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 (top 2% of genes corpus-wide)
• Clinical variants (ClinVar): 323 total — 13 pathogenic, 15 likely-pathogenic (top 10% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 4 regions constrained (≈3% of expected missense variation)
• GTEx eGene: eQTL in 12 tissues, sQTL in 5 (q < 0.05)
• Phenotypes (HPO): 97
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.26 (highly constrained)
• Transcription factor: yes — 13 downstream targets (CollecTRI)
• MANE Select transcript: NM_001202
• Interaction hub: 3,709 STRING partners (top 1% of genes corpus-wide)

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: 29 — 28 protein_coding, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000245451

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 1, TSL 3: 3, TSL 5: 1

ENST00000245451, ENST00000417573, ENST00000558489, ENST00000558961, ENST00000558984, ENST00000559087, ENST00000559501, ENST00000559642, ENST00000609748, ENST00000890805, ENST00000890806, ENST00000890807, ENST00000890808, ENST00000890809, ENST00000890810, ENST00000890811, ENST00000890812, ENST00000939836, ENST00000939837, ENST00000939838, ENST00000939839, ENST00000939840, ENST00000939841, ENST00000951376, ENST00001049235, ENST00001107398, ENST00001107399, ENST00001107400, ENST00001135440

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.

Highest expression (Bgee): pigmented layer of retina, retina, rectum, mucosa of transverse colon, coronary artery.

Genetic regulation across tissues (GTEx eQTL / sQTL)

BMP4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

17 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellum	eqtl	7.7e-16	+0.73	14:53948020:G:A
Brain Cerebellar Hemisphere	eqtl	1.4e-14	+0.67	14:53950804:A:G
Testis	eqtl	8.1e-09	-0.87	14:54180556:G:T
Brain Frontal Cortex BA9	eqtl	1.8e-07	-0.34	14:53958429:T:C
Brain Cortex	eqtl	5.2e-04	+0.27	14:53956049:G:T
Cells Cultured fibroblasts	eqtl	2.0e-03	-0.23	14:53757065:A:C
Skin Sun Exposed Lower leg	sqtl	2.0e-03	-0.29	14:53960339:T:G
Artery Tibial	sqtl	3.6e-03	-0.28	14:53964857:C:T
Thyroid	eqtl	1.3e-02	-0.46	14:54800289:C:T
Vagina	eqtl	1.6e-02	+0.62	14:54736704:C:T
Breast Mammary Tissue	sqtl	2.1e-02	+0.54	14:54269911:A:G
Colon Sigmoid	sqtl	2.6e-02	-0.37	14:53955681:C:G
Uterus	sqtl	3.5e-02	+3.61	14:54886536:C:T
Pituitary	eqtl	4.2e-02	+0.16	14:54268207:C:G
Brain Anterior cingulate cortex BA24	eqtl	4.3e-02	-0.50	14:53913279:GC:G
Ovary	eqtl	4.5e-02	+0.27	14:53633381:A:T
Brain Substantia nigra	eqtl	4.7e-02	-1.18	14:54683608:A:T

FANTOM5 promoters

showing 10 of 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

showing 100 of 282 tissues 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
ectocervix	UBERON:0012249	82.55	gold quality
vagina	UBERON:0000996	82.54	gold quality
skin of abdomen	UBERON:0001416	82.36	gold quality
right atrium auricular region	UBERON:0006631	82.23	gold quality
omental fat pad	UBERON:0010414	82.20	gold quality
peritoneum	UBERON:0002358	82.12	gold quality
colon	UBERON:0001155	82.03	gold quality
colonic epithelium	UBERON:0000397	81.94	gold quality
intestine	UBERON:0000160	81.90	gold quality
endocervix	UBERON:0000458	81.87	gold quality
left adrenal gland	UBERON:0001234	81.61	gold quality
large intestine	UBERON:0000059	81.58	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.44	gold quality
left adrenal gland cortex	UBERON:0035825	81.33	gold quality
right adrenal gland	UBERON:0001233	81.24	gold quality
right adrenal gland cortex	UBERON:0035827	80.95	gold quality
germinal epithelium of ovary	UBERON:0001304	80.66	silver quality
cardiac atrium	UBERON:0002081	80.58	gold quality
urinary bladder	UBERON:0001255	80.50	gold quality
adrenal cortex	UBERON:0001235	80.47	gold quality
metanephros cortex	UBERON:0010533	80.46	gold quality
eye	UBERON:0000970	80.29	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.11	gold quality
subcutaneous adipose tissue	UBERON:0002190	80.09	gold quality
zone of skin	UBERON:0000014	80.07	gold quality
right ovary	UBERON:0002118	79.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.80	gold quality
minor salivary gland	UBERON:0001830	79.76	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.62	gold quality
parietal pleura	UBERON:0002400	79.41	gold quality
calcaneal tendon	UBERON:0003701	79.38	gold quality
prostate gland	UBERON:0002367	79.35	gold quality
adrenal gland	UBERON:0002369	79.30	gold quality
ovary	UBERON:0000992	79.03	gold quality
adipose tissue	UBERON:0001013	78.91	gold quality
heart left ventricle	UBERON:0002084	78.90	gold quality
heart	UBERON:0000948	78.89	gold quality
body of uterus	UBERON:0009853	78.84	gold quality
esophagus	UBERON:0001043	78.82	gold quality
placenta	UBERON:0001987	78.82	gold quality
muscle of leg	UBERON:0001383	78.59	gold quality
cardiac ventricle	UBERON:0002082	78.40	gold quality
gastrocnemius	UBERON:0001388	78.36	gold quality
connective tissue	UBERON:0002384	78.09	gold quality
upper lobe of left lung	UBERON:0008952	77.93	gold quality
left uterine tube	UBERON:0001303	77.87	gold quality
right lung	UBERON:0002167	77.42	gold quality
right lobe of thyroid gland	UBERON:0001119	77.38	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	77.20	gold quality
saliva-secreting gland	UBERON:0001044	76.86	gold quality
buccal mucosa cell	CL:0002336	76.74	silver quality
lymph node	UBERON:0000029	76.64	gold quality
left lobe of thyroid gland	UBERON:0001120	76.55	gold quality
right uterine tube	UBERON:0001302	76.38	gold quality
tibial nerve	UBERON:0001323	76.25	gold quality
pleura	UBERON:0000977	76.00	silver quality
mouth mucosa	UBERON:0003729	75.89	gold quality
duodenum	UBERON:0002114	75.84	gold quality
smooth muscle tissue	UBERON:0001135	75.66	gold quality
palpebral conjunctiva	UBERON:0001812	75.63	gold quality
esophagus mucosa	UBERON:0002469	75.49	gold quality
tendon	UBERON:0000043	75.48	gold quality
colonic mucosa	UBERON:0000317	75.43	gold quality
pylorus	UBERON:0001166	75.35	gold quality
thyroid gland	UBERON:0002046	75.27	gold quality
upper lobe of lung	UBERON:0008948	75.23	gold quality
caecum	UBERON:0001153	75.00	gold quality
cerebellar hemisphere	UBERON:0002245	74.96	gold quality
cerebellar cortex	UBERON:0002129	74.92	gold quality
cardia of stomach	UBERON:0001162	74.84	silver 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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Choroid plexus	tissue	65.3
Placenta	tissue	41.7	not detected
Rectum	tissue	27.2	not detected
Colon	tissue	24.0	low
Vagina	tissue	23.0	not detected
Stomach 1	tissue	22.4	not detected
Ovary	tissue	22.2	not detected
Prostate	tissue	19.9	not detected
Spinal cord	tissue	17.8
Seminal vesicle	tissue	17.6	not detected
Urinary bladder	tissue	17.1	not detected
Tongue	tissue	16.5
Duodenum	tissue	16.0	low
Small intestine	tissue	15.7	medium
Heart muscle	tissue	15.2	medium
Gallbladder	tissue	13.5	not detected
Lung	tissue	12.6	not detected
Adrenal gland	tissue	12.6	medium
Superior colliculi	tissue	12.4
Esophagus	tissue	12.1	not detected
Breast	tissue	11.9	low
Adipose tissue	tissue	11.2	not detected
Skeletal muscle	tissue	10.7	medium
Cervix	tissue	10.3	not detected
Skin 1	tissue	9.3	not detected
Salivary gland	tissue	9.2	low
Lymph node	tissue	9.0	not detected
Smooth muscle	tissue	8.4	medium
Fallopian tube	tissue	7.6	not detected
Substantia nigra	tissue	7.3
Kidney	tissue	6.8	not detected
Medulla oblongata	tissue	6.7
Cerebral cortex	tissue	6.2	not detected
Occipital cortex	tissue	6.2
Spleen	tissue	6.1	not detected
Somatosensory cortex	tissue	6.1
Endometrium 1	tissue	6.0	not detected
Appendix	tissue	5.8	not detected
Hippocampal formation	tissue	5.3
Entorhinal cortex	tissue	5.3
Thalamus	tissue	4.9
Temporal cortex	tissue	4.9
Pons	tissue	4.8
Midbrain	tissue	4.8
Motor cortex	tissue	4.7
Thyroid gland	tissue	4.7	low
Retrosplenial cortex	tissue	4.6
Insular cortex	tissue	4.6
Pituitary gland	tissue	4.5
Retrosplenial and cingulate cortex	tissue	4.4
Amygdala	tissue	4.3
Cerebellum	tissue	4.2	not detected
Postcentral gyrus	tissue	4.2
Prefrontal cortex	tissue	4.0
Hypothalamus	tissue	4.0
Frontal cortex	tissue	3.9
Putamen	tissue	3.9
Tonsil	tissue	3.9	low
Septum	tissue	3.8
Periaqueductal gray	tissue	3.7

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Dorsal spinal cord (17.8), Blood vessel (14.9), Ventral spinal cord (11.2), Flocculonodular lobe (10.4), Vermis (10.4).

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)

Targeting BMP4 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

30 miRNAs:

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

gnomAD constraint: pLI 1, LOEUF 0.258, missense Z 1.75 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000245451 splits into 4 regions with different missense tolerance; 1 is missense-constrained (≈3% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
14:53,950,035–53,950,256	48 / 90.4	0.53	no
14:53,950,257–53,950,593	154 / 156.8	0.98	no
14:53,950,594–53,950,633	4 / 18.4	0.22	yes (p 8.0e-04)
14:53,950,634–53,952,222	249 / 284.6	0.87	no
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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88180) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 250 distinct phenotype terms.

Mouse phenotype (MP)	Records
embryonic growth retardation	5
decreased primordial germ cell number	4
embryonic lethality during organogenesis, complete penetrance	4
polydactyly	3
microphthalmia	3
circling	3
abnormal eye morphology	3
abnormal renal/urinary system morphology	2
hydronephrosis	2
anophthalmia	2
abnormal iris morphology	2
abnormal retina morphology	2
abnormal allantois morphology	2
renal hypoplasia	2
abnormal ureter development	2
kidney cyst	2
eyelids fail to open	2
abnormal optic disk morphology	2
perimembraneous ventricular septal defect	2
perinatal lethality, complete penetrance	2
prenatal lethality, complete penetrance	2
embryonic lethality during organogenesis, incomplete penetrance	2
abnormal nephrogenic zone morphology	2
abnormal inner ear morphology	1
absent semicircular canals	1

+225 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo pygmaeus	A1C2U3	100.0%	Diamond
Macaca mulatta	A1C2U6	100.0%	Diamond
Pan paniscus	A1C2U7	100.0%	Diamond
Pan troglodytes	A1C2V0	100.0%	Diamond
Gorilla gorilla gorilla	A1C2V5	100.0%	Diamond
Ovis aries	O18830	100.0%	Diamond
Bos taurus	O18836	100.0%	Diamond
Bos indicus	Q5RZV4	100.0%	Diamond
Hemitragus jemlahicus	Q5USV8	100.0%	Diamond
Bos gaurus	Q5USW1	100.0%	Diamond
Capra hircus	Q6T5B8	100.0%	Diamond
Macaca fascicularis	Q95J86	100.0%	Diamond
Papio hamadryas	O18828	99.7%	Diamond
Capra ibex	Q5USV9	99.7%	Diamond
Vulpes vulpes	Q6DTL9	99.5%	Diamond
Vulpes lagopus	Q6J1J2	99.5%	Diamond
Gallus gallus	O42220	99.2%	Diamond
Meleagris gallopavo	O42221	99.2%	Diamond
Canis lupus familiaris	Q6UKZ8	99.2%	Diamond
Coturnix coturnix	Q8AVB2	99.2%	Diamond
Excalfactoria chinensis	Q8UWD7	99.2%	Diamond
Sylvicapra grimmia	Q5USV6	98.9%	Diamond
Xenopus tropicalis	Q800C0	98.8%	Diamond
Taurotragus derbianus	Q5USW0	98.7%	Diamond
Bubalus bubalis	Q6X5V1	98.7%	Diamond
Drosophila melanogaster	P07713	98.3%	Diamond
Drosophila simulans	P91706	98.3%	Diamond
Sus scrofa	O18831	98.1%	Diamond
Anas platyrhynchos	Q8UWE0	98.1%	Diamond
Equus caballus	Q9GM97	98.1%	Diamond
Suncus murinus	Q8MJV5	98.0%	Diamond
Anser anser anser	Q8UWD9	97.9%	Diamond
Dama dama	Q29607	97.8%	Diamond
Antilocapra americana	Q5USV5	97.6%	Diamond
Aepyceros melampus	Q5USV7	97.3%	Diamond
Lepus capensis	Q8HY52	96.8%	Diamond
Oryctolagus cuniculus	O46564	95.7%	Diamond
Papio anubis	A9CB18	94.3%	Diamond
Xenopus laevis	Q91609	94.0%	Diamond
Felis catus	Q6X2S4	93.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC02331	ncRNA	105370503
CNIH1	protein-coding	10175
CDKN3	protein-coding	1033
MIR5580	ncRNA	100847076

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted secreted proteins, Predicted intracellular proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, Human disease related genes, Congenital malformations, Congenital malformations of eye, Congenital malformations of face and neck

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

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)

Type	Positions
Phosphoserine	91

Disulfide bonds (4)

Type	Positions
Disulfide bond	337–405, 341–407, 308–373
Interchain	372

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	143, 208, 350, 365

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 19; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

19 pathways:

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

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 (118): negative regulation of transcription by RNA polymerase II (GO:0000122), osteoblast differentiation (GO:0001649), ureteric bud development (GO:0001657), branching involved in ureteric bud morphogenesis (GO:0001658), kidney development (GO:0001822), mesonephros development (GO:0001823), 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), 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), mesoderm development (GO:0007498), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), post-embryonic development (GO:0009791), regulation of cell fate commitment (GO:0010453), gene expression (GO:0010467), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), positive regulation of epithelial to mesenchymal transition (GO:0010718), telencephalon development (GO:0021537), monocyte differentiation (GO:0030224), macrophage differentiation (GO:0030225), positive regulation of bone mineralization (GO:0030501), BMP signaling pathway (GO:0030509), positive regulation of BMP signaling pathway (GO:0030513), positive regulation of protein binding (GO:0032092), positive regulation of collagen biosynthetic process (GO:0032967), negative regulation of T cell differentiation in thymus (GO:0033085), negative regulation of immature T cell proliferation in thymus (GO:0033088), tendon cell differentiation (GO:0035990), deltoid tuberosity development (GO:0035993), regulation of protein import into nucleus (GO:0042306), odontogenesis (GO:0042476), positive regulation of apoptotic process (GO:0043065), positive regulation of programmed cell death (GO:0043068), positive regulation of endothelial cell differentiation (GO:0045603), positive regulation of epidermal cell differentiation (GO:0045606), negative regulation of myoblast differentiation (GO:0045662), positive regulation of osteoblast differentiation (GO:0045669), positive regulation of ossification (GO:0045778), negative regulation of cell cycle (GO:0045786), negative regulation of mitotic nuclear division (GO:0045839), negative regulation of striated muscle tissue development (GO:0045843), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944)

+58 more (showing top 60).

GO Molecular Function (7): 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)

GO Cellular Component (2): extracellular region (GO:0005576), endoplasmic reticulum lumen (GO:0005788)

Reactome top-level categories

8 top-level categories:

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

47 GO namespaces:

Category	Terms
cell differentiation	3
receptor ligand activity	3
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
kidney development	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
organ induction	1
regulation of heart morphogenesis	1
outflow tract morphogenesis	1
cardiac septum morphogenesis	1
anatomical structure morphogenesis	1
ventricular septum morphogenesis	1
cardiac conduction system development	1
atrial cardiac muscle tissue development	1
aortic valve development	1
heart valve morphogenesis	1
glycosaminoglycan binding	1
sulfur compound binding	1
protein binding	1
positive chemotaxis	1
transmembrane receptor protein serine/threonine kinase binding	1
binding	1
cellular anatomical structure	1
endoplasmic reticulum	1
intracellular organelle lumen	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 75 of 128 annotations. The rest are phylogenetic / computational / electronic (IEA).

showing 60 of 75 experimentally-supported GO terms:

GO term	NS	Evidence
BMP signaling pathway	BP	direct assay
blood vessel endothelial cell proliferation involved in sprouting angiogenesis	BP	direct assay
branching involved in ureteric bud morphogenesis	BP	direct assay
bronchus development	BP	direct assay
bud dilation involved in lung branching	BP	direct assay
cellular response to BMP stimulus	BP	mutant phenotype
epithelial cell proliferation involved in lung morphogenesis	BP	direct assay
epithelial tube branching involved in lung morphogenesis	BP	direct assay
heart induction	BP	mutant phenotype
heart morphogenesis	BP	mutant phenotype
hematopoietic progenitor cell differentiation	BP	direct assay
intermediate mesodermal cell differentiation	BP	direct assay
kidney development	BP	mutant phenotype
lung alveolus development	BP	direct assay
lung morphogenesis	BP	direct assay
lung vasculature development	BP	mutant phenotype
lymphoid progenitor cell differentiation	BP	mutant phenotype
macrophage differentiation	BP	direct assay
mesoderm development	BP	direct assay
mesonephros development	BP	expression pattern
monocyte differentiation	BP	direct assay
negative regulation of DNA-templated transcription	BP	direct assay
negative regulation of T cell differentiation in thymus	BP	mutant phenotype
negative regulation of branching involved in ureteric bud morphogenesis	BP	direct assay
negative regulation of cell cycle	BP	direct assay
negative regulation of cell population proliferation	BP	direct assay
negative regulation of gene expression	BP	direct assay
negative regulation of glomerular mesangial cell proliferation	BP	direct assay
negative regulation of glomerulus development	BP	direct assay
negative regulation of immature T cell proliferation in thymus	BP	mutant phenotype
negative regulation of mesenchymal cell proliferation involved in ureter development	BP	direct assay
negative regulation of metanephric S-shaped body morphogenesis	BP	direct assay
negative regulation of metanephric comma-shaped body morphogenesis	BP	direct assay
negative regulation of miRNA transcription	BP	direct assay
negative regulation of mitotic nuclear division	BP	direct assay
negative regulation of myoblast differentiation	BP	direct assay
negative regulation of striated muscle tissue development	BP	direct assay
negative regulation of thymocyte apoptotic process	BP	mutant phenotype
negative regulation of transcription by RNA polymerase II	BP	direct assay
nephric duct formation	BP	direct assay
odontogenesis	BP	genetic interaction
osteoblast differentiation	BP	direct assay
positive regulation of DNA-templated transcription	BP	direct assay
positive regulation of SMAD protein signal transduction	BP	direct assay
positive regulation of apoptotic process	BP	direct assay
positive regulation of bone mineralization	BP	direct assay
positive regulation of cardiac muscle fiber development	BP	mutant phenotype
positive regulation of cartilage development	BP	direct assay
positive regulation of cell population proliferation	BP	direct assay
positive regulation of collagen biosynthetic process	BP	direct assay
positive regulation of epidermal cell differentiation	BP	direct assay
positive regulation of epithelial cell proliferation	BP	direct assay
positive regulation of gene expression	BP	direct assay
positive regulation of ossification	BP	direct assay
positive regulation of osteoblast differentiation	BP	direct assay
positive regulation of p38MAPK cascade	BP	direct assay
positive regulation of primary miRNA processing	BP	direct assay
positive regulation of programmed cell death	BP	direct assay
positive regulation of protein binding	BP	direct assay
positive regulation of protein phosphorylation	BP	direct assay

Protein interactions and networks

STRING

showing 15 of 3,709 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BMP4	NOG	Q13253	925
BMP4	SHH	Q15465	907
BMP4	BMPR1A	P36894	897
BMP4	BMPR2	Q13873	892
BMP4	MSX1	P28360	886
BMP4	BMPR1B	P78366	882
BMP4	ACVR1	Q04771	871
BMP4	CHRD	Q9H2X0	867
BMP4	FGF8	P55075	860
BMP4	FGF2	P09038	853
BMP4	SMAD4	Q13485	839
BMP4	GREM1	O60565	838
BMP4	WNT3A	P56704	831
BMP4	FGF4	P08620	820
BMP4	SMAD5	Q99717	807

IntAct

Human interaction partners of BMP4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

13 partners by confidence:

Partner	Interaction type	MIscore	Records
BMPR1A	physical association	0.610	2
UBE2O	association	0.530	1
FSTL1	direct interaction	0.440	1
WFIKKN1	direct interaction	0.440	1
WFIKKN2	direct interaction	0.440	1
C12orf60	physical association	0.370	1
ZFYVE9	physical association	0.370	1
SLC22A23	association	0.350	2
A2ML1	association	0.350	1
CALR3	association	0.350	1
HS3ST1	association	0.350	1
PAAT	association	0.350	1
PROS1	association	0.350	1

BioGRID (138 interactions; top human partners by supporting records): BMPR1A (Reconstituted Complex; 3 records), BMPR2 (Reconstituted Complex; 3 records), CALR (Affinity Capture-MS; 2 records), CLU (Affinity Capture-MS; 2 records), DCAF16 (Affinity Capture-MS; 2 records), PDP1 (Affinity Capture-MS; 2 records), SLC22A23 (Affinity Capture-MS; 2 records), SOSTDC1 (Affinity Capture-Western; 2 records), SUFU (Affinity Capture-MS; 2 records), TWSG1 (Affinity Capture-MS; 2 records), UBE2O (Affinity Capture-MS; 2 records), ACVR2A (Reconstituted Complex), ADIPOQ (Affinity Capture-MS), AGO2 (Affinity Capture-RNA), APOD (Affinity Capture-MS)

SIGNOR signaling

showing 16 of 18 signaling 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

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
BMP2-BRIA complex	3	BMP2, BMP4, BMPR1A
BMP4-TWSG1 complex	2	BMP4, TWSG1
BMP4-BGN complex	2	BMP4, BGN

Ligand–receptor pairs (CellPhoneDB) (6)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

6 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
BMPR1B;ACVR2A	ligand	Signaling by BMP
BMPR1B;ACVR2B	ligand	Signaling by BMP
BMPR1A;ACVR2B	ligand	Signaling by BMP
BMPR1A;ACVR2A	ligand	Signaling by BMP
BMPR1B;BMPR2	ligand	Signaling by BMP
BMPR1A;BMPR2	ligand	Signaling by BMP

Disease & clinical

Genetic variants

Variant evidence for BMP4: 323 ClinVar records (28 pathogenic / likely pathogenic); 41 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	15
Uncertain significance	186
Likely benign	55
Benign	17

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 28 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
29616	NM_001202.6(BMP4):c.592C>T (p.Arg198Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
1458344	NM_001202.6(BMP4):c.205_214del (p.Arg69fs)	Pathogenic	criteria provided, single submitter	1
2662638	NM_001202.6(BMP4):c.277G>T (p.Glu93Ter)	Pathogenic	criteria provided, single submitter	1
807114	NM_001202.6(BMP4):c.635G>A (p.Trp212Ter)	Likely pathogenic	criteria provided, single submitter	1
1098358	NM_001202.6(BMP4):c.666del (p.Arg223fs)	Likely pathogenic	criteria provided, single submitter	1
1710338	NM_001202.6(BMP4):c.1118G>A (p.Cys373Tyr)	Likely pathogenic	criteria provided, single submitter	1
3370344	NM_001202.6(BMP4):c.602del (p.Asp201fs)	Likely pathogenic	criteria provided, single submitter	1
3899694	NM_001202.6(BMP4):c.245_248dup (p.Met83fs)	Likely pathogenic	criteria provided, single submitter	1
4291771	NM_001202.6(BMP4):c.253del (p.Asp85fs)	Likely pathogenic	criteria provided, single submitter	1
4813345	NM_001202.6(BMP4):c.533T>G (p.Ile178Arg)	Likely pathogenic	criteria provided, single submitter	1
4819603	NM_001202.6(BMP4):c.187del (p.Gln63fs)	Likely pathogenic	criteria provided, single submitter	1
4820256	NM_001202.6(BMP4):c.349del (p.Thr116_Val117insTer)	Likely pathogenic	criteria provided, single submitter	1
4849976	NM_001202.6(BMP4):c.449_455delinsGGC (p.Asn150fs)	Likely pathogenic	criteria provided, single submitter	1
4880600	NM_001202.6(BMP4):c.161del (p.Leu54fs)	Likely pathogenic	criteria provided, single submitter	1
4880816	NM_001202.6(BMP4):c.121_145del (p.His41fs)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore BMP4’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 21 predictions of 551):

Position(s)	Effect	Δscore	Sites
14:53950899	acceptor_gain	1.0000
14:53951851–53951852	donor_loss	1.0000	5
14:53950831	acceptor_gain	0.9900
14:53950897	acceptor_gain	0.9900
14:53952178	acceptor_gain	0.9900
14:53952230–53952231	acceptor_loss	0.9800	6
14:53950898	acceptor_gain	0.9700
14:53954823	donor_gain	0.9700
14:53955748	donor_gain	0.9600
14:53953271	donor_loss	0.9400	3

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Rectum Adenocarcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	favorable	3.49e-05
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.00031
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.00037

Disease associations

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

GenCC curated gene-disease

4 curated gene-disease records:

Disease	Classification	Inheritance	Records
microphthalmia with brain and digit anomalies	Definitive	Autosomal dominant	6
orofacial cleft 11	Strong	Autosomal dominant	2
Stickler syndrome	Moderate	Autosomal recessive
renal agenesis, unilateral	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
BMP4-related ocular growth disorder	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (14 panels, 12 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

14 panels:

Panel	Rating
Anophthalmia or microphthalmia	green
DDG2P	green
Deafness and congenital structural abnormalities	green
Fetal anomalies	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Limb disorders	green
Ocular coloboma	green
Paediatric disorders	green
Stickler syndrome	green
Structural eye disease	green
CAKUT	amber
Pituitary hormone deficiency	amber

Mondo (7): orofacial cleft 11 (MONDO:0010906), microphthalmia with brain and digit anomalies (MONDO:0011936), Peters anomaly (MONDO:0011414), dystonia 5 (MONDO:0007495), GTP cyclohydrolase I deficiency (MONDO:0100184), Stickler syndrome (MONDO:0019354), renal agenesis, unilateral (MONDO:0019636)

Orphanet (4): Microphthalmia with brain and digit anomalies (Orphanet:139471), Peters anomaly (Orphanet:708), Autosomal dominant dopa-responsive dystonia (Orphanet:98808), Stickler syndrome (Orphanet:828)

HPO phenotypes

showing 60 of 97 phenotypes (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:0000171	Microglossia
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000202	Orofacial cleft
HP:0000218	High palate
HP:0000220	Velopharyngeal insufficiency
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000324	Facial asymmetry
HP:0000327	Hypoplasia of the maxilla
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000403	Recurrent otitis media
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000411	Protruding ear
HP:0000482	Microcornea
HP:0000488	Retinopathy
HP:0000518	Cataract
HP:0000528	Anophthalmia
HP:0000541	Retinal detachment
HP:0000545	Myopia
HP:0000556	Retinal dystrophy
HP:0000567	Chorioretinal coloboma
HP:0000568	Microphthalmia
HP:0000589	Coloboma
HP:0000612	Iris coloboma
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000647	Sclerocornea
HP:0000689	Dental malocclusion
HP:0000750	Delayed speech and language development
HP:0000821	Hypothyroidism
HP:0000830	Anterior hypopituitarism
HP:0000835	Adrenal hypoplasia
HP:0000864	Abnormality of the hypothalamus-pituitary axis
HP:0000954	Single transverse palmar crease
HP:0001144	Orbital cyst
HP:0001155	Abnormality of the hand
HP:0001156	Brachydactyly
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001321	Cerebellar hypoplasia
HP:0001344	Absent speech
HP:0001357	Plagiocephaly
HP:0001508	Failure to thrive
HP:0001611	Hypernasal speech
HP:0001770	Toe syndactyly

GWAS associations

showing 30 of 41 associations:

Study	Trait	p-value
GCST006288_624	Heel bone mineral density	3e-72
GCST010002_203	Refractive error	2e-59
GCST006288_625	Heel bone mineral density	5e-58
GCST006979_1049	Heel bone mineral density	2e-42
GCST006288_294	Heel bone mineral density	5e-39
GCST007431_139	Lung function (FEV1/FVC)	3e-36
GCST006288_295	Heel bone mineral density	3e-35
GCST003989_8	Chin dimples	6e-32
GCST006979_1074	Heel bone mineral density	5e-29
GCST006288_353	Heel bone mineral density	4e-28
GCST007856_27	Colorectal cancer or advanced adenoma	2e-22
GCST006288_354	Heel bone mineral density	9e-20
GCST006291_84	Spherical equivalent or myopia (age of diagnosis)	1e-17
GCST003997_45	Myopia	5e-17
GCST006979_1050	Heel bone mineral density	5e-17
GCST90014268_4	Cataracts	7e-17
GCST002030_9	Primary tooth development (time to first tooth eruption)	9e-17
GCST007430_124	Peak expiratory flow	1e-13
GCST006979_1075	Heel bone mineral density	3e-11
GCST007856_83	Colorectal cancer or advanced adenoma	4e-10
GCST007856_99	Colorectal cancer or advanced adenoma	5e-10
GCST009462_34	Optic disc size	6e-10
GCST000270_1	Colorectal cancer	8e-10
GCST008059_224	Estimated glomerular filtration rate	2e-9
GCST002764_4	Optic cup area	5e-9
GCST010703_176	Brain morphology (MOSTest)	1e-8
GCST009724_88	Vertical cup-disc ratio (multi-trait analysis)	3e-8
GCST009962_13	High myopia	3e-8
GCST006988_123	Blond vs. brown/black hair color	4e-8
GCST003017_19	Colorectal cancer	5e-8

EFO canonical traits (from GWAS)

11 canonical traits:

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

2 disease descriptors:

Descriptor	Name	Tree numbers
C566440	Microphthalmia, Syndromic 6 *(supp.)*
C537884	Peters anomaly *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5350 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

23 measured of 32 human assays (33 total across all organisms); most potent 23 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
4-(6-(4-(piperazin-1-yl)phenyl)H-pyrazolo[1,5-a]pyridin-3-yl)quinoline	IC50	5 nM
4-(6-(4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline	IC50	10 nM
5-(6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline	IC50	32 nM
4-(6-(4-(2-(piperidin-1-yl)ethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline	IC50	90 nM
4-(6-(4-methoxyphenyl)H-pyrazolo[1,5-a]pyridin-3-yl)quinoline	IC50	150 nM
4-(3-(quinolin-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl)phenol	IC50	250 nM
7-chloro-4-(6-(4-(piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline	IC50	350 nM
6-(4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl)-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidine	IC50	450 nM
N,N-diethyl-2-(4-(3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl)phenoxy)ethanamine	IC50	500 nM
7-chloro-4-(6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline	IC50	500 nM
4-(6-phenylpyrazolo[1,5-a]pyrimidin-3-yl)quinoline	IC50	750 nM
LDN-193189	IC50	1120 nM
4-(3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)H-pyrrolo[1,2-a]pyrimidin-8-yl)quinoline	IC50	2600 nM
3-(3-fluoropyridin-4-yl)-6-(4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl)pyrazolo[1,5-a]pyrimidine	IC50	3300 nM
6-(3-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl)-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidine	IC50	4500 nM
4-(pyrazolo[1,5-a]pyrimidin-3-yl)quinoline	IC50	5000 nM
6-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidine	IC50	6330 nM
4-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]pyridine	IC50	6500 nM
4-(6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline	IC50	7260 nM
4-(6-(3-(piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline	IC50	20000 nM
CHEMBL3288258	KD	24000 nM
CHEMBL3288260	KD	34000 nM
CHEMBL3288259	KD	46000 nM

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	decreases expression, affects expression, affects binding, increases expression	5
Tretinoin	affects cotreatment, increases expression, affects expression, increases reaction	5
Valproic Acid	affects cotreatment, increases expression	5
Tetrachlorodibenzodioxin	decreases expression, increases expression	4
Particulate Matter	affects expression, decreases expression, increases abundance, affects splicing	4
bisphenol A	affects expression, decreases expression	3
trichostatin A	increases expression, affects cotreatment	3
Arsenic	increases expression, decreases expression, increases abundance	3
Cadmium	decreases reaction, increases abundance, increases expression, decreases expression	3
Tobacco Smoke Pollution	decreases expression, increases expression	3
Cadmium Chloride	decreases expression, decreases reaction, increases abundance, affects cotreatment, increases expression	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	affects cotreatment, decreases methylation, increases expression	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	affects cotreatment, increases expression	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	increases expression, affects cotreatment	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 303 trials:

NCT	Phase	Status	Title
NCT05657860	Phase 4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	Phase 4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	Phase 4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	Phase 4	RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00668824	Phase 4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	Phase 4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	Phase 4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	Phase 4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	Phase 4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	Phase 4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	Phase 4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	Phase 4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	Phase 4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	Phase 4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	Phase 4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	Phase 4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT02270736	Phase 3	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	Phase 3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	Phase 3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	Phase 3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	Phase 3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	Phase 3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	Phase 3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	Phase 3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	Phase 3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	Phase 3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	Phase 3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	Phase 3	UNKNOWN	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	Phase 3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	Phase 3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	Phase 3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	Phase 3	RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT04465188	Phase 2	WITHDRAWN	Scleral Buckling for Retinal Detachment Prevention in Genetically Confirmed Stickler Syndrome
NCT02304302	Phase 2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	Phase 2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	Phase 2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	Phase 2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00115375	Phase 2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	Phase 2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	Phase 2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	Phase 2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	Phase 2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	Phase 2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	Phase 2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	Phase 2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	Phase 2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	Phase 2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	Phase 2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	Phase 2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	Phase 2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE
NCT01841177	Phase 2	COMPLETED	Evaluating Precision of Therapy - Milrinone
NCT02046135	Phase 2	TERMINATED	Sodium Bicarbonate to Prevent Acute Kidney Injury in Children Undergoing Cardiac Surgery
NCT02133573	Phase 2	COMPLETED	Randomized Trial of Maternal Progesterone Therapy
NCT02232399	Phase 2	COMPLETED	Is Levosimendan Superior to Milrinone Regarding Acute Kidney Injury After Cardiac Surgery for Congenital Heart Disease?
NCT02492269	Phase 2	COMPLETED	Stress Response and Neurodevelopmental Outcome After Cardiac Surgery Utilizing CPB in Children: A Prospective, Double Blinded and Randomized Study
NCT02564796	Phase 2	TERMINATED	Erythropoietin to Prevent Unnecessary Transfusions In Patients With Cyanotic CHD - A Prospective Control Trial
NCT02618824	Phase 2	UNKNOWN	Role of Terminal Warm Blood Cardioplegia as Myocardial Protection in the Use of Histidine-Tryptophan-Ketoglutarate Cardioplegia in Complex Congenital Heart Surgery
NCT02769624	Phase 2	TERMINATED	Acute Effects of Inhaled Treprostinil in Fontan Patients
NCT02877238	Phase 2	COMPLETED	Remote Preconditioning and Myocardial Protection
NCT03082716	Phase 2	COMPLETED	Custodiol Versus Blood Cardioplegaia in Paediatric Cardiac Surgery

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for BMP4 across ~30M SureChEMBL compounds — explore on Sugi Predict.