ROBO1

Chr 3

roundabout guidance receptor 1

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

NCBI Gene: 6091 ENSG00000169855 UniProt: Q9Y6N7

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

Bilateral symmetric nervous systems have special midline structures that establish a partition between the two mirror image halves. Some axons project toward and across the midline in response to long-range chemoattractants emanating from the midline. The product of this gene is a member of the immunoglobulin gene superfamily and encodes an integral membrane protein that functions in axon guidance and neuronal precursor cell migration. This receptor is activated by SLIT-family proteins, resulting in a repulsive effect on glioma cell guidance in the developing brain. A related gene is located at an adjacent region on chromosome 3. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurooculorenal syndrome

UniProtNystagmus 8, congenital, autosomal recessive

UniProtPituitary hormone deficiency, combined or isolated, 8

Clinical highlights

Gene-disease validity (ClinGen)

congenital heart disease · ARLimitednot for standalone diagnostic reporting2 gene-disease associations curated in total

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

0.60

LOEUF

LOF

Mechanism· G2P

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GeneReview available — ROBO1