WDPCP

WD repeat containing planar cell polarity effector, the group of Ciliogenesis and planar polarity effector complex subunits

Basic information

Region (hg38): 2:63119559-63827843

Previous symbols: [ "C2orf86" ]

Links

ENSG00000143951 ∙ NCBI:51057 ∙ OMIM:613580 ∙ HGNC:28027 ∙ Uniprot:O95876 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bardet-Biedl syndrome 15 (Definitive), mode of inheritance: AR
• Bardet-Biedl syndrome 15 (Limited), mode of inheritance: AR
• heart defect - tongue hamartoma - polysyndactyly syndrome (Limited), mode of inheritance: AR
• Bardet-Biedl syndrome (Supportive), mode of inheritance: AR
• Bardet-Biedl syndrome 15 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital heart defects, hamartomas of tongue, and polysyndactyly; Bardet-Biedl syndrome 15	AR	Cardiovascular; Endocrine	Congenital heart defects, hamartomas of tongue, and polysyndactyly can include congenital cardiac anomalies, and awareness may allow early identification and management; In Bardet-Biedl syndrome, medical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficial	Cardiovascular; Craniofacial; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	20671153; 25427950; 36356613
Variants may modify severity of BBS and related disorders due to variants in other BBS-associated genes

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WDPCP gene.

• Bardet-Biedl syndrome (16 variants)
• Heart defect - tongue hamartoma - polysyndactyly syndrome (1 variants)
• Inborn genetic diseases (1 variants)
• Bardet-Biedl syndrome 15;Heart defect - tongue hamartoma - polysyndactyly syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WDPCP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	101		106
missense			242	9	1	252
nonsense	4	4				8
start loss			1			1
frameshift	14	2	1			17
inframe indel			4			4
splice donor/acceptor (+/-2bp)	1	10	2			13
splice region			16	19	1	36
non coding			28	69	9	106
Total	19	16	283	179	10

Highest pathogenic variant AF is 0.0000197

Variants in WDPCP

This is a list of pathogenic ClinVar variants found in the WDPCP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-63121372-T-C		Bardet-Biedl syndrome 15	Uncertain significance (Jan 12, 2018)
2-63121380-CTT-C		Bardet-Biedl syndrome	Benign (Jun 14, 2016)
2-63121400-TTG-T		Bardet-Biedl syndrome	Uncertain significance (Jun 14, 2016)
2-63121414-ACT-A		Bardet-Biedl syndrome	Uncertain significance (Jun 14, 2016)
2-63121424-G-C		Bardet-Biedl syndrome 15	Uncertain significance (Jan 12, 2018)
2-63121447-C-T		Bardet-Biedl syndrome 15	Uncertain significance (Jan 13, 2018)
2-63121465-G-C		Bardet-Biedl syndrome 15	Uncertain significance (Jan 12, 2018)
2-63121560-G-A		Bardet-Biedl syndrome 15	Uncertain significance (Jan 13, 2018)
2-63121679-C-T		Bardet-Biedl syndrome 15	Likely benign (Jan 12, 2018)
2-63121683-T-C		Bardet-Biedl syndrome 15	Benign (Jan 12, 2018)
2-63121811-C-T		Bardet-Biedl syndrome 15	Benign (Jan 13, 2018)
2-63121860-AAAAC-A		Bardet-Biedl syndrome	Uncertain significance (Jun 14, 2016)
2-63121902-T-G		Bardet-Biedl syndrome 15	Uncertain significance (Jan 12, 2018)
2-63122001-A-G		WDPCP-related disorder	Likely benign (Jan 22, 2021)
2-63122011-C-A		WDPCP-related disorder	Uncertain significance (May 31, 2024)
2-63122012-C-T		Bardet-Biedl syndrome	Likely benign (Sep 17, 2022)
2-63122017-C-T		Bardet-Biedl syndrome	Uncertain significance (Oct 31, 2019)
2-63122031-T-C		Bardet-Biedl syndrome 15 • WDPCP-related disorder	Uncertain significance (Jan 15, 2018)
2-63122036-A-G		Bardet-Biedl syndrome • WDPCP-related disorder	Likely benign (Jun 20, 2022)
2-63122037-G-T		Bardet-Biedl syndrome	Uncertain significance (Aug 02, 2023)
2-63122055-T-A		Bardet-Biedl syndrome	Uncertain significance (Sep 27, 2022)
2-63122060-C-A		Bardet-Biedl syndrome	Likely benign (Apr 23, 2021)
2-63152899-G-T		Bardet-Biedl syndrome	Likely benign (Jan 06, 2023)
2-63152904-A-G		WDPCP-related disorder	Uncertain significance (Jul 31, 2024)
2-63152906-T-C		Bardet-Biedl syndrome	Likely benign (Apr 23, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WDPCP	protein_coding	protein_coding	ENST00000272321	18	706460

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.09e-10	0.996	124667	1	123	124791	0.000497

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.898	345	395	0.873	0.0000197	4892
Missense in Polyphen		110	144.97	0.7588		1928
Synonymous	-0.489	151	144	1.05	0.00000713	1414
Loss of Function	2.68	23	41.6	0.552	0.00000210	493

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00190	0.00190
Ashkenazi Jewish	0.0000994	0.0000993
East Asian	0.000223	0.000223
Finnish	0.0000938	0.0000928
European (Non-Finnish)	0.000375	0.000371
Middle Eastern	0.000223	0.000223
South Asian	0.000494	0.000490
Other	0.000333	0.000330

dbNSFP

Source: dbNSFP

• Function: 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 (By similarity). {ECO:0000250|UniProtKB:Q32NR9, ECO:0000250|UniProtKB:Q8C456}.
• Disease: DISEASE: Bardet-Biedl syndrome 15 (BBS15) [MIM:615992]: A syndrome characterized by usually severe pigmentary retinopathy, early- onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. 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. {ECO:0000269|PubMed:20671153}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:25427950, ECO:0000269|PubMed:27158779}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=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. {ECO:0000269|PubMed:20671153}.

Intolerance Scores

• rvis_EVS: 0.47
• rvis_percentile_EVS: 78.74

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.218
• ghis: 0.522

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Wdpcp
• Phenotype: vision/eye phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; renal/urinary system phenotype; respiratory system phenotype; embryo phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); craniofacial phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: wdpcp
• Affected structure: pigment cell
• Phenotype tag: abnormal
• Phenotype quality: quality

Gene ontology

• Biological process: kidney development;auditory receptor cell morphogenesis;smoothened signaling pathway;regulation of fibroblast migration;regulation of embryonic cell shape;septin cytoskeleton organization;regulation of protein localization;embryonic digit morphogenesis;camera-type eye development;establishment of protein localization;regulation of focal adhesion assembly;digestive system development;roof of mouth development;cilium assembly;respiratory system development;cardiovascular system development;glomerular visceral epithelial cell migration;regulation of ruffle assembly;regulation of establishment of cell polarity
• Cellular component: plasma membrane;axoneme;cell cortex;apical plasma membrane;axonemal basal plate