ROBO3

Chr 11AR

roundabout guidance receptor 3

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.711 OMIM phenotype
Clinical SummaryROBO3
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Gene-Disease Validity (ClinGen)
gaze palsy, familial horizontal, with progressive scoliosis 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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 OE0.54 (0.410.71)
00.351.4
Missense OE0.94 (0.881.00)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 35 / 65.4Missense obs/exp: 743 / 791.1Syn Z: 1.35
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveROBO3-related familial horizontal gaze palsy with progressive scoliosisLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.76top 25%
GOF
0.73top 25%
LOF
0.3745th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

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.

3D Protein StructureAlphaFold
Clinical Literature
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