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AP1S1
adaptor related protein complex 1 subunit sigma 1
The AP1S1 gene provides instructions for making a protein that is part of a larger complex essential for sorting and transporting proteins within cells. The AP1S1 gene encodes the sigma 1 subunit of the adaptor protein complex 1 (AP-1).
AP1S1 is located on the long (q) arm of chromosome 7, at band 7q22.1. Arm ratio per GRCh38 - banding schematic.
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Overview
The AP1S1 gene, or adaptor related protein complex 1 subunit sigma 1, contains the genetic blueprint for a component of the AP-1 complex. This complex is crucial for maintaining cellular organisation by regulating the movement of molecules between different compartments inside the cell. It is especially important for pathways involving endosomes, the trans-Golgi network, and the cell surface.
What the gene does
The protein produced from the AP1S1 gene is the smallest subunit of the AP-1 complex, a heterotetramer composed of four different subunits. The AP-1 complex acts as a cargo-selective adaptor, binding to specific membrane proteins and vesicles. Its primary role involves recognising sorting signals on these 'cargo' proteins to ensure they are directed to the appropriate cellular destinations, such as lysosomes or the plasma membrane. This function is vital for processes like nutrient uptake, cell signalling, and maintaining cell surface integrity. The AP-1 complex helps form clathrin-coated vesicles, which are small sacs that bud off from membranes, encapsulating proteins for transport.
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Chromosome location
The AP1S1 gene is located on chromosome 7, specifically at position 7q22.1. This position indicates its precise address within the human genome. Genes on chromosome 7 are involved in a wide array of biological functions, and its location ensures that the AP1S1 gene's instructions can be accessed and utilised by the cell.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variations within the AP1S1 gene can include changes in its DNA sequence that may alter the protein's structure or function. Such variations might affect how the AP-1 complex is assembled or how effectively it performs its roles in intracellular trafficking. While many variants are harmless, some can disrupt normal cellular processes.
Sample of pathogenic variants
1 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
g.(?_100797796)_(100797818_?)del | - | Pathogenic | ★☆☆☆ | not provided |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Disruptions to the AP1S1 gene and its encoded protein can have several health implications, given its fundamental role in cellular transport. Conditions potentially associated with AP1S1 variants often involve impairments in cell function, particularly those requiring precise sorting and delivery of molecules. The inheritance pattern for conditions linked to AP1S1 is typically autosomal recessive.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic AP1S1 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The AP1S1 gene is featured on several UK NHS National Genomic Test Directory panels. It has a 'green' R code status for conditions including Hereditary neuropathy or pain disorder (R78), Intellectual disability (R29), Intestinal failure or congenital diarrhoea (R331), Monogenic hearing loss (R67), Palmoplantar keratodermas (R166), and Vici Syndrome and other autophagy disorders. This indicates that AP1S1 is considered clinically actionable for these conditions within the NHS.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the AP1S1 gene?
The AP1S1 gene provides instructions for making the sigma 1 subunit of the adaptor protein complex 1 (AP-1). This protein complex is essential for transporting and sorting other proteins within cells.
What is the function of the AP1S1 protein?
The AP1S1 protein is a component of the AP-1 complex, which helps in forming vesicles that transport molecules around the cell. It ensures that proteins and lipids reach their correct cellular destinations, playing a vital role in processes like nutrient uptake and cell signalling.
How are conditions related to AP1S1 inherited?
Conditions associated with the AP1S1 gene are generally inherited in an autosomal recessive manner. This means that an individual must inherit two copies of a pathogenic variant, one from each parent, to develop the condition.