BBS12

Bardet-Biedl syndrome 12, the group of Chaperonins

Basic information

Region (hg38): 4:122732701-122744942

Previous symbols: [ "C4orf24" ]

Links

ENSG00000181004 ∙ NCBI:166379 ∙ OMIM:610683 ∙ HGNC:26648 ∙ Uniprot:Q6ZW61 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bardet-Biedl syndrome 12 (Definitive), mode of inheritance: AR
• Bardet-Biedl syndrome 12 (Definitive), mode of inheritance: AR
• Bardet-Biedl syndrome 12 (Strong), mode of inheritance: AR
• Bardet-Biedl syndrome 12 (Definitive), mode of inheritance: AR
• Bardet-Biedl syndrome (Supportive), mode of inheritance: AR
• Bardet-Biedl syndrome 12 (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 12	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	17160889; 20827784; 20120035; 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 BBS12 gene.

• Bardet-Biedl syndrome (567 variants)
• Bardet-Biedl syndrome 12 (233 variants)
• not provided (52 variants)
• not specified (33 variants)
• BBS12-related condition (30 variants)
• Inborn genetic diseases (22 variants)
• Bardet-Biedl syndrome 1 (16 variants)
• Retinal dystrophy (14 variants)
• Retinitis pigmentosa (2 variants)
• Abnormality of the nervous system (1 variants)
• Visual impairment;Inability to walk;Abnormal cardiovascular system morphology;Polydactyly, postaxial, type A1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BBS12 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			3	215	9	227
missense	3	4	213	7	4	231
nonsense	11	20	2			33
start loss			1			1
frameshift	48	36	1			85
inframe indel		1	14			15
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			15	3	6	24
Total	62	61	249	225	19

Highest pathogenic variant AF is 0.0000131

Variants in BBS12

This is a list of pathogenic ClinVar variants found in the BBS12 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-122732738-C-T		Bardet-Biedl syndrome 12	Uncertain significance (Jan 12, 2018)
4-122732743-C-G		Bardet-Biedl syndrome 12	Uncertain significance (Jan 13, 2018)
4-122732771-G-A		Bardet-Biedl syndrome 12	Benign (Jan 13, 2018)
4-122732786-G-T		Bardet-Biedl syndrome 12	Uncertain significance (Jan 13, 2018)
4-122732793-C-T		Bardet-Biedl syndrome 12	Uncertain significance (Jan 13, 2018)
4-122732834-G-C		Bardet-Biedl syndrome 12	Likely benign (Jan 13, 2018)
4-122741685-T-A			Benign (May 11, 2021)
4-122741842-A-T		Bardet-Biedl syndrome 12	Benign (Jun 15, 2021)
4-122741893-A-C		Bardet-Biedl syndrome 12 • Bardet-Biedl syndrome • Inborn genetic diseases • BBS12-related disorder	Conflicting classifications of pathogenicity (May 09, 2023)
4-122741893-A-AT		Bardet-Biedl syndrome 12	Uncertain significance (Oct 12, 2018)
4-122741894-T-C		Bardet-Biedl syndrome 12 • Bardet-Biedl syndrome	Conflicting classifications of pathogenicity (May 01, 2022)
4-122741897-T-C		Inborn genetic diseases	Uncertain significance (Jun 10, 2022)
4-122741902-G-T		Bardet-Biedl syndrome	Uncertain significance (Apr 11, 2022)
4-122741904-T-C		Bardet-Biedl syndrome	Likely benign (Dec 18, 2018)
4-122741908-A-C		Bardet-Biedl syndrome	Likely benign (Jun 28, 2023)
4-122741910-A-G		Bardet-Biedl syndrome	Likely benign (Aug 30, 2023)
4-122741911-G-A		Bardet-Biedl syndrome • Bardet-Biedl syndrome 12	Uncertain significance (Mar 29, 2022)
4-122741913-C-A		Bardet-Biedl syndrome	Likely benign (Nov 18, 2020)
4-122741913-C-T		Bardet-Biedl syndrome 12 • Bardet-Biedl syndrome • BBS12-related disorder	Likely benign (Jan 27, 2024)
4-122741914-G-A		Bardet-Biedl syndrome	Uncertain significance (Nov 01, 2022)
4-122741915-TAAAC-T		Bardet-Biedl syndrome	Pathogenic (Mar 10, 2021)
4-122741919-CAAA-C		Bardet-Biedl syndrome 12	Uncertain significance (Oct 27, 2017)
4-122741921-A-G		Bardet-Biedl syndrome	Uncertain significance (Mar 24, 2022)
4-122741921-AAAG-A		Bardet-Biedl syndrome 12 • Bardet-Biedl syndrome • BBS12-related disorder	Uncertain significance (Jul 20, 2023)
4-122741926-A-C		Bardet-Biedl syndrome	Likely benign (Apr 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BBS12	protein_coding	protein_coding	ENST00000542236	1	12242

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.34e-7	0.904	125655	0	93	125748	0.000370

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.336	348	366	0.951	0.0000183	4633
Missense in Polyphen		97	109.01	0.88987		1431
Synonymous	1.13	124	141	0.879	0.00000732	1411
Loss of Function	1.70	14	22.7	0.616	0.00000123	300

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000322	0.000322
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000625	0.000624
Middle Eastern	0.0000544	0.0000544
South Asian	0.000229	0.000229
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis. As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). Involved in adipogenic differentiation (PubMed:19190184). {ECO:0000269|PubMed:19190184, ECO:0000269|PubMed:20080638}.
• Disease: DISEASE: Bardet-Biedl syndrome 12 (BBS12) [MIM:615989]: 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:17160889, ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:20120035, 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: 0.173

Intolerance Scores

• loftool: 0.876
• rvis_EVS: 1.38
• rvis_percentile_EVS: 94.6

Haploinsufficiency Scores

• pHI: 0.0549
• hipred: N
• hipred_score: 0.398
• ghis: 0.409

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.146

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Bbs12
• Phenotype: homeostasis/metabolism 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; vision/eye 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); skeleton phenotype; immune 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: bbs12
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: intraciliary transport;eating behavior;photoreceptor cell maintenance;negative regulation of fat cell differentiation;chaperone-mediated protein complex assembly
• Cellular component: cilium
• Molecular function: protein binding;ATP binding