The PACS-1 protein has a putative role in the localization of trans-Golgi network (TGN) membrane proteins. Mouse and rat homologs have been identified and studies of the homologous rat protein indicate a role in directing TGN localization of furin by binding to the protease's phosphorylated cytosolic domain. In addition, the human protein plays a role in HIV-1Nef-mediated downregulation of cell surface MHC-I molecules to the TGN, thereby enabling HIV-1 to escape immune surveillance.
The first two cases were identified in early 2011 by doctors in the Netherlands. As of late 2014, there were 20 cases identified worldwide.
Diagnosis is typically done using full genome or exome sequencing. Both methods are relatively expensive and not widely available. There are likely several more cases that will eventually be reported as knowledge of the mutation spreads and testing becomes more accessible.
In combination, these traits affect walking, talking, feeding, and learning skills. No impact on life expectancy has been found. As with many developmental disabilities, there is no "cure".
In order to improve quality of life and enhance life skills of affected individuals, care givers have found a number of tools and strategies. It is important to note that all of these may not be applicable to a particular individual, and reported effectiveness has varied. It is recommended to consult with a physician prior to initiating any form of treatment.
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^Wan L, Molloy SS, Thomas L, Liu G, Xiang Y, Rybak SL, Thomas G (Jul 1998). "PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization". Cell. 94 (2): 205–16. doi:10.1016/S0092-8674(00)81420-8. PMID9695949.
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Wan L, Molloy SS, Thomas L, Liu G, Xiang Y, Rybak SL, Thomas G (Jul 1998). "PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization". Cell. 94 (2): 205–16. doi:10.1016/S0092-8674(00)81420-8. PMID9695949.
Hirosawa M, Nagase T, Ishikawa K, Kikuno R, Nomura N, Ohara O (Oct 1999). "Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain". DNA Research. 6 (5): 329–36. doi:10.1093/dnares/6.5.329. PMID10574461.
Blagoveshchenskaya AD, Thomas L, Feliciangeli SF, Hung CH, Thomas G (Dec 2002). "HIV-1 Nef downregulates MHC-I by a PACS-1- and PI3K-regulated ARF6 endocytic pathway". Cell. 111 (6): 853–66. doi:10.1016/S0092-8674(02)01162-5. PMID12526811.