The ADGRG1 gene, formerly known as GPR56, provides instructions for making a protein that is critical for normal brain development. Before birth, the ADGRG1 protein appears to be essential for the normal growth and movement (migration) of nerve cells (neurons) in a part of the brain called the cerebral cortex. This outer layer of the brain carries out many important functions, such as sensation, voluntary muscle movement, thought, planning, and memory.
Although the ADGRG1 protein has been studied most extensively in the brain, it is active in many of the body's tissues. This protein interacts with other proteins on the cell surface to trigger a series of chemical signals within the cell. Studies suggest that ADGRG1 signaling may play an important role in attaching cells to one another (cell adhesion).
Health Conditions Related to Genetic Changes
At least eleven mutations in the ADGRG1 gene have been identified in people with a severe form of polymicrogyria called bilateral frontoparietal polymicrogyria (BFPP). This disorder causes intellectual disability, delayed development, problems with speech and movement, and recurrent seizures (epilepsy). Most of the identified mutations change a single protein building block (amino acid) in the ADGRG1 protein. These mutations interfere with the normal processing of the protein. The abnormal protein becomes trapped within the cell, where it is unable to reach the cell surface to carry out its normal signaling functions.
A loss of ADGRG1 protein function likely disrupts the normal migration of neurons in the developing brain. As a result, certain regions of the cerebral cortex—areas known as the frontal and parietal lobes—develop too many folds (called gyri), and the folds are unusually small. These brain abnormalities cause intellectual disability and the other neurological problems associated with bilateral frontoparietal polymicrogyria.More About This Health Condition
Other Names for This Gene
- 7-transmembrane protein with no EGF-like N-terminal domains-1
- G protein-coupled receptor 56
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Iguchi T, Sakata K, Yoshizaki K, Tago K, Mizuno N, Itoh H. Orphan G protein-coupled receptor GPR56 regulates neural progenitor cell migration via a G alpha 12/13 and Rho pathway. J Biol Chem. 2008 May 23;283(21):14469-78. doi: 10.1074/jbc.M708919200. Epub 2008 Mar 31. Citation on PubMed
- Jin Z, Tietjen I, Bu L, Liu-Yesucevitz L, Gaur SK, Walsh CA, Piao X. Disease-associated mutations affect GPR56 protein trafficking and cell surface expression. Hum Mol Genet. 2007 Aug 15;16(16):1972-85. Epub 2007 Jun 18. Citation on PubMed
- Ke N, Ma H, Diedrich G, Chionis J, Liu G, Yu DH, Wong-Staal F, Li QX. Biochemical characterization of genetic mutations of GPR56 in patients with bilateral frontoparietal polymicrogyria (BFPP). Biochem Biophys Res Commun. 2008 Feb 8;366(2):314-20. Epub 2007 Nov 26. Citation on PubMed
- Ke N, Sundaram R, Liu G, Chionis J, Fan W, Rogers C, Awad T, Grifman M, Yu D, Wong-Staal F, Li QX. Orphan G protein-coupled receptor GPR56 plays a role in cell transformation and tumorigenesis involving the cell adhesion pathway. Mol Cancer Ther. 2007 Jun;6(6):1840-50. Citation on PubMed
- Li S, Jin Z, Koirala S, Bu L, Xu L, Hynes RO, Walsh CA, Corfas G, Piao X. GPR56 regulates pial basement membrane integrity and cortical lamination. J Neurosci. 2008 May 28;28(22):5817-26. doi: 10.1523/JNEUROSCI.0853-08.2008. Citation on PubMed or Free article on PubMed Central
- Liu M, Parker RM, Darby K, Eyre HJ, Copeland NG, Crawford J, Gilbert DJ, Sutherland GR, Jenkins NA, Herzog H. GPR56, a novel secretin-like human G-protein-coupled receptor gene. Genomics. 1999 Feb 1;55(3):296-305. Citation on PubMed
- Parrini E, Ferrari AR, Dorn T, Walsh CA, Guerrini R. Bilateral frontoparietal polymicrogyria, Lennox-Gastaut syndrome, and GPR56 gene mutations. Epilepsia. 2009 Jun;50(6):1344-53. doi: 10.1111/j.1528-1167.2008.01787.x. Epub 2008 Oct 6. Citation on PubMed or Free article on PubMed Central
- Piao X, Hill RS, Bodell A, Chang BS, Basel-Vanagaite L, Straussberg R, Dobyns WB, Qasrawi B, Winter RM, Innes AM, Voit T, Ross ME, Michaud JL, Déscarie JC, Barkovich AJ, Walsh CA. G protein-coupled receptor-dependent development of human frontal cortex. Science. 2004 Mar 26;303(5666):2033-6. Citation on PubMed
- Shashidhar S, Lorente G, Nagavarapu U, Nelson A, Kuo J, Cummins J, Nikolich K, Urfer R, Foehr ED. GPR56 is a GPCR that is overexpressed in gliomas and functions in tumor cell adhesion. Oncogene. 2005 Mar 3;24(10):1673-82. Citation on PubMed
- Xu L, Begum S, Hearn JD, Hynes RO. GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis. Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9023-8. Epub 2006 Jun 6. Citation on PubMed or Free article on PubMed Central