BBS1

Summary

BBS1 (Bardet-Biedl syndrome 1, HGNC:966) is a protein-coding gene on chromosome 11q13.2, encoding BBSome complex member BBS1 (Q8NFJ9). The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.

Mutations in this gene have been observed in patients with the major form (type 1) of Bardet-Biedl syndrome. The encoded protein may play a role in eye, limb, cardiac and reproductive system development.

Source: NCBI Gene 582 — RefSeq curated summary.

At a glance

• Gene–disease (curated): BBS1-related ciliopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 1,148 total — 112 pathogenic, 88 likely-pathogenic
• Phenotypes (HPO): 153
• MANE Select transcript: NM_024649

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:966
Approved symbol	BBS1
Name	Bardet-Biedl syndrome 1
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23590
Ensembl gene	ENSG00000174483
Ensembl biotype	protein_coding
OMIM	209901
Entrez	582

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 25 protein_coding, 9 retained_intron, 7 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000318312, ENST00000393994, ENST00000455748, ENST00000524458, ENST00000524705, ENST00000524884, ENST00000524907, ENST00000525809, ENST00000526035, ENST00000526760, ENST00000526815, ENST00000527251, ENST00000527959, ENST00000528543, ENST00000529766, ENST00000529895, ENST00000529953, ENST00000529955, ENST00000532283, ENST00000532908, ENST00000533430, ENST00000533557, ENST00000533644, ENST00000534730, ENST00000851730, ENST00000851731, ENST00000851732, ENST00000851733, ENST00000851734, ENST00000851735, ENST00000851736, ENST00000851737, ENST00000851738, ENST00000851739, ENST00000851740, ENST00000851741, ENST00000851742, ENST00000851743, ENST00000933609, ENST00000967327, ENST00000967328, ENST00000967329, ENST00000967330

RefSeq mRNA: 1 — MANE Select: NM_024649 NM_024649

CCDS: CCDS8142

Canonical transcript exons

ENST00000318312 — 17 exons

Exon	Start	End
ENSE00002186644	66531951	66533598
ENSE00003462457	66521270	66521376
ENSE00003484056	66519617	66519748
ENSE00003506100	66515861	66515933
ENSE00003508847	66511205	66511239
ENSE00003520005	66511013	66511089
ENSE00003538542	66514406	66514678
ENSE00003565926	66526649	66526807
ENSE00003567775	66523456	66523576
ENSE00003573235	66510635	66510706
ENSE00003581807	66530894	66531028
ENSE00003596535	66523724	66523882
ENSE00003633941	66531656	66531742
ENSE00003644853	66529819	66529952
ENSE00003649871	66526123	66526192
ENSE00003689740	66515693	66515731
ENSE00003786891	66515540	66515586

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 95.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.2617 / max 157.9174, expressed in 1787 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115345	20.2617	1787

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	95.49	gold quality
left ovary	UBERON:0002119	93.29	gold quality
ovary	UBERON:0000992	93.12	gold quality
pituitary gland	UBERON:0000007	93.09	gold quality
right ovary	UBERON:0002118	92.85	gold quality
fallopian tube	UBERON:0003889	92.85	gold quality
right lobe of thyroid gland	UBERON:0001119	92.76	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.72	gold quality
thyroid gland	UBERON:0002046	92.64	gold quality
body of uterus	UBERON:0009853	92.58	gold quality
adenohypophysis	UBERON:0002196	92.56	gold quality
left lobe of thyroid gland	UBERON:0001120	92.52	gold quality
cerebellar hemisphere	UBERON:0002245	92.40	gold quality
cerebellar cortex	UBERON:0002129	92.37	gold quality
cerebellum	UBERON:0002037	92.34	gold quality
right frontal lobe	UBERON:0002810	92.09	gold quality
superior frontal gyrus	UBERON:0002661	91.66	gold quality
endocervix	UBERON:0000458	91.60	gold quality
nucleus accumbens	UBERON:0001882	91.57	gold quality
cortex of kidney	UBERON:0001225	91.55	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.53	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.52	gold quality
metanephros cortex	UBERON:0010533	91.51	gold quality
lower esophagus	UBERON:0013473	91.50	gold quality
primary visual cortex	UBERON:0002436	91.34	gold quality
myometrium	UBERON:0001296	91.30	gold quality
frontal cortex	UBERON:0001870	91.20	gold quality
anterior cingulate cortex	UBERON:0009835	91.13	gold quality
adult mammalian kidney	UBERON:0000082	91.11	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.09	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

83 targeting BBS1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785

Literature-anchored findings (GeneRIF, showing 36)

• This protein has amino acid sequence homolgy with mice. Missense mutation accounts for about 80% of all BBS1 mutations on a similar genetic background across populations. (PMID:12524598)
• Identification of a novel Bardet-Biedl syndrome protein, BBS7, that shares structural features with this protein. (PMID:12567324)
• BBS1 participates in complex inheritance and in different families, mutations in BBS1 can interact genetically with mutations at each of the other known BBS genes, as well as at unknown loci, to cause the phenotype (PMID:12677556)
• The presence of three mutant alleles in the BBS family correlates with a more severe Bardet-Biedl phenotype. (PMID:12837689)
• disease-associated alleles occur at relatively high frequencies in normal haplotypes (PMID:15517396)
• The cardinal feature of retinal degeneration in BBS1 can show a wide spectrum of disease expression. (PMID:17065520)
• A novel BBS1 mutation was identified, most probably a founder mutation, further confirming the Faroe Islands as a genetic isolate. (PMID:18669544)
• Although neither proband fulfilled the typical criteria for BBS, this diagnosis was confirmed on mutation analysis. (PMID:18766993)
• this report describes the identification and characterization of a splice donor site mutation that leads to missplicing of BBS1 transcripts in Bardet-Biedl syndrome. (PMID:21520335)
• Patients with BBS1 mutations had a milder phenotype than did patients with mutations in other BBS genes. (PMID:22410627)
• Our findings confirm the consistent pathogenicity of the BBS1 M390R mutation in Bardet-Biedl syndrome in patients homozygous for the common M390R mutation in the BBS1 gene. (PMID:22940089)
• Variants in BBS1 are significantly associated with nonsyndromic autosomal recessive RP and relatively mild forms of BBS. (PMID:23143442)
• Novel mutations (c.1110G>A and c.39delA (p.G13fs*41)) in BBS1 found in Tunisian families with Bardet-Biedl syndrome. (PMID:23432027)
• Exome sequencing identified a novel homozygous mutation (c.47+1G>T) in BBS1 that inactivates the splice donor site at the end of exon 1. (PMID:23559858)
• novel BBS1 mutations in Bardet-Biedl syndrome patients in Spain (PMID:24611592)
• Bardet-Biedl syndrome patients with missense mutations in BBS1 have lower biochemical cardiovascular disease markers compared with patients with BBS10 and other BBS1 mutations. (PMID:24611735)
• mediates endosomal recycling, sorting and signal transduction of Notch receptors (PMID:24681783)
• loss of BBS1, BBS4, or OFD1 led to decreased NF-kappaB activity and concomitant IkappaBbeta accumulation and that these defects were ameliorated with SFN treatment. (PMID:24691443)
• Results show that BBS1 and BBS3 regulates the ciliary traficking of PC1. (PMID:24939912)
• A homozygous BBS1 p.M390R mutation is associated with Bardet-Biedl syndrome. (PMID:25494902)
• We report a case in which whole-exome sequencing in a patient previously suspected to have Usher syndrome revealed disease-causing mutations in BBS1 and SLC26A4. (PMID:26022370)
• M390R mutation in BBS1 reduces surface expression of insulin receptor in fibroblasts derived from BBS patients. (PMID:26103456)
• BBS1 emerged as a novel predictor of overall survival in MPM. (PMID:26254420)
• Importantly, one Japanese and one Omani families carried compound biallelic mutations in two distinct genes (TMEM67/RPGRIP1L and TMEM138/BBS1, respectively). (PMID:27434533)
• Retrotransposon insertion in exon 13 was identified in a female with Bardet-Biedl syndrome carrying the most common BBS1 mutation (BBS1: Met390Arg). (PMID:30484961)
• Novel biallelic splice-site BBS1 variants in Bardet-Biedle syndrome: a case report of the first Japanese patient. (PMID:31997113)
• The BBSome assembly is spatially controlled by BBS1 and BBS4 in human cells. (PMID:32759308)
• A BBS1 SVA F retrotransposon insertion is a frequent cause of Bardet-Biedl syndrome. (PMID:33169370)
• BBS Proteins Affect Ciliogenesis and Are Essential for Hedgehog Signaling, but Not for Formation of iPSC-Derived RPE-65 Expressing RPE-Like Cells. (PMID:33572860)
• Bardet-Biedl syndrome proteins regulate intracellular signaling and neuronal function in patient-specific iPSC-derived neurons. (PMID:33630762)
• BBS1 branchpoint variant is associated with non-syndromic retinitis pigmentosa. (PMID:33910932)
• The Bardet-Biedl syndrome complex component BBS1 controls T cell polarity during immune synapse assembly. (PMID:34423835)
• Comparative Natural History of Visual Function From Patients With Biallelic Variants in BBS1 and BBS10. (PMID:34940782)
• Lethal neonatal respiratory failure due to biallelic variants in BBS1 and monoallelic variant in TTC21B. (PMID:35695966)
• Recurrence of a BBS1 variant in Bardet-Biedl patients from Prince Edward Island. (PMID:37612261)
• De-Suppression of Mesenchymal Cell Identities and Variable Phenotypic Outcomes Associated with Knockout of Bbs1. (PMID:37998397)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	bbs1	ENSDARG00000075169
mus_musculus	Bbs1	ENSMUSG00000006464
rattus_norvegicus	Bbs1	ENSRNOG00000019832
drosophila_melanogaster	BBS1	FBGN0035741
caenorhabditis_elegans	bbs-1	WBGENE00000241

Protein

Protein identifiers

BBSome complex member BBS1 — Q8NFJ9 (reviewed: Q8NFJ9)

Alternative names: BBS2-like protein 2, Bardet-Biedl syndrome 1 protein

All UniProt accessions (8): Q8NFJ9, E7EQH1, E9PJ28, E9PMB7, E9PPR3, E9PQD9, E9PQK2, E9PR55

UniProt curated annotations — full annotation on UniProt →

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. Plays a role in olfactory cilium biogenesis/maintenance and trafficking.

Subunit / interactions. Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10. Interacts with the C-terminus of RAB3IP. Interacts with CCDC28B and ALDOB. Interacts with PKD1.

Subcellular location. Cell projection. Cilium membrane. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriolar satellite.

Tissue specificity. Highly expressed in the kidney. Also found in fetal tissue, testis, retina, adipose tissue, heart, skeletal muscle and pancreas.

Disease relevance. Ciliary dysfunction leads to a broad spectrum of disorders, collectively termed ciliopathies. Overlapping clinical features include retinal degeneration, renal cystic disease, skeletal abnormalities, fibrosis of various organ, and a complex range of anatomical and functional defects of the central and peripheral nervous system. The ciliopathy range of diseases includes Meckel-Gruber syndrome, Bardet-Biedl syndrome, Joubert syndrome, nephronophtisis, Senior-Loken syndrome, and Jeune asphyxiating thoracic dystrophy among others. Single-locus allelism is insufficient to explain the variable penetrance and expressivity of such disorders, leading to the suggestion that variations across multiple sites of the ciliary proteome, including BBS1, influence the clinical outcome. Bardet-Biedl syndrome 1 (BBS1) [MIM:209900] A syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and intellectual disability. 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. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Based on a readthrough transcript which may produce a DPP3-BBS1 fusion protein.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NFJ9-1	1	yes
Q8NFJ9-2	3, DPP3-BBS1
Q8NFJ9-3	2

RefSeq proteins (1): NP_078925* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011047	Quinoprotein_ADH-like_sf	Homologous_superfamily
IPR028784	BBS1	Family
IPR032728	BBS1_N	Domain
IPR056419	GAE_BBS1	Domain

Pfam: PF14779, PF23304

UniProt features (24 total): sequence variant 18, splice variant 3, initiator methionine 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6XT9	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NFJ9-F1	90.05	0.76

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5620922	BBSome-mediated cargo-targeting to cilium
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-5617833	Cilium Assembly
R-HSA-5620920	Cargo trafficking to the periciliary membrane

MSigDB gene sets: 502 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_BEHAVIOR, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_ADULT_BEHAVIOR, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_VENTRICULAR_SYSTEM_DEVELOPMENT, chr11q13

GO Biological Process (31): microtubule cytoskeleton organization (GO:0000226), neuron migration (GO:0001764), lipid metabolic process (GO:0006629), visual perception (GO:0007601), sensory perception of smell (GO:0007608), photoreceptor cell morphogenesis (GO:0008594), fertilization (GO:0009566), dendrite development (GO:0016358), ventricular system development (GO:0021591), striatum development (GO:0021756), hippocampus development (GO:0021766), cerebral cortex development (GO:0021987), adult behavior (GO:0030534), response to endoplasmic reticulum stress (GO:0034976), olfactory behavior (GO:0042048), hormone metabolic process (GO:0042445), Golgi to plasma membrane protein transport (GO:0043001), fat cell differentiation (GO:0045444), photoreceptor cell maintenance (GO:0045494), brain morphogenesis (GO:0048854), cartilage development (GO:0051216), retina development in camera-type eye (GO:0060041), cilium assembly (GO:0060271), regulation of cilium beat frequency involved in ciliary motility (GO:0060296), neural precursor cell proliferation (GO:0061351), protein localization to cilium (GO:0061512), non-motile cilium assembly (GO:1905515), retina homeostasis (GO:0001895), intracellular protein localization (GO:0008104), protein transport (GO:0015031), cell projection organization (GO:0030030)

GO Molecular Function (6): patched binding (GO:0005113), smoothened binding (GO:0005119), phosphoprotein binding (GO:0051219), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (13): centrosome (GO:0005813), cytosol (GO:0005829), axoneme (GO:0005930), motile cilium (GO:0031514), centriolar satellite (GO:0034451), BBSome (GO:0034464), ciliary membrane (GO:0060170), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cilium (GO:0005929), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cargo trafficking to the periciliary membrane	1
Organelle biogenesis and maintenance	1
Assembly of the 9+0 primary cilium	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
anatomical structure development	4
cilium	3
brain development	2
pallium development	2
protein binding	2
cytoskeleton organization	1
microtubule-based process	1
cell migration	1
generation of neurons	1
primary metabolic process	1
sensory perception of light stimulus	1
sensory perception of chemical stimulus	1
photoreceptor cell development	1
cell morphogenesis involved in neuron differentiation	1
sexual reproduction	1
reproductive process	1
neuron projection development	1
system development	1
subpallium development	1
limbic system development	1
behavior	1
cellular response to stress	1
chemosensory behavior	1
metabolic process	1
regulation of hormone levels	1
Golgi to plasma membrane transport	1
protein transport	1
establishment of protein localization to plasma membrane	1
protein localization to plasma membrane	1
cell differentiation	1
retina homeostasis	1
multicellular organismal process	1
animal organ morphogenesis	1
signaling receptor binding	1
G protein-coupled receptor binding	1
DNA-binding transcription factor binding	1
binding	1
centriole	1
microtubule organizing center	1

Protein interactions and networks

STRING

1903 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BBS1	BBS9	P78514	999
BBS1	BBS2	Q9BXC9	999
BBS1	BBS7	Q8IWZ6	999
BBS1	BBS4	Q96RK4	999
BBS1	BBS5	Q8N3I7	999
BBS1	RAB3IP	Q96QF0	995
BBS1	TTC8	Q8TAM2	994
BBS1	BBS10	Q8TAM1	971
BBS1	RAB8A	P24407	938
BBS1	BBS12	Q6ZW61	921
BBS1	CEP290	O15078	898
BBS1	LEPR	P48357	872
BBS1	MKS1	Q9NXB0	871
BBS1	CCDC28B	Q9BUN5	862
BBS1	SSTR3	P32745	841

IntAct

135 interactions, top by confidence:

A	B	Type	Score
IQCB1	CEP290	psi-mi:“MI:0914”(association)	0.950
BBS1	BBS9	psi-mi:“MI:0915”(physical association)	0.940
BBS9	BBS1	psi-mi:“MI:0915”(physical association)	0.940
BBS1	BBS9	psi-mi:“MI:0914”(association)	0.940
BBS2	BBS9	psi-mi:“MI:0914”(association)	0.920
BBS1	BBS4	psi-mi:“MI:0915”(physical association)	0.920
BBS4	PCM1	psi-mi:“MI:0914”(association)	0.910
BBS7	BBS1	psi-mi:“MI:0914”(association)	0.910
BBS1	BBS7	psi-mi:“MI:0915”(physical association)	0.910
BBS1	BBS5	psi-mi:“MI:0914”(association)	0.900
BBS5	BBS9	psi-mi:“MI:0914”(association)	0.890
BBS2	BBS1	psi-mi:“MI:0915”(physical association)	0.880
BBS9	BBS7	psi-mi:“MI:0914”(association)	0.860
BBS7	BBS9	psi-mi:“MI:0914”(association)	0.860
LZTFL1	BBS9	psi-mi:“MI:0914”(association)	0.850
BBS4	BBIP1	psi-mi:“MI:0914”(association)	0.810
IFT43	TULP3	psi-mi:“MI:0914”(association)	0.790
BBS5	BBS7	psi-mi:“MI:0914”(association)	0.790

BioGRID (151): BBS1 (Affinity Capture-MS), BBS1 (Affinity Capture-MS), BBS1 (Affinity Capture-MS), BBS1 (Affinity Capture-MS), BBS1 (Affinity Capture-MS), BBS9 (Affinity Capture-MS), BBS4 (Affinity Capture-MS), BBS7 (Affinity Capture-MS), TTC8 (Affinity Capture-MS), DPP3 (Affinity Capture-MS), BBS2 (Affinity Capture-MS), BBS1 (Affinity Capture-MS), KIAA1279 (Affinity Capture-MS), BBS1 (Affinity Capture-MS), BBS1 (Affinity Capture-MS)

ESM2 similar proteins: A0A5F8AH41, A0AVI4, A7S641, O75843, P10937, P25235, P40935, P70345, Q06AU9, Q08DJ7, Q08DK0, Q0IJ33, Q14AI0, Q28647, Q28CM7, Q3V3N7, Q4R7D0, Q503C8, Q5FVF4, Q5R5N9, Q5RDY9, Q5XIL6, Q5ZI25, Q68F70, Q6IR55, Q6NWH5, Q6PD82, Q74ZJ1, Q7KNA0, Q7QIL2, Q80YU0, Q8CHY3, Q8CIM8, Q8IV36, Q8K304, Q8MRQ4, Q8NFJ9, Q8R1F6, Q8R307, Q8WW52

Diamond homologs: Q3V3N7, Q8NFJ9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
BBS1	“form complex”	“BBsome complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
BBSome-mediated cargo-targeting to cilium	12	96.1×	8e-20
Cargo trafficking to the periciliary membrane	9	36.0×	2e-10
Cilium Assembly	12	21.1×	4e-11
Organelle biogenesis and maintenance	12	12.8×	8e-09
Anchoring of the basal body to the plasma membrane	7	12.8×	7e-05
Regulation of PLK1 Activity at G2/M Transition	5	10.2×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
melanosome transport	6	56.0×	2e-07
protein localization to cilium	6	29.4×	9e-06
non-motile cilium assembly	8	28.4×	1e-07
cilium assembly	20	17.9×	4e-17
fat cell differentiation	7	15.5×	5e-05
axonogenesis	5	9.8×	8e-03
visual perception	8	7.8×	1e-03
protein transport	9	4.8×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1148 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	112
Likely pathogenic	88
Uncertain significance	358
Likely benign	466
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069654	NM_024649.5(BBS1):c.1025dup (p.Leu343fs)	Pathogenic
1069863	NC_000011.9:g.(?66296758)(66307295_?)del	Pathogenic
1069864	NC_000011.9:g.(?66283154)(66287229_?)del	Pathogenic
1069865	NC_000011.9:g.(?66288721)(66293683_?)del	Pathogenic
1070846	NM_024649.5(BBS1):c.421C>T (p.Gln141Ter)	Pathogenic
1074464	NM_024649.5(BBS1):c.382C>T (p.Gln128Ter)	Pathogenic
1075743	NC_000011.9:g.(?66278111)(66299528_?)del	Pathogenic
1075744	NC_000011.9:g.(?66291682)(66293673_?)del	Pathogenic
12144	NM_024649.5(BBS1):c.1645G>T (p.Glu549Ter)	Pathogenic
12145	NM_024649.5(BBS1):c.432+1G>A	Pathogenic
12146	NM_024649.5(BBS1):c.851del (p.Tyr284fs)	Pathogenic
1284769	NM_024649.5(BBS1):c.589C>T (p.Gln197Ter)	Pathogenic
1299580	NM_024649.5(BBS1):c.48-1G>A	Pathogenic
1426641	NC_000011.9:g.(?66283001)(66287229_?)del	Pathogenic
1448412	NM_024649.5(BBS1):c.1695+1G>A	Pathogenic
1451442	NM_024649.5(BBS1):c.1491del (p.Thr498fs)	Pathogenic
1451651	NM_024649.5(BBS1):c.1516C>T (p.Gln506Ter)	Pathogenic
1458135	NC_000011.9:g.(?66293574)(66299508_?)del	Pathogenic
1458982	NC_000011.9:g.(?66290917)(66291363_?)del	Pathogenic
1459324	NM_024649.5(BBS1):c.607del (p.Thr202_Met203insTer)	Pathogenic
1698560	NC_000011.9:g.(66278711_66281876)_(66291354_66293593)del	Pathogenic
188752	NM_024649.5(BBS1):c.436C>T (p.Arg146Ter)	Pathogenic
193740	NM_024649.5(BBS1):c.887del (p.Ile296fs)	Pathogenic
1943330	NM_024649.5(BBS1):c.145del (p.Asp49fs)	Pathogenic
1998644	NM_024649.5(BBS1):c.1035_1038del (p.Val346fs)	Pathogenic
2022007	NM_024649.5(BBS1):c.339del (p.Val112_Tyr113insTer)	Pathogenic
2033506	NM_024649.5(BBS1):c.690dup (p.Leu231fs)	Pathogenic
2045817	NM_024649.5(BBS1):c.951+2T>A	Pathogenic
2057607	NM_024649.5(BBS1):c.3G>A (p.Met1Ile)	Pathogenic
2064753	NM_024649.5(BBS1):c.1119dup (p.Thr374fs)	Pathogenic

SpliceAI

3139 predictions. Top by Δscore:

Variant	Effect	Δscore
11:66511005:A:AG	acceptor_gain	1.0000
11:66511011:A:AG	acceptor_gain	1.0000
11:66511012:G:GA	acceptor_gain	1.0000
11:66511012:GCA:G	acceptor_gain	1.0000
11:66511012:GCAAT:G	acceptor_gain	1.0000
11:66511086:CTAGG:C	donor_loss	1.0000
11:66511087:TAGG:T	donor_loss	1.0000
11:66511088:AGG:A	donor_loss	1.0000
11:66511088:AGGTG:A	donor_loss	1.0000
11:66511090:G:GG	donor_gain	1.0000
11:66511090:GTGA:G	donor_loss	1.0000
11:66511091:T:A	donor_loss	1.0000
11:66515530:A:AG	acceptor_gain	1.0000
11:66515530:ATT:A	acceptor_gain	1.0000
11:66515532:T:TA	acceptor_gain	1.0000
11:66515538:A:AG	acceptor_gain	1.0000
11:66515539:G:GG	acceptor_gain	1.0000
11:66519615:A:AG	acceptor_gain	1.0000
11:66519616:G:GG	acceptor_gain	1.0000
11:66519616:GACA:G	acceptor_gain	1.0000
11:66523882:GGTGA:G	donor_loss	1.0000
11:66523883:G:GA	donor_loss	1.0000
11:66523883:G:GG	donor_gain	1.0000
11:66523883:GTGAG:G	donor_loss	1.0000
11:66523884:T:G	donor_loss	1.0000
11:66526119:ATAG:A	acceptor_gain	1.0000
11:66526120:TA:T	acceptor_loss	1.0000
11:66526121:A:AG	acceptor_gain	1.0000
11:66526121:A:AT	acceptor_loss	1.0000
11:66526121:AG:A	acceptor_gain	1.0000

AlphaMissense

3812 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:66511032:T:A	W23R	0.996
11:66511032:T:C	W23R	0.996
11:66514581:T:A	V112D	0.991
11:66514661:T:A	W139R	0.991
11:66514661:T:C	W139R	0.991
11:66526678:C:A	R404S	0.990
11:66526175:T:C	L388P	0.989
11:66511034:G:C	W23C	0.988
11:66511034:G:T	W23C	0.988
11:66530922:T:C	L501P	0.987
11:66526135:A:C	S375R	0.985
11:66526137:C:A	S375R	0.985
11:66526137:C:G	S375R	0.985
11:66514663:G:C	W139C	0.984
11:66514663:G:T	W139C	0.984
11:66523557:T:C	L311P	0.981
11:66526758:G:C	K430N	0.981
11:66526758:G:T	K430N	0.981
11:66526793:G:C	R442P	0.981
11:66531738:T:A	I564N	0.981
11:66514560:C:A	A105E	0.979
11:66526679:G:C	R404P	0.978
11:66514566:C:A	A107D	0.977
11:66514662:G:C	W139S	0.977
11:66526677:G:C	K403N	0.977
11:66526677:G:T	K403N	0.977
11:66519689:G:C	G222R	0.976
11:66523836:T:A	V355D	0.976
11:66530895:T:A	V492D	0.976
11:66530941:C:A	N507K	0.974

dbSNP variants (sampled 300 via entrez): RS1000167429 (11:66510536 G>A,C), RS1000386143 (11:66523900 C>T), RS1000438556 (11:66523656 C>T), RS1000884600 (11:66529646 G>A), RS1001335171 (11:66529236 G>A), RS1001613808 (11:66524676 C>T), RS1001675588 (11:66518326 C>T), RS1001678181 (11:66510762 G>A), RS1001727865 (11:66517926 C>A), RS1001981077 (11:66524820 A>C,G), RS1002186647 (11:66518114 C>T), RS1002469650 (11:66517942 G>A,T), RS1002627096 (11:66512750 G>C), RS1002700933 (11:66526349 G>A), RS1002879367 (11:66526001 G>A)

Disease associations

OMIM: gene MIM:209901 | disease phenotypes: MIM:209900, MIM:248200, MIM:268000, MIM:276900

GenCC curated gene-disease

Disease	Classification	Inheritance
Bardet-Biedl syndrome 1	Definitive	Autosomal recessive
Bardet-Biedl syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
BBS1-related ciliopathy	Definitive	AR

Mondo (8): Bardet-Biedl syndrome 1 (MONDO:0008854), Bardet-Biedl syndrome (MONDO:0015229), BBS1-related ciliopathy (MONDO:1040043), inherited retinal dystrophy (MONDO:0019118), retinal disorder (MONDO:0005283), severe early-childhood-onset retinal dystrophy (MONDO:0009549), retinitis pigmentosa (MONDO:0019200), Usher syndrome (MONDO:0019501)

Orphanet (6): Bardet-Biedl syndrome (Orphanet:110), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Severe early-childhood-onset retinal dystrophy (Orphanet:364055), Retinitis pigmentosa (Orphanet:791), Stargardt disease (Orphanet:827), Usher syndrome (Orphanet:886)

HPO phenotypes

153 total (30 of 153 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000011	Neurogenic bladder
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000076	Vesicoureteral reflux
HP:0000077	Abnormality of the kidney
HP:0000085	Horseshoe kidney
HP:0000100	Nephrotic syndrome
HP:0000119	Abnormality of the genitourinary system
HP:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000137	Abnormality of the ovary
HP:0000147	Polycystic ovaries
HP:0000148	Vaginal atresia
HP:0000163	Abnormal oral cavity morphology
HP:0000218	High palate
HP:0000256	Macrocephaly
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000388	Otitis media
HP:0000400	Macrotia
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000470	Short neck
HP:0000483	Astigmatism
HP:0000486	Strabismus

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001241_12	Bipolar disorder	2.000000e-07
GCST008163_145	Height	8.000000e-06

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D020788	Bardet-Biedl Syndrome	C10.228.140.617.200; C11.270.684.624; C16.131.077.245.125; C16.320.184.125
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
D052245	Usher Syndromes	C09.218.458.341.186.500.500; C09.218.458.341.887.886; C10.597.751.418.341.186.500.500; C10.597.751.418.341.887.886; C10.597.751.941.162.625.500; C11.768.585.658.500.813; C11.966.075.375.500; C16.131.077.299.500; C16.320.290.684.500; C23.888.592.763.393.341.887.886
C537909	Bardet-Biedl syndrome 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression	3
bisphenol F	increases expression, affects cotreatment	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	increases expression, affects cotreatment	1
Coumestrol	decreases expression, affects cotreatment	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Phthalic Acids	decreases methylation	1
Smoke	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_VP78	KCi001-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

287 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT03746522	PHASE3	COMPLETED	Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Participants With Moderate to Severe Obesity
NCT04966741	PHASE3	COMPLETED	Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity
NCT05194124	PHASE3	COMPLETED	Phase 3 Crossover Trial of Two Formulations of Setmelanotide in Participants With Specific Gene Defects in the MC4R Pathway
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT05244304	PHASE3	COMPLETED	Phase 3, Randomized, Placebo-Controlled Study of Tinlarebant to Explore Safety and Efficacy in Adolescent Stargardt Disease
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT03490019	PHASE2	WITHDRAWN	Treatment of Bardet-Biedl-Syndrome With Metformin for Evaluation of a Possible Visual Improvement
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT01373476	PHASE2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	PHASE2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
NCT04489511	PHASE2	COMPLETED	Study of STG-001 in Subjects With Stargardt Disease
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)