BBS5

Bardet-Biedl syndrome 5, the group of BBSome

Basic information

Region (hg38): 2:169479480-169506655

Links

ENSG00000163093 ∙ NCBI:129880 ∙ OMIM:603650 ∙ HGNC:970 ∙ Uniprot:Q8N3I7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bardet-Biedl syndrome 5	AR	Cardiovascular; Endocrine	Individuals 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 beneficial	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	15137946; 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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	78	4	85
missense	2	5	135	4		146
nonsense	12	5	1			18
start loss	3	1				4
frameshift	13	8	2			23
splice donor/acceptor (+/-2bp)	2	16	1			19
Total	32	35	142	82	4

Highest pathogenic variant AF is 0.0000241966

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BBS5	protein_coding	protein_coding	ENST00000295240	12	46745

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000484	0.965	125684	0	64	125748	0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.850	148	180	0.822	0.00000876	2239
Missense in Polyphen		95	110.68	0.85836		1429
Synonymous	1.07	50	60.6	0.825	0.00000300	610
Loss of Function	1.95	12	21.8	0.550	0.00000102	272

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000438	0.000437
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000109	0.000109
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000345	0.000334
Middle Eastern	0.000109	0.000109
South Asian	0.0000657	0.0000653
Other	0.000326	0.000326

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