BBS1

Bardet-Biedl syndrome 1, the group of BBSome

Basic information

Region (hg38): 11:66510606-66533613

Links

ENSG00000174483 ∙ NCBI:582 ∙ OMIM:209901 ∙ HGNC:966 ∙ Uniprot:Q8NFJ9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bardet-Biedl syndrome 1 (Definitive), mode of inheritance: AR
• Bardet-Biedl syndrome 1 (Definitive), mode of inheritance: AR
• Bardet-Biedl syndrome 1 (Strong), mode of inheritance: AR
• Bardet-Biedl syndrome 1 (Definitive), mode of inheritance: AR
• Bardet-Biedl syndrome (Supportive), mode of inheritance: AR
• Bardet-Biedl syndrome 1 (Strong), mode of inheritance: AR
• ciliopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bardet-Biedl syndrome 1	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	12118255; 12567324; 12677556; 12837689; 12524598; 15314642; 20120035; 20301537; 22410627; 22773737; 22940089; 23143442; 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 BBS1 gene.

• Bardet-Biedl_syndrome (891 variants)
• Bardet-Biedl_syndrome_1 (401 variants)
• BBS1-related_disorder (207 variants)
• not_provided (89 variants)
• Inborn_genetic_diseases (74 variants)
• Retinal_dystrophy (54 variants)
• not_specified (43 variants)
• Retinitis_pigmentosa (15 variants)
• BBS1-related_ciliopathy (7 variants)
• concomitant_exotropia (1 variants)
• See_cases (1 variants)
• Bardet-Biedl_syndrome_1/7,_digenic (1 variants)
• Severe_early-childhood-onset_retinal_dystrophy (1 variants)
• Usher_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BBS1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024649.5. 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		2	15	273	1	291
missense	3	23	310	10	1	347
nonsense	27	19				46
start loss	4	3				7
frameshift	45	46	3			94
splice donor/acceptor (+/-2bp)	12	47	1			60
Total	91	140	329	283	2

Highest pathogenic variant AF is 0.00267752

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BBS1	protein_coding	protein_coding	ENST00000318312	17	23022

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.41e-12	0.723	125670	0	78	125748	0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.156	335	343	0.976	0.0000223	3790
Missense in Polyphen		87	93.871	0.9268		1060
Synonymous	-0.0290	146	146	1.00	0.00000912	1262
Loss of Function	1.64	23	33.2	0.692	0.00000194	358

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000535	0.000535
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000970	0.000971
European (Non-Finnish)	0.000256	0.000246
Middle Eastern	0.000109	0.000109
South Asian	0.000359	0.000359
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 proper BBSome complex assembly and its ciliary localization (PubMed:17574030, PubMed:22072986). Plays a role in olfactory cilium biogenesis/maintenance and trafficking (By similarity). {ECO:0000250|UniProtKB:Q3V3N7, ECO:0000269|PubMed:17574030, ECO:0000269|PubMed:22072986}.
• Disease: DISEASE: Bardet-Biedl syndrome 1 (BBS1) [MIM:209900]: 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:12118255, ECO:0000269|PubMed:12524598, ECO:0000269|PubMed:12567324, ECO:0000269|PubMed:12677556, ECO:0000269|PubMed:12920096, ECO:0000269|PubMed:15770229, ECO:0000269|PubMed:21052717, 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)

Intolerance Scores

• loftool: 0.166
• rvis_EVS: -0.26
• rvis_percentile_EVS: 34.88

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.132
• ghis: 0.621

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.568

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Low
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Low	Low	Low

Mouse Genome Informatics

• Gene name: Bbs1
• Phenotype: craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; taste/olfaction phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); 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); growth/size/body region phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: bbs1
• Affected structure: pancreatic B cell
• Phenotype tag: abnormal
• Phenotype quality: increased area

Gene ontology

• Biological process: retina homeostasis;visual perception;sensory perception of smell;Golgi to plasma membrane protein transport;photoreceptor cell maintenance;response to stimulus;cilium assembly;protein localization to cilium;non-motile cilium assembly
• Cellular component: centrosome;cytosol;axoneme;BBSome;ciliary basal body;ciliary membrane
• Molecular function: RNA polymerase II repressing transcription factor binding;patched binding;smoothened binding;protein binding