WDR19

Chr 4AR

WD repeat domain 19

Also known as: ATD5, CED4, CFAP66, DYF-2, FAP66, IFT144, NPHP13, ORF26

NCBI Gene: 57728 ENSG00000157796 UniProt: Q8NEZ3 OMIM: 608151

This protein is an essential component of the intraflagellar transport complex A (IFT-A) required for retrograde ciliary transport and entry of G protein-coupled receptors into cilia. Mutations cause autosomal recessive ciliopathies including Jeune syndrome, cranioectodermal dysplasia, nephronophthisis, Senior-Loken syndrome, and retinitis pigmentosa, affecting skeletal development, kidneys, and retina. The gene is extremely intolerant to loss-of-function variants (LOEUF 0.561), reflecting its critical role in ciliary function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the WD (tryptophan-aspartic acid) repeat family, which is a large family of structurally-related proteins known to participate in a wide range of cellular processes. Each WD repeat typically contains about 40 amino acids that are usually bracketed by glycine-histidine and tryptophan-aspartic acid (WD) dipeptides. This protein contains six WD repeats, three transmembrane domains, and a clathrin heavy-chain repeat. Mutations in this gene have been described in individuals with a wide range of disorders affecting function of the cilium. These disorders are known as ciliopathies, and include Jeune syndrome, Sensenbrenner syndromes, Senior-Loken syndrome, combined or isolated nephronophthisis (NPHP), and retinitis pigmentosa (RP). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Spermatogenic failure 72MIM #619867

Cranioectodermal dysplasia 4MIM #614378

Nephronophthisis 13MIM #614377

Senior-Loken syndrome 8MIM #616307

Short-rib thoracic dysplasia 5 with or without polydactylyMIM #614376

Clinical highlights

Gene-disease validity (ClinGen)

ciliopathy · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.56

LOEUF

LOF

Mechanism· G2P

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GeneReview available — WDR19