WDR19

WD repeat domain 19, the group of WD repeat domain containing|IFT-A complex

Basic information

Region (hg38): 4:39182503-39285810

Links

ENSG00000157796 ∙ NCBI:57728 ∙ OMIM:608151 ∙ HGNC:18340 ∙ Uniprot:Q8NEZ3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cranioectodermal dysplasia 4 (Definitive), mode of inheritance: AR
• asphyxiating thoracic dystrophy 5 (Definitive), mode of inheritance: AR
• Jeune syndrome (Supportive), mode of inheritance: AR
• cranioectodermal dysplasia (Supportive), mode of inheritance: AR
• Senior-Loken syndrome (Supportive), mode of inheritance: AR
• nephronophthisis 1 (Supportive), mode of inheritance: AR
• asphyxiating thoracic dystrophy 5 (Strong), mode of inheritance: AR
• nephronophthisis 13 (Strong), mode of inheritance: AR
• Senior-Loken syndrome 8 (Strong), mode of inheritance: AR
• cranioectodermal dysplasia 4 (Strong), mode of inheritance: AR
• ciliopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Short-rib thoracic dysplasia 5 with or without polydactyly; Cranioectodermal dysplasia 4; Nephronophthisis 13; Retinitis pigmentosa; Senior-Loken syndrome 8	AD/AR	General	Genetic knowledge may potentially be beneficial related to manifestations such as renal issues; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Dental; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary; Renal	19430947; 21378380; 22019273; 23559409; 23683095
Renal transplantation has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WDR19 gene.

• Asphyxiating thoracic dystrophy 5;Senior-Loken syndrome 8 (414 variants)
• Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5 (407 variants)
• not provided (124 variants)
• Cranioectodermal dysplasia 4 (99 variants)
• Asphyxiating thoracic dystrophy 5 (96 variants)
• Inborn genetic diseases (50 variants)
• Senior-Loken syndrome 8 (35 variants)
• not specified (34 variants)
• Nephronophthisis 13 (30 variants)
• Connective tissue disorder (24 variants)
• Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5;Nephronophthisis 13;Cranioectodermal dysplasia 4;Spermatogenic failure 72 (17 variants)
• Jeune thoracic dystrophy (15 variants)
• Spermatogenic failure 72;Asphyxiating thoracic dystrophy 5;Nephronophthisis 13;Cranioectodermal dysplasia 4;Senior-Loken syndrome 8 (14 variants)
• Asphyxiating thoracic dystrophy 5;Nephronophthisis 13;Cranioectodermal dysplasia 4;Spermatogenic failure 72;Senior-Loken syndrome 8 (12 variants)
• Cranioectodermal dysplasia 4;Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5;Spermatogenic failure 72;Nephronophthisis 13 (10 variants)
• Asphyxiating thoracic dystrophy 5;Nephronophthisis 13;Cranioectodermal dysplasia 4;Senior-Loken syndrome 8;Spermatogenic failure 72 (9 variants)
• Spermatogenic failure 72;Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5;Nephronophthisis 13;Cranioectodermal dysplasia 4 (9 variants)
• Senior-Loken syndrome 8;Spermatogenic failure 72;Asphyxiating thoracic dystrophy 5;Nephronophthisis 13;Cranioectodermal dysplasia 4 (8 variants)
• Cranioectodermal dysplasia (8 variants)
• Retinal dystrophy (7 variants)
• WDR19-related condition (5 variants)
• Asphyxiating thoracic dystrophy 5;Spermatogenic failure 72;Nephronophthisis 13;Cranioectodermal dysplasia 4;Senior-Loken syndrome 8 (4 variants)
• Asphyxiating thoracic dystrophy 5;Spermatogenic failure 72;Senior-Loken syndrome 8;Cranioectodermal dysplasia 4;Nephronophthisis 13 (4 variants)
• Nephronophthisis 13;Cranioectodermal dysplasia 4;Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5;Spermatogenic failure 72 (3 variants)
• Asphyxiating thoracic dystrophy 5;Senior-Loken syndrome 8;Nephronophthisis 13;Cranioectodermal dysplasia 4;Spermatogenic failure 72 (3 variants)
• Spermatogenic failure 72;Senior-Loken syndrome 8;Nephronophthisis 13;Cranioectodermal dysplasia 4;Asphyxiating thoracic dystrophy 5 (3 variants)
• WDR19-Related Disorders (3 variants)
• Spermatogenic failure 72;Asphyxiating thoracic dystrophy 5;Senior-Loken syndrome 8;Nephronophthisis 13;Cranioectodermal dysplasia 4 (3 variants)
• Nephronophthisis 13;Cranioectodermal dysplasia 4;Senior-Loken syndrome 8;Spermatogenic failure 72;Asphyxiating thoracic dystrophy 5 (2 variants)
• Cone dystrophy (2 variants)
• - (2 variants)
• Saldino-Mainzer syndrome (2 variants)
• Cranioectodermal dysplasia 4;Nephronophthisis 13;Spermatogenic failure 72;Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5 (2 variants)
• Retinitis pigmentosa (2 variants)
• Nephronophthisis 13;Cranioectodermal dysplasia 4;Spermatogenic failure 72;Asphyxiating thoracic dystrophy 5;Senior-Loken syndrome 8 (2 variants)
• Renal dysplasia and retinal aplasia (2 variants)
• Asphyxiating thoracic dystrophy 5;Nephronophthisis 13;Senior-Loken syndrome 8;Spermatogenic failure 72;Cranioectodermal dysplasia 4 (1 variants)
• Type IV short rib polydactyly syndrome (1 variants)
• Intellectual disability (1 variants)
• Leber congenital amaurosis (1 variants)
• Nephronophthisis 13;Senior-Loken syndrome 8 (1 variants)
• Asphyxiating thoracic dystrophy 5;Senior-Loken syndrome 8;Spermatogenic failure 72;Nephronophthisis 13;Cranioectodermal dysplasia 4 (1 variants)
• Asphyxiating thoracic dystrophy 5;Spermatogenic failure 72;Senior-Loken syndrome 8;Nephronophthisis 13;Cranioectodermal dysplasia 4 (1 variants)
• Asphyxiating thoracic dystrophy 5;Spermatogenic failure 72;Cranioectodermal dysplasia 4;Senior-Loken syndrome 8;Nephronophthisis 13 (1 variants)
• Asphyxiating thoracic dystrophy 5;Nephronophthisis 13;Cranioectodermal dysplasia 4;Senior-Loken syndrome 8 (1 variants)
• Senior-Loken syndrome 8;Nephronophthisis 13;Cranioectodermal dysplasia 4;Spermatogenic failure 72;Asphyxiating thoracic dystrophy 5 (1 variants)
• Bardet-Biedl syndrome (1 variants)
• Cranioectodermal dysplasia 4;Nephronophthisis 13;Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5;Spermatogenic failure 72 (1 variants)
• Nephronophthisis 13;Cranioectodermal dysplasia 4;Asphyxiating thoracic dystrophy 5;Spermatogenic failure 72;Senior-Loken syndrome 8 (1 variants)
• Stargardt-like macular dystrophy (1 variants)
• Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5;Spermatogenic failure 72;Nephronophthisis 13;Cranioectodermal dysplasia 4 (1 variants)
• Craniosynostosis syndrome (1 variants)
• Senior-Loken syndrome 8;Nephronophthisis 13 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WDR19 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			14	151	1	166
missense	2	8	402	8	5	425
nonsense	10	6	1			17
start loss			1			1
frameshift	15	3	1			19
inframe indel			4			4
splice donor/acceptor (+/-2bp)	2	19	1			22
splice region		2	30	25	5	62
non coding			22	117	38	177
Total	29	36	446	276	44

Highest pathogenic variant AF is 0.0000789

Variants in WDR19

This is a list of pathogenic ClinVar variants found in the WDR19 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-39182543-G-T		Cranioectodermal dysplasia 4 • Asphyxiating thoracic dystrophy 5 • not specified	Likely benign (Jan 13, 2018)
4-39182549-A-G		not specified • Asphyxiating thoracic dystrophy 5 • Cranioectodermal dysplasia 4 • Senior-Loken syndrome 8 • Nephronophthisis 13	Benign (Dec 05, 2021)
4-39182559-T-C		Asphyxiating thoracic dystrophy 5;Senior-Loken syndrome 8	Uncertain significance (Jun 13, 2023)
4-39182566-A-G		Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5 • Senior-Loken syndrome 8;Spermatogenic failure 72;Asphyxiating thoracic dystrophy 5;Nephronophthisis 13;Cranioectodermal dysplasia 4	Uncertain significance (Sep 12, 2022)
4-39182566-AAAT-A		Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5 • Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5;Nephronophthisis 13;Cranioectodermal dysplasia 4;Spermatogenic failure 72	Likely benign (Nov 24, 2023)
4-39182568-A-G		Cranioectodermal dysplasia 4 • Asphyxiating thoracic dystrophy 5 • Asphyxiating thoracic dystrophy 5;Senior-Loken syndrome 8	Conflicting classifications of pathogenicity (Jan 18, 2024)
4-39182572-C-T		Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5	Likely benign (Sep 06, 2022)
4-39182574-T-A		Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5	Likely benign (Aug 11, 2023)
4-39182579-A-G		Asphyxiating thoracic dystrophy 5;Senior-Loken syndrome 8	Likely benign (Jul 30, 2022)
4-39182583-C-T		Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5	Likely benign (Dec 12, 2023)
4-39185530-G-C			Benign (May 16, 2021)
4-39185716-TA-T		Asphyxiating thoracic dystrophy 5;Senior-Loken syndrome 8	Likely benign (Apr 01, 2022)
4-39185719-T-A		Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5	Likely benign (Mar 18, 2023)
4-39185721-T-G		Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5	Uncertain significance (Aug 22, 2021)
4-39185726-C-T		Asphyxiating thoracic dystrophy 5;Senior-Loken syndrome 8	Uncertain significance (Dec 29, 2021)
4-39185727-G-A		Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5 • Senior-Loken syndrome 8;Nephronophthisis 13;Cranioectodermal dysplasia 4;Asphyxiating thoracic dystrophy 5;Spermatogenic failure 72	Uncertain significance (Dec 11, 2023)
4-39185730-T-C		Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5	Uncertain significance (Nov 01, 2021)
4-39185733-T-C		Retinal dystrophy • Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5 • Senior-Loken syndrome 8	Conflicting classifications of pathogenicity (Aug 10, 2023)
4-39185737-A-C		Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5	Likely benign (Feb 14, 2023)
4-39185739-T-C		Asphyxiating thoracic dystrophy 5	Pathogenic (Nov 11, 2011)
4-39185761-C-T		Asphyxiating thoracic dystrophy 5;Senior-Loken syndrome 8 • Spermatogenic failure 72;Asphyxiating thoracic dystrophy 5;Nephronophthisis 13;Cranioectodermal dysplasia 4;Senior-Loken syndrome 8 • WDR19-related disorder	Likely benign (Dec 17, 2023)
4-39185762-G-A		Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5	Uncertain significance (Oct 10, 2021)
4-39185772-A-G		Asphyxiating thoracic dystrophy 5;Senior-Loken syndrome 8	Uncertain significance (Aug 16, 2022)
4-39185775-T-G		Jeune thoracic dystrophy • Senior-Loken syndrome 8;Asphyxiating thoracic dystrophy 5 • Cranioectodermal dysplasia 4	Uncertain significance (Jan 12, 2021)
4-39185778-C-T		Inborn genetic diseases	Uncertain significance (Sep 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WDR19	protein_coding	protein_coding	ENST00000399820	36	103407

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.63e-11	1.00	124550	0	93	124643	0.000373

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.50	573	684	0.838	0.0000347	8839
Missense in Polyphen		124	173.4	0.7151		2136
Synonymous	0.316	228	234	0.974	0.0000122	2413
Loss of Function	4.68	31	74.6	0.415	0.00000392	956

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000625	0.000620
Ashkenazi Jewish	0.0000998	0.0000994
East Asian	0.000465	0.000445
Finnish	0.0000468	0.0000464
European (Non-Finnish)	0.000458	0.000434
Middle Eastern	0.000465	0.000445
South Asian	0.000457	0.000425
Other	0.000866	0.000826

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport (PubMed:20889716). Involved in cilia function and/or assembly (By similarity). Associates with the BBSome complex to mediate ciliary transport (By similarity). {ECO:0000250|UniProtKB:Q3UGF1, ECO:0000269|PubMed:20889716}.
• Disease: DISEASE: Cranioectodermal dysplasia 4 (CED4) [MIM:614378]: A disorder primarily characterized by craniofacial, skeletal and ectodermal abnormalities. Clinical features include craniosynostosis, narrow rib cage, short limbs, brachydactyly, hypoplastic and widely spaced teeth, sparse hair, skin laxity and abnormal nails. Nephronophthisis leading to progressive renal failure, hepatic fibrosis, heart defects, and retinitis pigmentosa have also been described. {ECO:0000269|PubMed:22019273}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Short-rib thoracic dysplasia 5 with or without polydactyly (SRTD5) [MIM:614376]: A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. {ECO:0000269|PubMed:22019273}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Nephronophthisis 13 (NPHP13) [MIM:614377]: An autosomal recessive disorder resulting in end-stage renal disease. It is a progressive tubulo-interstitial kidney disorder histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts. {ECO:0000269|PubMed:22019273}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Senior-Loken syndrome 8 (SLSN8) [MIM:616307]: A renal- retinal disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life. {ECO:0000269|PubMed:23559409, ECO:0000269|PubMed:23683095}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Signal Transduction;Hedgehog ,off, state;Signaling by Hedgehog;Intraflagellar transport;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.0973

Intolerance Scores

• loftool: 0.548
• rvis_EVS: 0.56
• rvis_percentile_EVS: 81.71

Haploinsufficiency Scores

• pHI: 0.430
• hipred: N
• hipred_score: 0.492
• ghis: 0.540

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.265

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wdr19
• Phenotype: growth/size/body region phenotype; cellular phenotype; craniofacial 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; limbs/digits/tail phenotype; muscle phenotype; digestive/alimentary phenotype; 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); embryo phenotype; skeleton phenotype; vision/eye phenotype

Zebrafish Information Network

• Gene name: wdr19
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curved ventral

Gene ontology

• Biological process: cell morphogenesis;in utero embryonic development;gonad development;embryonic limb morphogenesis;embryonic camera-type eye development;intraciliary retrograde transport;intraciliary transport involved in cilium assembly;ear morphogenesis;embryonic cranial skeleton morphogenesis;nervous system process;digestive system development;ciliary receptor clustering involved in smoothened signaling pathway;smoothened signaling pathway involved in dorsal/ventral neural tube patterning;myotome development
• Cellular component: photoreceptor outer segment;nucleoplasm;cytoplasm;cytoskeleton;cilium;nuclear body;intraciliary transport particle A;motile cilium;photoreceptor connecting cilium;ciliary tip;non-motile cilium