Details for: BBS2

Gene ID: 583

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: BBS2

Ensembl ID: ENSG00000125124

Description: Bardet-Biedl syndrome 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • stromal cell CL0000499
    CSI 12.85
    rCSI 36.15%
    PRS 69.28
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 5.61
    rCSI 14.5%
    PRS 68.85
  • astrocyte of the cerebral cortex CL0002605
    CSI 4.45
    rCSI 9.98%
    PRS 55.79
  • retinal ganglion cell CL0000740
    CSI 4.27
    rCSI 9.44%
    PRS 59.5
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 4.06
    rCSI 12.7%
    PRS 59.45
  • melanocyte CL0000148
    CSI 3.99
    rCSI 2.96%
    PRS 66.83
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 3.94
    rCSI 6.62%
    PRS 55.18
  • interneuron CL0000099
    CSI 3.84
    rCSI 7.7%
    PRS 63.32
  • Mueller cell CL0000636
    CSI 3.62
    rCSI 8.27%
    PRS 65.03
  • Kupffer cell CL0000091
    CSI 3.48
    rCSI 7.95%
    PRS 74.5
  • chondrocyte CL0000138
    CSI 3.47
    rCSI 5.52%
    PRS 66.44
  • kidney connecting tubule epithelial cell CL1000768
    CSI 3.36
    rCSI 8.52%
    PRS 63.75
  • Bergmann glial cell CL0000644
    CSI 3.27
    rCSI 4.47%
    PRS 65.78
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 3.24
    rCSI 2.33%
    PRS 86.98
  • multi-ciliated epithelial cell CL0005012
    CSI 3.17
    rCSI 3.17%
    PRS 67.45
  • cerebellar granule cell CL0001031
    CSI 3.01
    rCSI 4.42%
    PRS 66.57
  • ciliated cell CL0000064
    CSI 2.94
    rCSI 4.76%
    PRS 69.37
  • glioblast CL0000030
    CSI 2.91
    rCSI 4.64%
    PRS 65.4
  • mature astrocyte CL0002627
    CSI 2.68
    rCSI 11.39%
    PRS 65.81
  • lung neuroendocrine cell CL1000223
    CSI 2.66
    rCSI 3.94%
    PRS 78.48
  • hepatic stellate cell CL0000632
    CSI 2.65
    rCSI 9.92%
    PRS 65.88
  • neural crest cell CL0011012
    CSI 2.63
    rCSI 2.08%
    PRS 61.45
  • blood vessel smooth muscle cell CL0019018
    CSI 2.58
    rCSI 20.98%
    PRS 67.53
  • luminal epithelial cell of mammary gland CL0002326
    CSI 2.55
    rCSI 4.63%
    PRS 85.81
  • pancreatic A cell CL0000171
    CSI 2.45
    rCSI 2.57%
    PRS 77.14
  • sncg GABAergic cortical interneuron CL4023015
    CSI 2.34
    rCSI 3.76%
    PRS 56.9
  • cerebral cortex endothelial cell CL1001602
    CSI 2.33
    rCSI 4.03%
    PRS 64.59
  • renal alpha-intercalated cell CL0005011
    CSI 2.31
    rCSI 3.09%
    PRS 81.35
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.27
    rCSI 2.83%
    PRS 53.19
  • mesodermal cell CL0000222
    CSI 2.25
    rCSI 2.7%
    PRS 71.92
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 2.23
    rCSI 5.8%
    PRS 74.18
  • GABAergic neuron CL0000617
    CSI 2.22
    rCSI 7.45%
    PRS 57.95
  • direct pathway medium spiny neuron CL4023026
    CSI 2.2
    rCSI 52.67%
    PRS 53.88
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.18
    rCSI 52.49%
    PRS 54.49
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 2.11
    rCSI 3.83%
    PRS 64.76
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.06
    rCSI 2.92%
    PRS 70.13
  • ionocyte CL0005006
    CSI 2.03
    rCSI 2.18%
    PRS 74.41
  • amacrine cell CL0000561
    CSI 2
    rCSI 5.8%
    PRS 62.92
  • peripheral nervous system neuron CL2000032
    CSI 1.93
    rCSI 2.63%
    PRS 65.16
  • ciliated epithelial cell CL0000067
    CSI 1.88
    rCSI 1.65%
    PRS 62.23
  • choroid plexus epithelial cell CL0000706
    CSI 1.85
    rCSI 3.04%
    PRS 63.02
  • keratinocyte CL0000312
    CSI 1.74
    rCSI 1.46%
    PRS 76.93
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.72
    rCSI 2.05%
    PRS 55.1
  • rod bipolar cell CL0000751
    CSI 1.7
    rCSI 3.05%
    PRS 66.87
  • inhibitory interneuron CL0000498
    CSI 1.68
    rCSI 3.89%
    PRS 61.74
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.64
    rCSI 5.14%
    PRS 56.97
  • Schwann cell CL0002573
    CSI 1.63
    rCSI 4.63%
    PRS 70.31
  • mesenchymal stem cell CL0000134
    CSI 1.56
    rCSI 17.08%
    PRS 81.74
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.56
    rCSI 2.01%
    PRS 56.51
  • type B pancreatic cell CL0000169
    CSI 1.55
    rCSI 3.44%
    PRS 72.7
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.43
    rCSI 2.53%
    PRS 54.31
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.42
    rCSI 5.1%
    PRS 53.31
  • cardiac muscle cell CL0000746
    CSI 1.41
    rCSI 2.03%
    PRS 63.3
  • retinal cone cell CL0000573
    CSI 1.39
    rCSI 2.24%
    PRS 63.38
  • retinal rod cell CL0000604
    CSI 1.27
    rCSI 2.24%
    PRS 69.92
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.27
    rCSI 3.08%
    PRS 53.4
  • retinal bipolar neuron CL0000748
    CSI 1.26
    rCSI 2.36%
    PRS 61.7
  • cardiac neuron CL0010022
    CSI 1.25
    rCSI 4%
    PRS 70.88
  • retina horizontal cell CL0000745
    CSI 1.16
    rCSI 1.76%
    PRS 70.46
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 1.14
    rCSI 2.72%
    PRS 60.38
  • parietal epithelial cell CL1000452
    CSI 1.13
    rCSI 3.02%
    PRS 64.91
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.11
    rCSI 4.18%
    PRS 55.68
  • lung ciliated cell CL1000271
    CSI 1.06
    rCSI 1.22%
    PRS 65.29
  • neural progenitor cell CL0011020
    CSI 0.98
    rCSI 4.32%
    PRS 62.46
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 0.93
    rCSI 2.12%
    PRS 68.42
  • forebrain radial glial cell CL0013000
    CSI 0.84
    rCSI 2.7%
    PRS 76.99
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.55
    rCSI 3.26%
    PRS 56.14

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.

Comma-separated if multiple.
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 [BBS2](/details-gene/583) (Bardet-Biedl syndrome 2) is a protein-coding gene located on chromosome 16q13. It is a critical component of the BBSome, a stable protein complex essential for the assembly and function of primary cilia. The BBSome mediates protein trafficking to the ciliary membrane, a process fundamental to a wide range of signaling pathways. Consequently, mutations in [BBS2](/details-gene/583) lead to Bardet-Biedl syndrome, a pleiotropic autosomal recessive disorder characterized by retinal degeneration, obesity, renal abnormalities, and polydactyly [Link](https://doi.org/10.1093/hmg/10.8.865). The gene's expression profile reflects its systemic importance, with significant expression observed in diverse cell types including [stromal cell](/details-cell/CL0000499), various epithelial cells of the kidney, and multiple neuronal and glial cell populations within the central nervous system and retina. ## Cellular Roles and Expression Landscape The expression pattern of [BBS2](/details-gene/583) underscores its fundamental role in ciliated cells across multiple tissues. **Overall**, the gene shows its highest significance in [stromal cell](/details-cell/CL0000499) (CSI: 12.85), suggesting a broad role in connective tissue development and maintenance. Its function in ciliogenesis is highlighted by its importance in cell types known to rely on ciliary function for their specialized roles. * **Renal System:** High significance in [kidney loop of Henle thin ascending limb epithelial cell](/details-cell/CL1001107) and [kidney connecting tubule epithelial cell](/details-cell/CL1000768) is consistent with the primary cilia's role in sensing fluid flow and regulating ion transport in the nephron. Dysfunction in these cells likely contributes to the renal cysts and abnormalities characteristic of Bardet-Biedl syndrome. * **Nervous System and Retina:** [BBS2](/details-gene/583) is prominently expressed in a wide array of neural cells, including [astrocyte of the cerebral cortex](/details-cell/CL0002605), [chandelier pvalb GABAergic cortical interneuron](/details-cell/CL4023036), and [interneuron](/details-cell/CL0000099). Within the retina, its significance in [retinal ganglion cell](/details-cell/CL0000740) and [Mueller cell](/details-cell/CL0000636) aligns with its critical function in `photoreceptor cell maintenance` ([GO:0045494](https://www.ebi.ac.uk/QuickGO/term/GO:0045494)), and defects here are the primary cause of the progressive vision loss (retinitis pigmentosa) seen in patients. * **Other Specialized Ciliated Cells:** The gene's relevance is also noted in [multi-ciliated epithelial cell](/details-cell/CL0005012), [melanocyte](/details-cell/CL0000148) (implicated in `melanosome transport`, [GO:0032402](https://www.ebi.ac.uk/QuickGO/term/GO:0032402)), and [chondrocyte](/details-cell/CL0000138), consistent with its role in skeletal development (`cartilage development`, [GO:0051216](https://www.ebi.ac.uk/QuickGO/term/GO:0051216))). ## Pathways and Molecular Function [BBS2](/details-gene/583) functions as a core subunit of the BBSome complex ([GO:0034464](https://www.ebi.ac.uk/QuickGO/term/GO:0034464)). This complex acts as a coat for transport vesicles, recognizing cargo destined for the primary cilium and facilitating its movement. According to Reactome, this process involves `BBSome-mediated cargo-targeting to cilium` ([R-HSA-5620922](https://reactome.org/content/detail/R-HSA-5620922)) and `cargo trafficking to the periciliary membrane` ([R-HSA-5620920](https://reactome.org/content/detail/R-HSA-5620920)), which are essential steps in the overall `cilium assembly` pathway ([R-HSA-5617833](https://reactome.org/content/detail/R-HSA-5617833)). Research has shown that the BBSome cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis [Link](https://doi.org/10.1016/j.cell.2007.03.053). The gene's involvement in these fundamental trafficking processes explains its pleiotropic effects. Its role in the `negative regulation of appetite by leptin-mediated signaling pathway` ([GO:0038108](https://www.ebi.ac.uk/QuickGO/term/GO:0038108)) is linked to the trafficking of receptors in hypothalamic neurons, providing a molecular basis for the hyperphagia and obesity seen in BBS. Similarly, its function in `sperm axoneme assembly` ([GO:0007288](https://www.ebi.ac.uk/QuickGO/term/GO:0007288)) is crucial for male fertility, and its involvement in `visual perception` ([GO:0007601](https://www.ebi.ac.uk/QuickGO/term/GO:0007601)) is tied to the maintenance of the photoreceptor outer segment, a highly modified primary cilium. ## Research Directions The widespread yet specific expression of [BBS2](/details-gene/583) provides a basis for investigating cell-type-specific contributions to the pathology of Bardet-Biedl syndrome. 1. **Hypothesis 1:** The high significance of [BBS2](/details-gene/583) in specific cortical interneurons, such as the [chandelier pvalb GABAergic cortical interneuron](/details-cell/CL4023036), suggests that it mediates the ciliary trafficking of specific ion channels or receptors essential for their inhibitory function. Disruption of [BBS2](/details-gene/583) could lead to an excitatory/inhibitory imbalance in cortical circuits, contributing to the cognitive and behavioral phenotypes observed in some individuals with BBS. 2. **Hypothesis 2:** The top-ranking significance of [BBS2](/details-gene/583) in [stromal cell](/details-cell/CL0000499), combined with its annotated role in `fat cell differentiation` ([GO:0045444](https://www.ebi.ac.uk/QuickGO/term/GO:0045444)), suggests that defective ciliary signaling in adipose-derived stromal cells impairs their ability to properly differentiate into mature adipocytes or sense systemic metabolic cues. This intrinsic defect in adipose tissue development and function may be a primary driver of the severe obesity phenotype in BBS, independent of hypothalamic dysregulation. **Experimental Approach for Hypothesis 2:** To test the role of [BBS2](/details-gene/583) in adipose stromal cell function, one could utilize a conditional knockout mouse model to specifically delete *Bbs2* in adipose stromal cell populations. Adipose-derived stromal cells (ASCs) would be isolated from these mice and controls, followed by *in vitro* induction of adipogenic differentiation. The efficiency of differentiation would be quantified by Oil Red O staining and qPCR for adipocyte marker genes (e.g., *Pparg*, *Adipoq*). Furthermore, the response of the resulting adipocytes to insulin and leptin could be measured via western blotting for key signaling intermediates (e.g., p-AKT) to determine if [BBS2](/details-gene/583) is required for metabolic sensing in this cell lineage. **Therapeutic Potential:** As Bardet-Biedl syndrome is a loss-of-function disorder, therapeutic strategies should focus on gene replacement or functional restoration rather than inhibition. Given the gene's widespread expression, systemic gene therapy presents significant challenges. However, for localized pathologies like retinitis pigmentosa, AAV-mediated delivery of a functional [BBS2](/details-gene/583) copy via intraocular injection represents a promising therapeutic avenue, a strategy that has shown success for other genetic retinal diseases. Modulating downstream pathways affected by ciliary dysfunction, while more complex, could also offer therapeutic benefits for systemic symptoms like obesity and renal disease.

Genular Protein ID: 3992601214

Symbol: BBS2_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q9BXC9 Q96CM0 Q96SN9

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 3 Ensembl 5 ExpressionAtlas 1 GO 35 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 5 MalaCards 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PIRSF 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 2 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: 11285252

Title: Positional cloning of a novel gene on chromosome 16q causing Bardet-Biedl syndrome (BBS2).

PubMed ID: 11285252

DOI: 10.1093/hmg/10.8.865

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 16823392

Title: Pitfalls of homozygosity mapping: an extended consanguineous Bardet-Biedl syndrome family with two mutant genes (BBS2, BBS10), three mutations, but no triallelism.

PubMed ID: 16823392

DOI: 10.1038/sj.ejhg.5201688

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: 20080638

Title: BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly.

PubMed ID: 20080638

DOI: 10.1073/pnas.0910268107

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: 33144677

Title: Dlec1 is required for spermatogenesis and male fertility in mice.

PubMed ID: 33144677

DOI: 10.1038/s41598-020-75957-y

PubMed ID: 25541840

Title: Association between missense mutations in the BBS2 gene and nonsyndromic retinitis pigmentosa.

PubMed ID: 25541840

DOI: 10.1001/jamaophthalmol.2014.5251

PubMed ID: 11567139

Title: Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive disorder.

PubMed ID: 11567139

DOI: 10.1126/science.1063525

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: 12872256

Title: Evaluation of multiplex capillary heteroduplex analysis: a rapid and sensitive mutation screening technique.

PubMed ID: 12872256

DOI: 10.1002/humu.10241

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: 15666242

Title: Antenatal presentation of Bardet-Biedl syndrome may mimic Meckel syndrome.

PubMed ID: 15666242

DOI: 10.1086/428679

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: 20120035

Title: Bardet-Biedl syndrome in Denmark -- report of 13 novel sequence variations in six genes.

PubMed ID: 20120035

DOI: 10.1002/humu.21204

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: 721
  • Mass: 79844
  • Checksum: EF97CAA28709A089
  • Sequence:
    • MLLPVFTLKL RHKISPRMVA IGRYDGTHPC LAAATQTGKV FIHNPHTRNQ HVSASRVFQS 
PLESDVSLLS INQAVSCLTA GVLNPELGYD ALLVGTQTNL LAYDVYNNSD LFYREVADGA 
NAIVLGTLGD ISSPLAIIGG NCALQGFNHE GSDLFWTVTG DNVNSLALCD FDGDGKKELL 
VGSEDFDIRV FKEDEIVAEM TETEIVTSLC PMYGSRFGYA LSNGTVGVYD KTSRYWRIKS 
KNHAMSIHAF DLNSDGVNEL ITGWSNGKVD ARSDRTGEVI FKDNFSSAIA GVVEGDYRMD 
GHIQLICCSV DGEIRGYLPG TAEMRGNLMD TSAEQDLIRE LSQKKQNLLL ELRNYEENAK 
AELASPLNEA DGHRGIIPAN TRLHTTLSVS LGNETQTAHT ELRISTSNDT IIRAVLIFAE 
GIFTGESHVV HPSIHNLSSS ICIPIVPPKD VPVDLHLKAF VGYRSSTQFH VFESTRQLPR 
FSMYALTSLD PASEPISYVN FTIAERAQRV VVWLGQNFLL PEDTHIQNAP FQVCFTSLRN 
GGHLHIKIKL SGEITINTDD IDLAGDIIQS MASFFAIEDL QVEADFPVYF EELRKVLVKV 
DEYHSVHQKL SADMADHSNL IRSLLVGAED ARLMRDMKTM KSRYMELYDL NRDLLNGYKI 
RCNNHTELLG NLKAVNQAIQ RAGRLRVGKP KNQVITACRD AIRSNNINTL FKIMRVGTAS 
S