BMP3

Summary

BMP3 (bone morphogenetic protein 3, HGNC:1070) is a protein-coding gene on chromosome 4q21.21, encoding Bone morphogenetic protein 3 (P12645). Growth factor of the TGF-beta superfamily that plays an essential role in developmental process by inducing and patterning early skeletal formation and by negatively regulating bone density.

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 suppresses osteoblast differentiation, and negatively regulates bone density, by modulating TGF-beta receptor availability to other ligands.

Source: NCBI Gene 651 — RefSeq curated summary.

At a glance

• Gene–disease (curated): coloboma (Moderate, GenCC)
• GWAS associations: 12
• Clinical variants (ClinVar): 83 total
• GTEx eGene: eQTL in 12 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.83 (unconstrained)
• MANE Select transcript: NM_001201
• Notable: 83 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1070
Approved symbol	BMP3
Name	bone morphogenetic protein 3
Location	4q21.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000152785
Ensembl biotype	protein_coding
OMIM	112263
Entrez	651

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

MANE Select: ENST00000282701

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000282701, ENST00000909109, ENST00001134491

RefSeq mRNA: 1 — MANE Select: NM_001201 NM_001201

CCDS: CCDS3588

Canonical transcript exons

ENST00000282701 — 3 exons

Exon	Start	End
ENSE00001007113	81030708	81031600
ENSE00001007115	81045738	81046648
ENSE00001549055	81053345	81057627

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 79.85.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4027 / max 28.5608, expressed in 129 samples.

Highest expression (Bgee): muscle layer of sigmoid colon, male germ line stem cell (sensu Vertebrata) in testis, rectum, transverse colon, mucosa of transverse colon.

Genetic regulation across tissues (GTEx eQTL / sQTL)

BMP3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

12 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellar Hemisphere	eqtl	8.2e-13	+1.62	4:80286532:G:GAGC
Brain Cerebellum	eqtl	4.7e-11	+2.01	4:80286532:G:GAGC
Adipose Subcutaneous	eqtl	6.6e-10	+0.37	4:81042000:A:G
Skin Not Sun Exposed Suprapubic	eqtl	3.0e-06	-0.23	4:80303750:A:C
Skin Sun Exposed Lower leg	eqtl	3.9e-06	-0.31	4:81058839:T:C
Nerve Tibial	eqtl	7.7e-04	-0.15	4:81058839:T:C
Cells Cultured fibroblasts	eqtl	3.8e-03	+0.60	4:80286532:G:GAGC
Esophagus Gastroesophageal Junction	eqtl	9.2e-03	+0.50	4:81024795:C:T
Colon Sigmoid	eqtl	1.1e-02	+0.17	4:80415641:T:C
Breast Mammary Tissue	eqtl	1.3e-02	+0.23	4:81020374:C:G
Artery Aorta	eqtl	1.5e-02	+0.33	4:80344209:A:G
Esophagus Muscularis	eqtl	4.5e-02	+0.27	4:81545294:A:G

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
48540	0.1753	71
48539	0.1668	69
48538	0.0606	25

Top tissues by expression

showing 100 of 275 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
muscle layer of sigmoid colon	UBERON:0035805	79.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.20	gold quality
rectum	UBERON:0001052	77.84	gold quality
transverse colon	UBERON:0001157	76.66	gold quality
mucosa of transverse colon	UBERON:0004991	74.15	gold quality
sigmoid colon	UBERON:0001159	73.32	gold quality
colon	UBERON:0001155	73.07	gold quality
lower esophagus muscularis layer	UBERON:0035833	72.57	gold quality
lower esophagus	UBERON:0013473	72.41	gold quality
large intestine	UBERON:0000059	72.16	gold quality
intestine	UBERON:0000160	71.39	gold quality
tibial nerve	UBERON:0001323	70.93	gold quality
small intestine Peyer’s patch	UBERON:0003454	70.61	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	69.25	gold quality
small intestine	UBERON:0002108	68.96	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	67.82	gold quality
palpebral conjunctiva	UBERON:0001812	67.08	silver quality
gall bladder	UBERON:0002110	65.41	gold quality
colonic epithelium	UBERON:0000397	64.85	gold quality
ileal mucosa	UBERON:0000331	62.47	silver quality
cortical plate	UBERON:0005343	61.54	gold quality
right uterine tube	UBERON:0001302	61.28	gold quality
pancreatic ductal cell	CL:0002079	59.81	silver quality
duodenum	UBERON:0002114	59.68	gold quality
ganglionic eminence	UBERON:0004023	59.33	gold quality
minor salivary gland	UBERON:0001830	58.63	gold quality
urinary bladder	UBERON:0001255	58.46	gold quality
bone marrow cell	CL:0002092	58.09	silver quality
left ovary	UBERON:0002119	56.65	gold quality
decidua	UBERON:0002450	56.55	gold quality
omental fat pad	UBERON:0010414	56.51	gold quality
peritoneum	UBERON:0002358	56.47	gold quality
saliva-secreting gland	UBERON:0001044	56.31	gold quality
mouth mucosa	UBERON:0003729	56.23	gold quality
right ovary	UBERON:0002118	56.06	gold quality
cranial nerve II	UBERON:0000941	56.00	silver quality
nasal cavity mucosa	UBERON:0001826	55.75	gold quality
adipose tissue of abdominal region	UBERON:0007808	55.72	gold quality
bone marrow	UBERON:0002371	55.67	gold quality
nasal cavity epithelium	UBERON:0005384	55.40	gold quality
smooth muscle tissue	UBERON:0001135	54.94	gold quality
endometrium epithelium	UBERON:0004811	54.86	gold quality
upper leg skin	UBERON:0004262	54.82	silver quality
ovary	UBERON:0000992	54.78	gold quality
fundus of stomach	UBERON:0001160	54.68	gold quality
embryo	UBERON:0000922	54.65	gold quality
tonsil	UBERON:0002372	54.57	gold quality
lung	UBERON:0002048	53.95	gold quality
mucosa of stomach	UBERON:0001199	53.93	gold quality
right lung	UBERON:0002167	53.65	gold quality
stomach	UBERON:0000945	53.62	gold quality
deltoid	UBERON:0001476	53.25	gold quality
esophagus	UBERON:0001043	52.96	gold quality
upper lobe of left lung	UBERON:0008952	52.91	gold quality
hair follicle	UBERON:0002073	52.77	gold quality
prefrontal cortex	UBERON:0000451	52.25	gold quality
upper lobe of lung	UBERON:0008948	51.66	gold quality
caecum	UBERON:0001153	51.30	gold quality
body of stomach	UBERON:0001161	51.28	gold quality
fallopian tube	UBERON:0003889	51.18	gold quality
epithelial cell of pancreas	CL:0000083	51.16	gold quality
quadriceps femoris	UBERON:0001377	51.10	gold quality
vermiform appendix	UBERON:0001154	51.09	gold quality
cerebellar vermis	UBERON:0004720	50.94	gold quality
adrenal tissue	UBERON:0018303	50.82	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
ventricular zone	UBERON:0003053	50.31	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
adipose tissue	UBERON:0001013	49.84	gold quality
vastus lateralis	UBERON:0001379	49.83	gold quality
lymph node	UBERON:0000029	49.71	gold quality
connective tissue	UBERON:0002384	49.48	gold quality
muscle tissue	UBERON:0002385	49.43	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
oviduct epithelium	UBERON:0004804	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
thymus	UBERON:0002370	49.16	gold quality
subcutaneous adipose tissue	UBERON:0002190	49.10	gold quality
calcaneal tendon	UBERON:0003701	49.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	49.03	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
hypothalamus	UBERON:0001898	48.26	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
colonic mucosa	UBERON:0000317	48.12	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
hindlimb stylopod muscle	UBERON:0004252	47.74	silver quality
metanephric glomerulus	UBERON:0004736	47.74	gold quality
renal glomerulus	UBERON:0000074	47.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.52

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 62 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Urinary bladder	tissue	8.9
Superior colliculi	tissue	8.3
Frontal cortex	tissue	7.9
Colon	tissue	6.8
Small intestine	tissue	6.8
Rectum	tissue	6.3
Ovary	tissue	5.1
Lung	tissue	5.1
Hippocampal formation	tissue	4.7
Entorhinal cortex	tissue	3.6
Duodenum	tissue	3.0
Cerebral cortex	tissue	2.7
Temporal cortex	tissue	2.7
Spinal cord	tissue	2.5
Amygdala	tissue	2.4
Periaqueductal gray	tissue	2.4
Retrosplenial cortex	tissue	2.4
Occipital cortex	tissue	2.3
Substantia nigra	tissue	2.2
Somatosensory cortex	tissue	2.2
Insular cortex	tissue	2.2
Prefrontal cortex	tissue	2.1
Retrosplenial and cingulate cortex	tissue	2.1
Motor cortex	tissue	1.9
Pons	tissue	1.8
Gallbladder	tissue	1.8
Thalamus	tissue	1.7
Ventral forebrain	tissue	1.6
Hypothalamus	tissue	1.5
Septum	tissue	1.5
Caudate putamen	tissue	1.5
Medulla oblongata	tissue	1.4
Cerebellum	tissue	1.4
Tonsil	tissue	1.4
Salivary gland	tissue	1.2
Putamen	tissue	1.2
Basal ganglia	tissue	1.1
Postcentral gyrus	tissue	1.1
Locus coeruleus	tissue	1.0
Choroid plexus	tissue	0.9
Midbrain	tissue	0.9
Fallopian tube	tissue	0.9
Stomach 1	tissue	0.8
Hippocampus	tissue	0.8
Bone marrow	tissue	0.8
Tongue	tissue	0.6
Olfactory bulb	tissue	0.6
Breast	tissue	0.5
Retina	tissue	0.5
Adipose tissue	tissue	0.5
Smooth muscle	tissue	0.5
Nucleus accumbens	tissue	0.5
Corpus callosum	tissue	0.5
Cervix	tissue	0.4
Adrenal gland	tissue	0.4
Lymph node	tissue	0.3
Appendix	tissue	0.3
Vagina	tissue	0.2
Prostate	tissue	0.2
Testis	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Subiculum (4.7), Habenula (3.6), Ventral hippocampus (3.3), Dorsal spinal cord (2.5), Dorsal hippocampus (2.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting BMP3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 222 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684

Functional genomics

gnomAD constraint: pLI 0.000226, LOEUF 0.835, missense Z -0.326 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000282701 — one region, missense o/e 1.08.

Literature-anchored findings (GeneRIF, showing 19)

• The expression signals of BMP3 mRNA in malignant schwannoma were relatively lower than in benign lesions (PMID:11642720)
• BMP-3 receptor specificity is controlled by the interaction of Lys-30 of BMP-3 with Glu-76 of ActRIIb (PMID:17924656)
• BMP3 silencing is an early and frequent event in colorectal tumors progressing via the serrated and traditional pathways. (PMID:18311777)
• These results demonstrate that BMP-3 stimulates mesenchymal stem cell proliferation via the TGF-beta/activin signaling pathway. (PMID:20143330)
• Data suggest that promotor region methylation of the BMP3 gene may cause gastric carcinoma in Chinese people. (PMID:20238409)
• Features supportive of positive selection in the BMP3 gene were found including the presence of an excess of nonsynonymous mutations in modern humans, and a significantly lower genetic diversity that deviates from neutrality (PMID:20532035)
• Circulating bone morphogenetic protein 1-3 isoform increases renal fibrosis. (PMID:21415150)
• a critical link between HNF1A-MODY-induced alterations in Bmp-3 expression and insulin gene levels (PMID:21628466)
• As an addition to PRKG2 and RASGEFIB genes, we propose to include BMP3 gene as the principal determinant of the observed common phenotype. (PMID:22303795)
• Bone morphogenic protein 3 signaling in the regulation of osteogenesis. (PMID:23127436)
• Methylation level in stool decreases dramatically following colorectal cancer resection (PMID:24993691)
• BMP3 - the biomarker of a currently in-use multi-target stool DNA test was commonly expressed in tumor tissue specimens, independent of Fecal Immunochemical Test result. (PMID:28044229)
• a novel microRNA miR-450b was essential for adipose-derived mesenchymal stem cell differentiation, which could promote osteogenic differentiation in vitro and enhance bone formation in vivo by directly suppressing BMP3. (PMID:29649414)
• This study demonstrated that there was a significantly higher frequency of BMP3 methylated DNA in plasma in patients with polyps versus healthy controls with a sensitivity and specificity of 40 and 94%, respectively. (PMID:29892846)
• Results found that BMP3 gene was extensively hypermethylated and downregulated in colorectal cancer (CRC) and suggest that BMP3 acts as a tumor suppressor or has a growth rate-limiting role in CRC development and progression. (PMID:31665064)
• Inhibition of BMP3 increases the inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis. (PMID:32568738)
• USF2 reduces BMP3 expression via transcriptional activation of miR-34a, thus promoting osteogenic differentiation of BMSCs. (PMID:34350522)
• LncRNA SNHG3 regulates the BMSC osteogenic differentiation in bone metastasis of breast cancer by modulating the miR-1273g-3p/BMP3 axis. (PMID:35081500)
• Overexpression of lncRNA A2M-AS1 inhibits cell growth and aggressiveness via regulating the miR-587/bone morphogenetic protein 3 axis in lung adenocarcinoma. (PMID:36461613)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	bmp3	ENSDARG00000060526
mus_musculus	Bmp3	ENSMUSG00000029335
rattus_norvegicus	Bmp3	ENSRNOG00000002381

Paralogs (31): TGFB2 (ENSG00000092969), BMP7 (ENSG00000101144), TGFB1 (ENSG00000105329), BMP5 (ENSG00000112175), BMP8B (ENSG00000116985), TGFB3 (ENSG00000119699), INHBA (ENSG00000122641), INHA (ENSG00000123999), BMP4 (ENSG00000125378), BMP2 (ENSG00000125845), GDF5 (ENSG00000125965), GDF1 (ENSG00000130283), BMP15 (ENSG00000130385), GDF15 (ENSG00000130513), GDF11 (ENSG00000135414), MSTN (ENSG00000138379), INHBE (ENSG00000139269), LEFTY2 (ENSG00000143768), GDF7 (ENSG00000143869), 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:88179) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 14 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased circulating calcium level	1
abnormal heart morphology	1
enlarged heart	1
abnormal maxilla morphology	1
abnormal spleen morphology	1
abnormal thymus morphology	1
enlarged thymus	1
abnormal testis morphology	1
small testis	1
decreased locomotor activity	1
decreased exploration in new environment	1
increased circulating creatine kinase level	1
increased trabecular bone volume	1
increased bone mineral density of femur	1

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	Q800B9	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
Columba livia	Q8UWD8	97.3%	Diamond
Lepus capensis	Q8HY52	96.8%	Diamond
Oryctolagus cuniculus	O46564	95.7%	Diamond
Xenopus laevis	Q91609	94.0%	Diamond
Epinephelus coioides	Q5I3Q2	91.0%	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
CFAP299-AS1	ncRNA	105377305
FGF5	protein-coding	2250
CFAP299	protein-coding	255119
PRKG2-AS2	ncRNA	124900726
PRKG2	protein-coding	5593
PRKG2-AS1	ncRNA	101928942
RASGEF1B	protein-coding	153020

Protein

Protein identifiers

Bone morphogenetic protein 3 — P12645 (reviewed: P12645)

Alternative names: Bone morphogenetic protein 3A, Osteogenin

All UniProt accessions (1): P12645

UniProt curated annotations — full annotation on UniProt →

Function. Growth factor of the TGF-beta superfamily that plays an essential role in developmental process by inducing and patterning early skeletal formation and by negatively regulating bone density. Antagonizes the ability of certain osteogenic BMPs to induce osteoprogenitor differentiation and ossification. Initiates signaling cascades by associating with type II receptor ACVR2B to activate SMAD2-dependent and SMAD-independent signaling cascades including TAK1 and JNK pathways.

Subunit / interactions. Homodimer; disulfide-linked. Interacts with type II receptor ACVR2B.

Subcellular location. Secreted.

Tissue specificity. Expressed in adult and fetal cartilage.

Induction. Highly expressed in fracture tissue, particularly in osteoblasts, osteoclasts and chondroblasts.

Similarity. Belongs to the TGF-beta family.

RefSeq proteins (1): NP_001192* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001839	TGF-b_C	Domain
IPR015615	TGF-beta-like	Family
IPR017197	BMP3/BMP3B	Family
IPR017948	TGFb_CS	Conserved_site
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF00019

UniProt features (35 total): strand 9, glycosylation site 5, sequence variant 5, disulfide bond 4, helix 3, turn 2, region of interest 2, compositionally biased region 2, signal peptide 1, propeptide 1, chain 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
2QCQ	Crystal structure of Bone Morphogenetic Protein-3 (BMP-3)	X-RAY DIFFRACTION	2.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P12645-F1	65.11	0.24

Human Protein Atlas

Protein class: Predicted secreted proteins, Plasma proteins

Protein evidence: Evidence at protein level

Functional residue map

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

Disulfide bonds (4)

Type	Positions
Disulfide bond	370–437, 399–469, 403–471
Interchain	436

Glycosylation sites (5)

Type	Positions
N-linked (glcnac…) asparagine	220, 463, 117, 141, 175

Function

Pathways and Gene Ontology

Reactome pathways

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

MSigDB gene sets: 143 (showing top): RNGTGGGC_UNKNOWN, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_OSTEOBLAST_DIFFERENTIATION, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_CELL_CELL_SIGNALING, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_OSSIFICATION, GOMF_CYTOKINE_ACTIVITY, SABATES_COLORECTAL_ADENOMA_DN, GOBP_CONNECTIVE_TISSUE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_OSSIFICATION, GOMF_SIGNALING_RECEPTOR_BINDING

GO Biological Process (8): skeletal system development (GO:0001501), osteoblast differentiation (GO:0001649), cell surface receptor protein serine/threonine kinase signaling pathway (GO:0007178), cell-cell signaling (GO:0007267), negative regulation of ossification (GO:0030279), cartilage development (GO:0051216), ossification (GO:0001503), cell differentiation (GO:0030154)

GO Molecular Function (4): signaling receptor binding (GO:0005102), cytokine activity (GO:0005125), growth factor activity (GO:0008083), BMP receptor binding (GO:0070700)

GO Cellular Component (2): extracellular exosome (GO:0070062), extracellular region (GO:0005576)

GO top-level categories

19 GO namespaces:

Category	Terms
ossification	2
receptor ligand activity	2
system development	1
animal gross anatomical part developmental process	1
cell differentiation	1
enzyme-linked receptor protein signaling pathway	1
cell communication	1
signaling	1
regulation of ossification	1
negative regulation of multicellular organismal process	1
skeletal system development	1
animal organ development	1
connective tissue development	1
multicellular organismal process	1
cellular developmental process	1
protein binding	1
transmembrane receptor protein serine/threonine kinase binding	1
extracellular vesicle	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 15 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of ossification	BP	direct assay
extracellular exosome	CC	high-throughput assay
BMP receptor binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 994 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BMP3	NDRG4	Q9ULP0	857
BMP3	AMBN	Q9NP70	758
BMP3	ACVR2B	Q13705	756
BMP3	ACVR2A	P27037	722
BMP3	IBSP	P21815	673
BMP3	SEPTIN9	Q9UHD8	650
BMP3	BMP1	P13497	585
BMP3	SPP1	P10451	582
BMP3	NOG	Q13253	559
BMP3	CHRD	Q9H2X0	554
BMP3	TFPI2	P48307	548
BMP3	SMOC2	Q9H3U7	532
BMP3	BMPR1B	P78366	519
BMP3	SFRP2	Q96HF1	493
BMP3	KRAS	P01116	491

IntAct

Human interaction partners of BMP3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
WFIKKN1	direct interaction	0.440	1
WFIKKN2	direct interaction	0.440	1
BMP2K	physical association	0.370	1
KDM1A	physical association	0.370	1
PRMT6	physical association	0.370	1

BioGRID (4 interactions; top human partners by supporting records): FBXO6 (Affinity Capture-MS), KDM1A (Two-hybrid), PRMT6 (Two-hybrid), YBX3 (Cross-Linking-MS (XL-MS))

Disease & clinical

Genetic variants

Variant evidence for BMP3: 83 ClinVar records (0 pathogenic / likely pathogenic); 12 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	2
Benign	3

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 23 predictions of 290):

Position(s)	Effect	Δscore	Sites
4:81045736	acceptor_loss	1.0000
4:81031601–81031602	donor_loss	0.9900	5
4:81045736–81045737	acceptor_loss	0.9900	5
4:81045740	acceptor_gain	0.8700
4:81046497	donor_gain	0.8700
4:81032743	donor_gain	0.8400
4:81031602	donor_loss	0.8100
4:81046650	donor_loss	0.8100
4:81046649–81046650	donor_loss	0.8000	5
4:81046648	donor_loss	0.7800	2

AlphaMissense

842 missense substitutions predicted likely pathogenic (of 3,083 scored), across 192 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M464	9	0.960	0.995
M60	9	0.896	0.980
F379	8	0.991	0.999
H416	8	0.989	0.995
F405	8	0.964	0.999
D246	8	0.958	0.980
F394	8	0.952	0.998
D381	8	0.950	0.980
D378	8	0.949	0.988
S421	8	0.918	0.998
D451	8	0.916	0.968
F116	8	0.893	0.983
N95	8	0.853	0.966
H59	8	0.770	0.914
C399	7	0.998	1.000
C437	7	0.998	0.999
C403	7	0.997	0.999
C469	7	0.997	0.999
C370	7	0.996	0.998
C471	7	0.996	0.999

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Bladder Urothelial Carcinoma, Lung Adenocarcinoma)

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	favorable	0.000335

Disease associations

OMIM: gene MIM:112263 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
coloboma	Moderate	Autosomal dominant

Mondo (1): coloboma (MONDO:0001476)

GWAS associations

12 associations:

Study	Trait	p-value
GCST010002_134	Refractive error	2e-65
GCST003997_34	Myopia	2e-23
GCST006291_115	Spherical equivalent or myopia (age of diagnosis)	6e-21
GCST009462_70	Optic disc size	2e-19
GCST90014268_32	Cataracts	3e-12
GCST012400_141	Low myopia vs hyperopia	1e-9
GCST001876_7	Pubertal anthropometrics	1e-7
GCST009959_13	Retinal detachment or retinal break	2e-7
GCST001858_10	Refractive error	1e-6
GCST007159_20	Corneal astigmatism	1e-6
GCST000175_17	Height	2e-6
GCST007160_11	Refractive astigmatism	3e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0001382	puberty
EFO:0004847	age at onset
EFO:1002040	Corneal astigmatism
EFO:0010698	retinal break

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D003103	Coloboma	C11.250.110; C11.270.147; C16.131.384.282

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
ethyl-p-hydroxybenzoate	increases expression	1
monomethylarsonous acid	increases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
Fulvestrant	decreases methylation, affects cotreatment	1
Air Pollutants	increases expression, increases abundance	1
Arsenic	increases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Lead	affects methylation	1
Rotenone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases methylation	1
Zearalenone	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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

4 trials:

NCT	Phase	Status	Title
NCT00368004	Not specified	TERMINATED	Family Studies of Uveal Coloboma
NCT01778543	Not specified	RECRUITING	Pathogenesis and Genetics of Microphthalmia, Anophthalmia and Uveal Coloboma (MAC)
NCT04833361	Not specified	COMPLETED	Potential Environmental Causes of Uveal Coloboma
NCT06293560	Not specified	RECRUITING	Microphthalmia, Anophthalmia, and Coloboma Genetic Epidemiology in Children