Normal Function
The GRIP1 gene provides instructions for making a protein that is able to attach (bind) to other proteins and is important for moving (targeting) proteins to the correct location in cells. For example, the GRIP1 protein targets two proteins called FRAS1 and FREM2 to the correct region of the cell so that they can 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 of many tissues. The complex is particularly important during development before birth. One of its roles is to anchor the top layer of skin by connecting the basement membrane of the top layer to the layer of skin below. The FRAS/FREM complex is also involved in the proper development of certain other organs and tissues, including the kidneys, although the mechanism is unclear.
In addition, the GRIP1 protein targets necessary proteins to the junctions (synapses) between nerve cells (neurons) in the brain where cell-to-cell communication occurs. GRIP1 may also be involved in the development of neurons.
Health Conditions Related to Genetic Changes
Fraser syndrome
At least two GRIP1 gene mutations have been found to cause Fraser syndrome; these mutations are involved in a small percentage of cases of this condition. Fraser syndrome affects development before birth and is characterized by eyes that are completely 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.
GRIP1 gene mutations alter the genetic blueprint that carries the instructions for making GRIP1 protein. If any GRIP1 protein is made, it is likely unable to function. Without GRIP1, FRAS1 and FREM2 do not get to the correct location to form the FRAS/FREM complex. Lack of the FRAS/FREM complex in the basement membrane of skin leads to detachment of the top layer of skin, causing blisters to form during development. These blisters likely prevent the proper formation of certain structures before birth, leading to cryptophthalmos and cutaneous syndactyly. It is unknown how lack of the FRAS/FREM complex leads to kidney abnormalities and other problems in Fraser syndrome.
More About This Health ConditionCongenital anomalies of kidney and urinary tract
MedlinePlus Genetics provides information about Congenital anomalies of kidney and urinary tract
More About This Health ConditionOther Names for This Gene
- glutamate receptor-interacting protein 1
- GRIP
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
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
- 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
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