ROBO3

Chr 11AR

roundabout guidance receptor 3

ENSG00000154134 UniProt: Q96MS0 OMIM: 608630

The ROBO3 protein is a transmembrane receptor that guides commissural axons across the midline during neural tube development by regulating responses to multiple guidance cues including NELL2, SLIT proteins, and Netrin-1. Mutations cause horizontal gaze palsy with progressive scoliosis, an autosomal recessive disorder with congenital absence of horizontal eye movements and progressive scoliosis due to failure of corticospinal and somatosensory tracts to cross at the medulla. This gene is extremely intolerant to loss-of-function variants, reflecting its critical role in early nervous system development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Receptor involved in axon guidance during development (PubMed:15105459). Acts as a multifunctional regulator of pathfinding that simultaneously mediates NELL2 repulsion, inhibits SLIT repulsion, and facilitates Netrin-1/NTN1 attraction. In spinal cord development plays a role in guiding commissural axons probably by preventing premature sensitivity to Slit proteins thus inhibiting Slit signaling through ROBO1/ROBO2. Binding OF NELL2 to the receptor ROBO3 promotes oligomerization of ROBO3, resulting in the repulsion of commissural axons in the midline. ROBO3 also indirectly boosts axon attraction to NTN1 without interacting with NTN1 itself (By similarity)

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Gaze palsy, familial horizontal, with progressive scoliosis, 1MIM #607313

Clinical highlights

Gene-disease validity (ClinGen)

gaze palsy, familial horizontal, with progressive scoliosis 1 · 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

0.71

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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