Nystagmus, congenital, autosomal recessive

Summary

Nystagmus, congenital, autosomal recessive (MONDO:0009762) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nystagmus, congenital, autosomal recessive
Mondo ID	MONDO:0009762
MeSH	C564938
OMIM	257400
DOID	DOID:0061178
UMLS	C3151571
MedGen	462921
GARD	0009609
Is cancer (heuristic)	no

Also known as: Nystagmus, congenital motor, autosomal recessive · nystagmus, congenital, autosomal recessive

Data availability: 4 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › congenital nystagmus › nystagmus, congenital, autosomal recessive

Related subtypes (9): nystagmus 2, congenital, autosomal dominant, nystagmus, hereditary vertical, spinocerebellar ataxia 27A, nystagmus 5, congenital, X-linked, nystagmus 6, congenital, X-linked, nystagmus 1, congenital, X-linked, nystagmus, myoclonic, nystagmus 3, congenital, autosomal dominant, nystagmus 7, congenital, autosomal dominant

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

4 retrieved; paginated sample, class counts are floors:

2 conflicting classifications of pathogenicity, 1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4845871	NM_002941.4(ROBO1):c.1111C>T (p.Gln371Ter)	ROBO1	Likely pathogenic	criteria provided, single submitter
1342665	NM_002941.4(ROBO1):c.4565C>T (p.Ser1522Leu)	ROBO1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2631840	NM_002941.4(ROBO1):c.1073G>A (p.Arg358His)	ROBO1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1447063	NM_002941.4(ROBO1):c.3396TCC[1] (p.Pro1134del)	ROBO1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ROBO1	Limited	Autosomal dominant	congenital heart disease	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ROBO1	Orphanet:95496	Pituitary stalk interruption syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ROBO1	HGNC:10249	ENSG00000169855	Q9Y6N7	Roundabout homolog 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ROBO1	Roundabout homolog 1	Receptor for SLIT1 and SLIT2 that mediates cellular responses to molecular guidance cues in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuro…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ROBO1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ganglionic eminence	1
tibia	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ROBO1	287	ubiquitous	marker	ventricular zone, ganglionic eminence, tibia

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ROBO1	2,359

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ROBO1	Q9Y6N7	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
SLIT2:ROBO1 increases RHOA activity	1	2855.0×	0.002	ROBO1
Regulation of cortical dendrite branching	1	2284.0×	0.002	ROBO1
Inactivation of CDC42 and RAC1	1	1427.5×	0.002	ROBO1
Role of ABL in ROBO-SLIT signaling	1	1268.9×	0.002	ROBO1
Regulation of commissural axon pathfinding by SLIT and ROBO	1	951.7×	0.002	ROBO1
Activation of RAC1	1	815.7×	0.002	ROBO1
Netrin-1 signaling	1	439.2×	0.004	ROBO1
Signaling by ROBO receptors	1	124.1×	0.012	ROBO1
Regulation of expression of SLITs and ROBOs	1	69.2×	0.019	ROBO1
Axon guidance	1	45.1×	0.025	ROBO1
Nervous system development	1	42.9×	0.025	ROBO1
Developmental Biology	1	14.5×	0.069	ROBO1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
chemorepulsion involved in postnatal olfactory bulb interneuron migration	1	8426.0×	0.002	ROBO1
negative regulation of negative chemotaxis	1	5617.3×	0.002	ROBO1
axon midline choice point recognition	1	3370.4×	0.002	ROBO1
negative regulation of mammary gland epithelial cell proliferation	1	3370.4×	0.002	ROBO1
Roundabout signaling pathway	1	2808.7×	0.002	ROBO1
negative regulation of chemokine-mediated signaling pathway	1	2407.4×	0.002	ROBO1
heart induction	1	2106.5×	0.002	ROBO1
endocardial cushion formation	1	1404.3×	0.002	ROBO1
positive regulation of vascular endothelial growth factor signaling pathway	1	1123.5×	0.002	ROBO1
positive regulation of vascular endothelial growth factor receptor signaling pathway	1	1053.2×	0.002	ROBO1
pulmonary valve morphogenesis	1	936.2×	0.003	ROBO1
cell migration involved in sprouting angiogenesis	1	648.1×	0.003	ROBO1
outflow tract septum morphogenesis	1	648.1×	0.003	ROBO1
positive regulation of Rho protein signal transduction	1	581.1×	0.003	ROBO1
positive regulation of axonogenesis	1	581.1×	0.003	ROBO1
aorta development	1	561.7×	0.003	ROBO1
aortic valve morphogenesis	1	432.1×	0.003	ROBO1
ventricular septum morphogenesis	1	432.1×	0.003	ROBO1
positive regulation of Notch signaling pathway	1	351.1×	0.004	ROBO1
homophilic cell-cell adhesion	1	140.4×	0.009	ROBO1
negative regulation of cell migration	1	111.6×	0.011	ROBO1
positive regulation of MAPK cascade	1	80.6×	0.015	ROBO1
negative regulation of gene expression	1	69.1×	0.016	ROBO1
nervous system development	1	45.9×	0.024	ROBO1
positive regulation of gene expression	1	38.7×	0.027	ROBO1
cell adhesion	1	37.5×	0.027	ROBO1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ROBO1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	ROBO1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ROBO1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.