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Gene Review

BMPR2  -  bone morphogenetic protein receptor, type...

Homo sapiens

Synonyms: BMP type II receptor, BMP type-2 receptor, BMPR-2, BMPR-II, BMPR3, ...
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Disease relevance of BMPR2


Psychiatry related information on BMPR2

  • Heterozygous mutations of a type II member of the TGF-beta cell signaling superfamily known as BMPR2 on chromosome 2q33 have been identified in many kindreds with FPAH, yet display both reduced penetrance and sex bias [5].
  • Dyslexia. Talk of two theories [6].
  • Conclusions Sweet Talk was associated with improved self-efficacy and adherence; engaging a classically difficult to reach group of young people [7].
  • OBJECTIVES: To describe the development of a theory-based intervention (Self-Care Talk) and to describe the process of evaluating the implementation of the intervention when it was pilot tested with older spouse caregivers of persons with dementia [8].
  • Mental health. Talk of a lay-off [9].

High impact information on BMPR2


Chemical compound and disease context of BMPR2


Biological context of BMPR2

  • Six members affected with familial primary pulmonary hypertension and 6 of 10 at risk for carriage have been undergone genotype analysis, and they have the same mutation in BMPR2, a transversion of thymine to guanine at position 354 in exon 3 [10].
  • One of these genes (BMPR2), which encodes bone morphogenetic protein receptor type II, was found to contain five mutations that predict premature termination of the protein product and two missense mutations [18].
  • Taken together, these studies illustrate the considerable heterogeneity of BMPR2 mutations that cause PPH, and they strongly suggest that additional factors, genetic and/or environmental, may be required for the development of the clinical phenotype [19].
  • To determine the mechanism of altered BMPR-II function, we employed transient transfection studies in cell lines and primary cultures of pulmonary vascular smooth muscle cells using green fluorescent protein (GFP)-tagged wild-type and mutant BMPR2 constructs and confocal microscopy to localize receptors [20].
  • Taken together, these results suggest a model in which proliferative effect of c-Src by vasoactive molecules is balanced by opposing effect of BMP signaling in basal state, and the loss of this balance due to BMPR2 mutations leads to increased c-Src activity and subsequently cell growth [21].

Anatomical context of BMPR2


Associations of BMPR2 with chemical compounds


Physical interactions of BMPR2


Regulatory relationships of BMPR2

  • The presence of BMPs in brain is not well studied, but preliminary in situ data indicate that the BMP relatives growth/differentiation factor (GDF)-1 and GDF-10 are distinctly but differentially expressed at high levels in neurons expressing BMPR-II and ActR-I [31].
  • OP-1 treatment stimulated mRNA expression of BMPR-IA and BMPR-II, but had little effect on ActR-I and BMPR-IB mRNA expression [32].
  • Signaling by BMPR-II in neurons may potentiate the tyrosine kinase pathway activated by NT-3 and GDNF [33].
  • Finally, two inhibitors of cyclin-dependent kinase 9 (a dominant negative CDK9 and flavopiridol) repressed activity from the MR and BMPR2 promoters [34].
  • Finally, we used sequence analysis to exclude mutations in the coding region of two candidate genes, bone morphogenetic protein type II receptor (BMPR2) and endothelial monocyte-activating polypeptide II (EMAP II), as candidates for ACD [35].

Other interactions of BMPR2


Analytical, diagnostic and therapeutic context of BMPR2

  • Thirteen children (age at diagnosis, 6 mo to 13 y; mean, 5.6 +/- 3.9 y) with invasively confirmed PPH were screened for BMPR2 mutations using denaturing HPLC and sequence analysis [39].
  • In addition, all children were scanned for BMPR2 deletions by Southern blot analysis [39].
  • CONCLUSION: Our results demonstrate the inherent problems associated with exon-by-exon sequencing and the importance of other screening methods such as Southern blot and RT-PCR in the identification of BMPR2 mutations [40].
  • Because the complementary approach used in this study is rapid and cost effective, screening for BMPR2 deletions/duplications by MLPA and real-time PCR should accompany direct sequencing in all PAH testing [41].
  • Methods. BMPR2 gene mutations were determined using nucleic acid sequencing in 24 patients with pulmonary arterial hypertension and scleroderma spectrum of disease and in 2 control groups, 96 healthy North American individuals and 100 Israeli Ashkenazi Jews [42].


  1. BMPR2 germline mutations in pulmonary hypertension associated with fenfluramine derivatives. Humbert, M., Deng, Z., Simonneau, G., Barst, R.J., Sitbon, O., Wolf, M., Cuervo, N., Moore, K.J., Hodge, S.E., Knowles, J.A., Morse, J.H. Eur. Respir. J. (2002) [Pubmed]
  2. Investigation of second genetic hits at the BMPR2 locus as a modulator of disease progression in familial pulmonary arterial hypertension. Machado, R.D., James, V., Southwood, M., Harrison, R.E., Atkinson, C., Stewart, S., Morrell, N.W., Trembath, R.C., Aldred, M.A. Circulation (2005) [Pubmed]
  3. Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. Trembath, R.C., Thomson, J.R., Machado, R.D., Morgan, N.V., Atkinson, C., Winship, I., Simonneau, G., Galie, N., Loyd, J.E., Humbert, M., Nichols, W.C., Morrell, N.W., Berg, J., Manes, A., McGaughran, J., Pauciulo, M., Wheeler, L. N. Engl. J. Med. (2001) [Pubmed]
  4. HIV-1 TAT represses transcription of the bone morphogenic protein receptor-2 in U937 monocytic cells. Caldwell, R.L., Gadipatti, R., Lane, K.B., Shepherd, V.L. J. Leukoc. Biol. (2006) [Pubmed]
  5. Mutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial hypertension. Machado, R.D., Aldred, M.A., James, V., Harrison, R.E., Patel, B., Schwalbe, E.C., Gruenig, E., Janssen, B., Koehler, R., Seeger, W., Eickelberg, O., Olschewski, H., Elliott, C.G., Glissmeyer, E., Carlquist, J., Kim, M., Torbicki, A., Fijalkowska, A., Szewczyk, G., Parma, J., Abramowicz, M.J., Galie, N., Morisaki, H., Kyotani, S., Nakanishi, N., Morisaki, T., Humbert, M., Simonneau, G., Sitbon, O., Soubrier, F., Coulet, F., Morrell, N.W., Trembath, R.C. Hum. Mutat. (2006) [Pubmed]
  6. Dyslexia. Talk of two theories. Ramus, F. Nature (2001) [Pubmed]
  7. A randomized controlled trial of Sweet Talk, a text-messaging system to support young people with diabetes. Franklin, V.L., Waller, A., Pagliari, C., Greene, S.A. Diabet. Med. (2006) [Pubmed]
  8. Developing and testing a self-care intervention for older adults in caregiving roles. Teel, C.S., Leenerts, M.H. Nursing research. (2005) [Pubmed]
  9. Mental health. Talk of a lay-off. Munro, R. Nursing times. (2001) [Pubmed]
  10. Mutation in the gene for bone morphogenetic protein receptor II as a cause of primary pulmonary hypertension in a large kindred. Newman, J.H., Wheeler, L., Lane, K.B., Loyd, E., Gaddipati, R., Phillips, J.A., Loyd, J.E. N. Engl. J. Med. (2001) [Pubmed]
  11. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. The International PPH Consortium. Lane, K.B., Machado, R.D., Pauciulo, M.W., Thomson, J.R., Phillips, J.A., Loyd, J.E., Nichols, W.C., Trembath, R.C. Nat. Genet. (2000) [Pubmed]
  12. Bone morphogenetic protein 2 is expressed by, and acts upon, mature epithelial cells in the colon. Hardwick, J.C., Van Den Brink, G.R., Bleuming, S.A., Ballester, I., Van Den Brande, J.M., Keller, J.J., Offerhaus, G.J., Van Deventer, S.J., Peppelenbosch, M.P. Gastroenterology (2004) [Pubmed]
  13. Bone morphogenetic protein 2 exerts diverse effects on cell growth in vitro and is expressed in human pancreatic cancer in vivo. Kleeff, J., Maruyama, H., Ishiwata, T., Sawhney, H., Friess, H., Büchler, M.W., Korc, M. Gastroenterology (1999) [Pubmed]
  14. Direct signaling by the BMP type II receptor via the cytoskeletal regulator LIMK1. Foletta, V.C., Lim, M.A., Soosairajah, J., Kelly, A.P., Stanley, E.G., Shannon, M., He, W., Das, S., Massague, J., Bernard, O., Soosairaiah, J. J. Cell Biol. (2003) [Pubmed]
  15. Overexpression of a dominant negative type II bone morphogenetic protein receptor inhibits the growth of human breast cancer cells. Pouliot, F., Blais, A., Labrie, C. Cancer Res. (2003) [Pubmed]
  16. Growth regulation of human prostate cancer cells by bone morphogenetic protein-2. Ide, H., Yoshida, T., Matsumoto, N., Aoki, K., Osada, Y., Sugimura, T., Terada, M. Cancer Res. (1997) [Pubmed]
  17. Pulmonary hypertension in transgenic mice expressing a dominant-negative BMPRII gene in smooth muscle. West, J., Fagan, K., Steudel, W., Fouty, B., Lane, K., Harral, J., Hoedt-Miller, M., Tada, Y., Ozimek, J., Tuder, R., Rodman, D.M. Circ. Res. (2004) [Pubmed]
  18. Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Deng, Z., Morse, J.H., Slager, S.L., Cuervo, N., Moore, K.J., Venetos, G., Kalachikov, S., Cayanis, E., Fischer, S.G., Barst, R.J., Hodge, S.E., Knowles, J.A. Am. J. Hum. Genet. (2000) [Pubmed]
  19. BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Machado, R.D., Pauciulo, M.W., Thomson, J.R., Lane, K.B., Morgan, N.V., Wheeler, L., Phillips, J.A., Newman, J., Williams, D., Galiè, N., Manes, A., McNeil, K., Yacoub, M., Mikhail, G., Rogers, P., Corris, P., Humbert, M., Donnai, D., Martensson, G., Tranebjaerg, L., Loyd, J.E., Trembath, R.C., Nichols, W.C. Am. J. Hum. Genet. (2001) [Pubmed]
  20. Functional analysis of bone morphogenetic protein type II receptor mutations underlying primary pulmonary hypertension. Rudarakanchana, N., Flanagan, J.A., Chen, H., Upton, P.D., Machado, R., Patel, D., Trembath, R.C., Morrell, N.W. Hum. Mol. Genet. (2002) [Pubmed]
  21. Bone morphogenetic protein receptor type II C-terminus interacts with c-Src: implication for a role in pulmonary arterial hypertension. Wong, W.K., Knowles, J.A., Morse, J.H. Am. J. Respir. Cell Mol. Biol. (2005) [Pubmed]
  22. Dysfunctional Smad signaling contributes to abnormal smooth muscle cell proliferation in familial pulmonary arterial hypertension. Yang, X., Long, L., Southwood, M., Rudarakanchana, N., Upton, P.D., Jeffery, T.K., Atkinson, C., Chen, H., Trembath, R.C., Morrell, N.W. Circ. Res. (2005) [Pubmed]
  23. Bone morphogenetic protein receptor type II is a receptor for growth differentiation factor-9. Vitt, U.A., Mazerbourg, S., Klein, C., Hsueh, A.J. Biol. Reprod. (2002) [Pubmed]
  24. BMP signaling controls PASMC KV channel expression in vitro and in vivo. Young, K.A., Ivester, C., West, J., Carr, M., Rodman, D.M. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  25. Identification of a novel mutation in the gene for bone morphogenetic protein receptor II in an Israeli patient with familial primary pulmonary hypertension. Cahn, A., Meiner, V., Leitersdorf, E., Berkman, N. Isr. Med. Assoc. J. (2004) [Pubmed]
  26. Chromosomal localization of three human genes encoding bone morphogenetic protein receptors. Aström, A.K., Jin, D., Imamura, T., Röijer, E., Rosenzweig, B., Miyazono, K., ten Dijke, P., Stenman, G. Mamm. Genome (1999) [Pubmed]
  27. Involvement of bone morphogenetic protein-6 in differential regulation of aldosterone production by angiotensin II and potassium in human adrenocortical cells. Inagaki, K., Otsuka, F., Suzuki, J., Kano, Y., Takeda, M., Miyoshi, T., Otani, H., Mimura, Y., Ogura, T., Makino, H. Endocrinology (2006) [Pubmed]
  28. Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily. Barbara, N.P., Wrana, J.L., Letarte, M. J. Biol. Chem. (1999) [Pubmed]
  29. Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs. Liu, F., Ventura, F., Doody, J., Massagué, J. Mol. Cell. Biol. (1995) [Pubmed]
  30. Inhibin is an antagonist of bone morphogenetic protein signaling. Wiater, E., Vale, W. J. Biol. Chem. (2003) [Pubmed]
  31. Bone morphogenetic proteins and their receptors: potential functions in the brain. Ebendal, T., Bengtsson, H., Söderström, S. J. Neurosci. Res. (1998) [Pubmed]
  32. Effects of osteogenic protein-1 (OP-1, BMP-7) on gene expression in cultured medial collateral ligament cells. Tsai, A.D., Yeh, L.C., Lee, J.C. J. Cell. Biochem. (2003) [Pubmed]
  33. Potentiating interactions between morphogenetic protein and neurotrophic factors in developing neurons. Bengtsson, H., Söderström, S., Kylberg, A., Charette, M.F., Ebendal, T. J. Neurosci. Res. (1998) [Pubmed]
  34. HIV-1 Tat interaction with cyclin T1 represses mannose receptor and the bone morphogenetic protein receptor-2 transcription. Caldwell, R.L., Lane, K.B., Shepherd, V.L. Arch. Biochem. Biophys. (2006) [Pubmed]
  35. Expanding the phenotype of alveolar capillary dysplasia (ACD). Sen, P., Thakur, N., Stockton, D.W., Langston, C., Bejjani, B.A. J. Pediatr. (2004) [Pubmed]
  36. Cloning and characterization of a human type II receptor for bone morphogenetic proteins. Rosenzweig, B.L., Imamura, T., Okadome, T., Cox, G.N., Yamashita, H., ten Dijke, P., Heldin, C.H., Miyazono, K. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  37. Effect of bone morphogenetic protein 2 (BMP2) on oestradiol and inhibin A production by sheep granulosa cells, and localization of BMP receptors in the ovary by immunohistochemistry. Souza, C.J., Campbell, B.K., McNeilly, A.S., Baird, D.T. Reproduction (2002) [Pubmed]
  38. Genomic analyses facilitate identification of receptors and signalling pathways for growth differentiation factor 9 and related orphan bone morphogenetic protein/growth differentiation factor ligands. Mazerbourg, S., Hsueh, A.J. Hum. Reprod. Update (2006) [Pubmed]
  39. Primary pulmonary hypertension in children may have a different genetic background than in adults. Grünig, E., Koehler, R., Miltenberger-Miltenyi, G., Zimmermann, R., Gorenflo, M., Mereles, D., Arnold, K., Naust, B., Wilkens, H., Benz, A., von Hippel, A., Ulmer, H.E., Kübler, W., Katus, H.A., Bartram, C.R., Schranz, D., Janssen, B. Pediatr. Res. (2004) [Pubmed]
  40. Gross BMPR2 gene rearrangements constitute a new cause for primary pulmonary hypertension. Cogan, J.D., Vnencak-Jones, C.L., Phillips, J.A., Lane, K.B., Wheeler, L.A., Robbins, I.M., Garrison, G., Hedges, L.K., Loyd, J.E. Genet. Med. (2005) [Pubmed]
  41. High frequency of BMPR2 exonic deletions/duplications in familial pulmonary arterial hypertension. Cogan, J.D., Pauciulo, M.W., Batchman, A.P., Prince, M.A., Robbins, I.M., Hedges, L.K., Stanton, K.C., Wheeler, L.A., Phillips, J.A., Loyd, J.E., Nichols, W.C. Am. J. Respir. Crit. Care Med. (2006) [Pubmed]
  42. Pulmonary hypertension in scleroderma spectrum of disease: lack of bone morphogenetic protein receptor 2 mutations. Morse, J., Barst, R., Horn, E., Cuervo, N., Deng, Z., Knowles, J. J. Rheumatol. (2002) [Pubmed]
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