BBS9

Bardet-Biedl syndrome 9, the group of BBSome

Basic information

Region (hg38): 7:33109556-33877180

Links

ENSG00000122507 ∙ NCBI:27241 ∙ OMIM:607968 ∙ HGNC:30000 ∙ Uniprot:Q3SYG4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bardet-Biedl syndrome 9 (Definitive), mode of inheritance: AR
• Bardet-Biedl syndrome 9 (Strong), mode of inheritance: AR
• Bardet-Biedl syndrome (Supportive), mode of inheritance: AR
• Bardet-Biedl syndrome 9 (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 9	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	16380913; 20301537; 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 BBS9 gene.

• Bardet-Biedl syndrome (658 variants)
• Bardet-Biedl syndrome 9 (234 variants)
• not provided (92 variants)
• Inborn genetic diseases (48 variants)
• BBS9-related condition (46 variants)
• not specified (45 variants)
• Bardet-Biedl syndrome 1 (10 variants)
• Retinal dystrophy (3 variants)
• Abnormality of the eye (2 variants)
• Intellectual disability (1 variants)
• Retinal vascular dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BBS9 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	150		156
missense			274	10	4	288
nonsense	18	16				34
start loss			1			1
frameshift	13	13	1			27
inframe indel			8			8
splice donor/acceptor (+/-2bp)	9	13	1			23
splice region			22	30	5	57
non coding		1	26	108	48	183
Total	40	43	317	268	52

Highest pathogenic variant AF is 0.0000591

Variants in BBS9

This is a list of pathogenic ClinVar variants found in the BBS9 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-33129597-G-A		Bardet-Biedl syndrome 9	Uncertain significance (Jan 12, 2018)
7-33129606-A-C		Bardet-Biedl syndrome 9	Uncertain significance (Jan 13, 2018)
7-33129624-G-C		Bardet-Biedl syndrome 9	Benign (Jan 12, 2018)
7-33129645-T-G		Bardet-Biedl syndrome 9	Uncertain significance (Jan 13, 2018)
7-33129646-C-G		Bardet-Biedl syndrome 9	Benign (Jan 13, 2018)
7-33129656-G-A		Bardet-Biedl syndrome 9	Uncertain significance (Jan 13, 2018)
7-33129748-T-G		Bardet-Biedl syndrome 9	Likely benign (Jan 12, 2018)
7-33129782-G-A		Bardet-Biedl syndrome 9	Uncertain significance (Jan 13, 2018)
7-33129794-G-A		Bardet-Biedl syndrome 9	Benign (Jan 12, 2018)
7-33129825-T-G		Bardet-Biedl syndrome 9	Uncertain significance (Jan 13, 2018)
7-33129847-T-G		Bardet-Biedl syndrome 9	Uncertain significance (Jan 13, 2018)
7-33129890-G-C		Bardet-Biedl syndrome 9	Uncertain significance (Jan 12, 2018)
7-33130012-T-TG		Bardet-Biedl syndrome	Uncertain significance (Jun 14, 2016)
7-33130048-T-C		Bardet-Biedl syndrome 9	Benign (Jan 13, 2018)
7-33145997-T-C			Benign (Nov 10, 2018)
7-33146261-A-G		Bardet-Biedl syndrome	Likely benign (Sep 09, 2023)
7-33146263-T-A		Bardet-Biedl syndrome	Uncertain significance (Jul 27, 2022)
7-33146263-T-G		Bardet-Biedl syndrome	Uncertain significance (Jul 06, 2022)
7-33146270-C-T		Bardet-Biedl syndrome	Likely benign (May 29, 2022)
7-33146271-C-A		Bardet-Biedl syndrome • BBS9-related disorder	Uncertain significance (Nov 10, 2023)
7-33146271-C-T		Bardet-Biedl syndrome • Bardet-Biedl syndrome 9 • BBS9-related disorder	Uncertain significance (Dec 24, 2023)
7-33146272-G-A		Bardet-Biedl syndrome • Bardet-Biedl syndrome 9 • BBS9-related disorder	Uncertain significance (Oct 05, 2022)
7-33146272-G-C		Bardet-Biedl syndrome	Uncertain significance (Oct 13, 2022)
7-33146272-G-T		Bardet-Biedl syndrome • Bardet-Biedl syndrome 9 • Inborn genetic diseases • BBS9-related disorder	Uncertain significance (Jan 05, 2024)
7-33146279-G-A		Bardet-Biedl syndrome	Pathogenic (Sep 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BBS9	protein_coding	protein_coding	ENST00000242067	22	476825

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.21e-17	0.970	125631	0	117	125748	0.000465

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.404	432	456	0.947	0.0000236	5777
Missense in Polyphen		128	149.38	0.85685		1892
Synonymous	-0.473	175	167	1.05	0.00000909	1699
Loss of Function	2.51	35	55.1	0.635	0.00000326	599

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00128	0.00127
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.000218	0.000217
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000541	0.000536
Middle Eastern	0.000218	0.000217
South Asian	0.000338	0.000327
Other	0.000327	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. Required for proper BBSome complex assembly and its ciliary localization. {ECO:0000269|PubMed:17574030, ECO:0000269|PubMed:22072986}.
• Disease: DISEASE: Note=A chromosomal aberration involving PTHB1 has been found in Wilms tumor. Translocation t(1;7)(q42;p15) with OBSCN. {ECO:0000269|PubMed:12618763}.; DISEASE: Bardet-Biedl syndrome 9 (BBS9) [MIM:615986]: 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:16380913, ECO:0000269|PubMed:26085087}. 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: 0.201

Intolerance Scores

• loftool: 0.157
• rvis_EVS: 1.05
• rvis_percentile_EVS: 91.37

Haploinsufficiency Scores

• pHI: 0.412
• hipred: Y
• hipred_score: 0.744
• ghis: 0.466

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.204

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Bbs9
• Phenotype: limbs/digits/tail phenotype; skeleton phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: bbs9
• Affected structure: pronephric proximal convoluted tubule
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: visual perception;protein transport;fat cell differentiation;response to stimulus;cilium assembly;protein localization to cilium
• Cellular component: pericentriolar material;cytosol;cilium;membrane;centriolar satellite;BBSome;ciliary transition zone;ciliary membrane
• Molecular function: molecular_function;protein binding