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URL of this page: https://medlineplus.gov/genetics/gene/grip1/

GRIP1 gene

glutamate receptor interacting protein 1

Normal Function

The GRIP1 gene provides instructions for making a protein that attaches to other proteins and helps transport them to their proper locations within the cell. As a result, the GRIP1 protein plays an important role in cellular organization.

The GRIP1 protein transports proteins made from the FRAS1 and FREM2 genes so that they can help form a group of proteins known as the FRAS/FREM complex. This complex is found in the thin, sheet-like structures (basement membranes) that separate and support the cells in many tissues. One of the roles of the FRAS/FREM complex is to anchor the basement membrane of the top layer of skin to the layer of skin below. The FRAS/FREM complex is also involved in the proper organization and development of certain organs and tissues, including the kidneys.

In addition, the GRIP1 protein moves necessary proteins to the junctions (synapses) between nerve cells (neurons) in the brain where cell-to-cell communication occurs. The GRIP1 protein may also be involved in the development of neurons.

Health Conditions Related to Genetic Changes

Fraser syndrome

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in the GRIP1 gene cause a small percentage of cases of Fraser syndrome. Fraser syndrome affects development before birth and is typically characterized by eyes that are covered by skin (cryptophthalmos), fusion of the skin between the fingers and toes (cutaneous syndactyly), and abnormalities of the kidneys and other organs and tissues.

The pathogenic variants in the GRIP1 gene that cause Fraser syndrome alter the instructions for making the GRIP1 protein. If any GRIP1 protein is made, it is unlikely to be able to function properly. Without GRIP1, the FRAS1 and FREM2 proteins cannot form the FRAS/FREM complex, and the movement (migration) and communication of cells in the different skin layers is disrupted. This leads to the cryptophthalmos and cutaneous syndactyly that is seen in affected individuals.

Through a mechanism that is not well understood, these changes also interfere with the self-destruction of cells that are no longer needed (apoptosis), which may contribute to the additional abnormalities seen in people with Fraser syndrome.

More About This Health Condition

Coloboma

MedlinePlus Genetics provides information about Coloboma

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Congenital anomalies of kidney and urinary tract

MedlinePlus Genetics provides information about Congenital anomalies of kidney and urinary tract

More About This Health Condition

Other Names for This Gene

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

  • Dong H, Zhang P, Song I, Petralia RS, Liao D, Huganir RL. Characterization of the glutamate receptor-interacting proteins GRIP1 and GRIP2. J Neurosci. 1999 Aug 15;19(16):6930-41. doi: 10.1523/JNEUROSCI.19-16-06930.1999. Citation on PubMed
  • Heisler FF, Lee HK, Gromova KV, Pechmann Y, Schurek B, Ruschkies L, Schroeder M, Schweizer M, Kneussel M. GRIP1 interlinks N-cadherin and AMPA receptors at vesicles to promote combined cargo transport into dendrites. Proc Natl Acad Sci U S A. 2014 Apr 1;111(13):5030-5. doi: 10.1073/pnas.1304301111. Epub 2014 Mar 17. Citation on PubMed or Free article on PubMed Central
  • Ikeda S, Akamatsu C, Ijuin A, Nagashima A, Sasaki M, Mochizuki A, Nagase H, Enomoto Y, Kuroda Y, Kurosawa K, Ishikawa H. Prenatal diagnosis of Fraser syndrome caused by novel variants of FREM2. Hum Genome Var. 2020 Oct 2;7:32. doi: 10.1038/s41439-020-00119-5. eCollection 2020. Citation on PubMed
  • Long J, Wei Z, Feng W, Yu C, Zhao YX, Zhang M. Supramodular nature of GRIP1 revealed by the structure of its PDZ12 tandem in complex with the carboxyl tail of Fras1. J Mol Biol. 2008 Feb 1;375(5):1457-68. doi: 10.1016/j.jmb.2007.11.088. Epub 2007 Dec 4. Citation on PubMed
  • Schanze D, Kayserili H, Satkin BN, Altunoglu U, Zenker M. Fraser syndrome due to mutations in GRIP1--clinical phenotype in two families and expansion of the mutation spectrum. Am J Med Genet A. 2014 Mar;164A(3):837-40. doi: 10.1002/ajmg.a.36343. Epub 2013 Dec 19. No abstract available. Citation on PubMed
  • Short K, Wiradjaja F, Smyth I. Let's stick together: the role of the Fras1 and Frem proteins in epidermal adhesion. IUBMB Life. 2007 Jul;59(7):427-35. doi: 10.1080/15216540701510581. Citation on PubMed
  • Takamiya K, Kostourou V, Adams S, Jadeja S, Chalepakis G, Scambler PJ, Huganir RL, Adams RH. A direct functional link between the multi-PDZ domain protein GRIP1 and the Fraser syndrome protein Fras1. Nat Genet. 2004 Feb;36(2):172-7. doi: 10.1038/ng1292. Epub 2004 Jan 18. Citation on PubMed
  • Vogel MJ, van Zon P, Brueton L, Gijzen M, van Tuil MC, Cox P, Schanze D, Kariminejad A, Ghaderi-Sohi S, Blair E, Zenker M, Scambler PJ, Ploos van Amstel HK, van Haelst MM. Mutations in GRIP1 cause Fraser syndrome. J Med Genet. 2012 May;49(5):303-6. doi: 10.1136/jmedgenet-2011-100590. Epub 2012 Apr 17. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.