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ARL13B
ARF like GTPase 13B
The ARL13B gene provides instructions for making a protein crucial for the proper formation and function of cilia, which are microscopic, hair-like structures on cell surfaces. ARL13B is a gene that encodes a protein essential for the specialised hair-like cellular structures called cilia.
ARL13B is located on the long (q) arm of chromosome 3, at band 3q11.1-q11.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The ARL13B gene, or ARF like GTPase 13B, is a vital component in the intricate machinery of human cells. It carries the genetic blueprint for a protein that is specifically localised to and plays a critical role in the function of cilia, which are small, membrane-bound protrusions found on various cell types. These structures are integral to many biological processes, including cell communication, fluid movement, and sensory reception across different organ systems. Changes within the ARL13B gene can disrupt the normal formation or operation of cilia, leading to a range of inherited disorders often referred to as ciliopathies.
What the gene does
The ARL13B protein functions as a small GTPase, a type of protein that acts as a molecular switch, cycling between active and inactive states by binding to GTP (guanosine triphosphate) or GDP (guanosine diphosphate), respectively. This cycling mechanism enables ARL13B to regulate various cellular processes, particularly within primary cilia. It is involved in the transport of other proteins into and out of cilia, a process vital for maintaining ciliary structure and signalling functions. The ARL13B protein also helps to establish and maintain the distinct protein composition of the ciliary membrane, which is crucial for signalling pathways involved in development and sensory functions. Its precise regulatory actions are fundamental for the proper assembly and maintenance of functional cilia.
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Chromosome location
The ARL13B gene is situated on chromosome 3, specifically within the long (q) arm, at position 11.1-q11.2. This genomic location refers to a precise segment of the chromosome where the gene can be found. The gene provides the instructions for synthesising a protein composed of 428 amino acids.
Protein structure
The ARL13B protein consists of 428 amino acids and contains several distinct structural regions. A 'Coiled coil' domain spans amino acids 192-245, which typically facilitates protein-protein interactions. Additionally, there are two large disordered regions: one from amino acids 207-287 and another from amino acids 318-428. These 'Disordered' regions are flexible segments of the protein that can adopt various shapes, often crucial for binding to multiple partners or undergoing post-translational modifications.
Key variants
Variants within the ARL13B gene refer to changes in its DNA sequence. These genetic changes can range from single nucleotide alterations to larger deletions or duplications. The varying impact of these variants on protein function can contribute to a spectrum of clinical presentations. Specific variants are associated with different forms of inherited conditions, influencing the severity and specific features of the disorder.
Sample of pathogenic variants
10 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 |
|---|---|---|---|---|
c.1147dup | p.Trp383fs | Pathogenic/Likely pathogenic | ★★☆☆ | Joubert syndrome 8 |
c.131-1G>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | Joubert syndrome 8 |
c.223G>A | p.Gly75Arg | Pathogenic | ★★☆☆ | Joubert syndrome and related disorders |
c.393_396del | p.Gln132fs | Pathogenic/Likely pathogenic | ★★☆☆ | Joubert syndrome 8 |
c.550del | p.Tyr184fs | Pathogenic/Likely pathogenic | ★★☆☆ | Joubert syndrome 8 |
c.73_74del | p.Leu25fs | Pathogenic/Likely pathogenic | ★★☆☆ | Joubert syndrome 8 |
c.830del | p.Asn277fs | Pathogenic/Likely pathogenic | ★★☆☆ | Joubert syndrome 8 |
c.830dup | p.Asn277fs | Pathogenic/Likely pathogenic | ★★☆☆ | Joubert syndrome and related disorders |
c.861C>A | p.Cys287Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Joubert syndrome 8 |
c.932dup | p.Asn311fs | Pathogenic/Likely pathogenic | ★★☆☆ | Joubert syndrome 8 |
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
Pathogenic variants in the ARL13B gene are associated with a group of genetic disorders known as ciliopathies. These conditions arise from defects in the structure or function of cilia. Ciliopathies are highly heterogeneous, meaning they can affect multiple organ systems and present with a wide range of signs and symptoms. While specific diseases are not individually listed for ARL13B, its involvement points to potential systemic effects characteristic of ciliopathies.
No disease links recorded for this gene in our reference set.
UK clinical status
In the UK, the ARL13B gene is recognised on several NHS Genomic Medicine Service national test panels. It is listed as ‘green’ for conditions such as Foetal anomalies (R21), Intellectual disability (R29), Neurological ciliopathies, Ophthalmological ciliopathies, Rare multisystem ciliopathy disorders, Renal ciliopathies, and Retinal disorders (R32), indicating that variants in ARL13B are considered primary causes of these conditions and are routinely assessed in diagnostic testing.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What are cilia, and why are they important?
Cilia are microscopic, hair-like appendages found on the surface of many cell types in the body. They play critical roles in various biological processes, including cell signalling, fluid movement (e.g., in airways), and sensory perception (e.g., in the eye and ear).
What are ciliopathies?
Ciliopathies are a group of genetic disorders caused by defects in the structure or function of cilia. These conditions can affect multiple organ systems, leading to a wide range of symptoms such as kidney disease, retinal degeneration, intellectual disability, and skeletal anomalies.
How is ARL13B related to inherited conditions?
Variants in the ARL13B gene can disrupt the normal function of the ARL13B protein, which is essential for healthy cilia. These disruptions can lead to the development of various ciliopathies, affecting different parts of the body depending on the specific variant and its impact.