Phosphofurin acidic cluster sorting protein 1, also known as PACS-1, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''PACS1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

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 The subtypes of HIV include two main subtypes, known as HIV type 1 (HIV-1) and HIV type 2 (HIV-2). These subtypes have distinct genetic differences and are associated with different epidemiological patterns and clinical characteristics. HIV-1 e ...

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

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 Global developmental delay is an umbrella term used when children are significantly delayed in two or more areas of development. It can be diagnosed when a child is delayed in one or more milestones, categorised into motor skills, speech delay, spe ...

intellectual disability Intellectual disability (ID), also known as general learning disability (in the United Kingdom), and formerly mental retardation (in the United States), Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010).Archive is a generalized neurodevelopmental ...

, and specific facial features.

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. Diagnosis is typically done using full genome or exome sequencing. 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 A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

* Repetitive self-stimulatory behavior *

Sensory processing disorder Sensory processing disorder (SPD), formerly known as sensory integration dysfunction, is a condition in which multisensory input is not adequately processed in order to provide appropriate responses to the demands of the environment. Sensory ...

* Delayed development of gross motor skills and

fine motor skills Fine may refer to: Characters * Fran Fine, the title character of ''The Nanny'' * Sylvia Fine (''The Nanny''), Fran's mother on ''The Nanny'' * Officer Fine, a character in ''Tales from the Crypt'', played by Vincent Spano Legal terms * Fine ...

* Delayed

cognitive development Cognitive development is a field of study in neuroscience and psychology focusing on a child's development in terms of information processing, conceptual resources, perceptual skill, language learning, and other aspects of the developed adult bra ...

* 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. *

physiotherapy Physical therapy (PT), also known as physiotherapy, is a healthcare profession, as well as the care provided by physical therapists who promote, maintain, or restore health through patient education, physical intervention, disease preventio ...

(PT) *

occupational therapy Occupational therapy (OT), also known as ergotherapy, is a healthcare profession. Ergotherapy is derived from the Greek wiktionary:ergon, ergon which is allied to work, to act and to be active. Occupational therapy is based on the assumption t ...

(OT) *

speech therapy Speech is the use of the human voice as a medium for language. Spoken language combines vowel and consonant sounds to form units of meaning like words, which belong to a language's lexicon. There are many different intentional speech acts, suc ...

(including

augmentative and alternative communication Augmentative and alternative communication (AAC) encompasses the communication methods used to supplement or replace speech or writing for those with impairments in the production or comprehension of spoken or written language. AAC is used by t ...

) (SPT) * behavioural therapy (

applied behavior analysis Applied behavior analysis (ABA), also referred to as behavioral engineering, is a behavior modification system based on the principles of respondent and operant conditioning. ABA is the applied form of behavior analysis; the other two are: ...

/intensive behavioural intervention etc.) * discrete trial teaching *

early intervention Early childhood intervention (ECI) is a support and educational system for very young children (aged birth to six years) who have been victims of, or who are at high risk for child abuse and/or neglect as well as children who have developmental d ...

programs * massage therapy and pediatric massage * feeding therapy *

music therapy Music therapy, an allied health profession, "is the clinical and evidence-based use of music interventions to accomplish individualized goals within a therapeutic relationship by a credentialed professional who has completed an approved music t ...

* hippotherapy *

hydrotherapy Hydrotherapy, formerly called hydropathy and also called water cure, is a branch of alternative medicine (particularly naturopathy), occupational therapy, and Physical therapy, physiotherapy, that involves the use of water for pain relief and ...