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PACS1

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PACS1
Identifiers
AliasesPACS1, MRD17, phosphofurin acidic cluster sorting protein 1, SHMS
External IDsOMIM: 607492; MGI: 1277113; HomoloGene: 9970; GeneCards: PACS1; OMA:PACS1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

55690

107975

Ensembl

ENSG00000175115

ENSMUSG00000024855

UniProt

Q6VY07

Q8K212

RefSeq (mRNA)

NM_018026
NM_178178

NM_153129
NM_001362451

RefSeq (protein)

NP_060496
NP_060496.2

Location (UCSC)Chr 11: 66.07 – 66.24 MbChr 19: 5.18 – 5.32 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Phosphofurin acidic cluster sorting protein 1 also known as PACS-1 is a protein that in humans is encoded by the PACS1 gene.[5][6][7]

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.[7]

Interactions

PACS1 has been shown to interact with Furin.[8]

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.[9][10]

Prevalence and diagnosis

The first two cases were identified in early 2011 by doctors in the Netherlands.[9] As of late 2014, there were 20 cases identified worldwide.[11]

Diagnosis is typically done using full genome or exome sequencing.[12] 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:

  • Widely spaced eyes and low-set ears
  • Down-slanting eye corners and mild uni-brow
  • Highly arched eyebrows and long eyelashes
  • Rounded “button” nose with a flat bridge
  • Wide mouth with down-turned corners
  • Thin upper lip and widely spaced teeth

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.[13]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000175115 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024855 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ 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.
  7. ^ a b "Entrez Gene: PACS1 phosphofurin acidic cluster sorting protein 1".
  8. ^ 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.
  9. ^ a b 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.
  10. ^ Online Mendelian Inheritance in Man (OMIM): 615009
  11. ^ http://www.pacs1.info/about/
  12. ^ Callaway E (2012). "Gene hunt is on for mental disability". Nature. 484 (7394): 302–3. doi:10.1038/484302a. PMID 22517145.
  13. ^ "Treatment". pacs1.info.

Further reading


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