ROBO1

Chr 3ARAD

roundabout guidance receptor 1

Also known as: CPHD8, DUTT1, NORS, NYS8, SAX3

The protein functions as a receptor for SLIT1 and SLIT2 that mediates axonal navigation and neuronal migration during brain development, particularly guiding axons at the ventral midline of the neural tube. Mutations cause congenital nystagmus, neurooculorenal syndrome, and combined or isolated pituitary hormone deficiency with both autosomal recessive and autosomal dominant inheritance patterns reported. The gene is highly constrained against loss-of-function mutations (LOEUF 0.597), reflecting its critical role in nervous system development.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/ADLOEUF 0.603 OMIM phenotypes
Clinical SummaryROBO1
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Gene-Disease Validity (ClinGen)
congenital heart disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📖
GeneReview available — ROBO1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.60LOEUF
pLI 0.000
Z-score 4.72
OE 0.46 (0.360.60)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.07Z-score
OE missense 0.90 (0.850.95)
825 obs / 916.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.46 (0.360.60)
00.351.4
Missense OE0.90 (0.850.95)
00.61.4
Synonymous OE1.17
01.21.6
LoF obs/exp: 41 / 89.1Missense obs/exp: 825 / 916.3Syn Z: -2.45
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateROBO1-related neurooculorenal syndromeLOFAR

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

DN
0.7133th %ile
GOF
0.6638th %ile
LOF
0.4528th %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

ROBO1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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