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URL of this page: https://medlineplus.gov/genetics/gene/adgrg1/

ADGRG1 gene

adhesion G protein-coupled receptor G1

Normal Function

The ADGRG1 (also known as GPR56) gene provides instructions for making a type of protein called a G protein-coupled receptor. G protein-coupled receptors are embedded in the outer membrane of cells, where they relay chemical signals from outside the cell to the cell’s interior. Studies suggest that ADGRG1 protein signaling plays an important role in attaching cells to one another (cell adhesion), which may be important for proper cell movement (migration).

The ADGRG1 protein is critical for normal brain development. Before birth, this protein plays an important role in the normal growth and 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. The ADGRG1 protein also plays a role in the development and repair of myelin, which is the protective covering that insulates nerve fibers and promotes the rapid transmission of nerve impulses.

Although the ADGRG1 protein has been studied most extensively in the brain, it is active in many of the body's tissues. ADGRG1 signaling may also play a role in immune system function and the development of the reproductive system.

Health Conditions Related to Genetic Changes

Polymicrogyria

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in the ADGRG1 gene have been associated with a severe form of polymicrogyria called bilateral frontoparietal polymicrogyria (BFPP). Polymicrogyria is characterized by the development of too many small folds on the surface of the brain. In people with BFPP, both the right and left sides of the brain have abnormal folds. Individuals with BFPP typically have intellectual disabilities; developmental delays; seizures; and problems with movement, which can include weakness and stiffness in the arms and legs. The pathogenic variants that are associated with BFPP cause cells to make a version of the protein that does not function properly. In some cases, the altered protein becomes trapped within the cell and cannot reach the cell surface where it is needed.

Pathogenic variants in the ADGRG1 gene have also been associated with a form of polymicrogyria that affects an area of the brain called the perisylvian region. Affected individuals typically have language problems, difficulty feeding as infants, excessive drooling, seizures, and intellectual disabilities that can range in severity.

The lack of functioning ADGRG1 proteins likely disrupts the normal migration of neurons in the developing brain. As a result, certain regions of the cerebral cortex develop too many folds that are unusually small. These brain abnormalities lead to the intellectual disabilities and other features seen in people with polymicrogyria.

More About This Health Condition

Other Names for This Gene

  • GPR56
  • TM7LN4
  • TM7XN1

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Bae BI, Tietjen I, Atabay KD, Evrony GD, Johnson MB, Asare E, Wang PP, Murayama AY, Im K, Lisgo SN, Overman L, Sestan N, Chang BS, Barkovich AJ, Grant PE, Topcu M, Politsky J, Okano H, Piao X, Walsh CA. Evolutionarily dynamic alternative splicing of GPR56 regulates regional cerebral cortical patterning. Science. 2014 Feb 14;343(6172):764-8. doi: 10.1126/science.1244392. Citation on PubMed
  • Carneiro F, Duarte J, Laranjeira F, Barbosa-Gouveia S, Couce ML, Fonseca MJ. Case Report: Diffuse Polymicrogyria Associated With a Novel ADGRG1 Variant. Front Pediatr. 2021 Aug 27;9:728077. doi: 10.3389/fped.2021.728077. eCollection 2021. Citation on PubMed
  • 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. doi: 10.1093/hmg/ddm144. 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. doi: 10.1016/j.bbrc.2007.11.071. 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. doi: 10.1158/1535-7163.MCT-07-0066. Citation on PubMed
  • Kim JE, Han JM, Park CR, Shin KJ, Ahn C, Seong JY, Hwang JI. Splicing variants of the orphan G-protein-coupled receptor GPR56 regulate the activity of transcription factors associated with tumorigenesis. J Cancer Res Clin Oncol. 2010 Jan;136(1):47-53. doi: 10.1007/s00432-009-0635-z. Citation on PubMed
  • Kuo CY, Tsai MH, Lin HH, Wang YC, Singh AK, Chang CC, Lin JJ, Hung PC, Lin KL. Identification and clinical characteristics of a novel missense ADGRG1 variant in bilateral Frontoparietal Polymicrogyria: The electroclinical change from infancy to adulthood after Callosotomy in three siblings. Epilepsia Open. 2023 Mar;8(1):154-164. doi: 10.1002/epi4.12685. Epub 2023 Jan 11. 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
  • 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, Descarie JC, Barkovich AJ, Walsh CA. G protein-coupled receptor-dependent development of human frontal cortex. Science. 2004 Mar 26;303(5666):2033-6. doi: 10.1126/science.1092780. 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. doi: 10.1038/sj.onc.1208395. Citation on PubMed
  • Singh AK, Lin HH. The role of GPR56/ADGRG1 in health and disease. Biomed J. 2021 Oct;44(5):534-547. doi: 10.1016/j.bj.2021.04.012. Epub 2021 May 4. 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. doi: 10.1073/pnas.0602681103. Epub 2006 Jun 6. Citation on PubMed or Free article on PubMed Central

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