BBS7

Mutations in this gene have been observed in patients with Bardet-Biedl syndrome type 7. The encoded protein may play a role in eye, limb, cardiac and reproductive system development. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq]

Full Name

Bardet-Biedl syndrome 7

Function

The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for proper BBSome complex assembly and its ciliary localization.

Biological Process

Brain development Source: Ensembl
Cilium assembly Source: BHF-UCL
Determination of left/right symmetry Source: BHF-UCL
Digestive tract morphogenesis Source: BHF-UCL
Eye development Source: Ensembl
Fat cell differentiation Source: BHF-UCL
Heart looping Source: BHF-UCL
Intracellular transport Source: GO_Central
Limb development Source: Ensembl
Melanosome transport Source: BHF-UCL
Non-motile cilium assembly Source: InterPro
Pigment granule aggregation in cell center Source: BHF-UCL
Positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: MGI
Primary palate development Source: Ensembl
Protein localization Source: GO_Central
Protein transport Source: UniProtKB-KW
Regulation of transcription by RNA polymerase II Source: MGI
Smoothened signaling pathway Source: Ensembl
Visual perception Source: UniProtKB-KW

Cellular Location

Cytoplasm; Cilium membrane; Centriolar satellite; Cilium basal body

Involvement in disease

Ciliary dysfunction leads to a broad spectrum of disorders, collectively termed ciliopathies. Overlapping clinical features include retinal degeneration, renal cystic disease, skeletal abnormalities, fibrosis of various organ, and a complex range of anatomical and functional defects of the central and peripheral nervous system. The ciliopathy range of diseases includes Meckel-Gruber syndrome, Bardet-Biedl syndrome, Joubert syndrome, nephronophtisis, Senior-Loken syndrome, and Jeune asphyxiating thoracic dystrophy among others. Single-locus allelism is insufficient to explain the variable penetrance and expressivity of such disorders, leading to the suggestion that variations across multiple sites of the ciliary proteome, including BBS7, influence the clinical outcome.
Bardet-Biedl syndrome 7 (BBS7): A syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease.