On this page
BBS10
Bardet-Biedl syndrome 10
The BBS10 gene provides instructions for making a protein critical for the proper formation and function of primary cilia, playing a significant role in various cellular processes. The BBS10 gene encodes a protein that acts as a chaperonin, assisting in the correct folding of other proteins, particularly those involved in primary cilia.
BBS10 is located on the long (q) arm of chromosome 12, at band 12q21.2. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 12 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The BBS10 gene, or Bardet-Biedl syndrome 10, is essential for producing a protein found in many cell types throughout the body. This protein is part of a complex that helps fold other proteins into their correct three-dimensional shapes, which is vital for their proper function. Specifically, BBS10 is involved in the development and maintenance of primary cilia, microscopic structures on cell surfaces that transmit crucial signals for cell growth, specialisation, and gene activity.
What the gene does
The protein encoded by the BBS10 gene functions as a chaperonin, a type of protein that helps other proteins achieve their proper folded structure. Research indicates that the BBS10 protein plays a key role in folding or stabilising proteins necessary for the normal formation and function of primary cilia. Primary cilia are finger-like projections found on most cells, acting as antennae that relay signals from the external environment into the cell's interior. This signalling is fundamental for sensory perception, including sight and smell, and regulates critical biological processes like cell growth, differentiation, and gene expression. The BBS10 protein is also instrumental in assembling the BBSome, a protein complex that manages the sorting and transport of proteins within primary cilia, which is crucial for their overall development and function.
Video: Genetics 101
Chromosome location
The BBS10 gene is situated on chromosome 12 at position 12q21.2. This genomic location specifies where the gene can be found within the human genome, providing its precise address on the long arm of chromosome 12.
Protein structure
The BBS10 protein consists of 723 amino acids. Domain architecture has not been experimentally characterised in detail for this protein, however, its function is known to involve chaperonin activity in protein folding.
Key variants
Genetic variations, known as pathogenic variants, in the BBS10 gene can disrupt its normal function. These alterations can impair the protein's ability to facilitate proper protein folding and cilial function. Such pathogenic variants are associated with specific inherited conditions.
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.1399del | p.Arg467fs | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.1623_1624insGT | p.Lys542fs | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.1701dup | p.Thr568fs | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.1812dup | p.Asn605Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.1892_1896del | p.Met631fs | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.253del | p.Thr85fs | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.466_467del | p.Ile156fs | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.488_489del | p.Arg163fs | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.725_737del | p.Gln242fs | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.9_10insAT | p.Ser4fs | 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 in the BBS10 gene are a significant cause of Bardet-Biedl syndrome. This is a rare, inherited disorder that impacts many bodily systems. It is estimated that pathogenic variants in BBS10 account for approximately 15 percent of all cases of Bardet-Biedl syndrome.
Inheritance pattern
Conditions caused by pathogenic BBS10 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 BBS10 gene is well-recognised within the UK clinical genomics community. It is listed as 'green' on several NHS Genomic Medicine Service PanelApp panels, including Bardet Biedl syndrome (R107), DDG2P, Foetal anomalies (R21), Intellectual disability, Limb disorders, Ophthalmological ciliopathies, Rare multisystem ciliopathy disorders, Renal ciliopathies, Retinal disorders (R32), Severe early-onset obesity (R149), and Skeletal dysplasia (R104). This indicates there is strong evidence for its association with these conditions, and it is routinely assessed in diagnostic testing.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the BBS10 gene?
The BBS10 gene provides instructions for making a protein that acts as a chaperonin, helping other proteins fold correctly. It is particularly important for the normal formation and function of primary cilia, which are crucial for cellular signalling and sensory perception.
What is Bardet-Biedl syndrome?
Bardet-Biedl syndrome is a rare, inherited genetic disorder that can affect multiple parts of the body. Pathogenic variants in the BBS10 gene are a common cause of this syndrome.
How does the BBS10 protein contribute to primary cilia function?
The BBS10 protein helps fold and stabilise other proteins that are essential for primary cilia. It also aids in assembling the BBSome, a complex responsible for sorting and transporting proteins within the cilia, which is vital for their proper development and function.
References
- Seo S, Baye LM, Schulz NP. BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly. Proceedings of the National Academy of Sciences of the United States of America. 2010. PMID: 20080638
- 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
- Marion V, Stoetzel C, Schlicht D. Transient ciliogenesis involving Bardet-Biedl syndrome proteins is a fundamental characteristic of adipogenic differentiation. Proceedings of the National Academy of Sciences of the United States of America. 2009. PMID: 19190184
- White DR, Ganesh A, Nishimura D. Autozygosity mapping of Bardet-Biedl syndrome to 12q21.2 and confirmation of FLJ23560 as BBS10. European journal of human genetics : EJHG. 2007. PMID: 17106446
- Stoetzel C, Laurier V, Davis EE. BBS10 encodes a vertebrate-specific chaperonin-like protein and is a major BBS locus. Nature genetics. 2006. PMID: 16582908
- Laurier V, Stoetzel C, Muller J. Pitfalls of homozygosity mapping: an extended consanguineous Bardet-Biedl syndrome family with two mutant genes (BBS2, BBS10), three mutations, but no triallelism. European journal of human genetics : EJHG. 2006. PMID: 16823392
- Adam MP, Bick S, Mirzaa GM. Bardet-Biedl Syndrome Overview. 1993. PMID: 20301537