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DLG4 gene

discs large MAGUK scaffold protein 4

Normal Function

The DLG4 gene provides instructions for making a protein that plays a role in nerve cells (neurons) in the brain. The DLG4 protein is found at synapses, which are the connections between neurons where cell-to-cell communication occurs. Connected nerve cells act as the "wiring" in the circuitry, carrying signals between the brain and the rest of the body. At synapses, the DLG4 protein interacts with other proteins to regulate a process called synaptic plasticity, which allows synapses to change and adapt over time in response to experiences. Synaptic plasticity is critical for learning and memory.

Health Conditions Related to Genetic Changes

DLG4-related synaptopathy

Variants (also called mutations) in the DLG4 gene cause DLG4-related synaptopathy. This condition affects neurological development and often causes intellectual disabilies, delayed development, movement disorders, and seizures. Most of the variants impair the normal function of the DLG4 protein by decreasing its ability to interact with the other proteins involved in synaptic plasticity or decreasing its ability to help synapses send signals. Other variants prevent the production of any normal DLG4 protein. As a result, synaptic plasticity and other synaptic functions are impaired. The signs and symptoms of DLG4-related synaptopathy are likely caused by the reduced ability of synapses to change and adapt during important periods of brain development.

More About This Health Condition

Other Names for This Gene

  • discs large, drosophila, homolog of, 4
  • postsynaptic density 95
  • PSD95
  • SAP90
  • synapse-associated protein 90

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


  • Levy AM, Gomez-Puertas P, Tumer Z. Neurodevelopmental Disorders Associated with PSD-95 and Its Interaction Partners. Int J Mol Sci. 2022 Apr 15;23(8):4390. doi: 10.3390/ijms23084390. Citation on PubMed
  • Moutton S, Bruel AL, Assoum M, Chevarin M, Sarrazin E, Goizet C, Guerrot AM, Charollais A, Charles P, Heron D, Faudet A, Houcinat N, Vitobello A, Tran-Mau-Them F, Philippe C, Duffourd Y, Thauvin-Robinet C, Faivre L. Truncating variants of the DLG4 gene are responsible for intellectual disability with marfanoid features. Clin Genet. 2018 Jun;93(6):1172-1178. doi: 10.1111/cge.13243. Epub 2018 Apr 14. Citation on PubMed
  • Rodriguez-Palmero A, Boerrigter MM, Gomez-Andres D, Aldinger KA, Marcos-Alcalde I, Popp B, Everman DB, Lovgren AK, Arpin S, Bahrambeigi V, Beunders G, Bisgaard AM, Bjerregaard VA, Bruel AL, Challman TD, Cogne B, Coubes C, de Man SA, Denomme-Pichon AS, Dye TJ, Elmslie F, Feuk L, Garcia-Minaur S, Gertler T, Giorgio E, Gruchy N, Haack TB, Haldeman-Englert CR, Haukanes BI, Hoyer J, Hurst ACE, Isidor B, Soller MJ, Kushary S, Kvarnung M, Landau YE, Leppig KA, Lindstrand A, Kleinendorst L, MacKenzie A, Mandrile G, Mendelsohn BA, Moghadasi S, Morton JE, Moutton S, Muller AJ, O'Leary M, Pacio-Miguez M, Palomares-Bralo M, Parikh S, Pfundt R, Pode-Shakked B, Rauch A, Repnikova E, Revah-Politi A, Ross MJ, Ruivenkamp CAL, Sarrazin E, Savatt JM, Schluter A, Schonewolf-Greulich B, Shad Z, Shaw-Smith C, Shieh JT, Shohat M, Spranger S, Thiese H, Mau-Them FT, van Bon B, van de Burgt I, van de Laar IMBH, van Drie E, van Haelst MM, van Ravenswaaij-Arts CM, Verdura E, Vitobello A, Waldmuller S, Whiting S, Zweier C, Prada CE, de Vries BBA, Dobyns WB, Reiter SF, Gomez-Puertas P, Pujol A, Tumer Z. DLG4-related synaptopathy: a new rare brain disorder. Genet Med. 2021 May;23(5):888-899. doi: 10.1038/s41436-020-01075-9. Epub 2021 Feb 17. Citation on PubMed
  • Vallejo D, Codocedo JF, Inestrosa NC. Posttranslational Modifications Regulate the Postsynaptic Localization of PSD-95. Mol Neurobiol. 2017 Apr;54(3):1759-1776. doi: 10.1007/s12035-016-9745-1. Epub 2016 Feb 16. Citation on PubMed

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