ROBO4

Chr 11

roundabout guidance receptor 4

Also known as: AOVD3, ECSM4, MRB

NCBI Gene: 54538 ENSG00000154133 UniProt: Q8WZ75

The ROBO4 protein functions as a receptor for Slit proteins and maintains endothelial barrier organization, playing a critical role in angiogenesis and vascular patterning. Mutations cause aortic valve disease 3, which follows autosomal dominant inheritance. The gene shows minimal constraint against loss-of-function variants (very low pLI score), suggesting the cardiovascular phenotype may involve specific functional alterations rather than simple protein loss.

ResearchSummary from RefSeq, OMIM, UniProt

Predicted to enable cell-cell adhesion mediator activity. Involved in establishment of endothelial barrier. Located in extracellular exosome. Implicated in aortic valve disease 3. Biomarker of pre-eclampsia and thyroid gland carcinoma. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtAortic valve disease 3

Clinical highlights

Gene-disease validity (ClinGen)

aortic valve disease 3 · ADModerateconsider for supplementary testing

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)

—

P/LP submissions

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P/LP missense

0.91

LOEUF

LOF*

Mechanism· G2P

Some data sources returned errors (1)

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