ROBO3

Chr 11AR

roundabout guidance receptor 3

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)

OMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

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

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.
1
Active trials
18
Pubs (1 yr)
P/LP submissions
P/LP missense
0.71
LOEUF
LOF
Mechanism· G2P
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.71LOEUF
pLI 0.000
Z-score 3.48
OE 0.54 (0.410.71)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.61Z-score
OE missense 0.94 (0.881.00)
743 obs / 791.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.54 (0.410.71)
00.351.4
Missense OE?0.94 (0.881.00)
00.61.4
Synonymous OE?0.90
01.21.6
LoF obs/exp: 35 / 65.4Missense obs/exp: 743 / 791.1Syn Z: 1.35

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ROBO3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.