Details for: BBS1

Gene ID: 582

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: BBS1

Ensembl ID: ENSG00000174483

Description: Bardet-Biedl syndrome 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • choroid plexus epithelial cell CL0000706
    CSI 5.12
    rCSI 8.38%
    PRS 95.09
  • lung ciliated cell CL1000271
    CSI 3.02
    rCSI 3.5%
    PRS 95.26
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 2.98
    rCSI 6.79%
    PRS 93.73
  • ciliated epithelial cell CL0000067
    CSI 2.96
    rCSI 2.6%
    PRS 93.71
  • mesothelial cell CL0000077
    CSI 2.57
    rCSI 10.06%
    PRS 90.82
  • Mueller cell CL0000636
    CSI 2.46
    rCSI 5.61%
    PRS 94.94
  • glioblast CL0000030
    CSI 2.24
    rCSI 3.57%
    PRS 94.47
  • L6b glutamatergic cortical neuron CL4023038
    CSI 2.09
    rCSI 6.53%
    PRS 93.39
  • ciliated cell CL0000064
    CSI 2.01
    rCSI 3.26%
    PRS 94.24
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.82
    rCSI 3.22%
    PRS 92.91
  • cardiac muscle cell CL0000746
    CSI 1.82
    rCSI 2.61%
    PRS 93.61
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.79
    rCSI 2.88%
    PRS 93.25
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.7
    rCSI 3.81%
    PRS 93.22
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 1.68
    rCSI 5.27%
    PRS 94.1
  • retinal cone cell CL0000573
    CSI 1.55
    rCSI 2.5%
    PRS 93.84
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.5
    rCSI 3.81%
    PRS 95.71
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.15
    rCSI 2.78%
    PRS 91.57
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.01
    rCSI 3.63%
    PRS 91.76
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.83
    rCSI 3.15%
    PRS 92.7
  • direct pathway medium spiny neuron CL4023026
    CSI 0.69
    rCSI 16.43%
    PRS 90.87
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.65
    rCSI 15.68%
    PRS 90.65
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.59
    rCSI 3.49%
    PRS 92.95

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [BBS1](/details-gene/582) is a protein-coding gene located on chromosome 11q13.2 that is a core component of the BBSome complex, a crucial multi-protein assembly required for ciliary biogenesis and function. Mutations in this gene are the most common cause of Bardet-Biedl syndrome ([OMIM: 209900](https://omim.org/entry/209900)), a pleiotropic ciliopathy characterized by obesity, retinal degeneration, and cognitive impairment [Link](https://doi.org/10.1038/ng935). Functionally, [BBS1](/details-gene/582) and the BBSome complex mediate the trafficking of membrane proteins to the primary cilium, a key sensory organelle on the surface of most vertebrate cells [Link](https://doi.org/10.1016/j.cell.2007.03.053). Reflecting this central role in ciliary biology, its expression is most significant in cell types that are heavily reliant on ciliary structures, such as [choroid plexus epithelial cell](/details-cell/CL0000706), [lung ciliated cell](/details-cell/CL1000271), and specialized cells of the central nervous system and retina. ## Cellular Roles and Expression Landscape The expression profile of [BBS1](/details-gene/582) underscores its fundamental role in the formation and maintenance of cilia across diverse tissues. **Overall**, the gene shows the highest significance in cells defined by the presence of motile or primary cilia. This includes a strong marker status in [choroid plexus epithelial cell](/details-cell/CL0000706) (CSI: 5.12), which utilizes cilia for cerebrospinal fluid circulation, as well as various ciliated cells of the respiratory tract, such as [lung ciliated cell](/details-cell/CL1000271) and [ciliated columnar cell of tracheobronchial tree](/details-cell/CL0002145), which are essential for mucociliary clearance. Beyond these classic examples, [BBS1](/details-gene/582) is also significantly expressed in multiple cell types within the central nervous system and the eye, where primary cilia act as critical signaling hubs. This includes high significance in glial cells like the retinal [Mueller cell](/details-cell/CL0000636) and [astrocyte of the cerebral cortex](/details-cell/CL0002605), as well as various neuronal subtypes, such as [L6b glutamatergic cortical neuron](/details-cell/CL4023038) and interneurons. Its notable expression in [retinal cone cell](/details-cell/CL0000573) is consistent with the critical role of the connecting cilium in trafficking proteins to the photoreceptor outer segment, a highly modified primary cilium. This broad but specific expression pattern highlights [BBS1](/details-gene/582) as a key operational gene in cells that depend on ciliary structure for motility, sensory perception, and developmental signaling. ## Pathways and Molecular Function The molecular functions of [BBS1](/details-gene/582) are intrinsically linked to its role as a subunit of the [BBSome](/details-gene/GO:0034464) ([GO:0034464](https://www.ebi.ac.uk/QuickGO/term/GO:0034464)). This complex is a central player in the Reactome pathway for [Cilium assembly](/details-gene/R-HSA-5617833) ([R-HSA-5617833](https://reactome.org/content/detail/R-HSA-5617833)), specifically in [Bbsome-mediated cargo-targeting to cilium](/details-gene/R-HSA-5620922) ([R-HSA-5620922](https://reactome.org/content/detail/R-HSA-5620922)). The BBSome functions as an adaptor, recognizing cargo proteins in the cytoplasm and facilitating their transport into the ciliary compartment, a process that involves cooperation with the GTPase Rab8 [Link](https://doi.org/10.1016/j.cell.2007.03.053). This transport function is critical for a wide range of biological processes. Its involvement in [Photoreceptor cell maintenance](/details-gene/GO:0045494) ([GO:0045494](https://www.ebi.ac.uk/QuickGO/term/GO:0045494)) and [Visual perception](/details-gene/GO:0007601) ([GO:0007601](https://www.ebi.ac.uk/QuickGO/term/GO:0007601)) explains the retinal degeneration seen in Bardet-Biedl syndrome. Similarly, its role in numerous neurodevelopmental processes, including [Brain morphogenesis](/details-gene/GO:0048854) ([GO:0048854](https://www.ebi.ac.uk/QuickGO/term/GO:0048854)), [Neuron migration](/details-gene/GO:0001764) ([GO:0001764](https://www.ebi.ac.uk/QuickGO/term/GO:0001764)), and [Hippocampus development](/details-gene/GO:0021766) ([GO:0021766](https://www.ebi.ac.uk/QuickGO/term/GO:0021766)), is consistent with its expression in cortical neurons and astrocytes and likely underlies the cognitive and behavioral phenotypes associated with its dysfunction. The molecular binding functions of [BBS1](/details-gene/582), such as [Smoothened binding](/details-gene/GO:0005119) ([GO:0005119](https://www.ebi.ac.uk/QuickGO/term/GO:0005119)), place it at the heart of key developmental signaling pathways like Sonic hedgehog, which are transduced through the primary cilium. ## Research Directions Given that mutations in [BBS1](/details-gene/582) lead to a complex, multi-system disorder, dissecting its cell-type-specific functions is crucial for understanding the pathophysiology of Bardet-Biedl syndrome and developing targeted therapies. **Proposed Hypotheses:** 1. The neurological and cognitive deficits in Bardet-Biedl syndrome may stem not only from broad developmental defects but also from impaired ciliary signaling in specific neuronal subtypes. We hypothesize that loss of [BBS1](/details-gene/582) function in cortical interneurons (e.g., [caudal gangionic eminence derived cortical interneuron](/details-cell/CL4023064)) disrupts the trafficking of key receptors and channels to their cilia, leading to imbalances in excitatory/inhibitory circuits. 2. Given its exceptionally high expression in the [choroid plexus epithelial cell](/details-cell/CL0000706), we hypothesize that [BBS1](/details-gene/582) dysfunction in this tissue impairs the motility of cilia responsible for cerebrospinal fluid (CSF) flow. This could lead to subtle alterations in CSF dynamics and composition, contributing to the hydrocephalus and other structural brain abnormalities ([Ventricular system development](/details-gene/GO:0021591) ([GO:0021591](https://www.ebi.ac.uk/QuickGO/term/GO:0021591))) observed in some ciliopathies. **Experimental Approach:** To test the second hypothesis, a conditional knockout mouse model could be generated to specifically delete [BBS1](/details-gene/582) in choroid plexus epithelial cells. High-resolution in vivo imaging (e.g., MRI) could be used to monitor ventricular volume and CSF flow patterns over time. Furthermore, CSF could be collected from these mice and analyzed via mass spectrometry-based proteomics and metabolomics to identify changes in composition compared to control animals. Cilia structure and beat frequency on choroid plexus explants could be directly assessed using high-speed video microscopy. **Therapeutic Potential:** As Bardet-Biedl syndrome is a loss-of-function disorder, the therapeutic strategy would involve gene augmentation or functional restoration rather than inhibition. The systemic nature of ciliopathies makes [BBS1](/details-gene/582) a challenging target for small molecule therapies. However, its crucial role in specific, accessible organs makes it a strong candidate for gene replacement therapy. For instance, adeno-associated virus (AAV)-mediated delivery of a functional [BBS1](/details-gene/582) transgene to the retina is a promising avenue for treating the progressive vision loss associated with the disease, while similar strategies could be explored for other affected organ systems.

Genular Protein ID: 534285564

Symbol: BBS1_HUMAN

Name: BBS2-like protein 2

UniProtKB Accession Codes:

Q8NFJ9 Q32MM9 Q32MN0 Q96SN4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 EMDB 1 Ensembl 2 ExpressionAtlas 1 GO 36 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 2 Orphanet 2 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12118255

Title: Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome.

PubMed ID: 12118255

DOI: 10.1038/ng935

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16554811

Title: Human chromosome 11 DNA sequence and analysis including novel gene identification.

PubMed ID: 16554811

DOI: 10.1038/nature04632

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 16327777

Title: Dissection of epistasis in oligogenic Bardet-Biedl syndrome.

PubMed ID: 16327777

DOI: 10.1038/nature04370

PubMed ID: 17574030

Title: A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis.

PubMed ID: 17574030

DOI: 10.1016/j.cell.2007.03.053

PubMed ID: 18000879

Title: Novel interaction partners of Bardet-Biedl syndrome proteins.

PubMed ID: 18000879

DOI: 10.1002/cm.20250

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 22072986

Title: A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened.

PubMed ID: 22072986

DOI: 10.1371/journal.pgen.1002358

PubMed ID: 24939912

Title: Bardet-Biedl syndrome proteins 1 and 3 regulate the ciliary trafficking of polycystic kidney disease 1 protein.

PubMed ID: 24939912

DOI: 10.1093/hmg/ddu267

PubMed ID: 12524598

Title: Evaluation of complex inheritance involving the most common Bardet-Biedl syndrome locus (BBS1).

PubMed ID: 12524598

DOI: 10.1086/346172

PubMed ID: 12567324

Title: Identification of a novel Bardet-Biedl syndrome protein, BBS7, that shares structural features with BBS1 and BBS2.

PubMed ID: 12567324

DOI: 10.1086/368204

PubMed ID: 12677556

Title: Genetic interaction of BBS1 mutations with alleles at other BBS loci can result in non-Mendelian Bardet-Biedl syndrome.

PubMed ID: 12677556

DOI: 10.1086/375178

PubMed ID: 12920096

Title: Further support for digenic inheritance in Bardet-Biedl syndrome.

PubMed ID: 12920096

DOI: 10.1136/jmg.40.8.e104

PubMed ID: 15770229

Title: Testing for triallelism: analysis of six BBS genes in a Bardet-Biedl syndrome family cohort.

PubMed ID: 15770229

DOI: 10.1038/sj.ejhg.5201372

PubMed ID: 21052717

Title: Mutation analysis in Bardet-Biedl syndrome by DNA pooling and massively parallel resequencing in 105 individuals.

PubMed ID: 21052717

DOI: 10.1007/s00439-010-0902-8

PubMed ID: 21258341

Title: TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum.

PubMed ID: 21258341

DOI: 10.1038/ng.756

PubMed ID: 21344540

Title: BBS genotype-phenotype assessment of a multiethnic patient cohort calls for a revision of the disease definition.

PubMed ID: 21344540

DOI: 10.1002/humu.21480

Sequence Information:

  • Length: 593
  • Mass: 65083
  • Checksum: 94C0C05667FE582D
  • Sequence:
    • MAAASSSDSD ACGAESNEAN SKWLDAHYDP MANIHTFSAC LALADLHGDG EYKLVVGDLG 
PGGQQPRLKV LKGPLVMTES PLPALPAAAA TFLMEQHEPR TPALALASGP CVYVYKNLRP 
YFKFSLPQLP PNPLEQDLWN QAKEDRIDPL TLKEMLESIR ETAEEPLSIQ SLRFLQLELS 
EMEAFVNQHK SNSIKRQTVI TTMTTLKKNL ADEDAVSCLV LGTENKELLV LDPEAFTILA 
KMSLPSVPVF LEVSGQFDVE FRLAAACRNG NIYILRRDSK HPKYCIELSA QPVGLIRVHK 
VLVVGSTQDS LHGFTHKGKK LWTVQMPAAI LTMNLLEQHS RGLQAVMAGL ANGEVRIYRD 
KALLNVIHTP DAVTSLCFGR YGREDNTLIM TTRGGGLIIK ILKRTAVFVE GGSEVGPPPA 
QAMKLNVPRK TRLYVDQTLR EREAGTAMHR AFQTDLYLLR LRAARAYLQA LESSLSPLST 
TAREPLKLHA VVQGLGPTFK LTLHLQNTST TRPVLGLLVC FLYNEALYSL PRAFFKVPLL 
VPGLNYPLET FVESLSNKGI SDIIKVLVLR EGQSAPLLSA HVNMPGSEGL AAA