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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

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

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

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 MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules (the other being MHC class II) and are found on the cell surface of all nucleated cells in the bodies of vertebrates. They also occur on pla ...

molecules to the TGN, thereby enabling HIV-1 to escape immune surveillance.

Interactions

PACS1 has been shown to

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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 their cognitive development, cognitive and developmental biology, physical development. It can be diagnosed when a child is delayed in one or more milest ...

, intellectual disability, 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 Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases a ...

Seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...

* Repetitive self-stimulatory behavior * Sensory processing disorder * Delayed development of

gross motor skills Gross motor skills are the abilities usually acquired during childhood as part of a child's motor learning. By the time they reach two years of age, almost all children are able to stand up, walk and run, walk up stairs, etc. These skills are bu ...

and

fine motor skills Fine motor skill (or dexterity) is the coordination of small muscles in movement with the eyes, hands and fingers. The complex levels of manual dexterity that humans exhibit can be related to the nervous system. Fine motor skills aid in the growt ...

* 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. *

physiotherapy Physical therapy (PT), also known as physiotherapy, is one of the allied health professions. It is provided by physical therapists who promote, maintain, or restore health through physical examination, diagnosis, management, prognosis, patient ...

(PT) *

occupational therapy Occupational therapy (OT) is a global healthcare profession. It involves the use of assessment and intervention to develop, recover, or maintain the meaningful activities, or ''occupations'', of individuals, groups, or communities. The field of ...

(OT) *

speech therapy Speech is a human vocal communication using language. Each language uses phonetic combinations of vowel and consonant sounds that form the sound of its words (that is, all English words sound different from all French words, even if they are th ...

(including augmentative and alternative communication) (SPT) *

behavioural therapy Behaviour therapy or behavioural psychotherapy is a broad term referring to clinical psychotherapy that uses techniques derived from behaviourism and/or cognitive psychology. It looks at specific, learned behaviours and how the environment, or oth ...

(

applied behavior analysis Applied behavior analysis (ABA), also called behavioral engineering, is a psychological intervention that applies empirical approaches based upon the principles of respondent and operant conditioning to change behavior of social significance. ...

/intensive behavioural intervention etc.) * discrete trial teaching * early intervention programs * massage therapy and pediatric massage * feeding therapy * music therapy *

hippotherapy Equine-assisted therapy (EAT) encompasses a range of treatments that involve activities with horses and other Equinae, equines to promote human physical and mental health. The use of EAT has roots in Ancient history, antiquity, and EAT applies to ...

* hydrotherapy