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BBS1
Bardet-Biedl syndrome 1
The BBS1 gene provides instructions for a protein that is crucial for the formation and function of primary cilia, playing a key role in cellular signalling and various developmental processes. BBS1 encodes a protein that is part of a complex called the BBSome, which helps transport proteins within primary cilia.
BBS1 is located on the long (q) arm of chromosome 11, at band 11q13.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The BBS1 gene, or Bardet-Biedl syndrome 1, is essential for producing a protein found in cells throughout the body. This protein is a component of the BBSome complex, which is critical for the proper formation and function of primary cilia. Primary cilia are microscopic, finger-like projections on cell surfaces that transmit signals both into and out of the cell.
Disruptions in the BBS1 gene's function are primarily associated with Bardet-Biedl syndrome, a rare inherited disorder affecting multiple body systems. Understanding BBS1 is important for diagnosing and researching ciliopathies, a group of genetic conditions caused by ciliary dysfunction.
What the gene does
The BBS1 gene directs the synthesis of a protein integral to primary cilia. These cilia are vital cellular organelles involved in sensing the extracellular environment and transmitting signals that regulate numerous cellular processes. The BBS1 protein is a key member of the BBSome, a multi-protein complex that helps sort and transport other proteins within these primary cilia. This transport mechanism is fundamental for maintaining the structural integrity and functional efficiency of cilia.
Primary cilia are involved in various biological activities, including the perception of sensory input like sight, hearing, and smell. They also play roles in signalling pathways that manage cell growth, division, differentiation (specialisation), and the regulation of specific genes. Therefore, the proper function of the BBS1 protein and the BBSome is indispensable for these diverse cellular and developmental processes.
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Chromosome location
The BBS1 gene is situated on chromosome 11 at position 11q13.2. This location refers to the long (q) arm of chromosome 11, specifically within region 1, band 3, sub-band 2. The BBS1 gene spans approximately 34 kilobases of DNA.
Protein structure
The BBS1 gene codes for a protein consisting of 593 amino acids. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants in the BBS1 gene can alter the function of the encoded protein, leading to health conditions. These genetic changes range from single nucleotide substitutions to larger deletions or insertions within the gene sequence. Pathogenic variants are those that significantly impair the protein's function, often resulting in the disruption of primary cilia activity.
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.1A>G | p.Met1Val | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.2T>C | p.Met1Thr | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome 1 |
c.382C>T | p.Gln128Ter | Pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.3G>A | p.Met1Ile | Pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.47+1G>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.48-1G>A | - | Pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.526C>T | p.Gln176Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.607del | p.Thr202_Met203insTer | Pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.667del | p.Thr223fs | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome 1 |
c.723+2T>G | - | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
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 within the BBS1 gene are predominantly associated with Bardet-Biedl syndrome. This is a rare, inherited disorder that impacts multiple organ systems. Variants in BBS1 represent a common genetic cause of Bardet-Biedl syndrome, accounting for a significant proportion of diagnosed cases.
Inheritance pattern
Conditions caused by pathogenic BBS1 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 BBS1 gene is well-recognised within the UK's NHS Genomic Medicine Service. It is listed on several NHS Genomic Test Directory panels, indicating its clinical relevance for diagnosing various conditions. These include panels for Bardet Biedl syndrome (R107), Retinal disorders (R32), Severe early-onset obesity (R149), and Foetal anomalies (R21). Its presence on panels like DDG2P (Deciphering Developmental Disorders) and Ophthalmological ciliopathies further highlights its importance in genetic diagnostics.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the BBS1 gene?
The BBS1 gene produces a protein that is a key component of the BBSome complex. This complex is vital for the proper formation and function of primary cilia, which are microscopic cellular projections involved in sensory input and cell signalling.
What condition is most commonly associated with BBS1 gene variants?
Pathogenic variants in the BBS1 gene are most commonly associated with Bardet-Biedl syndrome. This is a rare inherited disorder that can affect multiple parts of the body.
How does the BBS1 protein contribute to ciliary function?
The BBS1 protein, as part of the BBSome complex, helps sort and transport other essential proteins within primary cilia. This transport mechanism is crucial for maintaining the structure and function of these cilia, which are involved in various cellular communication and developmental processes.
References
- Muller J, Stoetzel C, Vincent MC. Identification of 28 novel mutations in the Bardet-Biedl syndrome genes: the burden of private mutations in an extensively heterogeneous disease. Human genetics. 2010. PMID: 20177705
- Nachury MV, Loktev AV, Zhang Q. A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. Cell. 2007. PMID: 17574030
- Mykytyn K, Nishimura DY, Searby CC. Evaluation of complex inheritance involving the most common Bardet-Biedl syndrome locus (BBS1). American journal of human genetics. 2003. PMID: 12524598
- Beales PL, Badano JL, Ross AJ. Genetic interaction of BBS1 mutations with alleles at other BBS loci can result in non-Mendelian Bardet-Biedl syndrome. American journal of human genetics. 2003. PMID: 12677556
- Mykytyn K, Nishimura DY, Searby CC. Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome. Nature genetics. 2002. PMID: 12118255
- Adam MP, Bick S, Mirzaa GM. Bardet-Biedl Syndrome Overview. 1993. PMID: 20301537