LRP6

Chr 12

LDL receptor related protein 6

Also known as: ADCAD2, EVR8, OPTA4, STHAG7

NCBI Gene: 4040 ENSG00000070018 UniProt: O75581

The LRP6 protein functions as a cell-surface coreceptor in the Wnt/beta-catenin signaling pathway, which is critical for retinal angiogenesis and bone formation. Mutations cause autosomal dominant disorders including exudative vitreoretinopathy, osteopetrosis, selective tooth agenesis, and coronary artery disease. This gene is highly constrained against loss-of-function variants (LOEUF 0.318), reflecting its essential role in development.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the low density lipoprotein (LDL) receptor gene family. LDL receptors are transmembrane cell surface proteins involved in receptor-mediated endocytosis of lipoprotein and protein ligands. The protein encoded by this gene functions as a receptor or, with Frizzled, a co-receptor for Wnt and thereby transmits the canonical Wnt/beta-catenin signaling cascade. Through its interaction with the Wnt/beta-catenin signaling cascade this gene plays a role in the regulation of cell differentiation, proliferation, and migration and the development of many cancer types. This protein undergoes gamma-secretase dependent RIP- (regulated intramembrane proteolysis) processing but the precise locations of the cleavage sites have not been determined.[provided by RefSeq, Dec 2009]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCoronary artery disease, autosomal dominant, 2

UniProtTooth agenesis, selective, 7

UniProtVitreoretinopathy, exudative 8

UniProtOsteopetrosis, autosomal dominant 4

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

168

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.32

LOEUF· LoF intol.

LOF

Mechanism· G2P

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