BBS2

Summary

BBS2 (Bardet-Biedl syndrome 2, HGNC:967) is a protein-coding gene on chromosome 16q13, encoding BBSome complex member BBS2 (Q9BXC9). The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.

This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation and cognitive disability. The proteins encoded by BBS gene family members are structurally diverse and the similar phenotypes exhibited by mutations in BBS gene family members is likely due to their shared roles in cilia formation and function. Many BBS proteins localize to the basal bodies, ciliary axonemes, and pericentriolar regions of cells. BBS proteins may also be involved in intracellular trafficking via microtubule-related transport. The protein encoded by this gene forms a multiprotein BBSome complex with seven other BBS proteins.

Source: NCBI Gene 583 — RefSeq curated summary.

At a glance

• Gene–disease (curated): BBS2-related ciliopathy (Definitive, ClinGen) — +4 more curated relationships
• Clinical variants (ClinVar): 1,365 total — 91 pathogenic, 130 likely-pathogenic
• Phenotypes (HPO): 157
• MANE Select transcript: NM_031885

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:967
Approved symbol	BBS2
Name	Bardet-Biedl syndrome 2
Location	16q13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000125124
Ensembl biotype	protein_coding
OMIM	606151
Entrez	583

Gene structure

Transcript identifiers

Ensembl transcripts: 116 — 58 retained_intron, 27 nonsense_mediated_decay, 22 protein_coding, 9 protein_coding_CDS_not_defined

ENST00000245157, ENST00000561853, ENST00000561877, ENST00000561951, ENST00000562012, ENST00000562059, ENST00000562813, ENST00000564123, ENST00000564459, ENST00000565378, ENST00000565781, ENST00000565859, ENST00000566210, ENST00000566410, ENST00000566452, ENST00000566495, ENST00000566689, ENST00000568104, ENST00000569192, ENST00000569342, ENST00000569941, ENST00000618027, ENST00000682000, ENST00000682001, ENST00000682005, ENST00000682021, ENST00000682038, ENST00000682047, ENST00000682088, ENST00000682096, ENST00000682113, ENST00000682146, ENST00000682187, ENST00000682188, ENST00000682201, ENST00000682205, ENST00000682348, ENST00000682360, ENST00000682370, ENST00000682420, ENST00000682429, ENST00000682449, ENST00000682470, ENST00000682473, ENST00000682482, ENST00000682492, ENST00000682493, ENST00000682543, ENST00000682561, ENST00000682597, ENST00000682623, ENST00000682658, ENST00000682705, ENST00000682723, ENST00000682735, ENST00000682737, ENST00000682757, ENST00000682855, ENST00000682857, ENST00000682875, ENST00000682919, ENST00000682930, ENST00000682948, ENST00000682960, ENST00000683008, ENST00000683020, ENST00000683099, ENST00000683170, ENST00000683212, ENST00000683248, ENST00000683343, ENST00000683347, ENST00000683384, ENST00000683396, ENST00000683410, ENST00000683443, ENST00000683485, ENST00000683504, ENST00000683533, ENST00000683609, ENST00000683644, ENST00000683660, ENST00000683669, ENST00000683690, ENST00000683719, ENST00000683757, ENST00000683858, ENST00000683875, ENST00000683904, ENST00000683910, ENST00000683959, ENST00000683976, ENST00000683978, ENST00000683992, ENST00000684020, ENST00000684044, ENST00000684057, ENST00000684076, ENST00000684128, ENST00000684194, ENST00000684205, ENST00000684246, ENST00000684402, ENST00000684446, ENST00000684531, ENST00000684635, ENST00000684640, ENST00000684673, ENST00000684684, ENST00000854960, ENST00000854961, ENST00000854962, ENST00000923962, ENST00000923963, ENST00000966324, ENST00000966325

RefSeq mRNA: 2 — MANE Select: NM_031885 NM_001377456, NM_031885

CCDS: CCDS32451

Canonical transcript exons

ENST00000245157 — 17 exons

Exon	Start	End
ENSE00002600848	56519746	56520024
ENSE00003522179	56509957	56510034
ENSE00003522669	56506120	56506224
ENSE00003529736	56505950	56506036
ENSE00003579061	56514453	56514680
ENSE00003646139	56510859	56510921
ENSE00003666720	56511159	56511284
ENSE00003676017	56502673	56502808
ENSE00003676244	56502317	56502456
ENSE00003900211	56484385	56484867
ENSE00004473830	56496967	56497079
ENSE00004473958	56497743	56497880
ENSE00004473997	56498437	56498568
ENSE00004474011	56501353	56501497
ENSE00004474090	56499778	56499907
ENSE00004474157	56485590	56485738
ENSE00004474164	56500854	56501025

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 98.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.7266 / max 506.2651, expressed in 1812 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157483	25.8169	1812
157484	0.6777	223
157482	0.2321	104

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	98.83	gold quality
right adrenal gland cortex	UBERON:0035827	98.06	gold quality
peripheral nervous system	UBERON:0000010	97.95	gold quality
nerve	UBERON:0001021	97.95	gold quality
tibial nerve	UBERON:0001323	97.95	gold quality
right adrenal gland	UBERON:0001233	97.83	gold quality
ventricular zone	UBERON:0003053	97.66	gold quality
left adrenal gland	UBERON:0001234	97.50	gold quality
caudate nucleus	UBERON:0001873	97.48	gold quality
left adrenal gland cortex	UBERON:0035825	97.44	gold quality
adrenal gland	UBERON:0002369	97.32	gold quality
calcaneal tendon	UBERON:0003701	97.27	gold quality
putamen	UBERON:0001874	97.22	gold quality
adrenal cortex	UBERON:0001235	97.14	gold quality
nucleus accumbens	UBERON:0001882	96.96	gold quality
right frontal lobe	UBERON:0002810	96.82	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.72	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.68	gold quality
sural nerve	UBERON:0015488	96.58	gold quality
amygdala	UBERON:0001876	96.35	gold quality
adenohypophysis	UBERON:0002196	96.18	gold quality
anterior cingulate cortex	UBERON:0009835	96.12	gold quality
spinal cord	UBERON:0002240	96.01	gold quality
endocervix	UBERON:0000458	95.98	gold quality
left ovary	UBERON:0002119	95.96	gold quality
embryo	UBERON:0000922	95.93	gold quality
ganglionic eminence	UBERON:0004023	95.93	gold quality
corpus callosum	UBERON:0002336	95.69	gold quality
hypothalamus	UBERON:0001898	95.67	gold quality
pituitary gland	UBERON:0000007	95.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting BBS2, 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-4455	100.00	65.48	1587
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-634	97.74	67.11	818
HSA-MIR-3935	96.33	66.79	797

Literature-anchored findings (GeneRIF, showing 17)

• Unaffected individuals in 2 pedigrees had 2 but not all 3 mutations that affecteds had which suggests that Bardet-Biedle syndrome might not be a single-gene recessive disease but a complex trait requiring three mutant alleles to manifest the phenotype. (PMID:11567139)
• Identification of a novel Bardet-Biedl syndrome protein, BBS7, that shares structural features with this protein. (PMID:12567324)
• The presence of three mutant alleles in the BBS family correlates with a more severe Bardet-Biedl phenotype. (PMID:12837689)
• A novel missense mutation found in BBS2 exon 4 and a novel intronic point mutation found in Bardet-Biedl syndrome patients. (PMID:12872256)
• BBS2 and BBS4 localized to cellular structures associated with motile cilia. (PMID:18299575)
• RET and BBS mutations modulate enteric innervation and cause syndromic Hirschsprung disease (PMID:19666486)
• Sequence analysis and subsequent RNA studies identified and confirmed a novel splice site mutation, c.472-2A>G, in BBS2. This mutation was also found in homozygous form in three subsequently studied Hutterite BBS patients from two different leuts. (PMID:20618352)
• Novel mutation (c.115+5G>A) in BBS2 found in Tunisian families with Bardet-Biedl syndrome. (PMID:23432027)
• Carrier frequency has been determined for two BBS2 mutations present in the Ashkenazi Jewish population. (PMID:23829372)
• we report here, for the first time, in Indian population, a novel, different profile of mutations in BBS genes (BBS3, BBS9, BBS10 and BBS2) compared to worldwide (BBS1 and 10) reports. (PMID:24400638)
• Our study shows that BBS2 mutations can cause nonsyndromic retinitis pigmentosa and highlights yet another candidate for this genetically heterogeneous condition. (PMID:25541840)
• A pair of heterozygous nonsense mutations in BBS2 gene was identified in the proband, one being novel and the other recurrent. The novel mutation, p.Y644X, resides in exon 16 and was also found in the heterozygous state in the mother (PMID:26078953)
• Authors found that within this structure, BBS2 and BBS7 form a tight dimer through a coiled-coil interaction and that BBS9 associates with the dimer via an interaction with the alpha-helical domain of BBS2. Interestingly, a BBS-associated mutation of BBS2 is located in its alpha-helical domain at the interface between BBS2 and BBS9, and binding experiments indicated that this mutation disrupts the BBS2-BBS9 interaction. (PMID:31530639)
• Correction of cilia structure and function alleviates multi-organ pathology in Bardet-Biedl syndrome mice. (PMID:32620959)
• Identification of a Novel Homozygous Missense (c.443A>T:p.N148I) Mutation in BBS2 in a Kashmiri Family with Bardet-Biedl Syndrome. (PMID:33688495)
• Dental Anomalies in Ciliopathies: Lessons from Patients with BBS2, BBS7, and EVC2 Mutations. (PMID:36672825)
• Clinical features of a novel compound heterozygous genotype of the BBS2 gene: a case report. (PMID:39175229)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bbs2	ENSDARG00000041621
mus_musculus	Bbs2	ENSMUSG00000031755
rattus_norvegicus	Bbs2	ENSRNOG00000019020
caenorhabditis_elegans		WBGENE00000242

Protein

Protein identifiers

BBSome complex member BBS2 — Q9BXC9 (reviewed: Q9BXC9)

Alternative names: Bardet-Biedl syndrome 2 protein

All UniProt accessions (28): Q9BXC9, A0A804F8L3, A0A804HHV5, A0A804HI33, A0A804HIE0, A0A804HIE1, A0A804HIK5, A0A804HIQ9, A0A804HIZ8, A0A804HJ30, A0A804HJQ5, A0A804HJV0, A0A804HJV2, A0A804HK25, A0A804HK50, A0A804HK51, A0A804HK97, A0A804HKF2, A0A804HKG1, A0A804HKI7, A0A804HKL9, A0A804HLC6, A0A804HLD7, A0A804HLF5, A0A804HLL2, H3BNS7, H3BQ79, H3BRL0

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.

Subunit / interactions. Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10. Interacts (via C-terminus) with BBS7. Interacts (via coiled coil domain) with MKKS. Interacts with CCDC28B and ALDOB. Interacts with DLEC1.

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

Tissue specificity. Widely expressed.

Disease relevance. Bardet-Biedl syndrome 2 (BBS2) [MIM:615981] 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. Retinitis pigmentosa 74 (RP74) [MIM:616562] A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (2): NP_001364385, NP_114091* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016616	Bardet-Biedl_syndrome_2_prot	Family
IPR029333	BBS2_GAE_dom	Domain
IPR029429	BBS2_Mid	Domain
IPR029430	BBS2_N	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR055379	BBS2_pf_dom	Domain
IPR055380	BBS2_hp_dom	Domain
IPR055381	BBS2_CtH_dom	Domain

Pfam: PF14781, PF14782, PF14783, PF23350, PF23351, PF23353

UniProt features (29 total): sequence variant 23, sequence conflict 4, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXC9-F1	89.49	0.68

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: 550 (showing top): GCM_MAP4K4, GOBP_PIGMENT_GRANULE_LOCALIZATION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_CARTILAGE_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_VESICLE_LOCALIZATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_ADULT_BEHAVIOR, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH, MODULE_128, GOBP_CELLULAR_PIGMENTATION

GO Biological Process (27): sperm axoneme assembly (GO:0007288), visual perception (GO:0007601), intracellular protein localization (GO:0008104), gene expression (GO:0010467), negative regulation of gene expression (GO:0010629), artery smooth muscle contraction (GO:0014824), striatum development (GO:0021756), hippocampus development (GO:0021766), cerebral cortex development (GO:0021987), adult behavior (GO:0030534), melanosome transport (GO:0032402), negative regulation of appetite by leptin-mediated signaling pathway (GO:0038108), negative regulation of multicellular organism growth (GO:0040015), positive regulation of multicellular organism growth (GO:0040018), vasodilation (GO:0042311), 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), cilium assembly (GO:0060271), regulation of cilium beat frequency involved in ciliary motility (GO:0060296), non-motile cilium assembly (GO:1905515), protein transport (GO:0015031), cell projection organization (GO:0030030), leptin-mediated signaling pathway (GO:0033210), response to leptin (GO:0044321)

GO Molecular Function (2): RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), protein binding (GO:0005515)

GO Cellular Component (15): cytosol (GO:0005829), microvillus (GO:0005902), membrane (GO:0016020), motile cilium (GO:0031514), stereocilium (GO:0032420), centriolar satellite (GO:0034451), BBSome (GO:0034464), ciliary basal body (GO:0036064), neuron projection (GO:0043005), ciliary membrane (GO:0060170), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cilium (GO:0005929), 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	5
cilium	4
anatomical structure development	3
pallium development	2
multicellular organism growth	2
regulation of multicellular organism growth	2
actin-based cell projection	2
plasma membrane bounded cell projection	2
developmental process involved in reproduction	1
axoneme assembly	1
sperm flagellum assembly	1
sensory perception of light stimulus	1
macromolecule localization	1
macromolecule biosynthetic process	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
tonic smooth muscle contraction	1
vascular associated smooth muscle contraction	1
subpallium development	1
limbic system development	1
behavior	1
melanosome localization	1
establishment of melanosome localization	1
pigment granule transport	1
negative regulation of appetite	1
leptin-mediated signaling pathway	1
negative regulation of developmental growth	1
negative regulation of multicellular organismal process	1
positive regulation of developmental growth	1
positive regulation of multicellular organismal process	1
blood vessel diameter maintenance	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
brain development	1

Protein interactions and networks

STRING

1570 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BBS2	BBS9	P78514	999
BBS2	BBS7	Q8IWZ6	999
BBS2	BBS5	Q8N3I7	999
BBS2	BBS1	Q8NFJ9	999
BBS2	BBS4	Q96RK4	999
BBS2	TTC8	Q8TAM2	996
BBS2	BBS10	Q8TAM1	980
BBS2	BBS12	Q6ZW61	924
BBS2	RAB3IP	Q96QF0	870
BBS2	MKS1	Q9NXB0	865
BBS2	CEP290	O15078	826
BBS2	RAB8A	P24407	812
BBS2	LZTFL1	Q9NQ48	798
BBS2	WDPCP	O95876	797
BBS2	MCHR1	Q99705	792

IntAct

170 interactions, top by confidence:

A	B	Type	Score
IQCB1	CEP290	psi-mi:“MI:0914”(association)	0.950
BBS1	BBS9	psi-mi:“MI:0914”(association)	0.940
BBS2	BBS7	psi-mi:“MI:0915”(physical association)	0.930
BBS7	BBS2	psi-mi:“MI:0915”(physical association)	0.930
BBS9	BBS2	psi-mi:“MI:0915”(physical association)	0.920
BBS2	BBS9	psi-mi:“MI:0915”(physical association)	0.920
BBS2	BBS9	psi-mi:“MI:0914”(association)	0.920
BBS2	BBS9	psi-mi:“MI:0403”(colocalization)	0.920
BBS4	PCM1	psi-mi:“MI:0914”(association)	0.910
BBS7	BBS1	psi-mi:“MI:0914”(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

BioGRID (84): MDFI (Two-hybrid), PSME3 (Two-hybrid), RBPMS (Two-hybrid), BBS2 (Affinity Capture-MS), BBS2 (Affinity Capture-MS), BBS2 (Affinity Capture-MS), BBS2 (Affinity Capture-MS), PSME3 (Two-hybrid), BBS2 (Affinity Capture-MS), BBS2 (Affinity Capture-MS), BBS2 (Affinity Capture-MS), BBS2 (Affinity Capture-MS), BBS2 (Affinity Capture-MS), BBS2 (Affinity Capture-MS), BBS2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IC37, A0JN52, A1A4K3, E9PY46, O49552, P0CR22, P0CR23, P0DKL4, P0DKL6, P33194, P59015, Q15269, Q15393, Q16531, Q1LVE8, Q21554, Q3U1J4, Q3V3N7, Q4PGM6, Q4WLI5, Q52E49, Q5B1X8, Q5R649, Q5RBI5, Q5RFQ3, Q6AX60, Q6E7D1, Q6L4S0, Q6P6Z0, Q6QNU4, Q7RYR4, Q805F9, Q811G0, Q8BU03, Q8NFJ9, Q8R2N2, Q921M3, Q93VQ0, Q969X6, Q96RY7

Diamond homologs: Q19640, Q98SP7, Q99MH9, Q9BXC9, Q9CWF6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
BBS2	“form complex”	“BBsome complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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	14	115.9×	6e-25
Cargo trafficking to the periciliary membrane	12	49.6×	5e-16
Cilium Assembly	15	27.2×	5e-16
Organelle biogenesis and maintenance	15	16.5×	7e-13

GO biological processes:

GO term	Partners	Fold	FDR
melanosome transport	5	48.5×	6e-06
non-motile cilium assembly	11	40.5×	7e-13
protein localization to cilium	7	35.5×	2e-07
photoreceptor cell maintenance	6	27.2×	7e-06
fat cell differentiation	8	18.4×	2e-06
heart looping	5	16.9×	5e-04
cilium assembly	18	16.8×	1e-14
axonogenesis	5	10.2×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1365 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	91
Likely pathogenic	130
Uncertain significance	461
Likely benign	502
Benign	37

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069250	NM_031885.5(BBS2):c.892del (p.Arg298fs)	Pathogenic
1072026	NM_031885.5(BBS2):c.175del (p.Gln59fs)	Pathogenic
1073279	NM_031885.5(BBS2):c.110del (p.Thr37fs)	Pathogenic
1073654	NM_031885.5(BBS2):c.2059+1G>T	Pathogenic
1075893	NM_031885.5(BBS2):c.1218_1219insGTAATGG (p.Ser407fs)	Pathogenic
1367251	NM_031885.5(BBS2):c.256_278dup (p.Val94fs)	Pathogenic
1367667	NM_031885.5(BBS2):c.2104_2110del (p.Ile702fs)	Pathogenic
1451417	NM_031885.5(BBS2):c.1572_1575del (p.His525fs)	Pathogenic
1456521	NM_031885.5(BBS2):c.1974T>G (p.Tyr658Ter)	Pathogenic
1456753	NM_031885.5(BBS2):c.113del (p.Gly38fs)	Pathogenic
1457831	NM_031885.5(BBS2):c.471+1G>C	Pathogenic
1458453	NC_000016.9:g.(?56534756)(56545206_?)del	Pathogenic
1522592	NM_031885.5(BBS2):c.718-2A>G	Pathogenic
2004007	NM_031885.5(BBS2):c.1179_1180del (p.Asn393fs)	Pathogenic
2028715	NM_031885.5(BBS2):c.362del (p.Asn121fs)	Pathogenic
2029762	NM_031885.5(BBS2):c.812del (p.Ala271fs)	Pathogenic
2035307	NM_031885.5(BBS2):c.1662del (p.Thr555fs)	Pathogenic
2045893	NM_031885.5(BBS2):c.1922del (p.Lys641fs)	Pathogenic
208564	NM_031885.5(BBS2):c.661del (p.Leu221fs)	Pathogenic
2121965	NM_031885.5(BBS2):c.89_90dup (p.Leu31fs)	Pathogenic
2125568	NM_031885.5(BBS2):c.613-1G>T	Pathogenic
217434	NM_031885.5(BBS2):c.263del (p.Gly88fs)	Pathogenic
2426987	NC_000016.9:g.(?56545061)(56545206_?)del	Pathogenic
2426988	NC_000016.9:g.(?56544751)(56545216_?)del	Pathogenic
2498311	NM_031885.5(BBS2):c.1555del (p.Leu519fs)	Pathogenic
266085	NC_000016.9:g.(56519651_56530879)_(56536720_56539861)del	Pathogenic
2707609	NM_031885.5(BBS2):c.528del (p.Glu178fs)	Pathogenic
2714025	NM_031885.5(BBS2):c.1393del (p.Ser465fs)	Pathogenic
2718334	NM_031885.5(BBS2):c.466del (p.Trp156fs)	Pathogenic
2735629	NM_031885.5(BBS2):c.307del (p.Tyr103fs)	Pathogenic

SpliceAI

4665 predictions. Top by Δscore:

Variant	Effect	Δscore
16:56466147:TGCAG:T	acceptor_loss	1.0000
16:56466149:CAGAT:C	acceptor_loss	1.0000
16:56466150:A:AG	acceptor_gain	1.0000
16:56466150:AGAT:A	acceptor_gain	1.0000
16:56466151:G:GA	acceptor_gain	1.0000
16:56466151:GA:G	acceptor_gain	1.0000
16:56466151:GAT:G	acceptor_gain	1.0000
16:56466151:GATG:G	acceptor_gain	1.0000
16:56466151:GATGC:G	acceptor_gain	1.0000
16:56466241:G:GA	donor_gain	1.0000
16:56466265:GATG:G	donor_gain	1.0000
16:56466267:TGG:T	donor_loss	1.0000
16:56466269:G:GC	donor_loss	1.0000
16:56466269:G:GG	donor_gain	1.0000
16:56466270:T:A	donor_loss	1.0000
16:56466274:A:G	donor_gain	1.0000
16:56466868:T:TA	acceptor_gain	1.0000
16:56466874:A:AG	acceptor_gain	1.0000
16:56466875:G:GG	acceptor_gain	1.0000
16:56466941:G:GT	donor_gain	1.0000
16:56466973:GACT:G	donor_gain	1.0000
16:56467290:AGAT:A	donor_gain	1.0000
16:56467291:GAT:G	donor_gain	1.0000
16:56467291:GATG:G	donor_gain	1.0000
16:56467294:G:GG	donor_gain	1.0000
16:56467885:A:AG	acceptor_gain	1.0000
16:56467888:T:TA	acceptor_gain	1.0000
16:56467891:T:A	acceptor_gain	1.0000
16:56467899:C:A	acceptor_gain	1.0000
16:56467902:A:AG	acceptor_gain	1.0000

AlphaMissense

4763 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:56505964:A:G	W264R	1.000
16:56505964:A:T	W264R	1.000
16:56506131:A:G	W236R	1.000
16:56506131:A:T	W236R	1.000
16:56502798:C:G	R272P	0.999
16:56506036:A:G	S240P	0.999
16:56506120:T:A	K239N	0.999
16:56506120:T:G	K239N	0.999
16:56506121:T:A	K239I	0.999
16:56506122:T:C	K239E	0.999
16:56506129:C:A	W236C	0.999
16:56506129:C:G	W236C	0.999
16:56506157:C:T	G227E	0.999
16:56506158:C:G	G227R	0.999
16:56506158:C:T	G227R	0.999
16:56506160:A:T	V226D	0.999
16:56510003:C:G	R189P	0.999
16:56484826:C:G	A701P	0.998
16:56502354:A:G	L348P	0.998
16:56502783:C:A	G277V	0.998
16:56502783:C:T	G277E	0.998
16:56502784:C:A	G277W	0.998
16:56502801:G:T	A271D	0.998
16:56505962:C:A	W264C	0.998
16:56505962:C:G	W264C	0.998
16:56505966:C:T	G263D	0.998
16:56505975:A:G	L260P	0.998
16:56506126:T:A	R237S	0.998
16:56506126:T:G	R237S	0.998
16:56506127:C:G	R237T	0.998

dbSNP variants (sampled 300 via entrez): RS1000051452 (16:56486435 A>T), RS1000103343 (16:56485744 C>A,T), RS1000187759 (16:56515131 G>A,C), RS1000535436 (16:56497258 C>G), RS1000872247 (16:56517929 C>G), RS1000934144 (16:56521917 T>A), RS1000959883 (16:56477496 C>G,T), RS1001044522 (16:56490718 A>G), RS1001051830 (16:56490952 A>G), RS1001052324 (16:56484241 T>A,C,G), RS1001109567 (16:56483880 T>C), RS1001138623 (16:56504091 T>C), RS1001218361 (16:56500668 G>A,T), RS1001246685 (16:56477142 G>A), RS1001416434 (16:56500268 T>C)

Disease associations

OMIM: gene MIM:606151 | disease phenotypes: MIM:615981, MIM:616562, MIM:209900, MIM:268000

GenCC curated gene-disease

Disease	Classification	Inheritance
Bardet-Biedl syndrome 2	Definitive	Autosomal recessive
retinitis pigmentosa 74	Definitive	Autosomal recessive
BBS2-related ciliopathy	Strong	Autosomal recessive
Bardet-Biedl syndrome	Supportive	Autosomal recessive
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
BBS2-related ciliopathy	Definitive	AR

Mondo (9): Bardet-Biedl syndrome 2 (MONDO:0014432), retinitis pigmentosa 74 (MONDO:0014692), Bardet-Biedl syndrome (MONDO:0015229), Bardet-Biedl syndrome 1 (MONDO:0008854), inherited retinal dystrophy (MONDO:0019118), BBS2-related ciliopathy (MONDO:1040048), focal segmental glomerulosclerosis (MONDO:0100313), retinitis pigmentosa (MONDO:0019200), retinal disorder (MONDO:0005283)

Orphanet (3): Bardet-Biedl syndrome (Orphanet:110), Retinitis pigmentosa (Orphanet:791), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

157 total (30 of 157 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000011	Neurogenic bladder
HP:0000028	Cryptorchidism
HP:0000041	Chordee
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000076	Vesicoureteral reflux
HP:0000085	Horseshoe kidney
HP:0000100	Nephrotic syndrome
HP:0000103	Polyuria
HP:0000119	Abnormality of the genitourinary system
HP:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000147	Polycystic ovaries
HP:0000163	Abnormal oral cavity morphology
HP:0000218	High palate
HP:0000233	Thin vermilion border
HP:0000278	Retrognathia
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
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:0000414	Bulbous nose

GWAS associations

0 associations (top):

MeSH disease descriptors (7)

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
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
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
C537909	Bardet-Biedl syndrome 1 (supp.)
C537910	Bardet-Biedl syndrome 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

45 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	4
sodium arsenite	decreases expression, increases abundance	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
(+)-JQ1 compound	increases expression	2
Resveratrol	affects cotreatment, increases expression	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Aflatoxin B1	increases methylation	2
aristolochic acid I	decreases expression	1
afuresertib	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
bisphenol S	increases methylation	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Copper	affects binding, increases expression	1
Disulfiram	affects binding, increases expression	1
Doxorubicin	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_A1MC	IBMS-iPSC-063-06	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT01129557	PHASE4	TERMINATED	Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease
NCT02399462	PHASE4	WITHDRAWN	Acthar for Treatment of Post-transplant FSGS
NCT02585804	PHASE4	COMPLETED	Treating to Reduce Albuminuria and Normalize Hemodynamic Function in Focal ScLerosis With dApagliflozin Trial Effects
NCT02633046	PHASE4	COMPLETED	Acthar for Treatment-Resistant or Treatment-Intolerant Proteinuria
NCT07219121	PHASE4	RECRUITING	Sparsentan in Posttransplant Immunoglobulin A Nephropathy or Focal Segmental Glomerulosclerosis
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
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
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
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
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline 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
NCT01164098	PHASE3	TERMINATED	Rituximab to Prevent Recurrence of Proteinuria
NCT02683889	PHASE3	COMPLETED	Use of Acthar in Patients With FSGS That Will be Undergoing Renal Transplantation
NCT03298698	PHASE3	UNKNOWN	Efficacy of Rituximab in Comparison to Continued Corticosteroid Treatment in Idiopathic Nephrotic Syndrome
NCT03493685	PHASE3	COMPLETED	Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS)
NCT05183646	PHASE3	RECRUITING	A Study of the Efficacy and Safety of DMX-200 in Patients With FSGS Who Are Receiving an ARB
NCT07220083	PHASE3	RECRUITING	A Study to Find Out if BI 764198 Helps Adults and Adolescents With a Kidney Condition Called Focal Segmental Glomerulosclerosis (FSGS)
NCT03490019	PHASE2	WITHDRAWN	Treatment of Bardet-Biedl-Syndrome With Metformin for Evaluation of a Possible Visual Improvement
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