PACS1

{{Short description|Protein-coding gene in the species Homo sapiens}}

Phosphofurin acidic cluster sorting protein 1, also known as PACS-1, is a protein that in humans is encoded by the PACS1 gene.{{cite journal | vauthors = Stove V, Naessens E, Stove C, Swigut T, Plum J, Verhasselt B | title = Signaling but not trafficking function of HIV-1 protein Nef is essential for Nef-induced defects in human intrathymic T-cell development | journal = Blood | volume = 102 | issue = 8 | pages = 2925–32 | date = Oct 2003 | pmid = 12855553 | doi = 10.1182/blood-2003-03-0833 | doi-access = free }}{{cite journal | vauthors = Hinners I, Wendler F, Fei H, Thomas L, Thomas G, Tooze SA | title = AP-1 recruitment to VAMP4 is modulated by phosphorylation-dependent binding of PACS-1 | journal = EMBO Reports | volume = 4 | issue = 12 | pages = 1182–9 | date = Dec 2003 | pmid = 14608369 | pmc = 1326413 | doi = 10.1038/sj.embor.7400018 }}{{cite web | title = Entrez Gene: PACS1 phosphofurin acidic cluster sorting protein 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55690}}

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.{{cite journal | vauthors = Wan L, Molloy SS, Thomas L, Liu G, Xiang Y, Rybak SL, Thomas G | title = PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization | journal = Cell | volume = 94 | issue = 2 | pages = 205–16 | date = Jul 1998 | pmid = 9695949 | doi = 10.1016/S0092-8674(00)81420-8 | s2cid = 15027198 | doi-access = free }}

Interactions

PACS1 has been shown to interact with Furin.

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.{{cite journal | vauthors = 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 | title = Recurrent de novo mutations in PACS1 cause defective cranial-neural-crest migration and define a recognizable intellectual-disability syndrome | journal = Am. J. Hum. Genet. | volume = 91 | issue = 6 | pages = 1122–7 | year = 2012 | pmid = 23159249 | pmc = 3516611 | doi = 10.1016/j.ajhg.2012.10.013 }}{{OMIM|615009}}

= Prevalence and diagnosis =

The first two cases were identified in early 2011 by doctors in the Netherlands. As of late 2014, there were 20 cases identified worldwide.{{cite web | url=http://www.pacs1.info/about/ | title=Domain Details Page }}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }}

Diagnosis is typically done using full genome or exome sequencing.{{cite journal | vauthors = Callaway E | title = Gene hunt is on for mental disability | journal = Nature | volume = 484 | issue = 7394 | pages = 302–3 | year = 2012 | pmid = 22517145 | doi = 10.1038/484302a | bibcode = 2012Natur.484..302C | doi-access = free }} 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:

Low muscle tone
Seizures
Repetitive self-stimulatory behavior
Sensory processing disorder
Delayed development of gross motor skills and fine motor skills
Delayed cognitive development
Chewing and swallowing difficulties
Digestion or bowel problems
Slow growth resulting in below average height and weight

= 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.{{Cite web |url=http://www.pacs1.info/treatment |title=Treatment |website=pacs1.info |access-date=2015-07-30 |archive-date=2016-03-04 |archive-url=https://web.archive.org/web/20160304223433/http://www.pacs1.info/treatment |url-status=dead }}

physiotherapy (PT)
occupational therapy (OT)
speech therapy (including augmentative and alternative communication) (SPT)
behavioural therapy (applied behavior analysis/intensive behavioural intervention etc.)
discrete trial teaching
early intervention programs
massage therapy and pediatric massage
feeding therapy
music therapy
hippotherapy
hydrotherapy