida. (PMID:12404109)
• demonstrated that the enhancement of expression of mRNA of BMP-4 by phosphate depletion mediates alkaline phosphatase induction in cultured mouse marrow stromal cell line ST2 (PMID:12445813)
• BMP2 and BMP4 differently affect activin A induction of erythropoiesis (PMID:12531697)
• trans-activation by GATA-4 and GATA-6 (PMID:12606287)
• evidence for the role of cytokines and BMP-4 in promoting hematopoietic differentiation of embryonic stem cells (PMID:12702499)
• BMP4 is a mechanosensitive, inflammatory factor playing a critical role in early steps of atherogenesis in the lesion-prone areas. (PMID:12766166)
• data demonstrate the existence and putative function of bone morphogenetic protein 4 signaling in normal ovarian surface epithelium and ovarian cancer cells (PMID:12865307)
• Deletion mutants of BMP folding variants are a new form of BMP antagonists and act through competition with osteoinductive BMP for BMP receptor binding. (PMID:14672349)
• BMP2 or 4 in pilomatricoma is responsible for induction of proalpha(1)(II) collagen mRNA in overlying epidermal cells resulting in deposition of type II collagen in dermo-epidermal junction. (PMID:15102076)
• biglycan modulates BMP-4-induced signaling to control osteoblast differentiation (PMID:15173106)
• results revealed a novel potent effect of PTH and vitamin D(3) plus BMPs in inducing bone development by human mesenchymal stem cells (PMID:15186723)
• BMP4 produced in ECs by oscillatory shear sress stimulates ROS release from the nox1-dependent NADPH oxidase leading to inflammation, a critical early atherogenic step. (PMID:15388638)
• BMP-4 increases the levels of osteopontin, BMP-2, alkaline phosphatase and core binding factor alpha 1 mRNAs in human periodontal (HPL) ligament cells. (PMID:15516325)
• Antiproliferative and prodifferentiation effects of BMP4 were Smad1 dependent with JNK also contributing to differentiation. (PMID:15516492)
• the role of BMP family members in the control of ovarian folliculogenesis (PMID:15591037)
• A polymorphism found in the BMP4 gene, affecting amino acid sequence, is associated with hip bone density in postmenopausal women, presumably via regulation of anabolic effects on the skeleton. (PMID:15777683)
• To analyze the expression of bone morphogenetic proteins (BMPs) in prostate and breast cancers with established metastasis in bone (PMID:15861517)
• BMPs influence the formation of the osteolytic prostate cancer metastases, and treatment modalities that inhibit BMP activity may limit the progression of the lytic component of prostate cancer metastases. (PMID:16126463)
• Retinoic acid induces both BMP-4 transcription and expression and its antiproliferative action in pituitary adenoma (PMID:16195406)
• OAZ can alter the intensity and duration of the BMP4 stimulus through Smad6 (PMID:16373339)
• BMP-4 may play a role in the regulation of ocular angiogenesis associated with diabetic retinopathy (DR) by stimulating vascular endothelial growth factor release from retinal pigment epithelial cells (PMID:16514669)
• BMP-4 is expressed in normal synovial tissue and was decreased in osteoarthritis and rheumatoid arthritis. (PMID:16542506)
• Topical and differential expression of BMP-2/4 and BMP-7 mRNA and protein was found in bursa tissue. (PMID:16719933)
• Recombinant human BMP4 infusion caused hypertension in mice in a vascular NADPH-oxidase-dependent manner. BMP4 is a novel mediator of endothelial dysfunction and hypertension. (PMID:16769910)
• GREMLIN 1 was expressed in the stroma of human basal cell carcinoma (BCC) tumors but not in normal skin in vivo. Bone morphogenetic protein (BMP) 2 and 4 are expressed by BCC cells. (PMID:17003113)
• BMP4 and Gremlin are regulators of myogenic progenitor proliferation. (PMID:17015616)
• The finding that BMP-4 subverts the ability of mammary epithelial cells to form polarized lumen-containing structures and endows them with invasive properties supports the involvement of this cytokine in the progression of breast cancer. (PMID:17189614)
• BMP4 is a key growth factor for maintenance of hematopoietic stem cells and contributes to the properties of stromal culture. (PMID:17253944)
• the BMP1 prodomain specifically binds and regulates signaling by BMP2 and BMP4 (PMID:17255107)
• strong BMP staining is seen in maturing chondrocytes, and thus may play a role in chondrocyte differentiation and/or apoptosis; BMP release by osteoclasts may promote osteoblastic differentiation at sites of bone remodeling (PMID:17262821)
• A link between autocrine BMP4 signalling mediated through the Rho GTPase family may collectively contribute to aggressive ovarian cancer behavior. (PMID:17272306)
• These results indicate that BMP-4 confers invasive phenotype during progression of colon cancer. (PMID:17275810)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	bmp4	ENSDARG00000019995
mus_musculus	Bmp4	ENSMUSG00000021835
rattus_norvegicus	Bmp4	ENSRNOG00000009694

Paralogs (31): TGFB2 (ENSG00000092969), BMP7 (ENSG00000101144), TGFB1 (ENSG00000105329), BMP5 (ENSG00000112175), BMP8B (ENSG00000116985), TGFB3 (ENSG00000119699), INHBA (ENSG00000122641), INHA (ENSG00000123999), BMP2 (ENSG00000125845), GDF5 (ENSG00000125965), GDF1 (ENSG00000130283), BMP15 (ENSG00000130385), GDF15 (ENSG00000130513), GDF11 (ENSG00000135414), MSTN (ENSG00000138379), INHBE (ENSG00000139269), LEFTY2 (ENSG00000143768), GDF7 (ENSG00000143869), BMP3 (ENSG00000152785), BMP6 (ENSG00000153162), GDF6 (ENSG00000156466), NODAL (ENSG00000156574), INHBB (ENSG00000163083), BMP10 (ENSG00000163217), GDF9 (ENSG00000164404), INHBC (ENSG00000175189), BMP8A (ENSG00000183682), GDF3 (ENSG00000184344), LEFTY1 (ENSG00000243709), GDF2 (ENSG00000263761), GDF10 (ENSG00000266524)

Protein

Protein identifiers

Bone morphogenetic protein 4 — P12644 (reviewed: P12644)

Alternative names: Bone morphogenetic protein 2B

All UniProt accessions (6): P12644, H0YLW3, H0YM53, H0YMP9, Q53XC5, V9GYF1

UniProt curated annotations — full annotation on UniProt →

Function. Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including neurogenesis, vascular development, angiogenesis and osteogenesis. Acts in concert with PTHLH/PTHRP to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction. Initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2. Once all three components are bound together in a complex at the cell surface, BMPR2 phosphorylates and activates BMPR1A. In turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes. Positively regulates the expression of odontogenic development regulator MSX1 via inducing the IPO7-mediated import of SMAD1 to the nucleus. Required for MSX1-mediated mesenchymal molar tooth bud development beyond the bud stage, via promoting Wnt signaling. Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, expression is repressed during the bell stage by MSX1-mediated inhibition of CTNNB1 signaling. Able to induce its own expression in dental mesenchymal cells and also in the neighboring dental epithelial cells via an MSX1-mediated pathway. Can also signal through non-canonical BMP pathways such as ERK/MAP kinase, PI3K/Akt, or SRC cascades. For example, induces SRC phosphorylation which, in turn, activates VEGFR2, leading to an angiogenic response.

Subunit / interactions. Homodimer; disulfide-linked. Interacts with GREM2. Part of a complex consisting of TWSG1 and CHRD. Interacts with the serine proteases, HTRA1 and HTRA3; the interaction with either inhibits BMP4-mediated signaling. The HTRA protease activity is required for this inhibition. Interacts with SOSTDC1. Interacts with FBN1 (via N-terminal domain) and FBN2. Interacts with type I receptor BMPR1A. Interacts with type II receptor BMPR2. Interacts with FSTL1; this interaction inhibits the activation of the BMP4/Smad1/5/8 signaling pathway. Interacts with SCUBE3. Interacts with TGFBR3.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed in the lung and lower levels seen in the kidney. Present also in normal and neoplastic prostate tissues, and prostate cancer cell lines.

Disease relevance. Microphthalmia, syndromic, 6 (MCOPS6) [MIM:607932] A disease characterized by microphthalmia/anophthalmia associated with facial, genital, skeletal, neurologic and endocrine anomalies. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. The disease is caused by variants affecting the gene represented in this entry. Non-syndromic orofacial cleft 11 (OFC11) [MIM:600625] A birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TGF-beta family.

RefSeq proteins (9): NP_001193, NP_001334841, NP_001334842, NP_001334843, NP_001334844, NP_001334845, NP_001334846, NP_570911, NP_570912 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001111	TGF-b_propeptide	Domain
IPR001839	TGF-b_C	Domain
IPR015615	TGF-beta-like	Family
IPR017948	TGFb_CS	Conserved_site
IPR029034	Cystine-knot_cytokine	Homologous_superfamily
IPR047833	BMP4_TGF_beta-like	Domain

Pfam: PF00019, PF00688

UniProt features (26 total): sequence variant 13, disulfide bond 4, glycosylation site 4, signal peptide 1, propeptide 1, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P12644-F1	79.12	0.47

Functional residue map

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

Post-translational modifications (1): 91

Disulfide bonds (4): 337–405, 341–407, 372, 308–373

Glycosylation sites (4): 143, 208, 350, 365

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-2129379	Molecules associated with elastic fibres
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-9754189	Germ layer formation at gastrulation
R-HSA-9758920	Formation of lateral plate mesoderm
R-HSA-9761174	Formation of intermediate mesoderm
R-HSA-9793380	Formation of paraxial mesoderm
R-HSA-9827857	Specification of primordial germ cells
R-HSA-9830364	Formation of the nephric duct
R-HSA-9830674	Formation of the ureteric bud
R-HSA-9834899	Specification of the neural plate border
R-HSA-1266738	Developmental Biology
R-HSA-1474165	Reproduction
R-HSA-1474244	Extracellular matrix organization
R-HSA-1566948	Elastic fibre formation
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-9758941	Gastrulation
R-HSA-9830369	Kidney development

MSigDB gene sets: 1114 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, GOBP_METANEPHRIC_NEPHRON_MORPHOGENESIS, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, RRAGTTGT_UNKNOWN, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_BINDING

GO Biological Process (189): negative regulation of transcription by RNA polymerase II (GO:0000122), osteoblast differentiation (GO:0001649), metanephros development (GO:0001656), ureteric bud development (GO:0001657), branching involved in ureteric bud morphogenesis (GO:0001658), kidney development (GO:0001822), mesonephros development (GO:0001823), neural tube closure (GO:0001843), positive regulation of protein phosphorylation (GO:0001934), positive regulation of endothelial cell proliferation (GO:0001938), endochondral ossification (GO:0001958), blood vessel endothelial cell proliferation involved in sprouting angiogenesis (GO:0002043), chondrocyte differentiation (GO:0002062), hematopoietic progenitor cell differentiation (GO:0002244), lymphoid progenitor cell differentiation (GO:0002320), heart morphogenesis (GO:0003007), renal system process (GO:0003014), heart induction (GO:0003129), secondary heart field specification (GO:0003139), outflow tract septum morphogenesis (GO:0003148), membranous septum morphogenesis (GO:0003149), sinoatrial node development (GO:0003163), aortic valve morphogenesis (GO:0003180), pulmonary valve morphogenesis (GO:0003184), endocardial cushion development (GO:0003197), cardiac septum development (GO:0003279), type B pancreatic cell development (GO:0003323), transcription by RNA polymerase II (GO:0006366), germ cell development (GO:0007281), endoderm development (GO:0007492), mesoderm development (GO:0007498), mesodermal cell fate determination (GO:0007500), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), post-embryonic development (GO:0009791), anterior/posterior axis specification (GO:0009948), specification of animal organ position (GO:0010159), regulation of cell fate commitment (GO:0010453), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629)

GO Molecular Function (8): cytokine activity (GO:0005125), growth factor activity (GO:0008083), heparin binding (GO:0008201), co-receptor binding (GO:0039706), chemoattractant activity (GO:0042056), BMP receptor binding (GO:0070700), protein binding (GO:0005515), protein serine/threonine kinase activator activity (GO:0043539)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Gastrulation	5
Metabolism of proteins	2
Kidney development	2
Developmental Biology	2
Elastic fibre formation	1
Post-translational protein modification	1
Reproduction	1
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	3
receptor ligand activity	3
kidney development	2
endothelial cell proliferation	2
heart field specification	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
ossification	1
mesonephric tubule development	1
branching morphogenesis of an epithelial tube	1
ureteric bud morphogenesis	1
animal organ development	1
renal system development	1
primary neural tube formation	1
tube closure	1
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
replacement ossification	1
endochondral bone morphogenesis	1
sprouting angiogenesis	1
cartilage development	1
hemopoiesis	1
hematopoietic progenitor cell differentiation	1
heart development	1
animal organ morphogenesis	1
system process	1
organ induction	1
regulation of heart morphogenesis	1
outflow tract morphogenesis	1
cardiac septum morphogenesis	1
glycosaminoglycan binding	1
sulfur compound binding	1
protein binding	1
positive chemotaxis	1
transmembrane receptor protein serine/threonine kinase binding	1

Protein interactions and networks

STRING

4242 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BMP4	BMPR1A	P36894	998
BMP4	BMPR2	Q13873	998
BMP4	BMPR1B	P78366	997
BMP4	NOG	Q13253	993
BMP4	CHRD	Q9H2X0	992
BMP4	ACVR1	Q04771	977
BMP4	ACVR2A	P27037	963
BMP4	BMP7	P18075	953
BMP4	ACVR2B	Q13705	928
BMP4	FST	P19883	918
BMP4	SHH	Q15465	917
BMP4	BMPER	Q8N8U9	913
BMP4	MSX1	P28360	909
BMP4	SMAD4	Q13485	907
BMP4	HJV	Q6ZVN8	903

IntAct

45 interactions, top by confidence:

A	B	Type	Score
BMPR1A	BMP4	psi-mi:“MI:0915”(physical association)	0.610
BMP4	BMPR1A	psi-mi:“MI:0407”(direct interaction)	0.610
BMP4	UBE2O	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
MMP3	MMP10	psi-mi:“MI:0914”(association)	0.530
Fstl1	BMP4	psi-mi:“MI:0407”(direct interaction)	0.440
Grem2	BMP4	psi-mi:“MI:0407”(direct interaction)	0.440
FSTL1	BMP4	psi-mi:“MI:0407”(direct interaction)	0.440
WFIKKN1	BMP4	psi-mi:“MI:0407”(direct interaction)	0.440
BMP4	WFIKKN2	psi-mi:“MI:0407”(direct interaction)	0.440
chrd	BMP4	psi-mi:“MI:0915”(physical association)	0.400
olfml3	BMP4	psi-mi:“MI:0915”(physical association)	0.400
C12orf60	BMP4	psi-mi:“MI:0915”(physical association)	0.370
BMP4	ZFYVE9	psi-mi:“MI:0915”(physical association)	0.370
BMP4	PROS1	psi-mi:“MI:0914”(association)	0.350
SLC22A23	BMP4	psi-mi:“MI:0914”(association)	0.350
IL5RA	POTEF	psi-mi:“MI:0914”(association)	0.350
CFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
FGF4	QSOX1	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
CRLF1	MANBA	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350
CBLN4	AGRN	psi-mi:“MI:0914”(association)	0.350
ADIPOQ	PLOD2	psi-mi:“MI:0914”(association)	0.350
IFNE	ACACB	psi-mi:“MI:0914”(association)	0.350
P3H1	FCHO1	psi-mi:“MI:0914”(association)	0.350

BioGRID (138): DCAF16 (Affinity Capture-MS), BMP4 (Affinity Capture-MS), TWSG1 (Affinity Capture-MS), UBE2O (Affinity Capture-MS), PDP1 (Affinity Capture-MS), SUFU (Affinity Capture-MS), PROS1 (Affinity Capture-MS), CALR (Affinity Capture-MS), BMP4 (Reconstituted Complex), BMP4 (Reconstituted Complex), BMP4 (Reconstituted Complex), BMP4 (Reconstituted Complex), BMP4 (Reconstituted Complex), RPL18 (Affinity Capture-MS), RPL26 (Affinity Capture-MS)

ESM2 similar proteins: A8E7N9, F1QWZ4, G5EBY8, G5EEL5, O08689, O13048, O18830, O18836, O35312, O42221, O95393, P09534, P12644, P25703, P27091, P30884, P30885, P34822, P35621, P48969, P48970, P54631, P85857, P92172, Q24735, Q26974, Q4AEG6, Q5RZV4, Q5USV6, Q5USV8, Q5USV9, Q5USW0, Q5USW1, Q66KL4, Q6DTL9, Q6J1J2, Q6T5B8, Q6X5V1, Q800B8, Q800B9

Diamond homologs: A1C2U3, A1C2U6, A1C2U7, A1C2V0, A1C2V5, A8E7N9, G5EEL5, O08689, O14793, O18828, O18830, O18831, O18836, O35312, O42220, O42221, O42222, O46576, O61643, O95390, O95393, P09534, P12644, P12645, P17491, P18075, P20722, P20863, P22003, P22004, P22444, P23359, P27091, P27539, P35621, P43026, P43027, P43028, P43029, P48970

SIGNOR signaling

18 interactions.

A	Effect	B	Mechanism
NOG	down-regulates	BMP4	binding
BMP4	up-regulates	MRTFA
YAP1	“up-regulates quantity by expression”	BMP4	“transcriptional regulation”
TEAD1	“up-regulates quantity by expression”	BMP4	“transcriptional regulation”
BMP4	up-regulates	BMPR1A/1B/2	binding
BMP4	up-regulates	BMP4	binding
BMP4	“up-regulates activity”	BMPR1A/1B/2	binding
POU5F1	“down-regulates quantity by repression”	BMP4	“transcriptional regulation”
EXT1	“up-regulates activity”	BMP4
TNF	“down-regulates quantity by repression”	BMP4	“transcriptional regulation”
NFKB1	“down-regulates quantity by repression”	BMP4	“transcriptional regulation”
RELA	“down-regulates quantity by repression”	BMP4	“transcriptional regulation”
BMP4	up-regulates	BMPR2	binding
SOSTDC1	“down-regulates activity”	BMP4
SMAD1/4	“up-regulates quantity by expression”	BMP4	“transcriptional regulation”
BMP4	up-regulates	BMPR1A	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	11
Uncertain significance	178
Likely benign	50
Benign	19

Top pathogenic / likely-pathogenic (24)

Variant ID	HGVS	Classification
1071168	NC_000014.8:g.(?_54416336)_54418690del	Pathogenic
1458344	NM_001202.6(BMP4):c.205_214del (p.Arg69fs)	Pathogenic
1527818	GRCh37/hg19 14q22.1-22.3(chr14:53241194-55803026)	Pathogenic
17700	NM_001202.6(BMP4):c.226_227del (p.Ser76fs)	Pathogenic
2422501	NC_000014.8:g.(?54410919)(55369403_?)del	Pathogenic
2662638	NM_001202.6(BMP4):c.277G>T (p.Glu93Ter)	Pathogenic
29615	NC_000014.9:g.(53815591_53825260)_(53983697_53984391)del	Pathogenic
29616	NM_001202.6(BMP4):c.592C>T (p.Arg198Ter)	Pathogenic
29617	NM_001202.6(BMP4):c.171dup (p.Glu58fs)	Pathogenic
3063322	GRCh37/hg19 14q22.2(chr14:54361222-54823763)x1	Pathogenic
3236537	NM_001202.6(BMP4):c.337C>G (p.Arg113Gly)	Pathogenic
3236538	NM_001202.6(BMP4):c.452A>T (p.Glu151Val)	Pathogenic
443201	GRCh37/hg19 14q22.1-22.2(chr14:53820659-55003253)x1	Pathogenic
1098358	NM_001202.6(BMP4):c.666del (p.Arg223fs)	Likely pathogenic
1710338	NM_001202.6(BMP4):c.1118G>A (p.Cys373Tyr)	Likely pathogenic
3236711	NM_001202.6(BMP4):c.371-2A>G	Likely pathogenic
3370344	NM_001202.6(BMP4):c.602del (p.Asp201fs)	Likely pathogenic
3899694	NM_001202.6(BMP4):c.245_248dup (p.Met83fs)	Likely pathogenic
3899988	NM_001202.6(BMP4):c.323dup (p.Arg109fs)	Likely pathogenic
4291771	NM_001202.6(BMP4):c.253del (p.Asp85fs)	Likely pathogenic
4813345	NM_001202.6(BMP4):c.533T>G (p.Ile178Arg)	Likely pathogenic
4819603	NM_001202.6(BMP4):c.187del (p.Gln63fs)	Likely pathogenic
4820256	NM_001202.6(BMP4):c.349del (p.Thr116_Val117insTer)	Likely pathogenic
807114	NM_001202.6(BMP4):c.635G>A (p.Trp212Ter)	Likely pathogenic

SpliceAI

941 predictions. Top by Δscore:

Variant	Effect	Δscore
14:53950896:CAGT:C	acceptor_gain	1.0000
14:53950899:T:C	acceptor_gain	1.0000
14:53950899:T:TC	acceptor_gain	1.0000
14:53951849:TGAC:T	donor_loss	1.0000
14:53951851:A:C	donor_loss	1.0000
14:53951852:CCTT:C	donor_gain	1.0000
14:53950820:TGCTG:T	acceptor_gain	0.9900
14:53950822:CTG:C	acceptor_gain	0.9900
14:53950831:T:C	acceptor_gain	0.9900
14:53950831:T:TC	acceptor_gain	0.9900
14:53950889:C:CC	acceptor_gain	0.9900
14:53950897:A:T	acceptor_gain	0.9900
14:53951851:A:AC	donor_gain	0.9900
14:53951852:C:CC	donor_gain	0.9900
14:53952178:T:C	acceptor_gain	0.9900
14:53952228:CT:C	acceptor_gain	0.9900
14:53952230:C:CC	acceptor_gain	0.9900
14:53953274:A:AC	donor_gain	0.9900
14:53953275:C:CT	donor_gain	0.9900
14:53953275:CTGA:C	donor_gain	0.9900
14:53950825:C:CC	acceptor_gain	0.9800
14:53950894:C:CT	acceptor_gain	0.9800
14:53950898:G:GC	acceptor_gain	0.9800
14:53951910:CAAG:C	donor_gain	0.9800
14:53951911:AAGA:A	donor_gain	0.9800
14:53952225:TGTCT:T	acceptor_gain	0.9800
14:53952230:C:CA	acceptor_loss	0.9800
14:53952231:T:A	acceptor_loss	0.9800
14:53953972:T:TA	donor_gain	0.9800
14:53956553:AGGTC:A	donor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000069301 (14:53956705 G>A), RS1000122303 (14:53955646 C>A,G,T), RS1000378415 (14:53953191 G>T), RS1000408046 (14:53953497 G>A,T), RS1000610396 (14:53952600 G>A), RS1000655593 (14:53951044 T>C), RS1000726193 (14:53954399 C>A,T), RS1000961474 (14:53952863 G>A), RS1001159899 (14:53954625 C>T), RS1001505117 (14:53952861 T>C), RS1001837521 (14:53954074 A>C,G), RS1002112777 (14:53958668 A>T), RS1002458587 (14:53955461 A>G), RS1002728416 (14:53957013 A>C,G), RS1002814822 (14:53955794 C>T)

Disease associations

OMIM: gene MIM:112262 | disease phenotypes: MIM:600625, MIM:607932, MIM:604229, MIM:128230, MIM:609340, MIM:244300, MIM:108300

GenCC curated gene-disease

Disease	Classification	Inheritance
microphthalmia with brain and digit anomalies	Definitive	Autosomal dominant
orofacial cleft 11	Strong	Autosomal dominant
Stickler syndrome	Moderate	Autosomal recessive
renal agenesis, unilateral	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
BMP4-related ocular growth disorder	Definitive	AD

Mondo (12): orofacial cleft 11 (MONDO:0010906), microphthalmia with brain and digit anomalies (MONDO:0011936), Peters anomaly (MONDO:0011414), intellectual disability (MONDO:0001071), dystonia 5 (MONDO:0007495), GTP cyclohydrolase I deficiency (MONDO:0100184), hereditary spastic paraplegia 28 (MONDO:0012256), Kapur-Toriello syndrome (MONDO:0009483), congenital heart disease (MONDO:0005453), Stickler syndrome (MONDO:0019354), primary amenorrhea (MONDO:1060208), renal agenesis, unilateral (MONDO:0019636)

Orphanet (7): Microphthalmia with brain and digit anomalies (Orphanet:139471), Peters anomaly (Orphanet:708), Autosomal dominant dopa-responsive dystonia (Orphanet:98808), Autosomal recessive spastic paraplegia type 28 (Orphanet:101008), Kapur-Toriello syndrome (Orphanet:2328), Stickler syndrome (Orphanet:828), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

157 total (30 of 157 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000046	Small scrotum
HP:0000089	Renal hypoplasia
HP:0000134	Female hypogonadism
HP:0000158	Macroglossia
HP:0000162	Glossoptosis
HP:0000171	Microglossia
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000202	Orofacial cleft
HP:0000204	Cleft upper lip
HP:0000218	High palate
HP:0000220	Velopharyngeal insufficiency
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000308	Microretrognathia
HP:0000316	Hypertelorism
HP:0000324	Facial asymmetry
HP:0000327	Hypoplasia of the maxilla
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000389	Chronic otitis media

GWAS associations

41 associations (top):

Study	Trait	p-value
GCST000270_1	Colorectal cancer	8.000000e-10
GCST000528_10	Parkinson’s disease	3.000000e-06
GCST001538_24	Immune reponse to smallpox (secreted IFN-alpha)	8.000000e-08
GCST001786_22	Dental caries	2.000000e-07
GCST001786_33	Dental caries	2.000000e-06
GCST002030_9	Primary tooth development (time to first tooth eruption)	9.000000e-17
GCST002764_13	Optic cup area	7.000000e-07
GCST002764_7	Optic cup area	5.000000e-09
GCST002919_14	Colorectal cancer	2.000000e-06
GCST003017_19	Colorectal cancer	5.000000e-08
GCST003372_2	Glomerular filtration rate (creatinine)	3.000000e-06
GCST003477_3	Monobrow thickness	4.000000e-07
GCST003564_3	Waist-to-hip ratio adjusted for body mass index	6.000000e-06
GCST003989_8	Chin dimples	6.000000e-32
GCST003997_38	Myopia	5.000000e-17
GCST006288_162	Heel bone mineral density	4.000000e-28
GCST006288_163	Heel bone mineral density	9.000000e-20
GCST006288_328	Heel bone mineral density	5.000000e-39
GCST006288_329	Heel bone mineral density	3.000000e-35
GCST006288_433	Heel bone mineral density	3.000000e-72
GCST006288_434	Heel bone mineral density	5.000000e-58
GCST006291_109	Spherical equivalent or myopia (age of diagnosis)	1.000000e-17
GCST006979_1001	Heel bone mineral density	5.000000e-29
GCST006979_1002	Heel bone mineral density	3.000000e-11
GCST006979_1049	Heel bone mineral density	2.000000e-42
GCST006979_1050	Heel bone mineral density	5.000000e-17
GCST006988_84	Blond vs. brown/black hair color	4.000000e-08
GCST007006_13	Logical memory (delayed recall) in normal cognition	4.000000e-07
GCST007430_124	Peak expiratory flow	1.000000e-13
GCST007431_118	Lung function (FEV1/FVC)	3.000000e-36

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0009270	heel bone mineral density
EFO:0004847	age at onset
EFO:0003924	hair color
EFO:0004874	memory performance
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0006939	cup-to-disc ratio measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C537008	Kapur Toriello syndrome (supp.)
C566440	Microphthalmia, Syndromic 6 (supp.)
C537884	Peters anomaly (supp.)
C563732	Spastic Paraplegia 28, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5350 (SINGLE PROTEIN)

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

ChEMBL bioactivities

20 potent at pChembl≥5 of 21 total, top 20 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.31	IC50	4.9	nM	CHEMBL513147
8.30	IC50	5	nM	CHEMBL467972
8.00	IC50	10	nM	CHEMBL469053
7.26	IC50	55	nM	CHEMBL511563
7.05	IC50	90	nM	CHEMBL469054
6.82	IC50	150	nM	CHEMBL467560
6.60	IC50	250	nM	CHEMBL467345
6.46	IC50	350	nM	CHEMBL468399
6.37	IC50	430	nM	DORSOMORPHIN
6.35	IC50	450	nM	CHEMBL466765
6.30	IC50	500	nM	CHEMBL511929
6.30	IC50	500	nM	CHEMBL511216
6.12	IC50	750	nM	CHEMBL469055
5.70	IC50	2000	nM	CHEMBL324153
5.58	IC50	2600	nM	CHEMBL467544
5.52	IC50	3000	nM	CHEMBL502351
5.48	IC50	3300	nM	CHEMBL468003
5.35	IC50	4500	nM	CHEMBL469019
5.30	IC50	5000	nM	CHEMBL512294
5.19	IC50	6500	nM	CHEMBL329350

PubChem BioAssay actives

20 with measured affinity, of 33 total; 20 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	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	0.0049	uM
4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyridin-3-yl]quinoline	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	0.0050	uM
4-[6-[4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	0.0100	uM
4-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	0.0550	uM
4-[6-[4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	0.0900	uM
4-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-3-yl]quinoline	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	0.1500	uM
4-(3-quinolin-4-ylpyrazolo[1,5-a]pyrimidin-6-yl)phenol	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	0.2500	uM
7-chloro-4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	0.3500	uM
6-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidine	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	0.4300	uM
6-[4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidine	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	0.4500	uM
7-chloro-4-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	0.5000	uM
N,N-diethyl-2-[4-(3-pyridin-4-ylpyrazolo[1,5-a]pyrimidin-6-yl)phenoxy]ethanamine	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	0.5000	uM
4-(6-phenylpyrazolo[1,5-a]pyrimidin-3-yl)quinoline	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	0.7500	uM
4-[2-[4-(3-pyridin-4-ylpyrazolo[1,5-a]pyrimidin-6-yl)phenoxy]ethyl]morpholine	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	2.0000	uM
4-[3-[4-(2-piperidin-1-ylethoxy)phenyl]pyrrolo[1,2-a]pyrimidin-8-yl]quinoline	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	2.6000	uM
5-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	3.0000	uM
3-(3-fluoro-4-pyridinyl)-6-[4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]pyrazolo[1,5-a]pyrimidine	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	3.3000	uM
6-[3-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidine	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	4.5000	uM
4-pyrazolo[1,5-a]pyrimidin-3-ylquinoline	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	5.0000	uM
6-(4-methoxyphenyl)-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidine	342849: Inhibition of BMP4-induced phosphorylation of SMAD 1/5/8 by cytoblot cellular ELISA	ic50	6.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression, decreases expression, increases abundance	6
Estradiol	affects expression, affects binding, increases expression, decreases expression	5
Tretinoin	increases expression, affects expression, increases reaction, affects cotreatment	5
Valproic Acid	increases expression, affects cotreatment	5
Tetrachlorodibenzodioxin	decreases expression, increases expression	4
bisphenol A	decreases expression, affects expression	3
trichostatin A	affects cotreatment, increases expression	3
Arsenic	increases expression, decreases expression, increases abundance	3
Cadmium	decreases expression, decreases reaction, increases abundance, increases expression	3
Tobacco Smoke Pollution	increases expression, decreases expression	3
Cadmium Chloride	decreases expression, decreases reaction, increases abundance, affects cotreatment, increases expression	3
Particulate Matter	decreases expression, increases abundance, affects splicing	3
methylmercuric chloride	decreases expression, increases expression	2
arsenite	decreases expression, increases expression, decreases reaction	2
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases methylation, increases expression, affects cotreatment	2
Chir 99021	increases expression, affects binding, affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance, affects splicing	2
Cannabidiol	decreases expression, increases expression	2
Doxorubicin	decreases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Silicon Dioxide	decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
PSB603	decreases reaction, increases expression	1
3,19-(2-bromobenzylidene)andrographolide	decreases expression, decreases response to substance	1
naringin	increases expression	1
lead acetate	affects cotreatment, increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3293908	Binding	Binding affinity to human recombinant BMP4 by surface plasmon resonance assay	Synthesis and biological evaluation of a unique heparin mimetic hexasaccharide for structure-activity relationship studies. — J Med Chem

Cellosaurus cell lines

7 cell lines: 4 cancer cell line, 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A0J2	SEES3-1V human BMP4, clone1	Embryonic stem cell	Male
CVCL_A0J3	SEES3-1V human BMP4, clone2	Embryonic stem cell	Male
CVCL_A0J4	SEES3-1V human BMP4, clone3	Embryonic stem cell	Male
CVCL_B9E7	Abcam A-549 BMP4 KO	Cancer cell line	Male
CVCL_D7L1	Ubigene A-549 BMP4 KO	Cancer cell line	Male
CVCL_SF36	HAP1 BMP4 (-) 1	Cancer cell line	Male
CVCL_XM03	HAP1 BMP4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT04465188	PHASE2	WITHDRAWN	Scleral Buckling for Retinal Detachment Prevention in Genetically Confirmed Stickler Syndrome
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)