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RAB23
RAB23, member RAS oncogene family
The RAB23 gene provides instructions for a protein critical in regulating intracellular transport and the hedgehog signalling pathway, important for proper embryonic development. RAB23 encodes a protein involved in vesicle trafficking, which moves molecules within cells, and the hedgehog signalling pathway, essential for cell growth and patterning during embryonic development.
RAB23 is located on the short (p) arm of chromosome 6, at band 6p12.1-p11.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The RAB23 gene, also known as RAB23, member RAS oncogene family, plays a significant role in cellular processes vital for development. It provides the genetic blueprint for a protein that helps manage the movement of substances within cells, a process called vesicle trafficking. Additionally, the RAB23 protein is an important regulator of the hedgehog signalling pathway, which orchestrates various aspects of embryonic growth and tissue formation.
Understanding the RAB23 gene's function offers insights into developmental biology and the mechanisms underlying certain genetic conditions.
What the gene does
The protein produced from the RAB23 gene is integral to several fundamental cellular activities. Its primary role involves vesicle trafficking, a mechanism where proteins and other molecules are transported inside sac-like structures called vesicles. This process typically begins when a cell membrane encloses external substances to form a vesicle, which is then internalised into the cell via endocytosis.
Once inside, the RAB23 protein guides these vesicles to their specific cellular destinations. Efficient vesicle trafficking is essential for delivering materials required to activate signalling pathways during development. Notably, the RAB23 protein regulates the hedgehog signalling pathway, a crucial developmental pathway that influences cell proliferation, specialisation, and the proper patterning of many bodily structures during embryonic development.
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Chromosome location
The RAB23 gene is situated on the short arm of chromosome 6, specifically located at position 6p12.1-p11.2. This chromosomal region contains the genetic instructions for the RAB23 protein, which consists of 237 amino acids.
Protein structure
The RAB23 protein contains several distinct functional regions essential for its activity. Key motifs include Switch 1, located between amino acids 28 and 46, and Switch 2, found between amino acids 65 and 84. These motifs are generally involved in the protein's ability to bind and hydrolyse GTP, a common feature of Rab family small GTPases. Additionally, a Disordered region spans amino acids 188 to 237, which may contribute to flexible interactions with other proteins.
Key variants
Variants within the RAB23 gene can alter the function of the encoded protein, potentially disrupting its role in vesicle trafficking and hedgehog signalling. These genetic changes can range from single nucleotide substitutions to larger deletions or insertions, and their impact on protein function can vary significantly. Such alterations may underlie the development of inherited conditions.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Pathogenic variants in the RAB23 gene are associated with Carpenter syndrome, an inherited condition characterised by a distinctive set of developmental abnormalities. This condition typically presents with irregular skull formation, and abnormalities of the fingers and toes, among other features. Carpenter syndrome follows an autosomal recessive inheritance pattern, meaning an individual must inherit two copies of a pathogenic variant (one from each parent) to be affected.
Inheritance pattern
Conditions caused by pathogenic RAB23 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
RAB23 is recognised by the UK's National Health Service (NHS) Genomic Medicine Service. It is included on several NHS national genomic test panels, indicating its clinical significance for diagnostic testing. These panels include those for DDG2P, Foetal anomalies (R21), Intellectual disability, Limb disorders, Rare syndromic craniosynostosis or isolated multisuture synostosis (R100), and Skeletal dysplasia (R104).
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the RAB23 gene?
The RAB23 gene provides instructions for a protein that manages vesicle trafficking, the movement of molecules within cells, and regulates the hedgehog signalling pathway, which is vital for embryonic development.
What condition is associated with RAB23 gene variants?
Variants in the RAB23 gene are primarily associated with Carpenter syndrome, a genetic disorder characterised by skull, finger, and toe abnormalities, among other developmental features.
How is Carpenter syndrome inherited?
Carpenter syndrome is inherited in an autosomal recessive manner. This means an individual must inherit two copies of a pathogenic RAB23 variant, one from each parent, to develop the condition.
References
- Jenkins D, Baynam G, De Catte L. Carpenter syndrome: extended RAB23 mutation spectrum and analysis of nonsense-mediated mRNA decay. Human mutation. 2011. PMID: 21412941
- Alessandri JL, Dagoneau N, Laville JM. RAB23 mutation in a large family from Comoros Islands with Carpenter syndrome. American journal of medical genetics. Part A. 2010. PMID: 20358613
- Perlyn CA, Marsh JL. Craniofacial dysmorphology of Carpenter syndrome: lessons from three affected siblings. Plastic and reconstructive surgery. 2008. PMID: 18317146
- Jenkins D, Seelow D, Jehee FS. RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity. American journal of human genetics. 2007. PMID: 17503333