TTC8

This gene encodes a protein that has been directly linked to Bardet-Biedl syndrome. The primary features of this syndrome include retinal dystrophy, obesity, polydactyly, renal abnormalities and learning disabilities. Experimentation in non-human eukaryotes suggests that this gene is expressed in ciliated cells and that it is involved in the formation of cilia. Alternate transcriptional splice variants have been characterized. [provided by RefSeq]

Full Name

tetratricopeptide repeat domain 8

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

Biological Process axon guidance Source:Ensembl
Biological Process camera-type eye photoreceptor cell differentiation Source:Ensembl
Biological Process cilium assembly Source:BHF-UCL1 Publication
Biological Process establishment of anatomical structure orientation Source:BHF-UCL1 Publication
Biological Process establishment of epithelial cell apical/basal polarity Source:Ensembl
Biological Process establishment of planar polarity Source:Ensembl
Biological Process fat cell differentiation Source:Ensembl
Biological Process inner ear receptor cell stereocilium organization Source:Ensembl
Biological Process multi-ciliated epithelial cell differentiation Source:Ensembl
Biological Process multicellular organism growth Source:Ensembl
Biological Process negative regulation of GTPase activity Source:Ensembl
Biological Process non-motile cilium assembly Source:GO_Central1 Publication
Biological Process olfactory bulb development Source:Ensembl
Biological Process protein localization to plasma membrane Source:Ensembl
Biological Process protein transport Source:UniProtKB-KW
Biological Process regulation of protein localization Source:Ensembl
Biological Process regulation of stress fiber assembly Source:Ensembl
Biological Process renal tubule development Source:Ensembl
Biological Process sensory perception of smell Source:Ensembl
Biological Process sensory processing Source:BHF-UCL1 Publication

Cellular Location

Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
Cell projection, cilium membrane
Cytoplasm
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriolar satellite
Cell projection, cilium

Involvement in disease

Retinitis pigmentosa 51 (RP51):
A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
Bardet-Biedl syndrome 8 (BBS8):
A syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and intellectual disability. 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.