BBS10

Summary

BBS10 (Bardet-Biedl syndrome 10, HGNC:26291) is a protein-coding gene on chromosome 12q21.2, encoding BBSome complex assembly protein BBS10 (Q8TAM1). Probable molecular chaperone that assists the folding of proteins upon ATP hydrolysis.

This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by progressive retinal degeneration, 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 is likely not a ciliary protein but rather has distant sequence homology to type II chaperonins. As a molecular chaperone, this protein may affect the folding or stability of other ciliary or basal body proteins. Inhibition of this protein’s expression impairs ciliogenesis in preadipocytes. Mutations in this gene cause Bardet-Biedl syndrome type 10.

Source: NCBI Gene 79738 — RefSeq curated summary.

At a glance

• Gene–disease (curated): BBS10-related ciliopathy (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 1,076 total — 106 pathogenic, 100 likely-pathogenic
• Phenotypes (HPO): 102
• MANE Select transcript: NM_024685

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26291
Approved symbol	BBS10
Name	Bardet-Biedl syndrome 10
Location	12q21.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23560
Ensembl gene	ENSG00000179941
Ensembl biotype	protein_coding
OMIM	610148
Entrez	79738

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000650064, ENST00000865227

RefSeq mRNA: 1 — MANE Select: NM_024685 NM_024685

CCDS: CCDS9014

Canonical transcript exons

ENST00000650064 — 2 exons

Exon	Start	End
ENSE00001669935	76344474	76347787
ENSE00003832438	76348162	76348415

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 91.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.9906 / max 157.8898, expressed in 1693 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132201	6.9775	1618
132200	1.0131	556

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	91.98	gold quality
endothelial cell	CL:0000115	89.16	silver quality
ventricular zone	UBERON:0003053	86.08	gold quality
ganglionic eminence	UBERON:0004023	85.76	gold quality
choroid plexus epithelium	UBERON:0003911	85.36	gold quality
pigmented layer of retina	UBERON:0001782	84.74	gold quality
cortical plate	UBERON:0005343	83.92	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.26	gold quality
germinal epithelium of ovary	UBERON:0001304	81.56	gold quality
islet of Langerhans	UBERON:0000006	81.22	gold quality
bronchial epithelial cell	CL:0002328	80.69	silver quality
primary visual cortex	UBERON:0002436	80.50	gold quality
right adrenal gland cortex	UBERON:0035827	80.42	gold quality
adrenal tissue	UBERON:0018303	80.18	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.13	gold quality
prefrontal cortex	UBERON:0000451	79.74	gold quality
right adrenal gland	UBERON:0001233	79.67	gold quality
adipose tissue	UBERON:0001013	79.54	gold quality
corpus epididymis	UBERON:0004359	79.39	gold quality
left adrenal gland	UBERON:0001234	79.20	gold quality
connective tissue	UBERON:0002384	79.12	gold quality
right lung	UBERON:0002167	78.93	gold quality
cauda epididymis	UBERON:0004360	78.92	silver quality
caput epididymis	UBERON:0004358	78.72	silver quality
subcutaneous adipose tissue	UBERON:0002190	78.70	gold quality
left adrenal gland cortex	UBERON:0035825	78.69	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.61	gold quality
right coronary artery	UBERON:0001625	78.60	gold quality
adrenal gland	UBERON:0002369	78.48	gold quality
tibial nerve	UBERON:0001323	78.18	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	76.21
E-ANND-3	no	2.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

90 targeting BBS10, 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-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 20)

• Detected in a family with high consanguinity and Bardet-Biedl syndrome. (PMID:17101080)
• the BBS10 and BBS12 proteins are located within the basal body of this primary cilium and inhibition of their expression impairs ciliogenesis, activates the GSK3 pathway, and induces PPAR nuclear accumulation, hence favoring adipogenesis (PMID:19190184)
• Using sequence analysis, the role of BBS6, 10 and 12 was assessed in a Bardet-Biedl syndrome patient population comprising 93 cases from 74 families. (PMID:20472660)
• This study confirms the high frequency of BBS10 mutations, particularly of the p.Cys91LeufsX5 allele in Bardet-Biedl syndrome. (PMID:20805367)
• Mutation in BBS10 modulates Bardet-Biedl syndrome in a sibling. (PMID:20827784)
• Mutations identified in the present study extend the body of evidence implicating the genes ARL6 and BBS10 in causing Bardet-Biedl syndrome. (PMID:23219996)
• We report two affected brothers from a consanguineous Pakistani Punjabi family, both the brothers were homozygous for c.1958_1967del, which is a novel deletion in BBS10 that is likely to be causing the Bardet-Biedl syndrome in this family. (PMID:23403234)
• Novel mutation (c.1181_1182insGCATTTATACC) in BBS10 (p.S396Lfs*6) found in Tunisian families with Bardet-Biedl syndrome. (PMID:23432027)
• 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)
• novel BBS10 mutations in Bardet-Biedl syndrome patients in Spain (PMID:24611592)
• A rare variant (c.1189A>G [p.Ile397Val]; rs202042386) confers risk of type 2 diabetes in a recessive state. (PMID:25439097)
• Two novel mutations and three previously reported variants, identified in the present study, further extend the body of evidence implicating BBS6, BBS7, BBS8, and BBS10 in causing Bardet-Biedl Syndrome. (PMID:28761321)
• Genetic analysis revealed compound heterozygous BBS10 mutations in the patient: a novel missense mutation c.98G>A (PMID:29666954)
• In the 64 BBS patients (44 males, 20 females) were studied, mutations were predominant in BBS10 and ARL6 genes; the c.272T>C; p.(I91T) mutation in ARL6 gene was a recurrent mutation (PMID:29806606)
• A consanguineous patient with Bardet Biedl syndrome was found to be homozygous for the variant of BBS10: NM_024685.3, c.39_46delGGCGTTGC, p.Ala14GlyfsTer79 (A14Gfs*79). Several other members of the pedigree had obesity or other features associated with this syndrome. (PMID:30335236)
• Next-Generation Sequencing in the Diagnosis of Patients with Bardet-Biedl Syndrome-New Variants and Relationship with Hyperglycemia and Insulin Resistance. (PMID:33138063)
• 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)
• Comparative Natural History of Visual Function From Patients With Biallelic Variants in BBS1 and BBS10. (PMID:34940782)
• Multi-Omics Studies Unveil Extraciliary Functions of BBS10 and Show Metabolic Aberrations Underlying Renal Disease in Bardet-Biedl Syndrome. (PMID:36012682)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	bbs10	ENSDARG00000069515
mus_musculus	Bbs10	ENSMUSG00000035759
rattus_norvegicus	Bbs10	ENSRNOG00000026913

Protein

Protein identifiers

BBSome complex assembly protein BBS10 — Q8TAM1 (reviewed: Q8TAM1)

Alternative names: Bardet-Biedl syndrome 10 protein

All UniProt accessions (1): Q8TAM1

UniProt curated annotations — full annotation on UniProt →

Function. Probable molecular chaperone that assists the folding of proteins upon ATP hydrolysis. Plays a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. Involved in adipogenic differentiation.

Subunit / interactions. Component of a complex composed at least of MKKS, BBS10, BBS12, TCP1, CCT2, CCT3, CCT4, CCT5 and CCT8.

Subcellular location. Cell projection. Cilium.

Disease relevance. Bardet-Biedl syndrome 10 (BBS10) [MIM:615987] 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. Adipocytes derived from BBS-patients’ dermal fibroblasts in culture exhibit higher propensity for fat accumulation when compared to controls. This strongly suggests that a peripheral primary dysfunction of adipogenesis participates in the pathogenesis of obesity in BBS.

Similarity. Belongs to the TCP-1 chaperonin family.

RefSeq proteins (1): NP_078961* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002423	Cpn60/GroEL/TCP-1	Family
IPR027409	GroEL-like_apical_dom_sf	Homologous_superfamily
IPR027410	TCP-1-like_intermed_sf	Homologous_superfamily
IPR027413	GROEL-like_equatorial_sf	Homologous_superfamily
IPR042619	BBS10	Family

Pfam: PF00118

UniProt features (37 total): sequence variant 32, sequence conflict 3, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAM1-F1	71.26	0.39

Functional residue map

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

Mutagenesis-validated functional residues (1):

Position	Phenotype
81	greatly decreases all interactions with bbs7, bbs9 and bbs12 indicating that this residue may be required for overall pr

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: 358 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_NEUROGENESIS, GOBP_NEURAL_RETINA_DEVELOPMENT, GOBP_CHAPERONE_MEDIATED_PROTEIN_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EYE_PHOTORECEPTOR_CELL_DIFFERENTIATION, chr12q21, GOBP_PHOTORECEPTOR_CELL_MAINTENANCE, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_CILIUM_ORGANIZATION, GOBP_DNA_DAMAGE_RESPONSE, GOBP_RESPONSE_TO_RADIATION

GO Biological Process (15): visual perception (GO:0007601), intracellular protein localization (GO:0008104), response to light stimulus (GO:0009416), neuronal action potential (GO:0019228), response to endoplasmic reticulum stress (GO:0034976), retinal cone cell differentiation (GO:0042670), regulation of protein-containing complex assembly (GO:0043254), negative regulation of neuron apoptotic process (GO:0043524), photoreceptor cell maintenance (GO:0045494), chaperone-mediated protein complex assembly (GO:0051131), retinal rod cell differentiation (GO:0060221), cone retinal bipolar cell differentiation (GO:1904390), non-motile cilium assembly (GO:1905515), photoreceptor cell differentiation (GO:0046530), retina development in camera-type eye (GO:0060041)

GO Molecular Function (4): ATP binding (GO:0005524), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (2): 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
camera-type eye photoreceptor cell differentiation	2
protein-containing complex assembly	2
sensory perception of light stimulus	1
macromolecule localization	1
response to radiation	1
action potential	1
transmission of nerve impulse	1
cellular response to stress	1
regulation of cellular component biogenesis	1
regulation of cellular component organization	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
retina homeostasis	1
multicellular organismal process	1
retinal bipolar neuron differentiation	1
cilium assembly	1
neuron differentiation	1
camera-type eye development	1
anatomical structure development	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
DNA-binding transcription factor binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3164 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BBS10	BBS12	Q6ZW61	999
BBS10	BBS7	Q8IWZ6	981
BBS10	BBS2	Q9BXC9	980
BBS10	BBS1	Q8NFJ9	971
BBS10	BBS5	Q8N3I7	969
BBS10	BBS9	P78514	949
BBS10	BBS4	Q96RK4	949
BBS10	MKS1	Q9NXB0	904
BBS10	TTC8	Q8TAM2	861
BBS10	WDPCP	O95876	855
BBS10	CEP290	O15078	848
BBS10	TRIM32	Q13049	805
BBS10	CCDC28B	Q9BUN5	801
BBS10	TMEM67	Q5HYA8	799
BBS10	LZTFL1	Q9NQ48	722

IntAct

37 interactions, top by confidence:

A	B	Type	Score
BBS10	BBS7	psi-mi:“MI:0915”(physical association)	0.750
DNAJC7	PLD2	psi-mi:“MI:0914”(association)	0.640
BBS10	BBS12	psi-mi:“MI:0915”(physical association)	0.580
BBS12	BBS10	psi-mi:“MI:0914”(association)	0.580
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
MKKS	TCP1	psi-mi:“MI:0914”(association)	0.530
BBS7	TCP1	psi-mi:“MI:0914”(association)	0.460
BBS10	BBS9	psi-mi:“MI:0915”(physical association)	0.400
BBS10	TCP1	psi-mi:“MI:0915”(physical association)	0.400
BBS10	HSP90AA4P	psi-mi:“MI:0915”(physical association)	0.400
YAE1	BBS10	psi-mi:“MI:0915”(physical association)	0.370
BBS10	CSNK1E	psi-mi:“MI:0915”(physical association)	0.370
BBS10	FRZB	psi-mi:“MI:0915”(physical association)	0.370
HDAC6	BBS10	psi-mi:“MI:0915”(physical association)	0.370
MAP3K7	BBS10	psi-mi:“MI:0915”(physical association)	0.370
BBS10	MAPK6	psi-mi:“MI:0915”(physical association)	0.370
MAPK8IP2	BBS10	psi-mi:“MI:0915”(physical association)	0.370
BBS10	NR4A1	psi-mi:“MI:0915”(physical association)	0.370
PTK2	BBS10	psi-mi:“MI:0915”(physical association)	0.370
BBS10	RASA1	psi-mi:“MI:0915”(physical association)	0.370
BBS10	RGS2	psi-mi:“MI:0915”(physical association)	0.370
BBS10	TNFSF11	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
ZNRD2	KRBA1	psi-mi:“MI:0914”(association)	0.350
BBS7	PER1	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): BBS10 (Affinity Capture-MS), BBS10 (Affinity Capture-MS), BBS10 (Affinity Capture-MS), BBS10 (Affinity Capture-MS), BBS10 (Affinity Capture-MS), BBS10 (Affinity Capture-MS), BBS10 (Affinity Capture-MS), HSP90AA4P (Affinity Capture-MS), BBS10 (Affinity Capture-MS), BBS10 (Affinity Capture-MS), BBS10 (Affinity Capture-MS), BBS10 (Two-hybrid), BBS10 (Two-hybrid), BBS10 (Two-hybrid), BBS10 (Two-hybrid)

ESM2 similar proteins: A4D1B5, A5PKN5, A7RV13, D3IUT5, O70167, O70173, O75747, P42695, Q12769, Q28HN9, Q3MHH2, Q3TCV3, Q3UPC7, Q3URV1, Q5BKL1, Q5EA76, Q5R8P3, Q5RB52, Q5RC62, Q5RD58, Q5SUD9, Q5ZK21, Q5ZL79, Q63517, Q66H58, Q66HC3, Q66KD9, Q6DFW0, Q6GN08, Q6ZQK0, Q6ZW61, Q8BJW5, Q8BKN5, Q8IV33, Q8K1K4, Q8N957, Q8NB91, Q8R3P6, Q8TAM1, Q91YN0

Diamond homologs: Q5R8P3, Q8TAM1, Q9DBI2, O15891, P39079, Q9HHA2, Q9W790

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 34 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	5	112.8×	6e-08
Cargo trafficking to the periciliary membrane	5	56.4×	9e-07
Cilium Assembly	7	34.6×	6e-08
Organelle biogenesis and maintenance	7	21.0×	9e-07

GO biological processes:

GO term	Partners	Fold	FDR
fat cell differentiation	5	31.2×	9e-05
cilium assembly	7	17.8×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

1076 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	106
Likely pathogenic	100
Uncertain significance	431
Likely benign	306
Benign	15

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1029918	NM_024685.4(BBS10):c.1365T>G (p.Tyr455Ter)	Pathogenic
1069258	NM_024685.4(BBS10):c.439C>T (p.Gln147Ter)	Pathogenic
1070972	NM_024685.4(BBS10):c.455_456del (p.His152fs)	Pathogenic
1072493	NM_024685.4(BBS10):c.313_314del (p.Lys105fs)	Pathogenic
1075020	NM_024685.4(BBS10):c.35dup (p.Ala13fs)	Pathogenic
1328	NM_024685.4(BBS10):c.271dup (p.Cys91fs)	Pathogenic
1331	NM_024685.4(BBS10):c.931T>G (p.Ser311Ala)	Pathogenic
1354861	NM_024685.4(BBS10):c.258del (p.Phe86fs)	Pathogenic
1369287	NM_024685.4(BBS10):c.467del (p.Ile156fs)	Pathogenic
1372511	NM_024685.4(BBS10):c.883A>T (p.Lys295Ter)	Pathogenic
1377847	NM_024685.4(BBS10):c.490dup (p.Thr164fs)	Pathogenic
1401301	NM_024685.4(BBS10):c.1080_1081del (p.Cys360_Glu361delinsTer)	Pathogenic
1444742	NM_024685.4(BBS10):c.1839T>A (p.Tyr613Ter)	Pathogenic
1445932	NM_024685.4(BBS10):c.1453dup (p.Thr485fs)	Pathogenic
1451238	NM_024685.4(BBS10):c.409C>T (p.Gln137Ter)	Pathogenic
1451637	NM_024685.4(BBS10):c.197+1G>A	Pathogenic
1454610	NM_024685.4(BBS10):c.2044dup (p.Met682fs)	Pathogenic
1455752	NM_024685.4(BBS10):c.953del (p.Asp317_Leu318insTer)	Pathogenic
1456053	NM_024685.4(BBS10):c.1290_1293del (p.Asn431fs)	Pathogenic
1456477	NM_024685.4(BBS10):c.391C>T (p.Gln131Ter)	Pathogenic
1457811	NM_024685.4(BBS10):c.1834del (p.Tyr612fs)	Pathogenic
1460369	NM_024685.4(BBS10):c.1330del (p.Ser444fs)	Pathogenic
166723	NM_024685.4(BBS10):c.1091del (p.Asn364fs)	Pathogenic
188992	NM_024685.4(BBS10):c.1599_1602del (p.Thr534fs)	Pathogenic
189071	NM_024685.4(BBS10):c.728_731del (p.Lys243fs)	Pathogenic
1967707	NM_024685.4(BBS10):c.1272del (p.Leu424fs)	Pathogenic
1992822	NM_024685.4(BBS10):c.1225del (p.Gln409fs)	Pathogenic
2035474	NM_024685.4(BBS10):c.1795_1796del (p.Val599fs)	Pathogenic
2119850	NM_024685.4(BBS10):c.1767C>G (p.Tyr589Ter)	Pathogenic
2136306	NM_024685.4(BBS10):c.180dup (p.Glu61fs)	Pathogenic

SpliceAI

151 predictions. Top by Δscore:

Variant	Effect	Δscore
12:76348256:G:A	donor_gain	0.9900
12:76348158:GTACC:G	donor_loss	0.9600
12:76348159:TACC:T	donor_loss	0.9600
12:76348160:ACC:A	donor_loss	0.9600
12:76348161:CC:C	donor_loss	0.9600
12:76348157:GGTA:G	donor_loss	0.9500
12:76348192:T:TA	donor_gain	0.9100
12:76347700:TCTAA:T	acceptor_gain	0.9000
12:76347701:C:G	acceptor_gain	0.9000
12:76348355:A:C	donor_gain	0.9000
12:76348161:CCTGG:C	donor_gain	0.8900
12:76347786:TC:T	acceptor_gain	0.8800
12:76347787:CC:C	acceptor_gain	0.8800
12:76348206:T:TA	donor_gain	0.8800
12:76348162:C:A	donor_loss	0.8700
12:76348186:AGCG:A	donor_gain	0.8700
12:76347788:C:CC	acceptor_gain	0.8600
12:76348261:C:A	donor_gain	0.8600
12:76347787:CCTGT:C	acceptor_loss	0.8500
12:76347788:C:CA	acceptor_loss	0.8500
12:76347789:T:A	acceptor_loss	0.8500
12:76348156:GGGTA:G	donor_loss	0.8500
12:76347784:CATC:C	acceptor_gain	0.8400
12:76347900:T:TA	donor_gain	0.8400
12:76348222:A:AC	donor_gain	0.8200
12:76347783:TCATC:T	acceptor_gain	0.8000
12:76347784:CATCC:C	acceptor_gain	0.8000
12:76348360:T:C	donor_gain	0.7900
12:76348294:T:TA	donor_gain	0.7700
12:76347803:A:C	acceptor_loss	0.7500

AlphaMissense

4747 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:76346144:A:G	L614P	0.974
12:76348215:G:C	S48R	0.965
12:76348215:G:T	S48R	0.965
12:76348217:T:G	S48R	0.965
12:76345934:T:A	K684I	0.960
12:76347250:A:C	F245L	0.960
12:76347250:A:T	F245L	0.960
12:76347252:A:G	F245L	0.960
12:76347727:A:C	F86L	0.956
12:76347727:A:T	F86L	0.956
12:76347729:A:G	F86L	0.956
12:76346875:A:C	F370L	0.950
12:76346875:A:T	F370L	0.950
12:76346877:A:G	F370L	0.950
12:76347288:A:G	S233P	0.950
12:76345905:A:G	C694R	0.949
12:76346165:T:A	E607V	0.947
12:76346189:A:T	V599D	0.946
12:76346993:A:T	V331D	0.943
12:76346085:C:G	A634P	0.942
12:76347287:G:A	S233F	0.942
12:76347734:T:A	K84I	0.941
12:76346783:C:T	G401E	0.938
12:76346075:A:G	L637P	0.932
12:76347704:A:G	L94P	0.932
12:76346079:C:G	A636P	0.929
12:76345933:T:A	K684N	0.924
12:76345933:T:G	K684N	0.924
12:76348271:C:G	G30R	0.923
12:76348271:C:T	G30R	0.923

dbSNP variants (sampled 300 via entrez): RS1000990130 (12:76346999 G>A), RS1001447104 (12:76349463 T>G), RS1001512051 (12:76348304 C>A,G), RS1002214668 (12:76346706 C>G,T), RS1002950898 (12:76344527 T>C), RS1003015245 (12:76349663 T>C,G), RS1003705267 (12:76345818 G>A,C), RS1005288416 (12:76349089 T>C,G), RS1005369606 (12:76347898 C>T), RS1005752201 (12:76348778 T>G), RS1007028438 (12:76344026 T>C), RS1007061047 (12:76344438 C>T), RS1007365409 (12:76345693 AC>A), RS1007763035 (12:76345657 A>G), RS1008920234 (12:76348678 C>T)

Disease associations

OMIM: gene MIM:610148 | disease phenotypes: MIM:209900, MIM:615987, MIM:268000, MIM:613091

GenCC curated gene-disease

Disease	Classification	Inheritance
Bardet-Biedl syndrome 10	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
BBS10-related ciliopathy	Definitive	AR

Mondo (11): Bardet-Biedl syndrome (MONDO:0015229), Bardet-Biedl syndrome 10 (MONDO:0014438), inherited retinal dystrophy (MONDO:0019118), optic atrophy (MONDO:0003608), Bardet-Biedl syndrome 1 (MONDO:0008854), retinitis pigmentosa (MONDO:0019200), intellectual disability (MONDO:0001071), macular degeneration (MONDO:0003004), postaxial polydactyly of fingers (MONDO:0017426), BBS10-related ciliopathy (MONDO:0700237), asphyxiating thoracic dystrophy 3 (MONDO:0013127)

Orphanet (9): Bardet-Biedl syndrome (Orphanet:110), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791), Jeune syndrome (Orphanet:474), Short rib-polydactyly syndrome, Majewski type (Orphanet:93269), Short rib-polydactyly syndrome, Saldino-Noonan type (Orphanet:93270), Short rib-polydactyly syndrome, Verma-Naumoff type (Orphanet:93271), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), OBSOLETE: Postaxial polydactyly of fingers (Orphanet:294942)

HPO phenotypes

102 total (30 of 102 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000011	Neurogenic bladder
HP:0000028	Cryptorchidism
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000085	Horseshoe kidney
HP:0000100	Nephrotic syndrome
HP:0000107	Renal cyst
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:0000548	Cone/cone-rod dystrophy

GWAS associations

0 associations (top):

MeSH disease descriptors (9)

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
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008268	Macular Degeneration	C11.768.585.439
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C565919	Bardet-Biedl Syndrome 10 (supp.)
C537909	Bardet-Biedl syndrome 1 (supp.)
C537602	Short rib-polydactyly syndrome, Verma-Naumoff type (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
trichostatin A	affects cotreatment, decreases expression	3
Cyclosporine	decreases expression	3
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	increases expression	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Phenobarbital	affects expression	1
Progesterone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Zinc	decreases expression	1
Aflatoxin M1	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	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_UG22	KCi002-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

283 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
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
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]
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)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa