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BBS2
Bardet-Biedl syndrome 2
BBS2 is located on the long (q) arm of chromosome 16, at band 16q13. Arm ratio per GRCh38 - banding schematic.
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Overview
BBS2 is located on chromosome 16 and encodes a 721-amino-acid protein that forms part of the BBSome complex. The BBSome functions as a coat complex that mediates the transport of membrane proteins into and out of primary cilia, structures that project from the cell surface and serve as sensory organelles. When BBS2 variants impair BBSome assembly or function, cells cannot maintain properly functioning cilia, resulting in widespread developmental and physiological abnormalities.
Pathogenic variants in BBS2 follow an autosomal recessive inheritance pattern, meaning that an individual must inherit altered copies from both parents to develop Bardet-Biedl syndrome. This condition features progressive vision loss, obesity, kidney abnormalities, polydactyly, and developmental delay. The gene is included on multiple NHS clinical panels for ciliopathies and developmental disorders.
What the gene does
The BBS2 protein is a core subunit of the BBSome, an octameric complex that regulates the ciliary membrane proteome. Primary cilia function as cellular antennae, detecting extracellular signals such as growth factors, hormones, and morphogens during embryonic development and throughout postnatal life. The BBSome acts as a selective trafficking module, escorting specific receptors and signalling molecules to the ciliary compartment and retrieving others for recycling or degradation.
BBS2 contributes to the structural integrity of the BBSome and facilitates its interaction with intraflagellar transport machinery, the molecular motors that move cargo along the ciliary axoneme. Without functional BBS2, cells cannot properly assemble or maintain cilia, and signalling pathways that depend on ciliary localisation become dysregulated. These pathways include Sonic Hedgehog signalling during limb patterning, photoreceptor function in the retina, renal tubule development, and hypothalamic circuits governing appetite and metabolism. Disruption of these processes underlies the diverse clinical features observed in Bardet-Biedl syndrome.
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Chromosome location
BBS2 is located on the long arm of chromosome 16 at position 16q13. The gene spans multiple exons encoding a transcript that translates into a 721-amino-acid polypeptide. This chromosomal region also contains other genes involved in developmental and metabolic processes, though BBS2 itself does not appear to have closely related paralogues elsewhere in the human genome.
Protein structure
The BBS2 protein contains a predicted coiled-coil domain spanning amino acids 325 to 369, which likely mediates protein-protein interactions necessary for BBSome assembly. Coiled coils are structural motifs in which two or more alpha helices wind around each other, providing stable interfaces for multiprotein complex formation. Beyond this region, the full domain architecture of BBS2 has not been comprehensively characterised experimentally, though structural studies of the assembled BBSome have begun to reveal how individual subunits contribute to the overall complex geometry.
Key variants
Pathogenic variants in BBS2 are distributed throughout the gene, including missense, nonsense, and frameshift changes. Most disease-causing variants disrupt either protein stability or the ability of BBS2 to interact with other BBSome components. Because Bardet-Biedl syndrome follows autosomal recessive inheritance, affected individuals typically carry two pathogenic variants, which may be the same (homozygous) or different (compound heterozygous).
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.1015del | p.Arg339fs | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome 2 |
c.1161del | p.Ser388fs | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.1163C>A | p.Ser388Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.1310_1344del | p.Leu437fs | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome 2 |
c.1662dup | p.Thr555fs | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.1822C>T | p.Gln608Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 40 |
c.1997_1998del | p.Thr666fs | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome 2 |
c.612+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome 2 |
c.717+1G>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome |
c.79A>C | p.Thr27Pro | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome 2 |
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 BBS2 cause Bardet-Biedl syndrome, a ciliopathy characterised by retinal degeneration leading to progressive vision loss, postaxial polydactyly, truncal obesity, learning difficulties, hypogonadism, and renal abnormalities. The severity and specific combination of features can vary among affected individuals, even within the same family. Additional manifestations may include diabetes, liver abnormalities, and cardiac defects. Early diagnosis and multidisciplinary management are important for addressing the progressive aspects of the condition, particularly renal disease and vision loss.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic BBS2 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
BBS2 holds green classification status on multiple NHS Genomic Medicine Service panels, including the Bardet-Biedl syndrome panel (R107), Fetal anomalies (R21), Intellectual disability (R29), Retinal disorders (R32), Severe early-onset obesity (R149), and Skeletal dysplasia (R104). It also appears on panels for ophthalmological ciliopathies, renal ciliopathies, rare multisystem ciliopathy disorders, and limb disorders. Green status indicates strong evidence supporting the gene-disease relationship, and BBS2 testing may be offered through the NHS for individuals presenting with clinical features suggestive of ciliopathy.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the BBS2 gene responsible for?
BBS2 encodes a protein that forms part of the BBSome complex, which is essential for building and maintaining primary cilia. These cilia act as sensory structures on cells, coordinating signals that guide development and regulate metabolism, vision, kidney function, and other physiological processes.
How is BBS2-related Bardet-Biedl syndrome inherited?
Bardet-Biedl syndrome caused by BBS2 variants follows an autosomal recessive pattern. An individual must inherit one pathogenic variant from each parent to develop the condition. Parents who each carry one variant are typically unaffected carriers.
Can BBS2 variants affect only vision, or do they cause other problems?
BBS2-related Bardet-Biedl syndrome is a multisystem disorder. While progressive vision loss due to retinal degeneration is a hallmark feature, affected individuals may also experience obesity, kidney disease, extra fingers or toes, developmental delay, and hormonal abnormalities. The range and severity of features can vary.