PACS1

Phosphofurin acidic cluster sorting protein 1
Identifiers
Symbols PACS1 ; MRD17
External IDs OMIM: 607492 MGI: 1277113 HomoloGene: 9970 GeneCards: PACS1 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 55690 107975
Ensembl ENSG00000175115 ENSMUSG00000024855
UniProt Q6VY07 Q8K212
RefSeq (mRNA) NM_018026 NM_153129
RefSeq (protein) NP_060496 NP_694769
Location (UCSC) Chr 11:
66.07 – 66.24 Mb		 Chr 19:
5.13 – 5.27 Mb
PubMed search

Phosphofurin acidic cluster sorting protein 1 also known as PACS-1 is a protein that in humans is encoded by the PACS1 gene.[1][2][3]

Function

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-1 Nef-mediated downregulation of cell surface MHC-I molecules to the TGN, thereby enabling HIV-1 to escape immune surveillance.[3]

Interactions

PACS1 has been shown to interact with Furin.[4]

Clinical significance

A de novo mutation c.607C>T in the PACS1 gene has been shown to result in a syndromic phenotype (colloquially called PACS1 Syndrome) that is characterized by global developmental delay, intellectual disability, and specific facial features.[5][6]

Prevalence and diagnosis

The first two cases were identified in early 2011 by doctors in the Netherlands.[5] As of late 2014, there were 20 cases identified worldwide.[7]

Diagnosis is typically done using full genome or exome sequencing.[8] 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.

Observed and reported traits

Individuals with the mutation have been reported to have similar facial features, such as:

Other common traits reported by care givers of affected individuals are:

Prognosis and treatment

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.[9]

References

  1. ↑ Stove V, Naessens E, Stove C, Swigut T, Plum J, Verhasselt B (Oct 2003). "Signaling but not trafficking function of HIV-1 protein Nef is essential for Nef-induced defects in human intrathymic T-cell development". Blood 102 (8): 2925–32. doi:10.1182/blood-2003-03-0833. PMID 12855553.
  2. ↑ Hinners I, Wendler F, Fei H, Thomas L, Thomas G, Tooze SA (Dec 2003). "AP-1 recruitment to VAMP4 is modulated by phosphorylation-dependent binding of PACS-1". EMBO Reports 4 (12): 1182–9. doi:10.1038/sj.embor.7400018. PMC 1326413. PMID 14608369.
  3. 1 2 "Entrez Gene: PACS1 phosphofurin acidic cluster sorting protein 1".
  4. ↑ 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. PMID 9695949.
  5. 1 2 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 (2012). "Recurrent de novo mutations in PACS1 cause defective cranial-neural-crest migration and define a recognizable intellectual-disability syndrome". Am. J. Hum. Genet. 91 (6): 1122–7. doi:10.1016/j.ajhg.2012.10.013. PMC 3516611. PMID 23159249.
  6. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 615009
  7. ↑ http://www.pacs1.info/about/
  8. ↑ Callaway E (2012). "Gene hunt is on for mental disability". Nature 484 (7394): 302–3. doi:10.1038/484302a. PMID 22517145.
  9. ↑ "Treatment". pacs1.info.

Further reading


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