WDPCP

Summary

WDPCP (WD repeat containing planar cell polarity effector, HGNC:28027) is a protein-coding gene on chromosome 2p15, encoding WD repeat-containing and planar cell polarity effector protein fritz homolog (O95876). Probable effector of the planar cell polarity signaling pathway which regulates the septin cytoskeleton in both ciliogenesis and collective cell movements.

This gene encodes a cytoplasmic WD40 repeat protein. A similar gene in frogs encodes a planar cell polarity protein that plays a critical role in collective cell movement and ciliogenesis by mediating septin localization. Mutations in this gene are associated with Bardet-Biedl syndrome 15 and may also play a role in Meckel-Gruber syndrome. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 51057 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliopathy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 17
• Clinical variants (ClinVar): 797 total — 29 pathogenic, 24 likely-pathogenic
• Phenotypes (HPO): 111
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_015910

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28027
Approved symbol	WDPCP
Name	WD repeat containing planar cell polarity effector
Location	2p15
Locus type	gene with protein product
Status	Approved
Aliases	hFrtz, fritz, BBS15, CPLANE5
Ensembl gene	ENSG00000143951
Ensembl biotype	protein_coding
OMIM	613580
Entrez	51057

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 13 protein_coding, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 3 retained_intron

ENST00000272321, ENST00000398544, ENST00000409120, ENST00000409199, ENST00000409354, ENST00000409562, ENST00000409835, ENST00000417238, ENST00000418148, ENST00000431065, ENST00000462652, ENST00000467687, ENST00000473678, ENST00000484073, ENST00000487280, ENST00000490935, ENST00000493315, ENST00000872046, ENST00000872047, ENST00000872048, ENST00000946852, ENST00000946853, ENST00000946854

RefSeq mRNA: 4 — MANE Select: NM_015910 NM_001042692, NM_001354044, NM_001354045, NM_015910

CCDS: CCDS42688, CCDS46301

Canonical transcript exons

ENST00000272321 — 18 exons

Exon	Start	End
ENSE00001070039	63259307	63259409
ENSE00001365513	63313248	63313311
ENSE00003468254	63487447	63487494
ENSE00003475421	63437421	63437554
ENSE00003493306	63404048	63404657
ENSE00003546224	63484604	63484663
ENSE00003554041	63174670	63174832
ENSE00003563027	63152914	63152945
ENSE00003579927	63433745	63433936
ENSE00003581314	63381906	63382094
ENSE00003583751	63492856	63492940
ENSE00003590873	63484917	63484987
ENSE00003602509	63153495	63153574
ENSE00003607336	63119559	63122056
ENSE00003615470	63439757	63439871
ENSE00003629485	63486542	63486586
ENSE00003640264	63378386	63378509
ENSE00003841481	63588197	63588477

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 97.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.0496 / max 597.1617, expressed in 1626 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
28705	1.5370	776
28708	1.3081	788
28713	1.0908	133
28707	0.8188	532
28706	0.5691	289
28711	0.5660	343
28709	0.4703	235
28710	0.2625	116
28714	0.1927	57
28704	0.1402	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	97.83	silver quality
kidney epithelium	UBERON:0004819	96.40	silver quality
mucosa of paranasal sinus	UBERON:0005030	94.15	gold quality
palpebral conjunctiva	UBERON:0001812	93.80	gold quality
superficial temporal artery	UBERON:0001614	93.34	gold quality
sperm	CL:0000019	93.20	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.10	silver quality
left ventricle myocardium	UBERON:0006566	93.02	gold quality
epithelial cell of pancreas	CL:0000083	92.87	gold quality
buccal mucosa cell	CL:0002336	92.56	silver quality
germinal epithelium of ovary	UBERON:0001304	92.50	gold quality
upper arm skin	UBERON:0004263	92.46	silver quality
cardia of stomach	UBERON:0001162	91.74	gold quality
bronchial epithelial cell	CL:0002328	91.38	gold quality
bronchus	UBERON:0002185	91.22	gold quality
myocardium	UBERON:0002349	90.64	silver quality
ventral tegmental area	UBERON:0002691	90.49	gold quality
corpus callosum	UBERON:0002336	90.00	gold quality
tibia	UBERON:0000979	89.99	gold quality
lateral globus pallidus	UBERON:0002476	89.89	gold quality
endothelial cell	CL:0000115	89.83	gold quality
inferior vagus X ganglion	UBERON:0005363	89.38	gold quality
subthalamic nucleus	UBERON:0001906	89.18	gold quality
dorsal plus ventral thalamus	UBERON:0001897	88.91	gold quality
medulla oblongata	UBERON:0001896	88.72	gold quality
epithelium of nasopharynx	UBERON:0001951	88.71	gold quality
substantia nigra pars reticulata	UBERON:0001966	88.15	gold quality
superior vestibular nucleus	UBERON:0007227	88.11	gold quality
superior surface of tongue	UBERON:0007371	87.94	gold quality
pylorus	UBERON:0001166	87.79	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.09
E-MTAB-11268	no	2142.60
E-MTAB-9067	no	434.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting WDPCP, 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-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-367-5P	98.84	67.18	902
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-3129-3P	97.85	67.63	1246
HSA-MIR-5583-5P	97.85	67.61	1243
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-1913	97.07	66.20	1417

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 3)

• study linked mutations in Fritz to Bardet-Biedl and Meckel-Gruber syndromes, a notable link given that other genes mutated in these syndromes also influence collective cell movement and ciliogenesis (PMID:20671153)
• Inflammatory cytokines cause reduced WDPCP expression, which contributes to impaired ciliogenesis in human rhinosinusitis. (PMID:28001338)
• Evidence for involvement of the alcohol consumption WDPCP gene in lipid metabolism, and liver cirrhosis. (PMID:37996473)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	wdpcp	ENSDARG00000074590
mus_musculus	Wdpcp	ENSMUSG00000020319
rattus_norvegicus	Wdpcp	ENSRNOG00000054331
drosophila_melanogaster	frtz	FBGN0086698

Protein

Protein identifiers

WD repeat-containing and planar cell polarity effector protein fritz homolog — O95876 (reviewed: O95876)

Alternative names: Bardet-Biedl syndrome 15 protein, WD repeat-containing and planar cell polarity effector protein

All UniProt accessions (7): O95876, A0A1D5RMS8, C9JDS5, E9PFG9, F8WBT2, H7BZ13, H7C375

UniProt curated annotations — full annotation on UniProt →

Function. Probable effector of the planar cell polarity signaling pathway which regulates the septin cytoskeleton in both ciliogenesis and collective cell movements. Together with FUZ and WDPCP proposed to function as core component of the CPLANE (ciliogenesis and planar polarity effectors) complex involved in the recruitment of peripheral IFT-A proteins to basal bodies. Binds phosphatidylinositol 3-phosphate with highest affinity, followed by phosphatidylinositol 4-phosphate and phosphatidylinositol 5-phosphate.

Subunit / interactions. Component of the CPLANE (ciliogenesis and planar polarity effectors) complex, composed of INTU, FUZ and WDPCP. Interacts with CPLANE1.

Subcellular location. Cell membrane. Cytoplasm. Cytoskeleton. Cilium axoneme. Cilium basal body.

Disease relevance. Bardet-Biedl syndrome 15 (BBS15) [MIM:615992] 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. Congenital heart defects, hamartomas of tongue, and polysyndactyly (CHDTHP) [MIM:217085] A disease characterized by a constellation of anomalies including tongue hamartomas, polysyndactyly, and congenital heart defects such as atrioventricular canal and coarctation of the aorta. The disease is caused by variants affecting the gene represented in this entry. Mutations in WDPCP may act as modifiers of the phenotypic expression of Bardet-Biedl syndrome and Meckel syndrome by interacting in trans with primary BBS and MKS loci.

Similarity. Belongs to the WD repeat fritz family.

Isoforms (3)

UniProt ID	Names	Canonical?
O95876-1	1	yes
O95876-2	2
O95876-3	3

RefSeq proteins (4): NP_001036157, NP_001340973, NP_001340974, NP_056994* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR024511	Frtz	Family
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily

Pfam: PF11768

UniProt features (63 total): strand 32, helix 13, turn 7, sequence variant 5, splice variant 3, repeat 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7Q3D	ELECTRON MICROSCOPY	3.35

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95876-F1	76.71	0.51

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 478 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GGGNRMNNYCAT_UNKNOWN, GOBP_EMBRYONIC_DIGIT_MORPHOGENESIS, GOBP_FOCAL_ADHESION_ASSEMBLY, GOBP_REGULATION_OF_RUFFLE_ASSEMBLY, GOBP_REGULATION_OF_FIBROBLAST_MIGRATION, AP4_Q6, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_NEURAL_TUBE_DEVELOPMENT, CHX10_01

GO Biological Process (28): establishment of planar polarity (GO:0001736), kidney development (GO:0001822), auditory receptor cell morphogenesis (GO:0002093), smoothened signaling pathway (GO:0007224), nervous system development (GO:0007399), regulation of fibroblast migration (GO:0010762), regulation of embryonic cell shape (GO:0016476), neural tube development (GO:0021915), septin cytoskeleton organization (GO:0032185), regulation of protein localization (GO:0032880), intraciliary transport (GO:0042073), embryonic digit morphogenesis (GO:0042733), camera-type eye development (GO:0043010), tongue morphogenesis (GO:0043587), cilium organization (GO:0044782), establishment of protein localization (GO:0045184), regulation of focal adhesion assembly (GO:0051893), digestive system development (GO:0055123), roof of mouth development (GO:0060021), cilium assembly (GO:0060271), respiratory system development (GO:0060541), circulatory system development (GO:0072359), podocyte cell migration (GO:0090521), regulation of ruffle assembly (GO:1900027), regulation of cilium assembly (GO:1902017), regulation of establishment of cell polarity (GO:2000114), cell projection organization (GO:0030030), embryonic organ development (GO:0048568)

GO Molecular Function (2): phosphatidylinositol binding (GO:0035091), protein binding (GO:0005515)

GO Cellular Component (10): plasma membrane (GO:0005886), cilium (GO:0005929), axoneme (GO:0005930), axonemal basal plate (GO:0097541), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell cortex (GO:0005938), membrane (GO:0016020), apical plasma membrane (GO:0016324), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
embryonic morphogenesis	2
system development	2
cilium organization	2
cell periphery	2
morphogenesis of a polarized epithelium	1
establishment of tissue polarity	1
animal organ development	1
renal system development	1
inner ear morphogenesis	1
cell morphogenesis involved in neuron differentiation	1
auditory receptor cell development	1
cell surface receptor signaling pathway	1
fibroblast migration	1
regulation of cell migration	1
regulation of cell shape	1
regulation of embryonic development	1
nervous system development	1
tube development	1
chordate embryonic development	1
epithelium development	1
cytoskeleton organization	1
intracellular protein localization	1
regulation of localization	1
cilium	1
transport along microtubule	1
embryonic limb morphogenesis	1
eye development	1
tongue development	1
sensory organ morphogenesis	1
organelle organization	1
plasma membrane bounded cell projection organization	1
establishment of localization	1
regulation of cell-matrix adhesion	1
focal adhesion assembly	1
regulation of cell-substrate junction assembly	1
anatomical structure development	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
protein localization to cilium	1

Protein interactions and networks

STRING

782 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WDPCP	FUZ	Q9BT04	916
WDPCP	INTU	Q9ULD6	893
WDPCP	MKS1	Q9NXB0	879
WDPCP	BBS12	Q6ZW61	872
WDPCP	CPLANE2	Q9BU20	858
WDPCP	BBS10	Q8TAM1	855
WDPCP	CCDC28B	Q9BUN5	820
WDPCP	TTC8	Q8TAM2	819
WDPCP	BBS5	Q8N3I7	816
WDPCP	BBS9	P78514	814
WDPCP	TRIM32	Q13049	802
WDPCP	BBS7	Q8IWZ6	800
WDPCP	BBS2	Q9BXC9	797
WDPCP	BBS1	Q8NFJ9	789
WDPCP	CEP290	O15078	774

IntAct

2 interactions, top by confidence:

A	B	Type	Score
sph	WDPCP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): WDPCP (Affinity Capture-RNA), WDPCP (Cross-Linking-MS (XL-MS)), WDPCP (Affinity Capture-RNA)

ESM2 similar proteins: A0A0R4IC37, A1A4K3, A2CEI4, B1WC10, E9PY46, F1QEB7, F4IDS7, O08658, O13046, O75694, O75717, O95876, P33194, P37199, P59328, Q08D69, Q10569, Q10570, Q16531, Q32NR9, Q3U1J4, Q4ADV7, Q566H4, Q5DQR4, Q5R649, Q5U1Z0, Q5ZLG9, Q6P6Z0, Q6PGF3, Q6PJI9, Q7XWP1, Q802U2, Q805F9, Q8BMG7, Q8C0M0, Q8C456, Q8CEC0, Q8CJF7, Q8K1X1, Q8NFP9

Diamond homologs: B1WC10, O95876, Q32NR9, Q8C456

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
WDPCP	“form complex”	“CPLANE complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	29
Likely pathogenic	24
Uncertain significance	399
Likely benign	254
Benign	12

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069076	NM_015910.7(WDPCP):c.1910_1913del (p.Gly637fs)	Pathogenic
1070497	NM_015910.7(WDPCP):c.979C>T (p.Gln327Ter)	Pathogenic
1075990	NM_015910.7(WDPCP):c.1751_1773del (p.Tyr584fs)	Pathogenic
1172573	GRCh37/hg19 2p15(chr2:63521229-63572056)x1	Pathogenic
1179146	NM_015910.7(WDPCP):c.1809_1812+6del	Pathogenic
1389598	NM_015910.7(WDPCP):c.1419_1420del (p.Leu474fs)	Pathogenic
1451406	NC_000002.11:g.(?63711718)(63815425_?)del	Pathogenic
1452795	NM_015910.7(WDPCP):c.301C>T (p.Arg101Ter)	Pathogenic
1459914	NC_000002.11:g.(?63540363)(63540466_?)del	Pathogenic
1460446	NC_000002.11:g.(?63486422)(63815425_?)del	Pathogenic
162668	NM_015910.7(WDPCP):c.552_553del (p.Cys185fs)	Pathogenic
1896883	NM_015910.7(WDPCP):c.340dup (p.Ser114fs)	Pathogenic
1983825	NM_015910.7(WDPCP):c.1342del (p.Val448fs)	Pathogenic
2118198	NM_015910.7(WDPCP):c.1198del (p.Glu400fs)	Pathogenic
2145983	NM_015910.7(WDPCP):c.1727_1728del (p.Arg576fs)	Pathogenic
2184993	NM_015910.7(WDPCP):c.925_931del (p.Asp309fs)	Pathogenic
2185680	NM_015910.7(WDPCP):c.1799del (p.Arg600fs)	Pathogenic
2196148	NM_015910.7(WDPCP):c.679C>T (p.Arg227Ter)	Pathogenic
2300005	NM_015910.7(WDPCP):c.74del (p.Gln25fs)	Pathogenic
2426235	NC_000002.11:g.(?63815311)(63815405_?)del	Pathogenic
2426236	NC_000002.11:g.(?63605501)(63605664_?)del	Pathogenic
2426237	NC_000002.11:g.(?63401785)(63401987_?)del	Pathogenic
2764775	NM_015910.7(WDPCP):c.216del (p.Glu72fs)	Pathogenic
2912313	NM_015910.7(WDPCP):c.1360G>T (p.Glu454Ter)	Pathogenic
3234011	NM_015910.7(WDPCP):c.720C>A (p.Cys240Ter)	Pathogenic
45	NM_015910.7(WDPCP):c.76-1G>T	Pathogenic
583791	NC_000002.12:g.(?63378386)(63404657_?)del	Pathogenic
917967	NM_015910.7(WDPCP):c.2078+1G>T	Pathogenic
943229	NM_015910.7(WDPCP):c.1872_1875dup (p.Ala626fs)	Pathogenic
1066952	NM_015910.7(WDPCP):c.75+1G>T	Likely pathogenic

SpliceAI

7334 predictions. Top by Δscore:

Variant	Effect	Δscore
2:63152946:C:CC	acceptor_gain	1.0000
2:63153594:T:TC	acceptor_gain	1.0000
2:63153598:T:TC	acceptor_gain	1.0000
2:63313242:ACT:A	donor_loss	1.0000
2:63313243:CTCA:C	donor_loss	1.0000
2:63313244:TCACC:T	donor_loss	1.0000
2:63313245:CACCA:C	donor_loss	1.0000
2:63313246:A:C	donor_loss	1.0000
2:63313247:C:A	donor_loss	1.0000
2:63313309:TAC:T	acceptor_gain	1.0000
2:63313310:AC:A	acceptor_gain	1.0000
2:63313311:CC:C	acceptor_gain	1.0000
2:63313312:C:CC	acceptor_gain	1.0000
2:63313312:CTACA:C	acceptor_loss	1.0000
2:63313313:T:A	acceptor_loss	1.0000
2:63313320:C:CT	acceptor_gain	1.0000
2:63378505:CTGTG:C	acceptor_gain	1.0000
2:63378510:C:CC	acceptor_gain	1.0000
2:63381900:TCTGA:T	donor_loss	1.0000
2:63381901:CTGA:C	donor_loss	1.0000
2:63381902:TGA:T	donor_loss	1.0000
2:63381903:GACCT:G	donor_loss	1.0000
2:63381905:C:CA	donor_loss	1.0000
2:63381905:CCTT:C	donor_gain	1.0000
2:63382092:CGC:C	acceptor_gain	1.0000
2:63382094:CCTAT:C	acceptor_loss	1.0000
2:63382095:C:CC	acceptor_gain	1.0000
2:63382099:C:CT	acceptor_gain	1.0000
2:63437415:CTCTA:C	donor_loss	1.0000
2:63437416:TCTA:T	donor_loss	1.0000

AlphaMissense

4919 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:63492886:A:G	W44R	0.996
2:63492886:A:T	W44R	0.996
2:63313279:G:T	A594D	0.995
2:63484627:A:G	W121R	0.995
2:63484627:A:T	W121R	0.995
2:63378493:G:C	S547R	0.994
2:63378493:G:T	S547R	0.994
2:63378495:T:G	S547R	0.994
2:63378503:A:G	L544P	0.994
2:63381993:A:G	W513R	0.994
2:63381993:A:T	W513R	0.994
2:63313287:A:C	F591L	0.992
2:63313287:A:T	F591L	0.992
2:63313289:A:G	F591L	0.992
2:63378400:G:C	F578L	0.992
2:63378400:G:T	F578L	0.992
2:63378402:A:G	F578L	0.992
2:63313251:A:C	F603L	0.991
2:63313251:A:T	F603L	0.991
2:63313253:A:G	F603L	0.991
2:63378386:C:A	R583M	0.991
2:63378386:C:G	R583T	0.991
2:63439870:A:G	L129P	0.991
2:63259366:G:T	A619D	0.990
2:63259393:G:T	A610E	0.990
2:63313280:C:G	A594P	0.990
2:63378481:G:C	F551L	0.990
2:63378481:G:T	F551L	0.990
2:63378483:A:G	F551L	0.990
2:63404156:A:G	W443R	0.990

dbSNP variants (sampled 300 via entrez): RS1000012252 (2:63585940 C>T), RS1000028927 (2:63516050 T>C), RS1000031640 (2:63730777 A>T), RS1000042321 (2:63755111 T>C), RS1000046423 (2:63138847 C>A), RS1000049687 (2:63829273 CTT>C), RS1000050231 (2:63163078 A>C), RS1000054063 (2:63300553 T>A), RS1000057685 (2:63306605 G>A,C), RS1000058489 (2:63154454 C>T), RS1000072000 (2:63717607 A>T), RS1000083962 (2:63397390 A>C), RS1000088556 (2:63549383 A>T), RS1000089990 (2:63710834 T>C), RS1000093186 (2:63532951 T>C)

Disease associations

OMIM: gene MIM:613580 | disease phenotypes: MIM:217085, MIM:615992, MIM:209900, MIM:311200, MIM:213300

GenCC curated gene-disease

Disease	Classification	Inheritance
Bardet-Biedl syndrome 15	Definitive	Autosomal recessive
heart defect - tongue hamartoma - polysyndactyly syndrome	Strong	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
ciliopathy	Definitive	AR

Mondo (9): heart defect - tongue hamartoma - polysyndactyly syndrome (MONDO:0009008), Bardet-Biedl syndrome 15 (MONDO:0014443), Bardet-Biedl syndrome (MONDO:0015229), optic atrophy (MONDO:0003608), inherited retinal dystrophy (MONDO:0019118), retinal disorder (MONDO:0005283), orofaciodigital syndrome (MONDO:0015375), Bardet-Biedl syndrome 1 (MONDO:0008854), Joubert syndrome (MONDO:0018772)

Orphanet (5): Bardet-Biedl syndrome (Orphanet:110), Heart defect-tongue hamartoma-polysyndactyly syndrome (Orphanet:1338), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Orofaciodigital syndrome (Orphanet:140997), Isolated Joubert syndrome (Orphanet:475)

HPO phenotypes

111 total (30 of 111 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000011	Neurogenic bladder
HP:0000028	Cryptorchidism
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:0000202	Orofacial cleft
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:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000548	Cone/cone-rod dystrophy
HP:0000551	Color vision defect
HP:0000556	Retinal dystrophy

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST001762_484	Obesity-related traits	8.000000e-07
GCST003061_8	Cutaneous malignant melanoma	1.000000e-06
GCST003991_16	Childhood ear infection	1.000000e-07
GCST006922_6	Regular attendance at a religious group	4.000000e-08
GCST007325_118	General risk tolerance (MTAG)	2.000000e-11
GCST007326_24	Number of sexual partners	3.000000e-08
GCST007709_6	General factor of neuroticism	4.000000e-08
GCST008161_24	Waist circumference adjusted for body mass index	6.000000e-06
GCST008860_13	Prostate cancer	2.000000e-14
GCST008919_6	Asthma and attention deficit hyperactivity disorder	3.000000e-08
GCST010796_251	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_252	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-10
GCST010796_253	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-10
GCST010796_254	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-10
GCST011358_1	Academic attainment (English)	1.000000e-06
GCST012354_6	Anxiety	3.000000e-16
GCST012355_26	Depression	4.000000e-13

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0007904	susceptibility to childhood ear infection measurement
EFO:0009592	social interaction measurement
EFO:0008579	risk-taking behaviour
EFO:0007660	neuroticism measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0004327	electrocardiography
EFO:0011015	educational attainment
EFO:0009863	anxiety measurement

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D020788	Bardet-Biedl Syndrome	C10.228.140.617.200; C11.270.684.624; C16.131.077.245.125; C16.320.184.125
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D009958	Orofaciodigital Syndromes	C05.116.099.370.652; C05.660.207.700; C16.131.077.676; C16.131.260.830.670; C16.131.621.207.700; C16.320.180.830.670; C16.320.714
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
C537909	Bardet-Biedl syndrome 1 (supp.)
C535849	Heart defect, tongue hamartoma and polysyndactyly (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	5
sodium arsenite	increases abundance, increases expression, decreases expression	2
Aflatoxin B1	decreases expression	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
butyraldehyde	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, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
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
NCT03490019	PHASE2	WITHDRAWN	Treatment of Bardet-Biedl-Syndrome With Metformin for Evaluation of a Possible Visual Improvement
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT01373476	PHASE2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	PHASE2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
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
NCT02882477	PHASE2/PHASE3	UNKNOWN	Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone and Incretin Based Therapy
NCT01834079	PHASE1/PHASE2	UNKNOWN	Study the Safety and Efficacy of Bone Marrow Derived Autologous Cells for the Treatment of Optic Nerve Disease
NCT04680143	PHASE1/PHASE2	COMPLETED	Systemic Erythropoietin Injection in Patients Having Optic Atrophy
NCT03011541	Not specified	RECRUITING	Stem Cell Ophthalmology Treatment Study II
NCT04580979	Not specified	COMPLETED	Natural History Study of FDXR Mutation-related Mitochondriopathy
NCT04594590	Not specified	COMPLETED	Natural History Study of SLC25A46 Mutation-related Mitochondriopathy
NCT04723160	Not specified	COMPLETED	Computer Aided Diagnosis of Multiple Eye Fundus Diseases From Color Fundus Photograph
NCT06390579	Not specified	COMPLETED	Building Research With Artificial Intelligence in Neuro-Ophthalmology
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10