BBS5

Summary

BBS5 (Bardet-Biedl syndrome 5, HGNC:970) is a protein-coding gene on chromosome 2q31.1, encoding BBSome complex member BBS5 (Q8N3I7). The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.

This gene encodes a protein that has been directly linked to Bardet-Biedl syndrome. The primary features of this syndrome include retinal dystrophy, obesity, polydactyly, renal abnormalities and learning disabilities. Experimentation in non-human eukaryotes suggests that this gene is expressed in ciliated cells and that it is required for the formation of cilia. Alternate transcriptional splice variants have been observed but have not been fully characterized.

Source: NCBI Gene 129880 — RefSeq curated summary.

At a glance

• Gene–disease (curated): BBS5-related ciliopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 475 total — 42 pathogenic, 26 likely-pathogenic
• Phenotypes (HPO): 109
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_152384

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:970
Approved symbol	BBS5
Name	Bardet-Biedl syndrome 5
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp762I194
Ensembl gene	ENSG00000163093
Ensembl biotype	protein_coding
OMIM	603650
Entrez	129880

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000295240, ENST00000392663, ENST00000443151, ENST00000469980, ENST00000472667, ENST00000475571, ENST00000857799, ENST00000857800, ENST00000950194, ENST00000950195

RefSeq mRNA: 1 — MANE Select: NM_152384 NM_152384

CCDS: CCDS2233

Canonical transcript exons

ENST00000295240 — 12 exons

Exon	Start	End
ENSE00001237617	169504481	169506655
ENSE00001833465	169479494	169479612
ENSE00003475994	169487987	169488114
ENSE00003513528	169497627	169497689
ENSE00003545029	169493741	169493836
ENSE00003559143	169482251	169482333
ENSE00003567011	169504303	169504326
ENSE00003570168	169487069	169487134
ENSE00003616350	169487806	169487855
ENSE00003628012	169499486	169499620
ENSE00003636306	169492874	169493009
ENSE00003672482	169503095	169503178

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 88.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.3632 / max 129.1825, expressed in 1667 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23545	7.3632	1667

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	88.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.77	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.56	gold quality
pituitary gland	UBERON:0000007	82.47	gold quality
adenohypophysis	UBERON:0002196	82.33	gold quality
Ammon’s horn	UBERON:0001954	81.05	gold quality
temporal lobe	UBERON:0001871	80.98	gold quality
amygdala	UBERON:0001876	80.95	gold quality
nucleus accumbens	UBERON:0001882	80.93	gold quality
calcaneal tendon	UBERON:0003701	80.85	gold quality
thyroid gland	UBERON:0002046	80.78	gold quality
hypothalamus	UBERON:0001898	80.62	gold quality
left lobe of thyroid gland	UBERON:0001120	80.57	gold quality
anterior cingulate cortex	UBERON:0009835	80.48	gold quality
right frontal lobe	UBERON:0002810	80.42	gold quality
ventricular zone	UBERON:0003053	80.30	gold quality
caudate nucleus	UBERON:0001873	80.23	gold quality
right lobe of thyroid gland	UBERON:0001119	80.13	gold quality
fallopian tube	UBERON:0003889	80.01	gold quality
primary visual cortex	UBERON:0002436	79.90	gold quality
brain	UBERON:0000955	79.79	gold quality
endometrium	UBERON:0001295	79.70	gold quality
cerebral cortex	UBERON:0000956	79.69	gold quality
putamen	UBERON:0001874	79.65	gold quality
skeletal muscle tissue	UBERON:0001134	79.60	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	79.59	gold quality
gastrocnemius	UBERON:0001388	79.45	gold quality
corpus callosum	UBERON:0002336	79.45	gold quality
superior frontal gyrus	UBERON:0002661	79.12	gold quality
left ovary	UBERON:0002119	79.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

85 targeting BBS5, 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-4692	100.00	67.32	2066
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-6715B-5P	99.64	69.63	1420

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 7)

• identified BBS5, a novel gene for Bardet-Biedl syndrome; it localizes to basal bodies, is under the regulatory control of daf-19, and is necessary for the generation of both cilia and flagella (PMID:15137946)
• Novel mutations in BBS5 highlight the importance of this gene in non-Caucasian Bardet-Biedl syndrome patients. (PMID:18203199)
• analysis of a novel splice variant of BBS5 that appears to be expressed only in the retina (PMID:26867008)
• The role of PITX2 in glaucoma may be mediated partly by regulating the expression of CXCL6 and BBS5 and thus affecting immune functions and intraocular pressure. (PMID:27520585)
• Novel compound heterozygous pathogenic BBS5 variants in Filipino siblings with Bardet-Biedl syndrome (BBS). (PMID:32811249)
• A mouse model of BBS identifies developmental and homeostatic effects of BBS5 mutation and identifies novel pituitary abnormalities. (PMID:33560420)
• 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)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bbs5	ENSDARG00000039827
mus_musculus	Bbs5	ENSMUSG00000063145
drosophila_melanogaster	BBS5	FBGN0037280
caenorhabditis_elegans		WBGENE00010974

Protein

Protein identifiers

BBSome complex member BBS5 — Q8N3I7 (reviewed: Q8N3I7)

Alternative names: Bardet-Biedl syndrome 5 protein

All UniProt accessions (4): A0A0S2Z626, A0A0S2Z6S7, F8WBR7, Q8N3I7

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 BBSome complex ciliary localization but not for the proper complex assembly.

Subunit / interactions. Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10. Binds to phosphoinositides. Interacts with CCDC28B. Interacts with SMO; the interaction is indicative for the association of SMO with the BBsome complex to facilitate ciliary localization of SMO. Interacts with PKD1. Interacts with DLEC1.

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

Disease relevance. Bardet-Biedl syndrome 5 (BBS5) [MIM:615983] 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. BBS5 may interact genetically with BBS1.

Similarity. Belongs to the BBS5 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N3I7-1	1	yes
Q8N3I7-2	2

RefSeq proteins (1): NP_689597* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006606	BBL5	Family
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR014003	BBS5_PH	Domain
IPR030804	BBS5/fem-3	Family

Pfam: PF07289

UniProt features (7 total): sequence variant 5, chain 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6XTB	ELECTRON MICROSCOPY	4.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N3I7-F1	88.87	0.73

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: 348 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PIGMENT_GRANULE_LOCALIZATION, GOBP_VESICLE_LOCALIZATION, GOBP_CELLULAR_PIGMENTATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_PIGMENTATION, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EMBRYONIC_HEART_TUBE_DEVELOPMENT, GOBP_EMBRYONIC_ORGAN_MORPHOGENESIS, GOBP_HEART_MORPHOGENESIS, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_CILIUM_ORGANIZATION, GOCC_CENTROSOME

GO Biological Process (7): heart looping (GO:0001947), visual perception (GO:0007601), protein transport (GO:0015031), melanosome transport (GO:0032402), motile cilium assembly (GO:0044458), cilium assembly (GO:0060271), cell projection organization (GO:0030030)

GO Molecular Function (3): phosphatidylinositol-3-phosphate binding (GO:0032266), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), protein binding (GO:0005515)

GO Cellular Component (12): cytosol (GO:0005829), axoneme (GO:0005930), centriolar satellite (GO:0034451), BBSome (GO:0034464), ciliary basal body (GO:0036064), 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
cilium	3
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
sensory perception of light stimulus	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
melanosome localization	1
establishment of melanosome localization	1
pigment granule transport	1
cilium assembly	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
cellular component organization	1
phosphatidylinositol phosphate binding	1
DNA-binding transcription factor binding	1
binding	1
cytoplasm	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
centrosome	1
protein-containing complex	1
microtubule organizing center	1
cell projection membrane	1
bounding membrane of organelle	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

878 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BBS5	BBS9	P78514	999
BBS5	BBS2	Q9BXC9	999
BBS5	BBS7	Q8IWZ6	999
BBS5	BBS4	Q96RK4	999
BBS5	BBS1	Q8NFJ9	999
BBS5	TTC8	Q8TAM2	991
BBS5	BBS10	Q8TAM1	969
BBS5	BBS12	Q6ZW61	918
BBS5	RAB3IP	Q96QF0	873
BBS5	RAB8A	P24407	840
BBS5	CCDC28B	Q9BUN5	836
BBS5	MKS1	Q9NXB0	825
BBS5	WDPCP	O95876	816
BBS5	IFT88	Q13099	798
BBS5	CEP290	O15078	795

IntAct

68 interactions, top by confidence:

A	B	Type	Score
BBS1	BBS9	psi-mi:“MI:0914”(association)	0.940
BBS4	PCM1	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
BBS5	BBS9	psi-mi:“MI:0915”(physical association)	0.890
BBS9	BBS5	psi-mi:“MI:0915”(physical association)	0.890
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
BBS5	BBS7	psi-mi:“MI:0914”(association)	0.790
NME3	NME4	psi-mi:“MI:0914”(association)	0.640
BBS2	IQCB1	psi-mi:“MI:0403”(colocalization)	0.630
SPOPL	SPOP	psi-mi:“MI:0914”(association)	0.590
IQCB1	BBS5	psi-mi:“MI:0915”(physical association)	0.570
IQCB1	BBS5	psi-mi:“MI:2364”(proximity)	0.570
IQCB1	BBS5	psi-mi:“MI:0403”(colocalization)	0.570
BBS1	PCM1	psi-mi:“MI:0915”(physical association)	0.570
BBS5	CRADD	psi-mi:“MI:0915”(physical association)	0.560
BBS5	KLC3	psi-mi:“MI:0915”(physical association)	0.560
BBS5		psi-mi:“MI:0915”(physical association)	0.560
KLC3	BBS5	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (37): BBS5 (Two-hybrid), KLC3 (Two-hybrid), BBS5 (Affinity Capture-MS), BBS1 (Affinity Capture-MS), BBS7 (Affinity Capture-MS), BBS4 (Affinity Capture-MS), BBS9 (Affinity Capture-MS), TTC8 (Affinity Capture-MS), BBS5 (Affinity Capture-MS), BBS5 (Affinity Capture-MS), BBS2 (Affinity Capture-MS), BBS5 (Affinity Capture-MS), BBS5 (Affinity Capture-MS), BBS5 (Affinity Capture-MS), BBS5 (Affinity Capture-MS)

ESM2 similar proteins: A0MQH0, A2AWA9, A4FUD6, A5PK00, B5DGH9, O35142, O43913, O55029, P11029, P35605, P35606, P60228, P60229, P70188, Q05AY2, Q1LUA8, Q25BN1, Q3T102, Q4R4I8, Q4R649, Q4R6G8, Q5F415, Q5R664, Q5R8I6, Q5R8K9, Q5RAN1, Q5RCC1, Q5ZLA5, Q641X8, Q66IS6, Q6DRI1, Q6P1X5, Q6P7L9, Q6PC62, Q7ZWB7, Q86VN1, Q8BHL5, Q8BPU7, Q8IWZ6, Q8K0F1

Diamond homologs: Q21626, Q4R649, Q66IS6, Q7ZWB7, Q8N3I7, Q9CZQ9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
BBS5	“form complex”	“BBsome complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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	9	178.8×	3e-17
Cargo trafficking to the periciliary membrane	7	69.5×	2e-10
Cilium Assembly	10	43.5×	6e-13
Organelle biogenesis and maintenance	10	26.4×	7e-11
Anchoring of the basal body to the plasma membrane	5	22.6×	7e-05

GO biological processes:

GO term	Partners	Fold	FDR
non-motile cilium assembly	8	83.0×	4e-12
fat cell differentiation	6	38.8×	7e-07
cilium assembly	13	34.2×	3e-15
visual perception	5	14.2×	4e-04
protein transport	6	9.4×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	42
Likely pathogenic	26
Uncertain significance	167
Likely benign	179
Benign	26

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1033147	NM_152384.3(BBS5):c.709del (p.Lys236_Ile237insTer)	Pathogenic
1072279	NM_152384.3(BBS5):c.559_560insGA (p.Ile187fs)	Pathogenic
1210083	NM_152384.3(BBS5):c.425T>G (p.Leu142Ter)	Pathogenic
1352811	NM_152384.3(BBS5):c.925C>T (p.Gln309Ter)	Pathogenic
1391909	NM_152384.3(BBS5):c.655del (p.Ala219fs)	Pathogenic
1412902	NM_152384.3(BBS5):c.406del (p.Met136fs)	Pathogenic
1453921	NM_152384.3(BBS5):c.520C>T (p.Gln174Ter)	Pathogenic
1457102	NC_000002.11:g.(?170336064)(170336142_?)del	Pathogenic
1459591	NC_000002.11:g.(?170359585)(170361092_?)del	Pathogenic
1679815	NM_152384.3:c.(?-60)(386+1_387-1)del	Pathogenic
1679817	NM_152384.3(BBS5):c.1A>G (p.Met1Val)	Pathogenic
1971348	NM_152384.3(BBS5):c.844G>T (p.Glu282Ter)	Pathogenic
2163400	NM_152384.3(BBS5):c.5_8dup (p.Leu4fs)	Pathogenic
2427373	NC_000002.11:g.(?170349364)(170350366_?)del	Pathogenic
2443002	NC_000002.12:g.169477282_169483199del	Pathogenic
2443003	NM_152384.3(BBS5):c.550_552dup (p.Asn184_Val185insAsn)	Pathogenic
2498300	NM_152384.3(BBS5):c.164T>C (p.Leu55Ser)	Pathogenic
2500153	NM_152384.3(BBS5):c.198del (p.Val67fs)	Pathogenic
2671574	NM_152384.3(BBS5):c.420dup (p.Lys141Ter)	Pathogenic
2726311	NM_152384.3(BBS5):c.58C>T (p.Gln20Ter)	Pathogenic
2793507	NM_152384.3(BBS5):c.562dup (p.Val188fs)	Pathogenic
2866613	NM_152384.3(BBS5):c.556_557delinsTA (p.Arg186Ter)	Pathogenic
2883010	NM_152384.3(BBS5):c.54dup (p.Ala19fs)	Pathogenic
3247206	NC_000002.11:g.(?170338741)(170343664_?)del	Pathogenic
3661134	NM_152384.3(BBS5):c.808G>T (p.Glu270Ter)	Pathogenic
3669260	NC_000002.12:g.169493742dup	Pathogenic
3679184	NM_152384.3(BBS5):c.623C>G (p.Ser208Ter)	Pathogenic
3715901	NM_152384.3(BBS5):c.2T>C (p.Met1Thr)	Pathogenic
3727601	NM_152384.3(BBS5):c.204dup (p.Val69fs)	Pathogenic
4731987	NM_152384.3(BBS5):c.568_603delinsTATTAAAACTATCATTCATATTTGCATG (p.His190_Ile201delinsTyrTer)	Pathogenic

SpliceAI

2105 predictions. Top by Δscore:

Variant	Effect	Δscore
2:169479608:GCGCA:G	donor_gain	1.0000
2:169479610:GCA:G	donor_gain	1.0000
2:169479613:G:GG	donor_gain	1.0000
2:169482329:TAGAG:T	donor_gain	1.0000
2:169482330:AGAGG:A	donor_loss	1.0000
2:169482331:GAG:G	donor_gain	1.0000
2:169482331:GAGGT:G	donor_loss	1.0000
2:169482332:AGGT:A	donor_loss	1.0000
2:169482333:GGT:G	donor_loss	1.0000
2:169482333:GGTG:G	donor_loss	1.0000
2:169482334:G:GG	donor_gain	1.0000
2:169482334:GTGA:G	donor_loss	1.0000
2:169482335:T:A	donor_loss	1.0000
2:169499485:GA:G	acceptor_gain	1.0000
2:169499617:AAAGG:A	donor_loss	1.0000
2:169499618:AAG:A	donor_loss	1.0000
2:169499619:AGGT:A	donor_loss	1.0000
2:169499620:GG:G	donor_loss	1.0000
2:169499621:G:A	donor_loss	1.0000
2:169499621:G:GA	donor_loss	1.0000
2:169503076:A:AG	acceptor_gain	1.0000
2:169503077:A:G	acceptor_gain	1.0000
2:169503079:ATCT:A	acceptor_gain	1.0000
2:169503080:T:G	acceptor_gain	1.0000
2:169503085:T:A	acceptor_gain	1.0000
2:169503093:A:AG	acceptor_gain	1.0000
2:169503094:G:GG	acceptor_gain	1.0000
2:169503176:GTG:G	donor_gain	1.0000
2:169503178:GGT:G	donor_loss	1.0000
2:169503179:GT:G	donor_loss	1.0000

AlphaMissense

2249 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:169493750:G:A	G178R	1.000
2:169493750:G:C	G178R	1.000
2:169493751:G:A	G178E	1.000
2:169493783:T:A	W189R	1.000
2:169493783:T:C	W189R	1.000
2:169493816:A:C	S200R	1.000
2:169493818:T:A	S200R	1.000
2:169493818:T:G	S200R	1.000
2:169497654:T:C	F216L	1.000
2:169497656:T:A	F216L	1.000
2:169497656:T:G	F216L	1.000
2:169499508:T:C	F235S	1.000
2:169487093:G:C	R56T	0.999
2:169492899:C:A	R138S	0.999
2:169492900:G:C	R138P	0.999
2:169492915:G:C	R143T	0.999
2:169492994:T:A	N169K	0.999
2:169492994:T:G	N169K	0.999
2:169492996:T:C	L170S	0.999
2:169493741:G:C	G175R	0.999
2:169493742:G:A	G175D	0.999
2:169493751:G:T	G178V	0.999
2:169493775:G:C	R186T	0.999
2:169493775:G:T	R186I	0.999
2:169493776:A:C	R186S	0.999
2:169493776:A:T	R186S	0.999
2:169493784:G:C	W189S	0.999
2:169493785:G:C	W189C	0.999
2:169493785:G:T	W189C	0.999
2:169493812:T:A	N198K	0.999

dbSNP variants (sampled 300 via entrez): RS1000021500 (2:169479887 G>T), RS1000026398 (2:169486351 A>G), RS1000240778 (2:169506371 T>G), RS1000502036 (2:169498826 A>G), RS1000515853 (2:169481029 A>G), RS1000541286 (2:169479736 C>A,G), RS1000705269 (2:169492470 T>C), RS1000720556 (2:169499109 G>C,T), RS1000939174 (2:169505341 G>A,C,T), RS1001059946 (2:169499856 G>A), RS1001076125 (2:169485483 G>C), RS1001100096 (2:169492819 C>A,T), RS1001144576 (2:169478622 A>G), RS1001180811 (2:169506237 C>A), RS1001252946 (2:169506422 T>G)

Disease associations

OMIM: gene MIM:603650 | disease phenotypes: MIM:209900, MIM:615983

GenCC curated gene-disease

Disease	Classification	Inheritance
Bardet-Biedl syndrome 5	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
BBS5-related ciliopathy	Definitive	AR

Mondo (7): cone dystrophy (MONDO:0000455), intellectual disability (MONDO:0001071), Bardet-Biedl syndrome (MONDO:0015229), inherited retinal dystrophy (MONDO:0019118), Bardet-Biedl syndrome 5 (MONDO:0014434), Bardet-Biedl syndrome 1 (MONDO:0008854), retinal disorder (MONDO:0005283)

Orphanet (4): Bardet-Biedl syndrome (Orphanet:110), Progressive cone dystrophy (Orphanet:1871), OBSOLETE: Inherited retinal disorder (Orphanet:71862), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

109 total (30 of 109 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:0000085	Horseshoe kidney
HP:0000100	Nephrotic syndrome
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: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:0000426	Prominent nasal bridge
HP:0000470	Short neck
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000543	Optic disc pallor
HP:0000548	Cone/cone-rod dystrophy

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007742_12	Iris heterochromicity	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009764	eye colour measurement

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
D000077765	Cone Dystrophy	C11.270.151; C11.768.216
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
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

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression	3
sodium arsenite	decreases expression, increases expression	2
bisphenol F	increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
afimoxifene	decreases expression, decreases reaction	1
nickel sulfate	increases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cannabidiol	increases expression	1
Doxorubicin	decreases expression	1
Estrogens	decreases expression, decreases reaction	1
Quercetin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_YC31	KCi003-A	Induced pluripotent stem cell	Male
CVCL_YC32	KCi003-B	Induced pluripotent stem cell	Male
CVCL_YC33	KCi003-C	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
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
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
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
NCT03490019	PHASE2	WITHDRAWN	Treatment of Bardet-Biedl-Syndrome With Metformin for Evaluation of a Possible Visual Improvement
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
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]
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT00078091	Not specified	TERMINATED	Genetics and Clinical Characteristics of Bardet-Biedl Syndrome
NCT00213811	Not specified	COMPLETED	Bardet-Biedl Syndrome Study: Clinical and Genetic Epidemiology Study in Adults
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT02329210	Not specified	RECRUITING	Clinical Registry Investigating Bardet-Biedl Syndrome
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT04461444	Not specified	RECRUITING	COhort for Bardet-Bield Syndrome and Alström Syndrome for Translational Research Monocentric Interventional Study
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT05183802	Not specified	APPROVED_FOR_MARKETING	An Expanded Access Protocol for Setmelanotide for Treatment of Bardet-Biedl Syndrome (BBS)
NCT05400278	Not specified	COMPLETED	Characterizing the Genotype and Phenotype in Adults With Bardet-Biedl Syndrome
NCT06239064	Not specified	ACTIVE_NOT_RECRUITING	Early Genetic Identification of Obesity
NCT06615011	Not specified	NOT_YET_RECRUITING	Bardet Beidle Syndrome in a Syrian Adolescent : a Rare Case Report
NCT07602803	Not specified	COMPLETED	The Effect of GLP1 Agonists on Weight Loss in BBS Cohort in the UK
NCT03990727	Not specified	UNKNOWN	Phenotype Correlates Genotype of Inherited Retina Dystrophies, Retinitis Pigmentosa, Con>Rod Dystrophies.