BBS5

Bardet-Biedl syndrome 5, the group of BBSome

Basic information

Region (hg38): 2:169479480-169506655

Links

ENSG00000163093NCBI:129880OMIM:603650HGNC:970Uniprot:Q8N3I7AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • Bardet-Biedl syndrome 5 (Strong), mode of inheritance: AR
  • Bardet-Biedl syndrome (Supportive), mode of inheritance: AR
  • Bardet-Biedl syndrome 5 (Strong), mode of inheritance: AR
  • Bardet-Biedl syndrome 5 (Definitive), mode of inheritance: AR
  • Bardet-Biedl syndrome 5 (Strong), mode of inheritance: AR
  • Bardet-Biedl syndrome 5 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Bardet-Biedl syndrome 5ARCardiovascular; EndocrineIndividuals have been described with congenital heart anomalies, and awareness may enable early diagnosis and management; Medical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficialCardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal15137946; 18203199; 20301537; 22410627; 25982971; 36356613
Variants may modify the severity of BBS and related disorders due to variants in other BBS-associated genes

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BBS5 gene.

  • Bardet-Biedl_syndrome (328 variants)
  • Bardet-Biedl_syndrome_5 (103 variants)
  • BBS5-related_disorder (82 variants)
  • not_provided (32 variants)
  • Inborn_genetic_diseases (29 variants)
  • not_specified (14 variants)
  • Retinal_dystrophy (3 variants)
  • Cone_dystrophy (3 variants)
  • Bardet-Biedl_syndrome_1 (2 variants)
  • Intellectual_disability (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BBS5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000152384.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
3
clinvar
78
clinvar
4
clinvar
85
missense
2
clinvar
5
clinvar
135
clinvar
4
clinvar
146
nonsense
12
clinvar
5
clinvar
1
clinvar
18
start loss
3
1
4
frameshift
13
clinvar
8
clinvar
2
clinvar
23
splice donor/acceptor (+/-2bp)
2
clinvar
16
clinvar
1
clinvar
19
Total 32 35 142 82 4

Highest pathogenic variant AF is 0.0000241966

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
BBS5protein_codingprotein_codingENST00000295240 1246745
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.000004840.9651256840641257480.000255
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.8501481800.8220.000008762239
Missense in Polyphen95110.680.858361429
Synonymous1.075060.60.8250.00000300610
Loss of Function1.951221.80.5500.00000102272

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0004380.000437
Ashkenazi Jewish0.0001990.000198
East Asian0.0001090.000109
Finnish0.0001850.000185
European (Non-Finnish)0.0003450.000334
Middle Eastern0.0001090.000109
South Asian0.00006570.0000653
Other0.0003260.000326

dbNSFP

Source: dbNSFP

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. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for BBSome complex ciliary localization but not for the proper complex assembly. {ECO:0000269|PubMed:17574030, ECO:0000269|PubMed:22072986}.;
Disease
DISEASE: Bardet-Biedl syndrome 5 (BBS5) [MIM:615983]: 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:15137946, ECO:0000269|PubMed:18203199, ECO:0000269|PubMed:21344540}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
BBSome-mediated cargo-targeting to cilium;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

pRec
0.225

Intolerance Scores

loftool
0.595
rvis_EVS
0.04
rvis_percentile_EVS
56.92

Haploinsufficiency Scores

pHI
0.372
hipred
N
hipred_score
0.270
ghis
0.553

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.252

Mouse Genome Informatics

Gene name
Bbs5
Phenotype
cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype; vision/eye phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype;

Zebrafish Information Network

Gene name
bbs5
Affected structure
cloaca
Phenotype tag
abnormal
Phenotype quality
cystic

Gene ontology

Biological process
heart looping;visual perception;protein transport;melanosome transport;motile cilium assembly;intracellular transport;response to stimulus;cilium assembly
Cellular component
cytosol;axoneme;centriolar satellite;BBSome;ciliary basal body;ciliary membrane
Molecular function
RNA polymerase II repressing transcription factor binding;protein binding;phosphatidylinositol-3-phosphate binding