Ask about this productRelated genes to: BBS4 antibody
- Gene:
- BBS4 NIH gene
- Name:
- Bardet-Biedl syndrome 4
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 15q24.1
- Locus Type:
- gene with protein product
- Date approved:
- 1995-07-11
- Date modifiied:
- 2019-01-25
Related products to: BBS4 antibody
Related articles to: BBS4 antibody
- The BBSome, an eight-protein complex implicated in Bardet-Biedl syndrome (BBS), plays a crucial role in various cellular processes including ciliary function. Although important aspects of its structural organization and protein interactions have been elucidated, additional questions remain regarding how these features relate to cargo recognition and complex dynamics. Using AlphaFold3, we generated a structural model closely matching recent cryo-EM data (α-carbon root means square deviation: 1.203 Å). Interface residue analysis of the model identified BBSome proteins BBS1 and BBS9 as central interaction hubs (most interface residues between two proteins), with BBS2 and BBS7 showing the most polar contacts. The common BBS1 pathogenic mutation, known to cause BBS, was predicted to destabilize the complex. BBS4 was also found to interact stably with pericentriolar material 1, suggesting a role in centriolar satellite localization. AlphaFold3-mediated analysis of BBSome interactions with G protein-coupled receptors (GPCRs) led to the identification of contact hotspots on BBS1, BBS4, and BBS5. These predictions were supported by immunoprecipitation and peptide competition assays. The modeling also suggested plausible interfaces between specific BBS proteins and metabolic signaling proteins, including melanocortin receptor accessory protein 2 (MRAP2) [an melanocortin-4 receptor (MC4R) chaperonin], the leptin receptor, and the insulin receptor. These predicted interfaces align with previously reported biochemical associations between BBS proteins and these receptors, supporting the idea that the BBSome regulates trafficking and signaling in metabolic pathways. Together, these findings provide new insights into BBSome structure and receptor interactions, offering a predictive framework to explore its role in ciliary trafficking and human disease. This study combines AI modeling and experimental validation to define key structural features and receptor interactions of the BBSome complex. The analysis identifies BBS1 and BBS9 as central hubs, reveals how the BBS1 mutation destabilizes the complex, and uncovers novel contacts with various receptors including those involved in metabolic regulation. These findings provide a predictive framework linking BBSome structure to ciliary signaling and metabolic regulation in Bardet-Biedl syndrome. - Source: PubMed
Publication date: 2026/03/31
Guo Deng FuRouabhi YounesTollefson MalloryVorhies KaiRahmouni Kamal - Primary cilia, microtubule-based sensory organelles that mediate cell-cell communication, may facilitate signaling in the brain through direct physical contacts (e.g., synapse-like structures). Similarly, specialized glial cells lining the third ventricle (3V) called tanycytes signal through physical interactions and can dynamically alter their morphology in response to external stimuli and physiological changes. Here, we identify robust cilia-tanycyte contacts; we term HUGS ( H ypothalamic, U nifying G lia-cilia S tructures) and discover that these connections are disrupted in a mouse ciliopathy model ( ) exhibiting hypothalamic dysfunction. These data provide insight into potentially new cell-cell signaling mechanisms deployed by neuronal cilia. . - Source: PubMed
Publication date: 2026/01/13
Schwantz Kara RBoone Jaelyn GBrewer Kathryn MBerbari Nicolas F - Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive genetic disorder. Polydactyly, obesity, pigmentary retinal degeneration, intellectual disability, kidney abnormalities and hypogonadism are common features. We report an infant who presented with obesity, micropenis, polydactyly and syndromic features, raising suspicion of a genetic syndrome. Infantile obesity is among the most common clinical findings in BBS. Whole-exome sequencing confirmed a mutation in the BBS4 gene which was homozygous and associated with BBS. The child was discharged in stable condition after 11 days of hospitalisation. On follow-up after 2 years of age, setmelanotide is planned to be initiated for his weight management. Infantile obesity, a rare and early manifestation, played a pivotal role in suspecting syndromic obesity, leading to targeted genetic investigations. The case highlights the importance of recognising early-onset obesity as a diagnostic clue for genetic syndromes by performing next-generation sequencing critical to make firm diagnosis of BBS. - Source: PubMed
Publication date: 2026/01/29
Akhila PatlollaNaik JyothiArun Babu Thirunavukkarasu - Primary cilia orchestrate several signaling pathways, and their disruption results in pleiotropic disorders called ciliopathies. Bardet-Beidl syndrome (BBS), one ciliopathy, provides insights into cilia function in many tissues. Using a mouse model of BBS, Bbs4 knockout (Bbs4), we found that adult Bbs4 pituitaries are hypoplastic and have increased gonadotroph populations. Similarly, pituitary deletion of IFT88, required for ciliogenesis, attenuated growth and increased gonadotrophs. The developing Bbs4 pituitary experienced mildly reduced Hedgehog (HH) signaling. Isolated Bbs4 pituitary stem cells exhibited reduced HH signal responsiveness and expression of stem cell markers. These data demonstrate that cilia and BBS function are necessary for pituitary growth. We propose that altered cilia-mediated patterning of the pituitary contribute to physiological features of ciliopathies such as BBS. - Source: PubMed
Publication date: 2026/01/07
Brewer Kathryn MBrewer Katlyn KRichardson Nicholas CReiter Jeremy FBerbari Nicolas FKonjikusic Mia J - Cilia were one of the characteristic traits of the last eukaryotic common ancestor and are highly conserved among eukaryotes. Their proteomic makeup is remarkably similar throughout all eukaryotic lineages. Recently, several ciliary transport proteins, namely the Bardet-Biedl Syndrome (BBS) proteins, were shown to traverse the nuclear envelope, and to modulate gene expression. Insects have been critically understudied in cilia biology since they only exhibit cilia on a subset of cells. We present evidence that the BBSome is largely conserved in multiple insect lineages. To examine BBS protein expression within insects, we profiled tissues, castes, and sexes of the honeybee Apis mellifera, a species where the genome encodes for multiple behavioural and morphological phenotypes. We find variation in expression profiles of putative BBSome-associated genes across different tissues, including those lacking cilia, indicating possible non-ciliary functions. We also demonstrate that expression of individual BBS proteins varies significantly between queens' and males' tissues, especially in neuronal tissue. Particularly high overexpression of BBS4 in glandular tissue indicates a cilia-independent role. Our findings provide evolutionary insight into the conservation of BBSome components across insects, suggesting potential additional roles for cilia proteins in non-ciliated tissues, providing candidate genes from diverse insect orders for future experimental work. - Source: PubMed
Publication date: 2025/10/02
Ewerling-Haehnel AlexanderKöhler InaGraebling IsaWierczeiko AnnaKotzurek ElisaGerber SusanneFoitzik SusanneColgan Thomas JMay-Simera Helen L