The PACS1 gene provides instructions for making a protein called phosphofurin acidic cluster sorting protein 1 (PACS1). The PACS1 protein is found in a complex network of membranes known as the trans-Golgi network, which sorts proteins and other molecules and sends them to their intended destinations inside or outside the cell. Within the trans-Golgi network, this protein helps transport certain molecules and proteins. The PACS1 protein is most active during development before birth.
Health Conditions Related to Genetic Changes
At least two mutations in the PACS1 gene have been found to cause PACS1 syndrome. This condition is characterized by intellectual disability, speech and language problems, and a distinct facial appearance. Many affected individuals have additional neurological, behavioral, and health problems. The most common mutation, which occurs in nearly everyone with PACS1 syndrome, results in the production of a protein with the protein building block (amino acid) arginine replaced with the amino acid tryptophan at position 203 (written as Arg203Trp or R203W).
PACS1 gene mutations are thought to impair the protein's ability to aid in the transport of molecules and proteins. Such an impairment likely results in the accumulation or misplacement of these substances within cells. The accumulated molecules and proteins may interfere with the function of the protein produced from the normal copy of the PACS1 gene, further disrupting the placement of these substances.
Research suggests that impaired PACS1 protein function disrupts normal development of structures in the face, leading to a distinct facial appearance. It is likely that the development of other body systems are similarly affected by impaired PACS1 protein function, leading to other signs and symptoms of PACS1 syndrome, but more research is needed to understand the mechanisms.More About This Health Condition
Other Names for This Gene
- cytosolic sorting protein PACS-1, human
- phosphofurin acidic cluster sorting protein 1, human
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Lusk L, Smith S, Martin C, Taylor C, Chung W. PACS1 Neurodevelopmental Disorder. 2020 Jul 16. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from http://www.ncbi.nlm.nih.gov/books/NBK559434/ Citation on PubMed
- Schuurs-Hoeijmakers JH, Landsverk ML, Foulds N, Kukolich MK, Gavrilova RH, Greville-Heygate S, Hanson-Kahn A, Bernstein JA, Glass J, Chitayat D, Burrow TA, Husami A, Collins K, Wusik K, van der Aa N, Kooy F, Brown KT, Gadzicki D, Kini U, Alvarez S, Fernández-Jaén A, McGehee F, Selby K, Tarailo-Graovac M, Van Allen M, van Karnebeek CD, Stavropoulos DJ, Marshall CR, Merico D, Gregor A, Zweier C, Hopkin RJ, Chu YW, Chung BH, de Vries BB, Devriendt K, Hurles ME, Brunner HG; DDD study. Clinical delineation of the PACS1-related syndrome--Report on 19 patients. Am J Med Genet A. 2016 Mar;170(3):670-5. doi: 10.1002/ajmg.a.37476. Epub 2016 Feb 3. Citation on PubMed
- Schuurs-Hoeijmakers JH, Oh EC, Vissers LE, Swinkels ME, Gilissen C, Willemsen MA, Holvoet M, Steehouwer M, Veltman JA, de Vries BB, van Bokhoven H, de Brouwer AP, Katsanis N, Devriendt K, Brunner HG. Recurrent de novo mutations in PACS1 cause defective cranial-neural-crest migration and define a recognizable intellectual-disability syndrome. Am J Hum Genet. 2012 Dec 7;91(6):1122-7. doi: 10.1016/j.ajhg.2012.10.013. Epub 2012 Nov 15. Citation on PubMed or Free article on PubMed Central
- Stern D, Cho MT, Chikarmane R, Willaert R, Retterer K, Kendall F, Deardorff M, Hopkins S, Bedoukian E, Slavotinek A, Schrier Vergano S, Spangler B, McDonald M, McConkie-Rosell A, Burton BK, Kim KH, Oundjian N, Kronn D, Chandy N, Baskin B, Guillen Sacoto MJ, Wentzensen IM, McLaughlin HM, McKnight D, Chung WK. Association of the missense variant p.Arg203Trp in PACS1 as a cause of intellectual disability and seizures. Clin Genet. 2017 Aug;92(2):221-223. doi: 10.1111/cge.12956. Epub 2017 Jan 23. Citation on PubMed or Free article on PubMed Central