BBS12

Summary

BBS12 (Bardet-Biedl syndrome 12, HGNC:26648) is a protein-coding gene on chromosome 4q27, encoding Chaperonin-containing T-complex member BBS12 (Q6ZW61). Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis.

The protein encoded by this gene is part of a complex that is involved in membrane trafficking. The encoded protein is a molecular chaperone that aids in protein folding upon ATP hydrolysis. This protein also plays a role in adipocyte differentiation. Defects in this gene are a cause of Bardet-Biedl syndrome type 12. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 166379 — RefSeq curated summary.

At a glance

• Gene–disease (curated): BBS12-related ciliopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 902 total — 74 pathogenic, 56 likely-pathogenic
• Phenotypes (HPO): 105
• MANE Select transcript: NM_152618

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26648
Approved symbol	BBS12
Name	Bardet-Biedl syndrome 12
Location	4q27
Locus type	gene with protein product
Status	Approved
Aliases	FLJ35630, FLJ41559
Ensembl gene	ENSG00000181004
Ensembl biotype	protein_coding
OMIM	610683
Entrez	166379

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000314218, ENST00000433287, ENST00000542236

RefSeq mRNA: 2 — MANE Select: NM_152618 NM_001178007, NM_152618

CCDS: CCDS3728

Canonical transcript exons

ENST00000314218 — 2 exons

Exon	Start	End
ENSE00001233134	122741883	122744939
ENSE00003850136	122732704	122732884

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 88.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.4823 / max 58.5584, expressed in 1596 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49542	2.6760	1249
49541	1.8063	1102

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.89	gold quality
sperm	CL:0000019	86.26	gold quality
bronchial epithelial cell	CL:0002328	84.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.51	gold quality
bronchus	UBERON:0002185	82.98	gold quality
kidney epithelium	UBERON:0004819	80.05	silver quality
germinal epithelium of ovary	UBERON:0001304	80.04	gold quality
secondary oocyte	CL:0000655	78.47	gold quality
islet of Langerhans	UBERON:0000006	77.66	gold quality
cartilage tissue	UBERON:0002418	77.02	gold quality
jejunal mucosa	UBERON:0000399	76.82	gold quality
caput epididymis	UBERON:0004358	76.12	gold quality
stromal cell of endometrium	CL:0002255	75.99	gold quality
palpebral conjunctiva	UBERON:0001812	75.07	gold quality
left ventricle myocardium	UBERON:0006566	74.63	gold quality
eye	UBERON:0000970	74.47	gold quality
epithelium of nasopharynx	UBERON:0001951	73.61	gold quality
adult mammalian kidney	UBERON:0000082	73.52	gold quality
calcaneal tendon	UBERON:0003701	73.51	gold quality
cortical plate	UBERON:0005343	73.49	gold quality
thyroid gland	UBERON:0002046	73.26	gold quality
left lobe of thyroid gland	UBERON:0001120	73.24	gold quality
kidney	UBERON:0002113	73.13	gold quality
right lobe of thyroid gland	UBERON:0001119	72.99	gold quality
pigmented layer of retina	UBERON:0001782	72.66	gold quality
heart left ventricle	UBERON:0002084	72.51	gold quality
corpus epididymis	UBERON:0004359	72.32	gold quality
right atrium auricular region	UBERON:0006631	72.04	gold quality
cardiac ventricle	UBERON:0002082	72.02	gold quality
ileal mucosa	UBERON:0000331	71.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting BBS12, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-590-5P	99.25	70.76	930
HSA-MIR-6797-3P	99.17	66.94	668
HSA-MIR-4520-2-3P	99.14	69.28	1009

Literature-anchored findings (GeneRIF, showing 7)

• BBS12 accounts for approximately 5% of all BBS cases and defines a novel branch of the type II chaperonin superfamily (PMID:17160889)
• 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)
• Mutation in BBS12 accounts for Bardet-Biedl syndrome and termination of pregnancy of a fetus. (PMID:20827784)
• BBS12 inactivation increases glucose absorption by mature human adipocytes, increases insulin sensitivity, enhances glucose absorption and increases triglyceride content. (PMID:22958920)
• novel BBS12 mutations in Bardet-Biedl syndrome patients in Spain (PMID:24611592)
• Exome sequencing in a Romanian Bardet-Biedl syndrome cohort revealed an overabundance of causal BBS12 variants. (PMID:37293956)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	bbs12	ENSDARG00000016112
mus_musculus	Bbs12	ENSMUSG00000051444
rattus_norvegicus	Bbs12	ENSRNOG00000068263

Paralogs (13): PIKFYVE (ENSG00000115020), CCT4 (ENSG00000115484), TCP1 (ENSG00000120438), MKKS (ENSG00000125863), CCT6B (ENSG00000132141), CCT7 (ENSG00000135624), HSPD1 (ENSG00000144381), CCT6A (ENSG00000146731), CCT5 (ENSG00000150753), CCT8 (ENSG00000156261), CCT3 (ENSG00000163468), CCT2 (ENSG00000166226), CCT8L2 (ENSG00000198445)

Protein

Protein identifiers

Chaperonin-containing T-complex member BBS12 — Q6ZW61 (reviewed: Q6ZW61)

Alternative names: Bardet-Biedl syndrome 12 protein

All UniProt accessions (2): C9J8H7, Q6ZW61

UniProt curated annotations — full annotation on UniProt →

Function. Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis. As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. Involved in adipogenic differentiation.

Subunit / interactions. Component of the chaperonin-containing T-complex (TRiC), a heterooligomeric complex of about 850 to 900 kDa that forms two stacked rings, 12 to 16 nm in diameter. Interacts with MKKS.

Subcellular location. Cell projection. Cilium.

Disease relevance. Bardet-Biedl syndrome 12 (BBS12) [MIM:615989] 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. BBS12 subfamily.

RefSeq proteins (2): NP_001171478, NP_689831* (*=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
IPR042984	BBS12	Family

Pfam: PF00118

UniProt features (32 total): sequence variant 29, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZW61-F1	73.92	0.47

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: 327 (showing top): GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_BEHAVIOR, GOBP_NEGATIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_CHAPERONE_MEDIATED_PROTEIN_COMPLEX_ASSEMBLY, NKX61_01, GOBP_EATING_BEHAVIOR, SOX9_B1, GOBP_PHOTORECEPTOR_CELL_MAINTENANCE, GOBP_CILIUM_ORGANIZATION, GOBP_FAT_CELL_DIFFERENTIATION, AACTTT_UNKNOWN, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, HAND1E47_01, GOBP_CELL_PROJECTION_ORGANIZATION

GO Biological Process (8): intraciliary transport (GO:0042073), eating behavior (GO:0042755), fat cell differentiation (GO:0045444), photoreceptor cell maintenance (GO:0045494), negative regulation of fat cell differentiation (GO:0045599), stem cell differentiation (GO:0048863), chaperone-mediated protein complex assembly (GO:0051131), negative regulation of stem cell differentiation (GO:2000737)

GO Molecular Function (2): ATP binding (GO:0005524), 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
cell differentiation	2
negative regulation of cell differentiation	2
cilium	1
transport along microtubule	1
cilium organization	1
feeding behavior	1
retina homeostasis	1
multicellular organismal process	1
fat cell differentiation	1
regulation of fat cell differentiation	1
protein-containing complex assembly	1
stem cell differentiation	1
regulation of stem cell differentiation	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate 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

610 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BBS12	BBS10	Q8TAM1	999
BBS12	BBS7	Q8IWZ6	977
BBS12	BBS9	P78514	927
BBS12	BBS2	Q9BXC9	924
BBS12	BBS4	Q96RK4	921
BBS12	BBS1	Q8NFJ9	921
BBS12	BBS5	Q8N3I7	918
BBS12	WDPCP	O95876	872
BBS12	TTC8	Q8TAM2	868
BBS12	MKS1	Q9NXB0	853
BBS12	TRIM32	Q13049	817
BBS12	CCDC28B	Q9BUN5	817
BBS12	CEP290	O15078	806
BBS12	TMEM67	Q5HYA8	739
BBS12	LZTFL1	Q9NQ48	732

IntAct

33 interactions, top by confidence:

A	B	Type	Score
BBS12	MKKS	psi-mi:“MI:0915”(physical association)	0.830
MKKS	BBS12	psi-mi:“MI:0915”(physical association)	0.830
MKKS	BBS12	psi-mi:“MI:0914”(association)	0.830
BBS12	BBS7	psi-mi:“MI:0915”(physical association)	0.780
BBS12	BBS7	psi-mi:“MI:0914”(association)	0.780
BBS7	BBS12	psi-mi:“MI:0915”(physical association)	0.780
BBS10	BBS12	psi-mi:“MI:0915”(physical association)	0.580
BBS12	BBS10	psi-mi:“MI:0914”(association)	0.580
BBS12	FERMT2	psi-mi:“MI:0915”(physical association)	0.530
MKKS	TCP1	psi-mi:“MI:0914”(association)	0.530
PTPDC1	DCAF7	psi-mi:“MI:0914”(association)	0.510
BBS12	BBS2	psi-mi:“MI:0915”(physical association)	0.500
BBS12	BBS9	psi-mi:“MI:0915”(physical association)	0.400
BBS10	TCP1	psi-mi:“MI:0915”(physical association)	0.400
BBS12	BBS1	psi-mi:“MI:0915”(physical association)	0.400
BBS12	BBS4	psi-mi:“MI:0915”(physical association)	0.400
BBS12	PTPDC1	psi-mi:“MI:0915”(physical association)	0.000
BBS12	PPP2R1A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): MKKS (Affinity Capture-MS), BBS7 (Affinity Capture-MS), BBS12 (Affinity Capture-MS), PTPDC1 (Affinity Capture-MS), BBS12 (Affinity Capture-MS), PPP2R1A (Affinity Capture-MS), BBS12 (Affinity Capture-RNA), MKKS (Affinity Capture-MS), BBS7 (Affinity Capture-MS), PDS5A (Cross-Linking-MS (XL-MS))

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: A5PKN5, Q5RC62, Q5SUD9, Q6ZW61, Q54CL2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 12 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	8	361.1×	2e-18
Cargo trafficking to the periciliary membrane	7	158.0×	3e-13
Cilium Assembly	8	79.1×	3e-13
Organelle biogenesis and maintenance	8	48.0×	2e-11

GO biological processes:

GO term	Partners	Fold	FDR
photoreceptor cell maintenance	5	149.4×	3e-09
non-motile cilium assembly	6	145.3×	2e-10
fat cell differentiation	6	90.6×	1e-09
visual perception	7	46.4×	1e-09
cilium assembly	7	42.9×	2e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	74
Likely pathogenic	56
Uncertain significance	364
Likely benign	290
Benign	19

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069432	NM_152618.3(BBS12):c.1827C>G (p.Tyr609Ter)	Pathogenic
1070921	NM_152618.3(BBS12):c.1705del (p.Leu569fs)	Pathogenic
1071214	NM_152618.3(BBS12):c.398del (p.Pro133fs)	Pathogenic
1072321	NM_152618.3(BBS12):c.664dup (p.Ala222fs)	Pathogenic
1073661	NM_152618.3(BBS12):c.1088_1089del (p.Leu363fs)	Pathogenic
1074975	NM_152618.3(BBS12):c.867_874del (p.Val290fs)	Pathogenic
1076399	NM_152618.3(BBS12):c.890_893del (p.Ala297fs)	Pathogenic
1147	NM_152618.3(BBS12):c.1063C>T (p.Arg355Ter)	Pathogenic
1149	NM_152618.3(BBS12):c.1483_1484del (p.Glu495fs)	Pathogenic
1285360	NM_152618.3(BBS12):c.1156_1157delinsTA (p.Arg386Ter)	Pathogenic
1324316	NM_152618.3(BBS12):c.683del (p.Gln228fs)	Pathogenic
1372670	NM_152618.3(BBS12):c.1193dup (p.Asn398fs)	Pathogenic
1384347	NM_152618.3(BBS12):c.27_30del (p.Asn9fs)	Pathogenic
1391679	NM_152618.3(BBS12):c.58del (p.Ser20fs)	Pathogenic
1400771	NM_152618.3(BBS12):c.1082_1083insGGGT (p.Asp362fs)	Pathogenic
1419351	NM_152618.3(BBS12):c.1394_1395del (p.Val465fs)	Pathogenic
1440165	NM_152618.3(BBS12):c.1392_1395del (p.Cys464fs)	Pathogenic
1447228	NM_152618.3(BBS12):c.1724G>A (p.Trp575Ter)	Pathogenic
1455603	NM_152618.3(BBS12):c.1048C>T (p.Gln350Ter)	Pathogenic
1455670	NM_152618.3(BBS12):c.469_470del (p.Leu157fs)	Pathogenic
1456901	NM_152618.3(BBS12):c.1463_1464del (p.Ile488fs)	Pathogenic
1910974	NM_152618.3(BBS12):c.2092_2093del (p.Gln698fs)	Pathogenic
195415	NM_152618.3(BBS12):c.1704G>A (p.Trp568Ter)	Pathogenic
1994803	NM_152618.3(BBS12):c.1208dup (p.Leu404fs)	Pathogenic
2021516	NM_152618.3(BBS12):c.2036del (p.Asp678_Leu679insTer)	Pathogenic
2021723	NM_152618.3(BBS12):c.1117_1118insT (p.Asn373fs)	Pathogenic
2081712	NM_152618.3(BBS12):c.2099del (p.Asn700fs)	Pathogenic
2092347	NM_152618.3(BBS12):c.572_576del (p.Gly191fs)	Pathogenic
2131605	NM_152618.3(BBS12):c.1554del (p.Arg518fs)	Pathogenic
2203571	NM_152618.3(BBS12):c.420_423del (p.Cys140fs)	Pathogenic

SpliceAI

264 predictions. Top by Δscore:

Variant	Effect	Δscore
4:122741877:TTGCA:T	acceptor_loss	1.0000
4:122741878:TGCA:T	acceptor_loss	1.0000
4:122741879:GCAG:G	acceptor_loss	1.0000
4:122741880:CAGAT:C	acceptor_loss	1.0000
4:122741881:A:AG	acceptor_gain	1.0000
4:122741881:A:AT	acceptor_loss	1.0000
4:122741882:G:GA	acceptor_gain	1.0000
4:122741882:GATC:G	acceptor_gain	1.0000
4:122741969:G:GT	donor_gain	1.0000
4:122741882:GATCA:G	acceptor_gain	0.9900
4:122732881:CGAG:C	donor_loss	0.9800
4:122732883:AGG:A	donor_loss	0.9800
4:122732884:GGTT:G	donor_loss	0.9800
4:122732885:G:GA	donor_loss	0.9800
4:122732918:C:G	donor_gain	0.9800
4:122741882:GAT:G	acceptor_gain	0.9800
4:122736714:G:GT	donor_gain	0.9700
4:122732880:GCGAG:G	donor_gain	0.9600
4:122741882:GA:G	acceptor_gain	0.9500
4:122732836:TGGG:T	donor_gain	0.9400
4:122732889:GTA:G	donor_gain	0.9200
4:122736714:GAA:G	donor_gain	0.9200
4:122732887:TAGTA:T	donor_loss	0.9100
4:122741874:T:TA	acceptor_gain	0.9100
4:122741970:A:T	donor_gain	0.8800
4:122732891:A:AG	donor_gain	0.8600
4:122732892:G:GG	donor_gain	0.8600
4:122734043:C:T	donor_gain	0.8600
4:122741874:T:A	acceptor_loss	0.8600
4:122742051:A:AG	donor_gain	0.8600

AlphaMissense

4649 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:122742175:T:A	W95R	0.995
4:122742175:T:C	W95R	0.995
4:122743909:T:A	W673R	0.992
4:122743909:T:C	W673R	0.992
4:122742178:A:C	S96R	0.990
4:122742180:C:A	S96R	0.990
4:122742180:C:G	S96R	0.990
4:122743675:T:A	W595R	0.990
4:122743675:T:C	W595R	0.990
4:122743918:G:C	A676P	0.976
4:122743528:T:C	C546R	0.973
4:122743899:G:C	K669N	0.971
4:122743899:G:T	K669N	0.971
4:122743943:T:C	L684P	0.969
4:122743919:C:A	A676E	0.967
4:122742980:T:C	L363P	0.966
4:122743913:G:C	R674P	0.965
4:122743466:G:C	R525P	0.964
4:122743520:A:T	E543V	0.964
4:122743684:T:G	Y598D	0.964
4:122743448:T:C	F519S	0.963
4:122743530:T:G	C546W	0.963
4:122743911:G:C	W673C	0.962
4:122743911:G:T	W673C	0.962
4:122741948:T:C	L19P	0.961
4:122743916:G:C	R675P	0.961
4:122743906:G:C	A672P	0.960
4:122742101:T:C	L70P	0.959
4:122743688:T:C	L599P	0.959
4:122742592:A:C	S234R	0.955

dbSNP variants (sampled 300 via entrez): RS1000012849 (4:122727681 T>C), RS1000075456 (4:122717866 C>A), RS10001016 (4:122707941 T>A), RS1000218437 (4:122719347 G>A), RS1000223051 (4:122719457 G>A,T), RS1000225447 (4:122707236 T>A), RS1000271721 (4:122724850 G>A,T), RS1000319364 (4:122712621 C>T), RS1000348776 (4:122725927 A>T), RS1000370606 (4:122724334 T>C), RS1000380784 (4:122699280 G>A), RS1000449888 (4:122739262 G>C), RS1000452701 (4:122712957 A>C,G), RS1000505051 (4:122717799 A>G), RS1000555507 (4:122718039 T>G)

Disease associations

OMIM: gene MIM:610683 | disease phenotypes: MIM:615989, MIM:209900, MIM:268000, MIM:174200

GenCC curated gene-disease

Disease	Classification	Inheritance
Bardet-Biedl syndrome 12	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
BBS12-related ciliopathy	Definitive	AR

Mondo (8): Bardet-Biedl syndrome 12 (MONDO:0014440), Bardet-Biedl syndrome (MONDO:0015229), Bardet-Biedl syndrome 1 (MONDO:0008854), retinitis pigmentosa (MONDO:0019200), polydactyly, postaxial, type A1 (MONDO:0008266), inherited retinal dystrophy (MONDO:0019118), BBS12-related ciliopathy (MONDO:1040045), congenital nervous system disorder (MONDO:0002320)

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

HPO phenotypes

105 total (30 of 105 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000011	Neurogenic bladder
HP:0000028	Cryptorchidism
HP:0000072	Hydroureter
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:0000148	Vaginal atresia
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

10 associations (top):

Study	Trait	p-value
GCST003542_2	Night sleep phenotypes	1.000000e-06
GCST004861_53	Itch intensity from mosquito bite	2.000000e-37
GCST004862_186	Itch intensity from mosquito bite adjusted by bite size	5.000000e-13
GCST004862_195	Itch intensity from mosquito bite adjusted by bite size	6.000000e-07
GCST004862_48	Itch intensity from mosquito bite adjusted by bite size	1.000000e-08
GCST004863_135	Mosquito bite size	3.000000e-39
GCST004865_77	Itch intensity from mosquito bite adjusted by bite size	2.000000e-11
GCST009257_3	Caudate nucleus volume	4.000000e-06
GCST009391_1207	Metabolite levels	1.000000e-06
GCST009798_57	Asthma	8.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004830	caudate nucleus volume
EFO:0010419	triacylglycerol 54:1 measurement

MeSH disease descriptors (5)

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
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C565921	Bardet-Biedl Syndrome 12 (supp.)
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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases expression	3
Formaldehyde	decreases expression, increases expression	2
Cyclosporine	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
ferrous chloride	decreases expression	1
avobenzone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
bisphenol S	increases methylation, affects cotreatment	1
jinfukang	decreases expression	1
NSC 689534	affects binding, increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	affects expression, increases abundance	1
Cisplatin	decreases expression	1
Copper	affects binding, increases expression	1
Doxorubicin	affects response to substance	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Quercetin	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1

Clinical trials (associated diseases)

274 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
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
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
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in 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
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
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
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)