Repulsive guidance molecule A

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External IDsGeneCards: [1]
RefSeq (mRNA)



RefSeq (protein)



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Repulsive guidance molecule A (RGMa) is a bone morphogenetic protein (BMP) co-receptor of the repulsive guidance molecule family. Together with BMPR1A and BMPR1B, as well as ACVR2A and BMPR2, it binds BMPs thereby activating the intracellular SMAD1/5/8 signalling pathway.[1] In humans this protein is encoded by the RGMA gene.[2]


RGMa is a repulsive guidance molecule for retinal axons.[3] Furthermore, neogenin functions as a receptor for RGM.[4] Neogenin overexpression and RGM downexpression in the developing embryonic neural tube induces apoptosis. The apoptotic activity of neogenin in the neural tube is associated with cleavage of its cytoplasmic domain by caspases.[5]

RGMA belongs to a family of repulsive guidance molecules that are (glycosylphosphatidylinositol)-linked cell-membrane-associated proteins. The three proteins, RGMa (this protein), RGMb and RGMc are 40-50% identical to each other, and share similarities in predicted protein domains and overall structure. All three RGM proteins appear capable of binding selected BMPs (bone morphogenetic proteins).[6]

RGMs may play inhibitory roles in prostate cancer by suppressing cell growth, adhesion, migration and invasion. RGMs can coordinate Smad-dependent and Smad-independent signalling of BMPs in prostate cancer and breast cancer cells.[7][8]


  1. Corradini, Elena; Babitt, Jodie L.; Lin, Herbert Y. (October 2009). "The RGM/DRAGON family of BMP co-receptors". Cytokine & Growth Factor Reviews. 20 (5–6): 389–398. doi:10.1016/j.cytogfr.2009.10.008. PMC 3715994.
  2. "Entrez Gene: RGMA RGM domain family, member A".
  3. Monnier PP, Sierra A, Macchi P, Deitinghoff L, Andersen JS, Mann M, Flad M, Hornberger MR, Stahl B, Bonhoeffer F, Mueller BK (September 2002). "RGM is a repulsive guidance molecule for retinal axons". Nature. 419 (6905): 392–5. doi:10.1038/nature01041. PMID 12353034.
  4. Rajagopalan S, Deitinghoff L, Davis D, Conrad S, Skutella T, Chedotal A, Mueller BK, Strittmatter SM (August 2004). "Neogenin mediates the action of repulsive guidance molecule". Nat. Cell Biol. 6 (8): 756–62. doi:10.1038/ncb1156. PMID 15258590.
  5. Matsunaga E, Tauszig-Delamasure S, Monnier PP, Mueller BK, Strittmatter SM, Mehlen P, Chédotal A (August 2004). "RGM and its receptor neogenin regulate neuronal survival". Nat. Cell Biol. 6 (8): 749–55. doi:10.1038/ncb1157. PMID 15258591.
  6. Severyn CJ, Shinde U, Rotwein P (September 2009). "Molecular biology, genetics and biochemistry of the repulsive guidance molecule family". Biochem. J. 422 (3): 393–403. doi:10.1042/BJ20090978. PMC 4242795. PMID 19698085.
  7. Li J, Ye L, Sanders AJ, Jiang WG (March 2012). "Repulsive guidance molecule B (RGMB) plays negative roles in breast cancer by coordinating BMP signaling". J Cell Biochem. 113 (7): 2523–31. doi:10.1002/jcb.24128. PMID 22415859.
  8. Li J, Ye L, Kynaston HG, Jiang WG (February 2012). "Repulsive guidance molecules, novel bone morphogenetic protein co-receptors, are key regulators of the growth and aggressiveness of prostate cancer cells". Int. J. Oncol. 40 (2): 544–50. doi:10.3892/ijo.2011.1251. PMID 22076499.

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