BMP7 (bone morphogenetic protein 7)

Gene

• Entrez ID: 655
• Gene name: Bone morphogenetic protein 7
• Gene symbol: BMP7
• Synonyms: OP-1
• Chromosome: 20
• Chromosome location: 20q13.31
• Summary: 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, which plays a role in bone, kidney and brown adipose tissue development. Additionally, this protein induces ectopic bone formation and may promote fracture healing in human patients. [provided by RefSeq, Jul 2016]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1555815731	G>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT002000	hsa-miR-22-3p	Luciferase reporter assay, qRT-PCR, Western blot	19011694
MIRT002000	hsa-miR-22-3p	Luciferase reporter assay	24163368
MIRT005882	hsa-miR-342-3p	Luciferase reporter assay, Northern blot, qRT-PCR	21172025
MIRT007204	hsa-miR-34a-5p	Western blot	23226240
MIRT023527	hsa-miR-1-3p	Microarray	18668037
MIRT052250	hsa-let-7b-5p	CLASH	23622248
MIRT437421	hsa-miR-542-3p	Luciferase reporter assay, qRT-PCR, Western blot	24503542
MIRT437421	hsa-miR-542-3p	Luciferase reporter assay, qRT-PCR, Western blot	26610487
MIRT660231	hsa-miR-6855-5p	HITS-CLIP	23824327
MIRT660232	hsa-miR-3170	HITS-CLIP	23824327
MIRT660233	hsa-miR-193b-5p	HITS-CLIP	23824327
MIRT660234	hsa-miR-24-3p	HITS-CLIP	23824327
MIRT660235	hsa-miR-4284	HITS-CLIP	23824327
MIRT660236	hsa-miR-7155-5p	HITS-CLIP	23824327
MIRT660237	hsa-miR-637	HITS-CLIP	23824327
MIRT660238	hsa-miR-8089	HITS-CLIP	23824327
MIRT660239	hsa-miR-4700-5p	HITS-CLIP	23824327
MIRT660240	hsa-miR-4667-5p	HITS-CLIP	23824327
MIRT660241	hsa-miR-4772-3p	HITS-CLIP	23824327
MIRT660242	hsa-miR-330-5p	HITS-CLIP	23824327
MIRT660243	hsa-miR-326	HITS-CLIP	23824327
MIRT660244	hsa-miR-1304-3p	HITS-CLIP	23824327
MIRT660245	hsa-miR-6890-3p	HITS-CLIP	23824327
MIRT732128	hsa-miR-137	Luciferase reporter assay, Western blot	26617798

Transcription factors

Transcription factor	Regulation	Reference
HDAC2	Repression	17452977
LDB1	Unknown	17452977
LMO4	Activation	17452977
LMO4	Repression	17452977

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001501	Process	Skeletal system development	TAS	2357959
GO:0001503	Process	Ossification	IEA
GO:0001656	Process	Metanephros development	IEP	18437684
GO:0001657	Process	Ureteric bud development	ISS
GO:0001707	Process	Mesoderm formation	IEA
GO:0001823	Process	Mesonephros development	IEP	18437684
GO:0001837	Process	Epithelial to mesenchymal transition	TAS	14679171
GO:0003272	Process	Endocardial cushion formation	ISS
GO:0003344	Process	Pericardium morphogenesis	ISS
GO:0005125	Function	Cytokine activity	IBA	21873635
GO:0005515	Function	Protein binding	IPI	9872992, 18184661, 18339631, 31515488, 32296183
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005615	Component	Extracellular space	IDA	17977014
GO:0007411	Process	Axon guidance	IEA
GO:0008083	Function	Growth factor activity	IEA
GO:0008201	Function	Heparin binding	IEA
GO:0009880	Process	Embryonic pattern specification	IEA
GO:0010628	Process	Positive regulation of gene expression	IDA	28124060
GO:0010664	Process	Negative regulation of striated muscle cell apoptotic process	ISS
GO:0010718	Process	Positive regulation of epithelial to mesenchymal transition	IEA
GO:0010800	Process	Positive regulation of peptidyl-threonine phosphorylation	IDA	19736306
GO:0010862	Process	Positive regulation of pathway-restricted SMAD protein phosphorylation	IBA	21873635
GO:0010862	Process	Positive regulation of pathway-restricted SMAD protein phosphorylation	IDA	9311995, 16049014, 17244894, 19736306
GO:0010862	Process	Positive regulation of pathway-restricted SMAD protein phosphorylation	TAS	11580864
GO:0016358	Process	Dendrite development	TAS	11580864
GO:0021502	Process	Neural fold elevation formation	ISS
GO:0030326	Process	Embryonic limb morphogenesis	IEA
GO:0030501	Process	Positive regulation of bone mineralization	IDA	18436533
GO:0030509	Process	BMP signaling pathway	IBA	21873635
GO:0030509	Process	BMP signaling pathway	IDA	16049014, 18436533
GO:0030509	Process	BMP signaling pathway	IMP	18326817
GO:0030855	Process	Epithelial cell differentiation	IEA
GO:0030902	Process	Hindbrain development	ISS
GO:0031982	Component	Vesicle	IEA
GO:0032088	Process	Negative regulation of NF-kappaB transcription factor activity	ISS
GO:0032355	Process	Response to estradiol	IEA
GO:0033280	Process	Response to vitamin D	IEA
GO:0034116	Process	Positive regulation of heterotypic cell-cell adhesion	IDA	15100360
GO:0034504	Process	Protein localization to nucleus	IDA	17244894
GO:0042326	Process	Negative regulation of phosphorylation	IDA	17244894
GO:0042475	Process	Odontogenesis of dentin-containing tooth	IEA
GO:0043065	Process	Positive regulation of apoptotic process	IEA
GO:0043401	Process	Steroid hormone mediated signaling pathway	IMP	17244894
GO:0043407	Process	Negative regulation of MAP kinase activity	IDA	17244894
GO:0043434	Process	Response to peptide hormone	IEA
GO:0045665	Process	Negative regulation of neuron differentiation	IDA	16325379
GO:0045666	Process	Positive regulation of neuron differentiation	IEA
GO:0045669	Process	Positive regulation of osteoblast differentiation	IDA	18436533
GO:0045746	Process	Negative regulation of Notch signaling pathway	IEA
GO:0045786	Process	Negative regulation of cell cycle	IDA	11502704
GO:0045839	Process	Negative regulation of mitotic nuclear division	IDA	17244894
GO:0045892	Process	Negative regulation of transcription, DNA-templated	IDA	15100360, 17244894
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IDA	14517293, 15100360, 16049014
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IMP	27923061
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0048596	Process	Embryonic camera-type eye morphogenesis	IEA
GO:0048738	Process	Cardiac muscle tissue development	ISS
GO:0048754	Process	Branching morphogenesis of an epithelial tube	IEA
GO:0048762	Process	Mesenchymal cell differentiation	IDA	9693150
GO:0048812	Process	Neuron projection morphogenesis	IDA	16325379
GO:0050768	Process	Negative regulation of neurogenesis	IEA
GO:0051216	Process	Cartilage development	IEA
GO:0060037	Process	Pharyngeal system development	ISS
GO:0060272	Process	Embryonic skeletal joint morphogenesis	IEA
GO:0060393	Process	Regulation of pathway-restricted SMAD protein phosphorylation	IDA	16049014
GO:0060395	Process	SMAD protein signal transduction	IBA	21873635
GO:0060395	Process	SMAD protein signal transduction	IDA	17244894
GO:0060411	Process	Cardiac septum morphogenesis	ISS
GO:0060445	Process	Branching involved in salivary gland morphogenesis	IEA
GO:0060485	Process	Mesenchyme development	ISS
GO:0060548	Process	Negative regulation of cell death	IDA	12631064
GO:0060686	Process	Negative regulation of prostatic bud formation	IEA
GO:0060687	Process	Regulation of branching involved in prostate gland morphogenesis	IEA
GO:0060710	Process	Chorio-allantoic fusion	ISS
GO:0061384	Process	Heart trabecula morphogenesis	ISS
GO:0062023	Component	Collagen-containing extracellular matrix	IEA
GO:0070487	Process	Monocyte aggregation	IDA	15100360
GO:0070700	Function	BMP receptor binding	IBA	21873635
GO:0071456	Process	Cellular response to hypoxia	ISS
GO:0071773	Process	Cellular response to BMP stimulus	IMP	18326817
GO:0072040	Process	Negative regulation of mesenchymal cell apoptotic process involved in nephron morphogenesis	IEA
GO:0072125	Process	Negative regulation of glomerular mesangial cell proliferation	IDA	17244894
GO:0072133	Process	Metanephric mesenchyme morphogenesis	IEA
GO:0072134	Process	Nephrogenic mesenchyme morphogenesis	IEA
GO:0072136	Process	Metanephric mesenchymal cell proliferation involved in metanephros development	IEA
GO:0090336	Process	Positive regulation of brown fat cell differentiation	IMP	27923061
GO:1900006	Process	Positive regulation of dendrite development	IDA	11580864
GO:1900106	Process	Positive regulation of hyaluranon cable assembly	IDA	15100360
GO:1901223	Process	Negative regulation of NIK/NF-kappaB signaling	ISS
GO:1905069	Process	Allantois development	ISS
GO:1905312	Process	Positive regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis	IEA
GO:2000121	Process	Regulation of removal of superoxide radicals	ISS

Other IDs

• MIM: 112267
• HGNC: 1074
• e!Ensembl: ENSG00000101144

Protein

• UniProt ID: P18075
• Protein name: Bone morphogenetic protein 7 (BMP-7) (Osteogenic protein 1) (OP-1) (Eptotermin alfa)
• Protein function: Growth factor of the TGF-beta superfamily that plays important role in various biological processes, including embryogenesis, hematopoiesis, neurogenesis and skeletal morphogenesis (PubMed:31208997). Initiates the canonical BMP signaling cascade by associating with type I receptor ACVR1 and type II receptor ACVR2A (PubMed:9748228, PubMed:12667445). Once all three components are bound together in a complex at the cell surface, ACVR2A phosphorylates and activates ACVR1. In turn, ACVR1 propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes (PubMed:12478285). For specific functions such as growth cone collapse in developing spinal neurons and chemotaxis of monocytes, uses also BMPR2 as type II receptor (PubMed:31208997). Can also signal through non-canonical pathways such as P38 MAP kinase signaling cascade that promotes brown adipocyte differentiation through activation of target genes, including members of the SOX family of transcription factors (PubMed:27923061).
• PDB: 1BMP, 1LX5, 1LXI, 1M4U
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00688	TGFb_propeptide	34 → 280	TGF-beta propeptide	Family
  PF00019	TGF_beta	329 → 430	Transforming growth factor beta like domain	Domain

• Sequence:

  MHVRSLRAAAPHSFVALWAPLFLLRSALADFSLDNEVHSSFIHRRLRSQERREMQREILS
  ILGLPHRPRPHLQGKHNSAPMFMLDLYNAMAVEEGGGPGGQGFSYPYKAVFSTQGPPLAS
  LQDSHFLTDADMVMSFVNLVEHDKEFFHPRYHHREFRFDLSKIPEGEAVTAAEFRIYKDY
  IRERFDNETFRISVYQVLQEHLGRESDLFLLDSRTLWASEEGWLVFDITATSNHWVVNPR
  HNLGLQLSVETLDGQSINPKLAGLIGRHGPQNKQPFMVAFFKATEVHFRSIRSTGSKQRS
  QNRSKTPKNQEALRMANVAENSSSDQRQACKKHELYVSFRDLGWQDWIIAPEGYAAYYCE
  GECAFPLNSYMNATNHAIVQTLVHFINPETVPKPCCAPTQLNAISVLYFDDSSNVILKKY
  RNMVVRACGCH

• Sequence length: 431

Pathways

KEGG:

Cytokine-cytokine receptor interaction
TGF-beta signaling pathway
Axon guidance
Hippo signaling pathway

Reactome:

Molecules associated with elastic fibres

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Congenital anomalies of kidney and urinary tract	Cakut	rs267606865, rs121908436, rs281875326, rs879255515, rs75462234, rs869320679, rs760905589, rs797045022, rs869320624, rs745597204, rs1114167358, rs1555879360, rs-1, rs1577330805, rs1008555507	7590254
Gastric cancer	Hereditary Diffuse Gastric Cancer	rs137854571, rs63751108, rs34612342, rs121908383, rs121909144, rs121909775, rs121909219, rs121909223, rs63750871, rs80359530, rs121964873, rs121913530, rs606231203, rs121918505, rs587776802, rs28933369, rs121912469, rs80358011, rs397507262, rs80359439, rs397507333, rs80359543, rs80358831, rs80359596, rs80358920, rs80358972, rs80359659, rs397507404, rs397514661, rs80359516, rs200495564, rs80358419, rs80359274, rs80359283, rs80358427, rs80358428, rs80358435, rs81002805, rs397507660, rs397507663, rs80359391, rs80359443, rs81002797, rs80359466, rs397507752, rs80359484, rs80359603, rs397507954, rs80359058, rs80359071, rs397507981, rs80359121, rs80357086, rs80357064, rs397508936, rs80357695, rs80357661, rs397509035, rs80357544, rs80357577, rs80357881, rs80357296, rs80356923, rs80356866, rs80357504, rs80357390, rs80357239, rs80358099, rs397509284, rs80357258, rs199474738, rs199474747, rs587779204, rs63750439, rs267608076, rs587779246, rs63749999, rs267608078, rs63751327, rs267607719, rs267607734, rs63750706, rs63751711, rs587779047, rs587779075, rs267607949, rs63750633, rs63750803, rs63751618, rs267608154, rs200640585, rs80358018, rs80357857, rs80357882, rs180177103, rs587779815, rs587779865, rs587779872, rs587780059, rs121912666, rs587780088, rs587780104, rs200432447, rs180177100, rs587780226, rs587780784, rs587776416, rs587781276, rs587781629, rs587781694, rs587781727, rs587781730, rs587781807, rs587781894, rs587781948, rs121913344, rs587782292, rs587782350, rs587782558, rs587782719, rs587782885, rs587783057, rs730881833, rs730881411, rs730881336, rs139770721, rs730881869, rs730881633, rs730882007, rs786203115, rs765123255, rs1553333738, rs762083530, rs786202800, rs17174393, rs55996097, rs750621215, rs786203451, rs747604569, rs764389018, rs786204433, rs786204862, rs772821016, rs779582317, rs863225406, rs193922343, rs759965045, rs63749919, rs760228510, rs746481984, rs762307622, rs876659736, rs876660933, rs747727055, rs1450394308, rs876658348, rs876658431, rs876659326, rs876660444, rs730881369, rs878853865, rs753862052, rs587780024, rs138941496, rs886040739, rs886040744, rs886040347, rs878854957, rs886040123, rs398122662, rs886040942, rs1057517104, rs1057516320, rs1057516683, rs879254046, rs1057517253, rs587781927, rs985033810, rs1057519989, rs775464903, rs374230313, rs758304323, rs1060501599, rs758081262, rs1060500126, rs1060502734, rs587776408, rs1060501695, rs1114167816, rs1114167596, rs1114167667, rs1555460315, rs1135402788, rs1554086196, rs730881919, rs773356478, rs769237459, rs1553653158, rs587782087, rs1555107263, rs1555119940, rs1403784434, rs1342519012, rs751710099, rs1553616361, rs1553619721, rs1270783041, rs775036118, rs1555288557, rs1555460548, rs1555461154, rs1298667185, rs1553622218, rs63751101, rs1349928568, rs771936821, rs1021662947, rs1555921011, rs81002831, rs1555124506, rs1555574803, rs1060502716, rs1555605362, rs747057367, rs1565385010, rs1567554500, rs1567516230, rs1558644995, rs1555591308, rs778306619, rs1566231194, rs1603328466, rs1570406302, rs1586108714, rs768362387, rs1597713777, rs1060502926, rs1597867185, rs1591517571, rs1591663236, rs1593903006, rs1555284779, rs1597096243, rs45459799, rs1597360340, rs587781905, rs864622481, rs1601753141, rs1966858562, rs1966967065, rs1967016153, rs1967113484, rs2080473458, rs1591387978, rs1224428422, rs1597747184, rs2082309297, rs2051929740, rs147542208	16367923
Prostate cancer	Malignant neoplasm of prostate	rs121909139, rs121909140, rs121909141, rs121909142, rs121909143, rs606231169, rs606231170, rs137852584, rs137852578, rs137852580, rs137852581, rs137852582	17013881, 19283074
Pulmonary fibrosis	Pulmonary Fibrosis	rs121918666, rs199422300, rs121917737, rs121917834, rs199422294, rs201159197, rs199422297, rs199422305, rs751381953, rs876661305, rs878853260, rs863223336, rs786205702, rs1555811762, rs1060502990, rs1555903332, rs1554038539, rs1554042899, rs938938578	17975199
Multiple congenital anomalies	Multiple congenital anomalies	rs-1, rs1057517732	17003840, 20506283, 24429398

Unknown
Disease name	Disease term	dbSNP ID	References
Mental depression	Unipolar Depression, Major Depressive Disorder	rs587778876, rs587778877	21896235
Endometriosis	Endometriosis	rs1800629, rs-1, rs1143634	21063030
Alveolitis	Alveolitis, Fibrosing		17975199
Endometrioma	Endometrioma		21063030
Prostatic neoplasms	Prostatic Neoplasms		19283074, 17013881
Stomach neoplasms	Malignant neoplasm of stomach, Stomach Neoplasms		16367923