ROBO1

Summary

ROBO1 (roundabout guidance receptor 1, HGNC:10249) is a protein-coding gene on chromosome 3p12.3, encoding Roundabout homolog 1 (Q9Y6N7). 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 neuronal development.

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.

Source: NCBI Gene 6091 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurooculorenal syndrome (Definitive, GenCC) — +4 more curated relationships
• GWAS associations: 27
• Clinical variants (ClinVar): 755 total — 16 pathogenic, 27 likely-pathogenic
• Phenotypes (HPO): 75
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_002941

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10249
Approved symbol	ROBO1
Name	roundabout guidance receptor 1
Location	3p12.3
Locus type	gene with protein product
Status	Approved
Aliases	DUTT1, FLJ21882, SAX3
Ensembl gene	ENSG00000169855
Ensembl biotype	protein_coding
OMIM	602430
Entrez	6091

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000436010, ENST00000464233, ENST00000466906, ENST00000467549, ENST00000472273, ENST00000484514, ENST00000488735, ENST00000492990, ENST00000495273, ENST00000495961, ENST00000498428, ENST00000618846

RefSeq mRNA: 3 — MANE Select: NM_002941 NM_001145845, NM_002941, NM_133631

CCDS: CCDS46872, CCDS54610, CCDS54611

Canonical transcript exons

ENST00000464233 — 31 exons

Exon	Start	End
ENSE00001149746	78717275	78717413
ENSE00001149757	78746743	78746900
ENSE00001222668	78714397	78714524
ENSE00001813242	79125456	79125539
ENSE00001891694	78597239	78598927
ENSE00001895048	79589824	79589961
ENSE00001915645	79767752	79767998
ENSE00002398020	78717763	78717883
ENSE00003460630	78670096	78670301
ENSE00003461877	78657098	78657269
ENSE00003522352	78651732	78651929
ENSE00003537895	78627321	78627569
ENSE00003539683	78661993	78662114
ENSE00003539864	78661030	78661261
ENSE00003552845	78633935	78634042
ENSE00003554545	78668134	78668302
ENSE00003564114	78606733	78607041
ENSE00003580013	78614648	78614800
ENSE00003592781	78631161	78631305
ENSE00003596884	78646148	78646190
ENSE00003620103	78647629	78647655
ENSE00003622650	78659686	78659807
ENSE00003628491	78685746	78685917
ENSE00003637405	78668484	78668565
ENSE00003643393	78635773	78636108
ENSE00003663726	78600113	78600309
ENSE00003668687	78688648	78688772
ENSE00003678371	78639744	78639898
ENSE00003689368	78617635	78618041
ENSE00003725731	78938601	78938927
ENSE00003787830	78667883	78668049

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.7158 / max 323.5080, expressed in 1452 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
43205	6.5562	1327
43204	5.5867	1238
43203	1.9486	1030
43215	0.5133	163
43197	0.4019	82
43217	0.1769	38
43216	0.1696	82
43196	0.1612	64
43214	0.0901	36
43198	0.0556	27

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.00	gold quality
ganglionic eminence	UBERON:0004023	98.88	gold quality
tibia	UBERON:0000979	97.58	gold quality
embryo	UBERON:0000922	97.49	gold quality
penis	UBERON:0000989	97.35	gold quality
calcaneal tendon	UBERON:0003701	97.07	gold quality
cortical plate	UBERON:0005343	96.86	gold quality
cervix squamous epithelium	UBERON:0006922	96.50	gold quality
periodontal ligament	UBERON:0008266	96.33	gold quality
gingival epithelium	UBERON:0001949	96.20	gold quality
gingiva	UBERON:0001828	96.08	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.00	gold quality
skin of hip	UBERON:0001554	95.97	gold quality
urethra	UBERON:0000057	95.87	gold quality
mammalian vulva	UBERON:0000997	95.85	gold quality
stromal cell of endometrium	CL:0002255	95.25	gold quality
epithelium of nasopharynx	UBERON:0001951	95.16	gold quality
tongue squamous epithelium	UBERON:0006919	95.12	silver quality
upper leg skin	UBERON:0004262	95.03	gold quality
squamous epithelium	UBERON:0006914	95.02	gold quality
cartilage tissue	UBERON:0002418	94.70	gold quality
cervix epithelium	UBERON:0004801	94.69	gold quality
adrenal tissue	UBERON:0018303	94.58	gold quality
synovial joint	UBERON:0002217	94.05	gold quality
esophagus squamous epithelium	UBERON:0006920	93.94	gold quality
visceral pleura	UBERON:0002401	93.60	gold quality
tendon	UBERON:0000043	93.59	gold quality
upper arm skin	UBERON:0004263	93.46	gold quality
mucosa of urinary bladder	UBERON:0001259	93.23	gold quality
palpebral conjunctiva	UBERON:0001812	93.10	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	4276.80
E-GEOD-81608	yes	19.16
E-HCAD-5	yes	17.85
E-GEOD-93593	yes	17.38
E-MTAB-5061	yes	15.21
E-CURD-119	yes	12.30
E-ENAD-27	yes	10.73
E-HCAD-25	yes	10.31
E-ANND-3	yes	9.48
E-GEOD-83139	yes	8.08
E-MTAB-4850	no	14.09

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

6 targets.

Target	Regulation
HES1	Activation
HEY1	Activation
HEYL	Activation
NOTCH1	Activation
ROBO2	Repression
SLIT3	Activation

Upstream regulators (CollecTRI, top): FOXG1, NFIA, NFIB, NFIX, ZBTB18

miRNA regulators (miRDB)

159 targeting ROBO1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Tumour specific promoter region methylation of ROBO1 in human cancers (PMID:12082532)
• a slight disturbance in neuronal axon crossing across the midline between brain hemispheres, dendrite guidance, or another function of ROBO1 may manifest as a specific reading disability in humans (PMID:16254601)
• Both medulloblastoma and glioma tumors express Robo1. (PMID:16636676)
• Expression of Robo1 is mainly in tumor cells, whereas Robo4 is primarily in endothelial cells of tumor vessels. Therefore, the Robo proteins provide potential target structures for the anti-tumorigenic and anti-angiogenic therapy of colorectal carcinoma. (PMID:16685377)
• The ROBO1 is overexpressed in hepatocellular carcinoma and shed into serum in humans. These observations suggest that ROBO1 is a potential new serologic marker for hepatocellular carcinoma and may represent a new therapeutic target. (PMID:16740745)
• heparin/HS is an integral component of the minimal Slit-Robo signaling complex and serves to stabilize the relatively weak Slit-Robo interaction (PMID:17062560)
• Dutt1 is silenced by promoter hypermethylation in lung cancer (PMID:17671114)
• The minimal Robo1-binding region required for Slit activation has been mapped to the N-terminal immunoglobulin (Ig)1-2 domains. (PMID:17671369)
• the crystal structures of the first two Ig domains of Robo1 (Ig1-2), and the minimal complex between these proteins (Slit2 D2-Robo1 Ig1). (PMID:17848514)
• a chemorepulsive effect mediated by interaction of Slit2 and Robo1 participates in glioma cell guidance in the brain. (PMID:17968499)
• mRNA expression of ROBO1 in lymphocytes was significantly reduced in the autistic group (PMID:18270976)
• Robo1 is essential for Robo4-mediated filopodia induction (PMID:18948384)
• Inactivation of ROBO1/DUTT1 could be used as molecular signature for early detection and prognosis of the head and neck cancer. (PMID:19104841)
• Data uncover a previously unknown function of USP33 and reveal a new player in Slit-Robo signaling in cancer cell migration. (PMID:19706539)
• These results describe a Slit-miR-218-Robo1 regulatory circuit whose disruption may contribute to gastric cancer metastasis. (PMID:20300657)
• these findings reveal that through interacting with Robo1, Slit2 is a novel and potent lymphangiogenic factor and contributes to tumor lymphatic metastasis. (PMID:20438712)
• ROBO1 may function beyond the receptor through stepwise cleavages and translocation to the nucleus. (PMID:20471383)
• While replication will be critical, the present results strongly support ROBO1 as the first gene discovered to be associated with language deficits affecting normal variation in language ability. (PMID:20949370)
• This study proposed that the expression of ROBO1 in the anterior neocortex may mark the early location of the human motor cortex, including its corticospinal projection neurons, allowing further study of their early differentiation. (PMID:21060114)
• Engagement of Robo1 by Slit2 recruits Hakai to E-cad, culminating in E-cad ubiquitination and lysosomal degradation. (PMID:21283129)
• Data show direct interaction between miR-218 and the 3’UTR of mRNAs encoding ROBO1, survivin (BIRC5), and connexin43 (GJA1). (PMID:21385904)
• three major members (Slit2/3 and Robo1) of Slit/Robo family are widely expressed in the human normal and malignant ovarian tissues; but Slit/Robo signaling may not play an important role in regulating human ovarian cancer cell proliferation and migration (PMID:21465248)
• SLIT-ROBO signaling potentially contributes to the development of diabetic retinopathy. (PMID:21686327)
• studies demonstrate a novel role for Slit2/Robo1 axis in HIV replication and may contribute to the understanding of HIV-1 pathogenesis (PMID:21857494)
• Robo1 expression correlates negatively with invasive ductal carcinoma brain metastasis, and correlates positively with the age and prognosis of IDC patients. (PMID:21875486)
• distinct ROBO1 variants may influence the risk of wet and dry AMD, and the effects of ROBO1 on AMD risk may be modulated by RORA variants. (PMID:21998696)
• The results of this study indicated that normal crossing of the auditory pathways requires an adequate ROBO1 expression level. (PMID:22262894)
• data suggests the importance of abrogation of SLIT2-ROBO1 and SLIT2-ROBO2 interactions in the initiation and progression of CACX and also for early diagnosis and prognosis of the disease (PMID:22719878)
• we report that the tumorigenic potential of breast cancer cells is determined by an interaction between the Robo1 receptor and its ligand Slit2 (PMID:22826604)
• breast cancer cell migration and invasion was promoted when miRNA- 218 was significantly down regulated, in the way of up-regulation of Robo1. (PMID:22898079)
• Data indicate that slit2N alters the localization and binding of Robo1 to WASp and LSP1 in HIV-1-gp120-treated immature dendritic cells (iDCs). (PMID:23119100)
• Downregulation of miRNA-218 and upregulation of ROBO-1 were first demonstrated in pancreatic cancer. (PMID:23733161)
• Low Robo1 expression was associated with cell proliferation and migration in ICC and was one of the adverse prognostic factors in patients with these tumors. (PMID:23953227)
• No genetic association of ROBO1 with developmental dyslexia was found in Indian population. (PMID:23954868)
• Frameshift mutations of ROBO1 and ROBO2 genes and alteration of ROBO2 expression in gastric and colorectal cancers suggest that both genes might play roles in the pathogenesis of both cancers. (PMID:24247621)
• ROBO1 contributs to the deficits in developmental dyslexia and its correlated phenotypes. (PMID:24430574)
• Family-based analysis shows association of SNPs in ROBO1 with reading diasbilities. (PMID:24612512)
• Full-length Robo1 is present almost exclusively as a dimer; parallel studies demonstrate the biological activity of Slit2 and its interaction with Robo1. (PMID:24673457)
• Lower expression of ROBO1 is associated with prostate cancer disease progression. (PMID:24752651)
• In this review, we summarize recent findings demonstrating that the neuronal guidance cues, Slit and Roundabout (Robo), prevent the migration of multiple leukocyte subsets towards diverse inflammatory chemoattractants. (PMID:24777535)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	robo1	ENSDARG00000026784
danio_rerio		ENSDARG00000078366
mus_musculus	Robo1	ENSMUSG00000022883
rattus_norvegicus	Robo1	ENSRNOG00000029614

Paralogs (36): CNTN1 (ENSG00000018236), CDON (ENSG00000064309), NEO1 (ENSG00000067141), SDK2 (ENSG00000069188), IGSF9B (ENSG00000080854), IGSF9 (ENSG00000085552), NRCAM (ENSG00000091129), MXRA5 (ENSG00000101825), IGDCC4 (ENSG00000103742), CNTN3 (ENSG00000113805), IGSF21 (ENSG00000117154), CNTN6 (ENSG00000134115), CHL1 (ENSG00000134121), PTPRQ (ENSG00000139304), CNTN4 (ENSG00000144619), BOC (ENSG00000144857), SDK1 (ENSG00000146555), HMCN2 (ENSG00000148357), NCAM1 (ENSG00000149294), CNTN5 (ENSG00000149972), IGSF10 (ENSG00000152580), ROBO4 (ENSG00000154133), ROBO3 (ENSG00000154134), NCAM2 (ENSG00000154654), VCAM1 (ENSG00000162692), NFASC (ENSG00000163531), PRTG (ENSG00000166450), DSCAM (ENSG00000171587), IGDCC3 (ENSG00000174498), VSIG10 (ENSG00000176834), DSCAML1 (ENSG00000177103), CNTN2 (ENSG00000184144), ROBO2 (ENSG00000185008), VSIG10L (ENSG00000186806), DCC (ENSG00000187323), L1CAM (ENSG00000198910)

Protein

Protein identifiers

Roundabout homolog 1 — Q9Y6N7 (reviewed: Q9Y6N7)

Alternative names: Deleted in U twenty twenty, H-Robo-1

All UniProt accessions (6): Q9Y6N7, A0A087WZ85, A0A0A0MSX4, F8WEV8, H7C4Y7, H7C545

UniProt curated annotations — full annotation on UniProt →

Function. 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 neuronal development. Interaction with the intracellular domain of FLRT3 mediates axon attraction towards cells expressing NTN1. In axon growth cones, the silencing of the attractive effect of NTN1 by SLIT2 may require the formation of a ROBO1-DCC complex. Plays a role in the regulation of cell migration via its interaction with MYO9B; inhibits MYO9B-mediated stimulation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA. May be required for lung development.

Subunit / interactions. Homodimer. Dimerization is mediated by the extracellular domain and is independent of SLIT liganding. Interacts with SLIT1. Interacts with SLIT2. Interacts with FLRT3. Interacts with MYO9B (via Rho-GAP domain).

Subcellular location. Cell membrane. Cell projection. Axon. Endoplasmic reticulum-Golgi intermediate compartment membrane.

Tissue specificity. Widely expressed, with exception of kidney.

Post-translational modifications. Ubiquitinated. May be deubiquitinated by USP33.

Disease relevance. Neurooculorenal syndrome (NORS) [MIM:620305] An autosomal recessive syndrome characterized by variable clinical features including congenital renal anomalies, neurodevelopmental defects, intellectual impairment, cardiac defects, and ocular anomalies. Some affected individuals present in utero with renal agenesis and structural brain abnormalities incompatible with life. The disease is caused by variants affecting the gene represented in this entry. Nystagmus 8, congenital, autosomal recessive (NYS8) [MIM:257400] A form of nystagmus, a condition defined as conjugated, spontaneous and involuntary ocular oscillations that appear at birth or during the first three months of life. Other associated features may include mildly decreased visual acuity, strabismus, astigmatism, and occasionally head nodding. NYS8 patients manifest bilateral horizontal nystagmus in the absence of other neurologic signs or symptoms. Brain imaging is normal. The disease may be caused by variants affecting the gene represented in this entry. Pituitary hormone deficiency, combined or isolated, 8 (CPHD8) [MIM:620303] An autosomal dominant disorder characterized by short stature due to growth hormone deficiency, variable deficiencies of other pituitary hormones, and pituitary abnormalities. Many CPHD8 patients present with pituitary stalk interruption syndrome that is characterized by pituitary gland insufficiency, thin or discontinuous pituitary stalk, anterior pituitary hypoplasia, and ectopic positioning of the posterior pituitary gland. The disease may be caused by variants affecting the gene represented in this entry.

Miscellaneous. Maps within a region of overlapping homozygous deletions characterized in both small cell lung cancer cell lines (SCLC) and in a breast cancer cell line. The promoter region of ROBO1 shows complete hypermethylation of CpG sites in the BT-20 breast tumor cell lines, some primary invasive breast carcinomasa and some primary clear cell renal cell carcinomas (CC-RCC). Incomplete.

Similarity. Belongs to the immunoglobulin superfamily. ROBO family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9Y6N7-1	1	yes
Q9Y6N7-2	2
Q9Y6N7-3	3
Q9Y6N7-4	4
Q9Y6N7-5	5
Q9Y6N7-6	6

RefSeq proteins (3): NP_001139317, NP_002932, NP_598334 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR032986	Robo1_Ig-like3	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051170	Neural/epithelial_adhesion	Family

Pfam: PF00041, PF07679, PF13927

UniProt features (163 total): strand 65, sequence variant 20, compositionally biased region 17, helix 10, domain 8, modified residue 8, splice variant 7, sequence conflict 6, region of interest 5, glycosylation site 5, disulfide bond 5, turn 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
2V9T	X-RAY DIFFRACTION	1.7
3WIH	X-RAY DIFFRACTION	1.7
4HLJ	X-RAY DIFFRACTION	1.8
2V9R	X-RAY DIFFRACTION	2
6A77	X-RAY DIFFRACTION	2
6A78	X-RAY DIFFRACTION	2.1
6A79	X-RAY DIFFRACTION	2.31
2V9Q	X-RAY DIFFRACTION	2.5
5OPE	X-RAY DIFFRACTION	2.54
5O5I	X-RAY DIFFRACTION	3.01
5O5G	X-RAY DIFFRACTION	3.03
2EO9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6N7-F1	60.19	0.30

Antibody-complex structures (SAbDab): 4 — 3WIH, 6A77, 6A78, 6A79

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (8): 940, 948, 1038, 1055, 1073, 1114, 1240, 1297

Disulfide bonds (5): 89–147, 191–240, 283–330, 372–428, 476–525

Glycosylation sites (5): 160, 463, 790, 820, 827

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-373752	Netrin-1 signaling
R-HSA-376176	Signaling by ROBO receptors
R-HSA-428540	Activation of RAC1
R-HSA-428542	Regulation of commissural axon pathfinding by SLIT and ROBO
R-HSA-428543	Inactivation of CDC42 and RAC1
R-HSA-428890	Role of ABL in ROBO-SLIT signaling
R-HSA-8985586	SLIT2:ROBO1 increases RHOA activity
R-HSA-8985801	Regulation of cortical dendrite branching
R-HSA-9010553	Regulation of expression of SLITs and ROBOs
R-HSA-1266738	Developmental Biology
R-HSA-422475	Axon guidance
R-HSA-9675108	Nervous system development

MSigDB gene sets: 629 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_FOREBRAIN_NEURON_DEVELOPMENT, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_OLFACTORY_BULB_INTERNEURON_DIFFERENTIATION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEURON_RECOGNITION, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, GOBP_OUTFLOW_TRACT_SEPTUM_MORPHOGENESIS, GOBP_REGULATION_OF_MAMMARY_GLAND_EPITHELIAL_CELL_PROLIFERATION, GOBP_VENTRICULAR_SEPTUM_MORPHOGENESIS, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_RESPONSE_TO_PEPTIDE

GO Biological Process (31): cell migration involved in sprouting angiogenesis (GO:0002042), heart induction (GO:0003129), outflow tract septum morphogenesis (GO:0003148), aortic valve morphogenesis (GO:0003180), pulmonary valve morphogenesis (GO:0003184), endocardial cushion formation (GO:0003272), cell adhesion (GO:0007155), homophilic cell-cell adhesion (GO:0007156), nervous system development (GO:0007399), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), axon midline choice point recognition (GO:0016199), chemorepulsion involved in postnatal olfactory bulb interneuron migration (GO:0021836), negative regulation of cell migration (GO:0030336), positive regulation of vascular endothelial growth factor receptor signaling pathway (GO:0030949), negative regulation of mammary gland epithelial cell proliferation (GO:0033600), positive regulation of Rho protein signal transduction (GO:0035025), Roundabout signaling pathway (GO:0035385), aorta development (GO:0035904), positive regulation of MAPK cascade (GO:0043410), positive regulation of Notch signaling pathway (GO:0045747), positive regulation of axonogenesis (GO:0050772), negative regulation of negative chemotaxis (GO:0050925), ventricular septum morphogenesis (GO:0060412), negative regulation of chemokine-mediated signaling pathway (GO:0070100), positive regulation of vascular endothelial growth factor signaling pathway (GO:1900748), chemotaxis (GO:0006935), axon guidance (GO:0007411), brain development (GO:0007420), cell differentiation (GO:0030154), tube development (GO:0035295)

GO Molecular Function (4): axon guidance receptor activity (GO:0008046), LRR domain binding (GO:0030275), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (9): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cilium (GO:0005929), cell surface (GO:0009986), axon (GO:0030424), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Signaling by ROBO receptors	7
Axon guidance	2
Nervous system development	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
heart valve morphogenesis	2
gene expression	2
regulation of gene expression	2
sprouting angiogenesis	1
blood vessel endothelial cell migration	1
organ induction	1
heart field specification	1
regulation of heart morphogenesis	1
outflow tract morphogenesis	1
cardiac septum morphogenesis	1
aortic valve development	1
pulmonary valve development	1
endocardial cushion morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cellular process	1
cell-cell adhesion	1
system development	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
axon choice point recognition	1
postnatal olfactory bulb interneuron migration	1
negative chemotaxis	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
positive regulation of signal transduction	1
regulation of vascular endothelial growth factor receptor signaling pathway	1
vascular endothelial growth factor receptor signaling pathway	1
mammary gland epithelial cell proliferation	1
regulation of mammary gland epithelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
negative regulation of multicellular organismal process	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
cell surface receptor signaling pathway	1
artery development	1
MAPK cascade	1
regulation of MAPK cascade	1

Protein interactions and networks

STRING

2162 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ROBO1	SLIT1	O75093	999
ROBO1	SLIT3	O75094	999
ROBO1	SLIT2	O94813	999
ROBO1	SRGAP1	Q7Z6B7	992
ROBO1	DNAAF4	Q8WXU2	844
ROBO1	NTN1	O95631	815
ROBO1	FOXP2	O15409	802
ROBO1	SRGAP2	O75044	796
ROBO1	SRGAP3	O43295	784
ROBO1	KIAA0319	Q5VV43	773
ROBO1	DCDC2	Q9UHG0	741
ROBO1	ARHGAP1	Q07960	657
ROBO1	DCC	P43146	595
ROBO1	CDC42	P21181	593
ROBO1	ROBO4	Q8WZ75	589

IntAct

77 interactions, top by confidence:

A	B	Type	Score
APBA2	USP20	psi-mi:“MI:0915”(physical association)	0.880
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
APBA2	USP33	psi-mi:“MI:0915”(physical association)	0.660
BRK1	CYFIP1	psi-mi:“MI:0914”(association)	0.640
SLIT2	ROBO1	psi-mi:“MI:0407”(direct interaction)	0.560
USP33	ROBO1	psi-mi:“MI:0915”(physical association)	0.560
SRGAP2	ROBO1	psi-mi:“MI:0407”(direct interaction)	0.560
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
GDPD5	GOLIM4	psi-mi:“MI:0914”(association)	0.530
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
CLEC4A	SEMA7A	psi-mi:“MI:0914”(association)	0.530
CMKLR1	SC5D	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
ROBO1	ARHGAP4	psi-mi:“MI:0407”(direct interaction)	0.440
Slit2	ROBO1	psi-mi:“MI:0407”(direct interaction)	0.440
ROBO1	HMGA1	psi-mi:“MI:0915”(physical association)	0.400
ROBO1	ROBO1	psi-mi:“MI:0915”(physical association)	0.400
ROBO1	ROBO2	psi-mi:“MI:0915”(physical association)	0.400
ROBO1	MPIG6B	psi-mi:“MI:0915”(physical association)	0.400
ROBO1	ROBO4	psi-mi:“MI:0915”(physical association)	0.400
		psi-mi:“MI:0914”(association)	0.350
SRGAP1	SRGAP2	psi-mi:“MI:0914”(association)	0.350
SRGAP3	NKTR	psi-mi:“MI:0914”(association)	0.350

BioGRID (120): ARPP19 (Co-fractionation), ROBO1 (Affinity Capture-MS), ROBO1 (Affinity Capture-MS), ROBO1 (Proximity Label-MS), ROBO1 (Affinity Capture-MS), ROBO1 (Affinity Capture-RNA), ROBO1 (Affinity Capture-MS), ROBO1 (Affinity Capture-Western), USP33 (Affinity Capture-Western), ROBO1 (Affinity Capture-RNA), ROBO1 (Proximity Label-MS), ROBO1 (Proximity Label-MS), ROBO1 (Proximity Label-MS), USP33 (Affinity Capture-Western), ROBO1 (Affinity Capture-MS)

ESM2 similar proteins: A0A6I8TCE0, B0X4T2, F1NY98, O00533, O35158, O55005, O60469, O89026, O97394, P12960, P14781, P16092, P17790, P18460, P18461, P21802, P21803, P28685, P29074, P35331, P35832, P57097, P70232, P97686, Q12860, Q12866, Q28106, Q32MD9, Q3UH53, Q4KMG0, Q60805, Q61851, Q63198, Q7Z5N4, Q7ZXX1, Q810U4, Q8AV58, Q8AXZ4, Q8JG38, Q8VHZ8

Diamond homologs: A0A1Y9G8H0, A0A452E9Y6, A1KZ92, A2A8L5, A2AJ76, A4IFW2, A4IGL7, A4IIW9, A5JUY8, A7MBJ4, A8WGA3, A8WQH2, B0BNK7, B3A0P3, D2HFT7, D3YXG0, D4A1J9, D4ABX8, G5EBF1, G5EG78, H2A0M7, O15146, O35158, O55005, O89026, P05164, P07202, P09933, P0C6S8, P0C7J6, P11247, P11678, P14650, P16621, P22079, P23468, P35419, P49290, P70193, P80025

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ABL1	down-regulates	ROBO1	phosphorylation
NFIA	“up-regulates quantity”	ROBO1	“transcriptional regulation”
NFIB	“up-regulates quantity”	ROBO1	“transcriptional regulation”
NFIX	“up-regulates quantity”	ROBO1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
NCAM signaling for neurite out-growth	5	19.1×	3e-04
Signaling by ROBO receptors	5	8.7×	3e-03
Axon guidance	12	7.6×	2e-05
Nervous system development	12	7.3×	2e-05
RAC1 GTPase cycle	7	6.0×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
axon guidance	9	9.3×	4e-04
nervous system development	10	5.2×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

755 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	27
Uncertain significance	406
Likely benign	192
Benign	46

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1077087	NM_002941.4(ROBO1):c.4156G>T (p.Gly1386Ter)	Pathogenic
1077089	NM_002941.4(ROBO1):c.687C>G (p.Tyr229Ter)	Pathogenic
1321867	NM_002941.4(ROBO1):c.2630_2631del (p.Pro877fs)	Pathogenic
1343417	NM_002941.4(ROBO1):c.1265A>G (p.Asp422Gly)	Pathogenic
1931046	NM_002941.4(ROBO1):c.4510C>T (p.Arg1504Ter)	Pathogenic
2664558	NM_002941.4(ROBO1):c.583C>T (p.Arg195Ter)	Pathogenic
2698892	NM_002941.4(ROBO1):c.554_555dup (p.Pro186fs)	Pathogenic
2826192	NM_002941.4(ROBO1):c.1116T>A (p.Cys372Ter)	Pathogenic
2877025	NM_002941.4(ROBO1):c.3952del (p.Leu1318fs)	Pathogenic
3253348	NM_002941.4(ROBO1):c.2467C>T (p.Arg823Ter)	Pathogenic
3573521	NM_002941.4(ROBO1):c.856C>T (p.Arg286Ter)	Pathogenic
4081917	NM_002941.4(ROBO1):c.4615C>T (p.Gln1539Ter)	Pathogenic
4753505	NM_002941.4(ROBO1):c.661C>T (p.Arg221Ter)	Pathogenic
4759665	NM_002941.4(ROBO1):c.3379C>T (p.Arg1127Ter)	Pathogenic
996034	NM_002941.4(ROBO1):c.1342+1G>A	Pathogenic
996098	NM_002941.4(ROBO1):c.2882+1G>T	Pathogenic
1077088	NM_002941.4(ROBO1):c.850G>T (p.Glu284Ter)	Likely pathogenic
1077098	NC_000003.11:g.78945148_79288919del	Likely pathogenic
1098921	GRCh37/hg19 3p12.3(chr3:78653578-79071345)x1	Likely pathogenic
1321866	NM_002941.4(ROBO1):c.4015_4018del (p.Ala1339fs)	Likely pathogenic
1691767	NM_002941.4(ROBO1):c.2840-2A>G	Likely pathogenic
2017623	NM_002941.4(ROBO1):c.917+2T>C	Likely pathogenic
2444348	NM_002941.4(ROBO1):c.1463G>A (p.Trp488Ter)	Likely pathogenic
2632617	NM_002941.4(ROBO1):c.2168G>A (p.Trp723Ter)	Likely pathogenic
2690686	NM_002941.4(ROBO1):c.3808G>T (p.Glu1270Ter)	Likely pathogenic
2690687	NM_002941.4(ROBO1):c.1501C>T (p.Arg501Ter)	Likely pathogenic
2692578	NM_002941.4(ROBO1):c.2440_2442+4del	Likely pathogenic
3037653	NM_002941.4(ROBO1):c.455dup (p.Tyr152Ter)	Likely pathogenic
3700011	NM_002941.4(ROBO1):c.1343-1G>T	Likely pathogenic
4072288	NM_002941.4(ROBO1):c.4478del (p.Pro1493fs)	Likely pathogenic

SpliceAI

6231 predictions. Top by Δscore:

Variant	Effect	Δscore
3:78607039:GAT:G	acceptor_gain	1.0000
3:78607039:GATC:G	acceptor_loss	1.0000
3:78607040:ATC:A	acceptor_loss	1.0000
3:78607041:TCTAA:T	acceptor_loss	1.0000
3:78607042:C:CC	acceptor_gain	1.0000
3:78607042:C:CG	acceptor_loss	1.0000
3:78607043:T:G	acceptor_loss	1.0000
3:78614646:A:AC	donor_gain	1.0000
3:78614647:C:CC	donor_gain	1.0000
3:78614647:CCAT:C	donor_gain	1.0000
3:78614797:CGGC:C	acceptor_gain	1.0000
3:78614801:C:CC	acceptor_gain	1.0000
3:78617630:CTCA:C	donor_loss	1.0000
3:78617633:A:C	donor_loss	1.0000
3:78617634:C:CG	donor_loss	1.0000
3:78617634:CCAG:C	donor_gain	1.0000
3:78617667:TTCAG:T	donor_gain	1.0000
3:78618039:CGT:C	acceptor_gain	1.0000
3:78627316:CATA:C	donor_loss	1.0000
3:78627317:ATACC:A	donor_loss	1.0000
3:78627318:TACC:T	donor_loss	1.0000
3:78627319:A:C	donor_loss	1.0000
3:78627319:ACCT:A	donor_gain	1.0000
3:78627320:CCTC:C	donor_gain	1.0000
3:78627322:T:TA	donor_gain	1.0000
3:78627565:CATAG:C	acceptor_gain	1.0000
3:78627567:TAG:T	acceptor_gain	1.0000
3:78627569:GCTA:G	acceptor_loss	1.0000
3:78627570:C:CC	acceptor_gain	1.0000
3:78631156:CTTA:C	donor_loss	1.0000

AlphaMissense

10767 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:78717307:C:A	W295C	1.000
3:78717307:C:G	W295C	1.000
3:78717308:C:G	W295S	1.000
3:78717309:A:G	W295R	1.000
3:78717309:A:T	W295R	1.000
3:78938799:A:G	W101R	1.000
3:78938799:A:T	W101R	1.000
3:78651825:A:G	C907R	0.999
3:78667954:A:G	F632S	0.999
3:78668190:C:A	W581C	0.999
3:78668190:C:G	W581C	0.999
3:78668192:A:G	W581R	0.999
3:78668192:A:T	W581R	0.999
3:78668203:A:T	V577D	0.999
3:78668547:A:C	Y523D	0.999
3:78670180:C:A	W488C	0.999
3:78670180:C:G	W488C	0.999
3:78670182:A:G	W488R	0.999
3:78670182:A:T	W488R	0.999
3:78685850:A:G	L413P	0.999
3:78688709:A:G	F370S	0.999
3:78717350:A:G	F281S	0.999
3:78717774:A:G	L256P	0.999
3:78717828:T:G	Y238S	0.999
3:78717829:A:C	Y238D	0.999
3:78717867:A:G	L225P	0.999
3:78746788:C:A	W204C	0.999
3:78746788:C:G	W204C	0.999
3:78746789:C:G	W204S	0.999
3:78746790:A:G	W204R	0.999

dbSNP variants (sampled 300 via entrez): RS1000007181 (3:79746356 A>C), RS1000008175 (3:79584266 A>G,T), RS1000012716 (3:78761146 C>G,T), RS1000017536 (3:79697763 C>A), RS1000022861 (3:79288162 G>A,T), RS1000023649 (3:79327719 T>C), RS1000025527 (3:78746089 A>T), RS1000029560 (3:79458256 G>A,C), RS1000030585 (3:79144701 A>G,T), RS1000033220 (3:78951816 C>A,T), RS1000033370 (3:79446476 T>C), RS1000035444 (3:78746408 T>C), RS1000038093 (3:79106573 T>C,G), RS1000039034 (3:79108420 A>G), RS1000039460 (3:79105435 T>A,C)

Disease associations

OMIM: gene MIM:602430 | disease phenotypes: MIM:610805, MIM:620305, MIM:187500, MIM:207500, MIM:301800, MIM:310700, MIM:257400, MIM:620303, MIM:613680

GenCC curated gene-disease

Disease	Classification	Inheritance
neurooculorenal syndrome	Definitive	Autosomal recessive
pituitary hormone deficiency, combined or isolated, 8	Strong	Autosomal dominant
pituitary stalk interruption syndrome	Supportive	Autosomal dominant
congenital heart disease	Limited	Autosomal dominant
nystagmus, congenital, autosomal recessive	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital heart disease	Limited	AR
congenital heart disease	Limited	AD

Mondo (13): congenital anomaly of kidney and urinary tract (MONDO:0019719), neurooculorenal syndrome (MONDO:0957210), congenital heart disease (MONDO:0005453), pituitary stalk interruption syndrome (MONDO:0019828), tetralogy of fallot (MONDO:0008542), imperforate anus (MONDO:0001046), hypopituitarism (MONDO:0005152), congenital nystagmus (MONDO:0005712), nystagmus, congenital, autosomal recessive (MONDO:0009762), pituitary hormone deficiency, combined or isolated, 8 (MONDO:0957208), THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome (MONDO:0013362), intellectual disability (MONDO:0001071), bilateral renal agenesis (MONDO:0015986)

Orphanet (8): Renal or urinary tract malformation (Orphanet:93545), Pituitary stalk interruption syndrome (Orphanet:95496), Tetralogy of Fallot (Orphanet:3303), Non-syndromic anorectal malformation (Orphanet:557), THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome (Orphanet:363444), Renal agenesis, bilateral (Orphanet:1848), NON RARE IN EUROPE: Idiopathic infantile nystagmus (Orphanet:651), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

75 total (30 of 75 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000122	Unilateral renal agenesis
HP:0000238	Hydrocephalus
HP:0000289	Broad philtrum
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000407	Sensorineural hearing impairment
HP:0000410	Mixed hearing impairment
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000540	Hypermetropia
HP:0000639	Nystagmus
HP:0000786	Primary amenorrhea
HP:0000821	Hypothyroidism
HP:0000823	Delayed puberty
HP:0000835	Adrenal hypoplasia
HP:0000864	Abnormality of the hypothalamus-pituitary axis
HP:0000873	Diabetes insipidus
HP:0001089	Iris atrophy
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001320	Cerebellar vermis hypoplasia
HP:0001335	Bimanual synkinesia
HP:0001338	Partial agenesis of the corpus callosum
HP:0001508	Failure to thrive
HP:0001522	Death in infancy

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST000189_37	Protein quantitative trait loci	4.000000e-06
GCST000271_5	Brain imaging in schizophrenia (dorsolateral prefrontal cortex interaction)	4.000000e-06
GCST002208_6	Liver enzyme levels (aspartate transaminase)	6.000000e-06
GCST003139_22	Glomerular filtration rate in chronic kidney disease	2.000000e-06
GCST003171_1	Visceral adipose tissue	8.000000e-07
GCST003181_3	Staphylococcus aureus nasal carriage (intermittent)	2.000000e-06
GCST003979_9	Excessive daytime sleepiness	3.000000e-08
GCST003999_15	Nose size	5.000000e-08
GCST004162_24	Carotid plaque burden	2.000000e-06
GCST004412_4	Craniofacial microsomia	2.000000e-120
GCST004727_1	Facial emotion recognition	2.000000e-06
GCST004731_2	Facial emotion recognition (fearful faces)	4.000000e-06
GCST006479_30	Diverticular disease	9.000000e-06
GCST006575_4	Takayasu arteritis	7.000000e-06
GCST007201_16	Schizophrenia	8.000000e-07
GCST008179_13	Moderate-to-late spontaneous preterm birth	2.000000e-06
GCST009391_1386	Metabolite levels	3.000000e-06
GCST009391_688	Metabolite levels	6.000000e-06
GCST010002_432	Refractive error	2.000000e-09
GCST010988_101	Adult body size	1.000000e-09
GCST011349_45	Gamma glutamyl transferase levels	3.000000e-08
GCST011743_34	HDL cholesterol levels in HIV infection	9.000000e-06
GCST011768_1	Schizophrenia	2.000000e-09
GCST012190_3	Body mass index and diastolic blood pressure (bivariate analysis)	2.000000e-06
GCST012488_8	L1-L4 bone mineral density x serum urate levels interaction	3.000000e-06
GCST012490_281	Femur bone mineral density x serum urate levels interaction	4.000000e-09
GCST90020027_299	Waist-hip index	3.000000e-08

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0004555	glycoprotein measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0007758	intermittent Staphylococcus aureus carrier status
EFO:0007875	excessive daytime sleepiness measurement
EFO:0006501	carotid plaque build
EFO:0008329	facial emotion recognition measurement
EFO:0009959	diverticular disease
EFO:0006917	spontaneous preterm birth
EFO:0010368	lysophosphatidylethanolamine 18:1 measurement
EFO:0008529	kynurenine measurement
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004340	body mass index
EFO:0006336	diastolic blood pressure
EFO:0004531	urate measurement
EFO:0007701	spine bone mineral density
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D001006	Anus, Imperforate	C06.198.050; C16.131.314.094
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D007018	Hypopituitarism	C10.228.140.617.738.300; C19.700.482
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D020417	Nystagmus, Congenital	C10.292.562.675.300; C11.590.400.300; C16.614.643
D013771	Tetralogy of Fallot	C14.240.400.849; C14.280.400.849; C16.131.240.400.849
C566906	Cakut (supp.)
C564938	Nystagmus, Congenital Motor, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

58 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Acetaminophen	affects expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	3
Aflatoxin B1	affects cotreatment, decreases expression, decreases methylation	3
aristolochic acid I	decreases expression	2
entinostat	decreases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Quercetin	decreases expression, increases phosphorylation	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	affects cotreatment, decreases methylation, increases methylation	1
trichostatin A	decreases expression	1
nickel chloride	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects methylation	1
(+)-JQ1 compound	increases expression	1
Decitabine	affects methylation	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1U7	Abcam U-87MG ROBO1 KO	Cancer cell line	Male
CVCL_E1G2	Abcam HeLa ROBO1 KO	Cancer cell line	Female
CVCL_TJ46	HAP1 ROBO1 (-) 1	Cancer cell line	Male
CVCL_XS28	HAP1 ROBO1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

304 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE