WNT5A

Chr 3

Wnt family member 5A

Also known as: hWNT5A

NCBI Gene: 7474 ENSG00000114251 UniProt: P41221

WNT5A encodes a secreted signaling protein that serves as a ligand for frizzled receptors and can either activate or inhibit canonical Wnt signaling depending on receptor context, playing essential roles in embryonic axis extension, limb outgrowth, and chondrogenesis. Mutations cause autosomal dominant Robinow syndrome, which involves skeletal abnormalities and distinctive facial features. This gene is highly constrained against loss-of-function variation (pLI 0.99), indicating that such variants are likely to be pathogenic.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene encodes a member of the WNT family that signals through both the canonical and non-canonical WNT pathways. This protein is a ligand for the seven transmembrane receptor frizzled-5 and the tyrosine kinase orphan receptor 2. This protein plays an essential role in regulating developmental pathways during embryogenesis. This protein may also play a role in oncogenesis. Mutations in this gene are the cause of autosomal dominant Robinow syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtRobinow syndrome, autosomal dominant 1

Clinical highlights

Gene-disease validity (ClinGen)

autosomal dominant Robinow syndrome · ADModerateconsider for supplementary testing

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

338

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.27

LOEUF· LoF intol.

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Mechanism

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