BBIP1
protein-codingBBSome interacting protein 1, the group of BBSome
Gene summary
This gene encodes one of eight proteins that form the BBSome complex and is essential for its assembly. The BBSome complex is involved in trafficking signal receptors to and from the cilia. Mutations in this gene result in Bardet-Biedl syndrome 18. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]
- NCRNA00081
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~20.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0005308
Submitter: ClinGen
*BBIP1* was first reported in relation to autosomal recessive ciliopathy-*BBIP1* (MONDO:0005308) in 2013 (Scheidecker et al., PMID: 24026985). Individuals with ciliopathy-*BBIP1* presented with Bardet-Biedl syndrome, including retinitis pigmentosa, obesity, kidney failure, intellectual disability, hypogonadotrophic hypogonadism, polydactyly and brachydactyly. At the time of curation, four individuals with ciliopathy-*BBIP1* were described in the literature or in ClinVar. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no differences in molecular mechanism and inheritance pattern and no significant phenotypic variability. *BBIP1* has previously been associated with only one disease entity: autosomal recessive Bardet-Biedl syndrome 18 (MIM #615995). Four variants (3 nonsense and 1 splice-affecting variant, all homozygous) that have been reported in four probands in three publications and one ClinVar entry (PMIDs: 24026985, 32055034, 37239474 and VCV000626905.3) are included in this curation. The mechanism of pathogenicity is reported to be loss of function. This gene-disease relationship is also supported by experimental evidence, showing *BBIP1* expression in the primary cilium, its physical interaction and functional role within the BBsome, a functional role for ciliogenesis and microtubule acetylation and ciliopathy phenotypes in knockdown zebrafish embryos (PMIDs: 19081074, 25964651, 24026985). In summary, there is definitive evidence supporting the relationship between *BBIP1* and autosomal recessive ciliopathy-*BBIP1*. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Kidney Cystic and Ciliopathy Disorders GCEP on the 8th of September 2025 (SOP version 11).
Inheritance Pattern: AR
Disease ID:MONDO:0014446
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0014446
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014446
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0015229
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0014446
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Gastrointestinal; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal
Intervention: Endocrine
Rationale: Medical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficial
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to BBIP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001195305.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 12 | 13 | |||
| missense | 49 | 4 | 53 | |||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 13 | 13 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 1 | 1 | 65 | 16 | 0 | 83 |
Highest pathogenic variant AF is 0.000010418444
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001182234.1 | 3 | MANE Select | |
| Ensembl | ENSP00000436622.2 | 3 | MANE Select | |
| RefSeq | NP_001182233.1 | 4 | Standard | |
| RefSeq | NP_001182235.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| bbip1 | Danio rerio | Structure: Kupffer's vesicle Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- BBSome-mediated cargo-targeting to cilium
- Cargo trafficking to the periciliary membrane
- Cilium Assembly
- Organelle biogenesis and maintenance
Biological Process
- protein transport
- cilium assembly
- receptor localization to non-motile cilium
Molecular Function
- protein binding
Cellular Component
- cytoplasm
- cytosol
- BBSome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000454061
- Coding exons
- 4
- Length
- 20545
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.522 | 35 | 44.8 | 0.781 | 0.00000217 | 642 |
| Missense (PolyPhen) | 2 | 4.2348 | 0.47228 | 43 | ||
| Synonymous | 0.251 | 16 | 17.3 | 0.923 | 9.38e-7 | 195 |
| Loss of Function | 0.623 | 4 | 5.59 | 0.716 | 2.34e-7 | 90 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- 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. Required for primary cilia assembly and BBSome stability. Regulates cytoplasmic microtubule stability and acetylation. {ECO:0000269|Ref.4}.;
- Disease
- DISEASE: Bardet-Biedl syndrome 18 (BBS18) [MIM:615995]: 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. {ECO:0000269|PubMed:24026985}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Low | Medium |