Alternative titles; symbols
HGNC Approved Gene Symbol: BBIP1
Cytogenetic location: 10q25.2 Genomic coordinates (GRCh38): 10:110,898,730-110,919,366 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 10q25.2 | Bardet-Biedl syndrome 18 | 615995 | Autosomal recessive | 3 |
BBIP10 functions in ciliogenesis and stabilization of cytoplasmic microtubules (Loktev et al., 2008).
Using tandem affinity purification to identify proteins that interacted with BBS4 (600374) in a human retinal pigment epithelium (RPE) cell line, followed by database analysis and cDNA amplification, Loktev et al. (2008) obtained a full-length cDNA encoding a protein that they called 'BBSome-interacting protein of 10 kD,' or BBIP10. The deduced protein contains 92 amino acids. Orthologs of BBIP10 were present in many ciliated organisms, but not in plants, amoeba, or fungi. Immunofluorescence microscopy showed that BBIP10 colocalized precisely with BBS4 in primary cilium of RPE cells. SDS-PAGE detected BBIP10 at an apparent molecular mass of 10 kD.
Loktev et al. (2008) found that BBIP10 cosedimented with an approximately 440-kD ciliary protein complex consisting of 7 BBS proteins (e.g., BBS1; 209901). BBIP10 also eluted in much lower molecular mass fractions with other protein partners. Knockdown of BBIP10 in RPE cells via small interfering RNA compromised assembly of the ciliary protein complex and caused failure of ciliogenesis. Knockdown of the complex components BBS1 or BBS5 (603650) or of the complex-interacting protein PCM1 (600299) resulted in a similar failure of ciliogenesis in RPE cells. Depletion of BBIP10 or BBS8 (TTC8; 608132) increased the frequency of centrosome splitting in interphase cells. Depletion of BBIP10 alone also diminished the density of cytoplasmic microtubules, increased the amount of unpolymerized alpha-tubulin (see 602529), and reduced tubulin acetylation. The role of BBIP10 in cytoplasmic microtubule stabilization and acetylation appeared to be independent of its role in assembly of the ciliary protein complex.
Hartz (2010) mapped the BBIP1 gene to chromosome 10q25.2 based on an alignment of the BBIP1 sequence (GenBank AK021501) with the genomic sequence (GRCh37).
In a 49-year-old Italian man, born of consanguineous parents, with Bardet-Biedl syndrome (BBS18; 615995), Scheidecker et al. (2014) identified a homozygous truncating mutation in the BBIP1 gene (L58X; 613605.0001). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. No BBIP1 protein could be detected in patient fibroblasts, consistent with a loss of function. The patient had retinitis pigmentosa, obesity, kidney failure, cognitive disability, and brachydactyly. In vitro functional expression studies in HEK cells showed that the mutant L58X protein was not incorporated into the BBSome, and morpholino knockout of the Bbip1 ortholog in zebrafish embryos recapitulated the ciliopathy phenotype.
From a cohort of 125 families with ciliopathies, Shamseldin et al. (2020) identified 1 patient with BBS who was homozygous for a splice site mutation in the BBIP1 gene (613605.0002).
From a cohort of 10 Pakistani families with BBS, Nawaz et al. (2023) identified a 14-year-old girl (family B) who was homozygous for a c.160A-T transversion in the BBIP1 gene, resulting in a lys54-to-ter (K54X) substitution. Her unaffected parents were heterozygous for the mutation, which was not found in her unaffected brother. The mutation was predicted to result in a truncated protein of only 53 amino acids, which would activate nonsense-mediated decay machinery causing degradation of the mutant mRNA, with no functional protein being produced. The mutation was deemed a 'variant of unknown significance' by ACMG criteria.
Loktev et al. (2008) found that knockdown of Bbip10 in zebrafish embryos caused abnormalities in the Kupffer vesicle, a ciliated structure involved in left-right patterning. Bbip10-depleted embryos also showed reduced retrograde transport of melanosomes, which was rescued by human BBIP10 mRNA.
Scheidecker et al. (2014) found that morpholino knockdown of the Bbip1 ortholog in zebrafish embryos resulted in cystic dilations of the pronephros. Pronephric cilia of morphants failed to maintain a parallel orientation to the anteroposterior axis of the duct and were shorter than in controls. These findings suggested that the cysts developed as a consequence of impaired pronephric flow. Other features in morphants included increased frequency of situs inversus compared to wildtype and abnormal and disorganized retinal development.
In a 49-year-old Italian man, born of consanguineous parents, with Bardet-Biedl syndrome (BBS18; 615995), Scheidecker et al. (2014) identified a homozygous c.173T-G transversion in exon 3 of the BBIP1 gene, resulting in a leu58-to-ter (L58X) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the Exome Variant Server database or in 160 control exomes. No BBIP1 protein could be detected in patient fibroblasts, consistent with a loss of function. The patient had retinitis pigmentosa, obesity, kidney failure, cognitive disability, and brachydactyly. In vitro functional expression studies in HEK cells showed that the mutant L58X protein was not incorporated into the BBSome.
In a patient with Bardet-Biedl syndrome (BBS18; 615995), Shamseldin et al. (2020) identified homozygosity for a splice site mutation (c.38-6T-C, NM_001195305.1) in the BBIP1 gene. Aberrant splicing was confirmed by RT-PCR, with 86% nonsense-mediated decay.
Hartz, P. A. Personal Communication. Baltimore, Md. 10/12/2010.
Loktev, A. V., Zhang, Q., Beck, J. S., Searby, C. C., Scheetz, T. E., Bazan, J. F., Slusarski, D. C., Sheffield, V. C., Jackson, P. K., Nachury, M. V. A BBSome subunit links ciliogenesis, microtubule stability, and acetylation. Dev. Cell 15: 854-865, 2008. [PubMed: 19081074] [Full Text: https://doi.org/10.1016/j.devcel.2008.11.001]
Nawaz, H., Mujahid, Khan, S. A., Bibi, F., Waqas, A., Bari, A., Fardous, Khan, N., Muhammad, N., Khan, A., Paracha, S. A., Alam, Q., Kamal, M. A., Rafeeq, M. M., Muhammad, N., Haq, F. U., Khan, S., Mahmood, A., Khan, S., Umair, M. Biallelic variants in seven different genes associated with clinically suspected Bardet-Biedl syndrome. Genes 14: 1113, 2023. [PubMed: 37239474] [Full Text: https://doi.org/10.3390/genes14051113]
Scheidecker, S., Etard, C., Pierce, N. W., Geoffroy, V., Schaefer, E., Muller, J., Chennen, K., Flori, E., Pelletier, V., Poch, O., Marion, V., Stoetzel, C., Strahle, U., Nachury, M. V., Dollfus, H. Exome sequencing of Bardet-Biedl syndrome patient identifies a null mutation in the BBSome subunit BBIP1 (BBS18). J. Med. Genet. 51: 132-136, 2014. [PubMed: 24026985] [Full Text: https://doi.org/10.1136/jmedgenet-2013-101785]
Shamseldin, H. E., Shaheen, R., Ewida, N., Bubshait, D. K., Alkuraya, H., Almardawi, E., Howaidi, A., Sabr, Y., Abdalla, E. M., Alfaifi, A. Y., Alghamdi, J. M., Alsagheir, A., and 29 others. The morbid genome of ciliopathies: an update. Genet. Med. 22: 1051-1060, 2020. Note: Erratum: Genet. Med. 24: 966, 2022. [PubMed: 32055034] [Full Text: https://doi.org/10.1038/s41436-020-0761-1]