SLIT3

Summary

SLIT3 (slit guidance ligand 3, HGNC:11087) is a protein-coding gene on chromosome 5q34-q35.1, encoding Slit homolog 3 protein (O75094). May act as molecular guidance cue in cellular migration, and function may be mediated by interaction with roundabout homolog receptors.

The protein encoded by this gene is secreted, likely interacting with roundabout homolog receptors to effect cell migration. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6586 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital anomaly of kidney and urinary tract (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 13
• Clinical variants (ClinVar): 789 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_003062

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11087
Approved symbol	SLIT3
Name	slit guidance ligand 3
Location	5q34-q35.1
Locus type	gene with protein product
Status	Approved
Aliases	slit2, MEGF5, SLIT1, Slit-3
Ensembl gene	ENSG00000184347
Ensembl biotype	protein_coding
OMIM	603745
Entrez	6586

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 retained_intron, 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000332966, ENST00000518092, ENST00000518140, ENST00000519486, ENST00000519560, ENST00000521130, ENST00000521150

RefSeq mRNA: 2 — MANE Select: NM_003062 NM_001271946, NM_003062

CCDS: CCDS4369, CCDS64311

Canonical transcript exons

ENST00000519560 — 36 exons

Exon	Start	End
ENSE00001291276	168752955	168753098
ENSE00001291696	168748302	168748434
ENSE00001292515	168685687	168685927
ENSE00001293568	168669783	168669991
ENSE00001296906	168707976	168708100
ENSE00001297106	168710895	168711058
ENSE00001303397	168722933	168723004
ENSE00001304112	168712283	168712354
ENSE00001305501	168671198	168671483
ENSE00001309009	168696292	168696431
ENSE00001310283	168673177	168673331
ENSE00001313097	168749472	168749635
ENSE00001315650	168722256	168722327
ENSE00001316861	168724416	168724484
ENSE00001320550	168700582	168700679
ENSE00001328042	169300513	169301139
ENSE00002131713	168661740	168666689
ENSE00003459673	168785907	168785978
ENSE00003485839	168789560	168789631
ENSE00003495075	168883265	168883336
ENSE00003501905	169244705	169244776
ENSE00003504453	168760862	168760936
ENSE00003528161	169251388	169251459
ENSE00003537988	168823260	168823331
ENSE00003552724	169193479	169193550
ENSE00003573166	168817300	168817463
ENSE00003587321	168844584	168844655
ENSE00003597496	168795507	168795578
ENSE00003603909	168686979	168687116
ENSE00003626537	168774235	168774378
ENSE00003629737	168762539	168762689
ENSE00003640835	168753864	168754007
ENSE00003654554	168692607	168692700
ENSE00003663122	168683966	168684096
ENSE00003672087	168772781	168772944
ENSE00003675724	168806446	168806587

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 95.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.4552 / max 447.9879, expressed in 1040 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64748	12.4934	984
64744	2.8698	667
64740	2.7993	691
64746	1.5935	566
64725	0.6879	100
64739	0.5825	316
64728	0.3012	168
64742	0.2530	147
64745	0.2105	127
64741	0.1895	103

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right coronary artery	UBERON:0001625	95.79	gold quality
popliteal artery	UBERON:0002250	94.78	gold quality
tibial artery	UBERON:0007610	94.76	gold quality
saphenous vein	UBERON:0007318	94.14	gold quality
gall bladder	UBERON:0002110	93.83	gold quality
aorta	UBERON:0000947	93.62	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.47	gold quality
vena cava	UBERON:0004087	93.03	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.94	gold quality
coronary artery	UBERON:0001621	92.85	gold quality
left coronary artery	UBERON:0001626	92.66	gold quality
cardiac atrium	UBERON:0002081	92.65	gold quality
right atrium auricular region	UBERON:0006631	92.63	gold quality
ascending aorta	UBERON:0001496	92.17	gold quality
thoracic aorta	UBERON:0001515	92.16	gold quality
omental fat pad	UBERON:0010414	92.08	gold quality
peritoneum	UBERON:0002358	92.07	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.05	gold quality
adipose tissue	UBERON:0001013	91.79	gold quality
descending thoracic aorta	UBERON:0002345	91.61	gold quality
periodontal ligament	UBERON:0008266	91.60	gold quality
upper arm skin	UBERON:0004263	91.45	gold quality
connective tissue	UBERON:0002384	91.13	gold quality
colonic epithelium	UBERON:0000397	90.57	gold quality
pericardium	UBERON:0002407	90.56	gold quality
right lung	UBERON:0002167	90.30	gold quality
upper lobe of left lung	UBERON:0008952	89.92	gold quality
parietal pleura	UBERON:0002400	89.40	gold quality
upper lobe of lung	UBERON:0008948	89.24	gold quality
synovial joint	UBERON:0002217	89.16	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	2501.91
E-MTAB-11268	yes	2176.96
E-HCAD-56	yes	1304.08
E-HCAD-35	yes	540.98
E-CURD-119	yes	25.49
E-ANND-3	yes	19.41
E-MTAB-9543	yes	15.01
E-MTAB-6678	yes	11.65
E-MTAB-10290	no	262.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

169 targeting SLIT3, 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-1277-5P	100.00	73.95	5056
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4725-3P	99.96	69.53	2520

Literature-anchored findings (GeneRIF, showing 30)

• Analysis of alternative splicing and conserved domains in human and mouse slit genes (PMID:12141424)
• Many variants in SLIT3 tend to associate with schizophrenia susceptibility in the Chinese Han population. (PMID:15231749)
• data suggest that Slit proteins play a key role in guiding dorsally projecting cranial motoneurons and in facilitating their neural tube exit (PMID:16162649)
• In fetal and embryonic stem cell cultures Slit-3 inhibited neurite outgrowth. (PMID:16840550)
• Slits are negative regulators of Sdf1 and Cxcr4 in breast cancer cells. (PMID:18829537)
• functions to promote angiogenesis in coordinating organogenesis during embryonic development (PMID:19741192)
• Slit3 inhibits Robo3-induced invasion of synovial fibroblasts in rheumatoid arthritis. (PMID:20298552)
• The chemorepellent Slit3 promotes monocyte migration. (PMID:21078908)
• SLIT3 duplication on 5q35.1 predisposes to major depressive disorder (PMID:21152026)
• 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)
• Slit3 treatment increased the in vivo homing efficiency of CD34 HSPCs to the BM in NOD/SCID mice, whereas Slit3-exposed HSPC migration in vitro was inhibited. Results support a role for Slit3 in human HSPC migration in vitro and homing in vivo. (PMID:22614124)
• results implicate the involvement of miR-218-2 and its host gene SLIT3 in thyroid cancer cell invasion, migration, and proliferation (PMID:23720784)
• SLIT3-ROBO4 activation promotes vascular network formation in human engineered tissue and angiogenesis in vivo. (PMID:24090675)
• High SLIT3 expression is associated with high-grade gliomas. (PMID:24158112)
• SLIT3 is increased with labour, and both amnion and myometrial studies describe a pro-inflammatory effect of SLIT3 in these tissues. (PMID:24286238)
• Estrogen-dependent expression of SLIT3 may play a key role in regulating nerve-vessel interactions within the complex microenvironment of endometriosis lesions. (PMID:25051436)
• Results show that silencing of Slit3 promoted proliferation, migration and invasion of A549 cells and induced epithelial-mesenchymal transition suggesting that Slit3 functions as a tumor suppressor in lung carcinoma. (PMID:26045181)
• Overexpression of Slit3 induces its tumor suppressive effects in Breast cancer. (PMID:26542734)
• This study suggests that Slit3 acts as a tumor suppressor in hepatocellular carcinoma by repressing the tumor growth and thus tumor progression (PMID:29859044)
• High genetic risk scores of SLIT3, PLEKHA5 and PPP2R2C variants increase susceptibility to increased insulin resistance by 50% and its risk may be exacerbated by consuming more than 10 cups coffee/week or 220 mg caffeine/day. (PMID:30454882)
• SLIT3 and SPARCL1 can be regulated by DNA methylation and down-regulated in lung adenocarcinoma (PMID:31154721)
• the level of gingival crevicular fluid SLIT3 was higher in patients with periodontitis than in healthy individuals and was closely associated with clinical attachment loss and radiographic bone loss (PMID:31696592)
• Identification of slit3 as a locus affecting nicotine preference in zebrafish and human smoking behaviour. (PMID:32209227)
• Single-nucleotide polymorphism rs10036727 in the SLIT3 gene is associated with osteoporosis at the femoral neck in older Mexican postmenopausal women. (PMID:32762475)
• Isolated congenital diaphragm hernia associated with homozygous SLIT3 gene variant in dizygous twins. (PMID:33933663)
• LncRNA ubiquitin-binding protein domain protein 10 antisense RNA 1 inhibits colon adenocarcinoma progression via the miR-515-5p/slit guidance ligand 3 axis. (PMID:35034539)
• LncRNA PGM5-AS1 Inhibits the Progression of Bladder Cancer by Regulating miR-587/SLIT3 Axis. (PMID:36017912)
• Abnormal expression of SLIT3 induces intravillous vascularization dysplasia in ectopic pregnancy. (PMID:36793891)
• Stromal Cell-SLIT3/Cardiomyocyte-ROBO1 Axis Regulates Pressure Overload-Induced Cardiac Hypertrophy. (PMID:38414132)
• The Role of SLIT3-ROBO4 Signaling in Endoplasmic Reticulum Stress-Induced Delayed Corneal Epithelial and Nerve Regeneration. (PMID:38700874)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slit3	ENSDARG00000034268
mus_musculus	Slit3	ENSMUSG00000056427
rattus_norvegicus	Slit3	ENSRNOG00000007377

Paralogs (25): SLITRK3 (ENSG00000121871), LRFN3 (ENSG00000126243), LRFN1 (ENSG00000128011), SLIT2 (ENSG00000145147), LRFN2 (ENSG00000156564), LRRC38 (ENSG00000162494), SLITRK5 (ENSG00000165300), LRFN5 (ENSG00000165379), LRTM2 (ENSG00000166159), LINGO1 (ENSG00000169783), LRRN2 (ENSG00000170382), LRRN3 (ENSG00000173114), LRFN4 (ENSG00000173621), LINGO2 (ENSG00000174482), LRRN1 (ENSG00000175928), SLITRK1 (ENSG00000178235), GP5 (ENSG00000178732), SLITRK4 (ENSG00000179542), LRRC55 (ENSG00000183908), SLITRK6 (ENSG00000184564), SLITRK2 (ENSG00000185985), LRRC70 (ENSG00000186105), SLIT1 (ENSG00000187122), TLR9 (ENSG00000239732), TPBGL (ENSG00000261594)

Protein

Protein identifiers

Slit homolog 3 protein — O75094 (reviewed: O75094)

Alternative names: Multiple epidermal growth factor-like domains protein 5

All UniProt accessions (1): O75094

UniProt curated annotations — full annotation on UniProt →

Function. May act as molecular guidance cue in cellular migration, and function may be mediated by interaction with roundabout homolog receptors.

Subcellular location. Secreted.

Tissue specificity. Predominantly expressed in thyroid.

Isoforms (4)

UniProt ID	Names	Canonical?
O75094-1	1	yes
O75094-2	2
O75094-3	3
O75094-4	4

RefSeq proteins (2): NP_001258875, NP_003053* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000372	LRRNT	Domain
IPR000483	Cys-rich_flank_reg_C	Domain
IPR000742	EGF	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR001791	Laminin_G	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR006207	Cys_knot_C	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR013032	EGF-like_CS	Conserved_site
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR051355	Notch/Slit_guidance	Family

Pfam: PF00008, PF01462, PF01463, PF02210, PF12661, PF13855

UniProt features (100 total): disulfide bond 37, repeat 20, domain 19, glycosylation site 13, sequence variant 6, splice variant 3, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75094-F1	80.48	0.25

Functional residue map

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

Disulfide bonds (37): 284–293, 441–464, 443–485, 505–511, 509–518, 667–690, 669–711, 920–931, 925–941, 943–952, 959–970, 964–982, 984–993, 1000–1011, 1005–1020, 1022–1031, 1038–1051, 1045–1060, 1062–1071, 1078–1089 …

Glycosylation sites (13): 72, 192, 563, 622, 784, 792, 797, 928, 1008, 1025, 1181, 1247, 1406

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-373752	Netrin-1 signaling
R-HSA-376176	Signaling by ROBO receptors
R-HSA-428542	Regulation of commissural axon pathfinding by SLIT and ROBO
R-HSA-1266738	Developmental Biology
R-HSA-422475	Axon guidance
R-HSA-9675108	Nervous system development

MSigDB gene sets: 727 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_FOREBRAIN_NEURON_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, RNGTGGGC_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, GOBP_OLFACTORY_BULB_INTERNEURON_DIFFERENTIATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, LEE_NEURAL_CREST_STEM_CELL_DN

GO Biological Process (17): aortic valve morphogenesis (GO:0003180), atrioventricular valve morphogenesis (GO:0003181), axon guidance (GO:0007411), negative regulation of cell population proliferation (GO:0008285), negative regulation of gene expression (GO:0010629), negative regulation of cell growth (GO:0030308), cellular response to hormone stimulus (GO:0032870), Roundabout signaling pathway (GO:0035385), axon extension involved in axon guidance (GO:0048846), negative chemotaxis (GO:0050919), response to cortisol (GO:0051414), ventricular septum morphogenesis (GO:0060412), apoptotic process involved in luteolysis (GO:0061364), negative regulation of chemokine-mediated signaling pathway (GO:0070100), nervous system development (GO:0007399), animal organ morphogenesis (GO:0009887), cell differentiation (GO:0030154)

GO Molecular Function (4): calcium ion binding (GO:0005509), heparin binding (GO:0008201), Roundabout binding (GO:0048495), protein binding (GO:0005515)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), mitochondrion (GO:0005739), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-4 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
heart valve morphogenesis	2
negative regulation of cellular process	2
aortic valve development	1
atrioventricular valve development	1
axonogenesis	1
neuron projection guidance	1
cell population proliferation	1
regulation of cell population proliferation	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
response to hormone	1
cellular response to chemical stimulus	1
cellular response to endogenous stimulus	1
cell surface receptor signaling pathway	1
axon guidance	1
axon extension	1
chemotaxis	1
response to glucocorticoid	1
response to alcohol	1
response to ketone	1
ventricular septum development	1
cardiac septum morphogenesis	1
luteolysis	1
apoptotic process involved in development	1
negative regulation of cytokine-mediated signaling pathway	1
negative regulation of G protein-coupled receptor signaling pathway	1
chemokine-mediated signaling pathway	1
regulation of chemokine-mediated signaling pathway	1
system development	1
anatomical structure morphogenesis	1
animal organ development	1
cellular developmental process	1
metal ion binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
signaling receptor binding	1

Protein interactions and networks

STRING

3224 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLIT3	ROBO2	Q9HCK4	999
SLIT3	ROBO1	Q9Y6N7	999
SLIT3	ROBO4	Q8WZ75	998
SLIT3	ROBO3	Q96MS0	985
SLIT3	SRGAP1	Q7Z6B7	921
SLIT3	NTN1	O95631	890
SLIT3	GPC1	P35052	890
SLIT3	SEMA3A	Q14563	768
SLIT3	DCC	P43146	747
SLIT3	SRGAP2	O75044	734
SLIT3	SRGAP3	O43295	727
SLIT3	PLXNA1	Q9UIW2	684
SLIT3	UNC5C	O95185	679
SLIT3	NKX6-1	P78426	678
SLIT3	NKX6-2	Q9C056	678

IntAct

13 interactions, top by confidence:

A	B	Type	Score
SLIT3	H1-5	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
SLIT3		psi-mi:“MI:0915”(physical association)	0.400
SLIT3		psi-mi:“MI:0915”(physical association)	0.370
SLIT3	NEC2	psi-mi:“MI:0915”(physical association)	0.370
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
VPS35	ILVBL	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
GATA2	ILVBL	psi-mi:“MI:0914”(association)	0.350
CTNNA1	MYO1G	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): SLIT3 (Affinity Capture-MS), HIST1H1B (Proximity Label-MS), SLIT3 (Proximity Label-MS), SLIT3 (Affinity Capture-MS), SLIT3 (Proximity Label-MS), RPL10A (Cross-Linking-MS (XL-MS)), SLIT3 (Affinity Capture-RNA), SLIT3 (Two-hybrid)

ESM2 similar proteins: C0STK7, G5EFX6, G5EG78, O15455, O35103, O35367, O42235, O60938, O62702, O73798, O75094, O77742, O88280, O94813, P08953, P24014, P24348, P46023, Q04833, Q0PV50, Q3ZBN5, Q58A48, Q5RI43, Q5TJ59, Q65YW8, Q65Z91, Q6AXL3, Q6R5N8, Q6X0I2, Q8C031, Q8SXT3, Q965M2, Q99983, Q99MB1, Q99MQ4, Q9BXN1, Q9CQ76, Q9DE66, Q9HCJ2, Q9JI18

Diamond homologs: A0A1D5PUP4, A0JP86, A2ASQ1, A3KN33, A5YT95, E9Q7X7, G4V4G1, G5ECE3, O00468, O00634, O09118, O15230, O62650, O75094, O75445, O88280, O94813, O95631, O95633, O95980, P02468, P02469, P07942, P0DKM7, P0DKM8, P0DKM9, P10184, P10669, P11046, P11047, P15215, P15800, P16895, P19883, P21674, P25304, P31514, P31515, P31696, P47931

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	486
Likely benign	190
Benign	45

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
684623	NM_004787.4(SLIT2):c.292G>A (p.Ala98Thr)	Pathogenic
684624	NM_004787.4(SLIT2):c.2712A>T (p.Lys904Asn)	Pathogenic
992921	NM_003062.4(SLIT3):c.1528C>T (p.Arg510Cys)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

10041 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:168673263:A:G	L1252P	1.000
5:168710906:A:C	F903C	1.000
5:168710963:C:G	C884S	1.000
5:168710964:A:G	C884R	1.000
5:168710964:A:T	C884S	1.000
5:168711013:C:A	W867C	1.000
5:168711013:C:G	W867C	1.000
5:168711031:A:C	C861W	1.000
5:168712339:A:C	N833K	1.000
5:168712339:A:T	N833K	1.000
5:168712349:A:G	L830P	1.000
5:168722322:A:G	L806P	1.000
5:168722933:A:G	L804P	1.000
5:168722999:A:G	L782P	1.000
5:168749539:G:C	C690W	1.000
5:168749540:C:G	C690S	1.000
5:168749541:A:G	C690R	1.000
5:168749541:A:T	C690S	1.000
5:168749630:A:G	L660P	1.000
5:168749632:G:C	N659K	1.000
5:168749632:G:T	N659K	1.000
5:168753011:A:C	N639K	1.000
5:168753011:A:T	N639K	1.000
5:168753025:A:G	S635P	1.000
5:168753027:A:G	L634P	1.000
5:168753083:G:C	N615K	1.000
5:168753083:G:T	N615K	1.000
5:168753936:A:G	L586P	1.000
5:168762539:A:G	L537P	1.000
5:168772848:G:C	C464W	1.000

dbSNP variants (sampled 300 via entrez): RS1000001766 (5:168814187 G>A), RS1000013424 (5:169163606 T>G), RS1000018307 (5:168691343 A>T), RS1000023682 (5:169022502 TAA>T), RS1000024201 (5:168828040 A>C), RS1000032867 (5:169203893 T>A), RS1000038147 (5:169157669 C>A), RS1000054871 (5:169022749 ACT>A), RS1000058641 (5:169100097 G>A,C), RS1000061035 (5:168777089 A>T), RS1000062295 (5:169234632 T>C), RS1000062420 (5:169046539 T>A,C), RS1000068657 (5:169129489 T>C), RS1000071096 (5:169284949 C>G), RS1000077089 (5:168939585 T>C,G)

Disease associations

OMIM: gene MIM:603745 | disease phenotypes: MIM:610805

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital anomaly of kidney and urinary tract	Moderate	Autosomal dominant
congenital diaphragmatic hernia	Moderate	Autosomal recessive

Mondo (2): congenital anomaly of kidney and urinary tract (MONDO:0019719), congenital diaphragmatic hernia (MONDO:0005711)

Orphanet (1): Renal or urinary tract malformation (Orphanet:93545)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000110_1	Echocardiographic traits	1.000000e-07
GCST000110_2	Echocardiographic traits	5.000000e-06
GCST003844_9	QRS duration	1.000000e-09
GCST005648_39	Serum metabolite concentrations in chronic kidney disease	9.000000e-10
GCST006055_3	Response to long-chain n-3 polyunsaturated fatty acid supplementation (change in triglyceride levels)	4.000000e-07
GCST008176_1	Gestational age at birth (child effect)	3.000000e-07
GCST008178_7	Early spontaneous preterm birth	2.000000e-07
GCST009107_18	Body mass index variance	2.000000e-09
GCST009121_19	Body mass index	2.000000e-13
GCST009180_8	Pars orbitalis volume	4.000000e-06
GCST010988_226	Adult body size	7.000000e-11
GCST011743_37	HDL cholesterol levels in HIV infection	5.000000e-06
GCST012163_7	Adiponectin levels x Mediterranean diet adherence interaction	7.000000e-06

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004295	left ventricular function
EFO:0004298	cardiovascular measurement
EFO:0005054	QRS complex
EFO:0007681	triglyceride change measurement
EFO:0005112	gestational age
EFO:0006917	spontaneous preterm birth
EFO:0004340	body mass index
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004502	adiponectin measurement
EFO:0008111	diet measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065630	Hernias, Diaphragmatic, Congenital	C16.131.433; C23.300.707.960.500.116
C566906	Cakut (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11189015	Efficacy	3	hydrochlorothiazide	Essential hypertension
rs2784917	Toxicity	3	etoposide

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2784917	SLIT1	3	0.00	1	etoposide
rs11189015	SLIT1	3	0.00	1	hydrochlorothiazide

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	5
bisphenol A	increases methylation, increases expression, affects cotreatment	3
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	3
sodium arsenite	affects methylation, affects cotreatment, decreases expression, increases abundance	2
mercuric bromide	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance, affects methylation	2
Dexamethasone	decreases expression, affects cotreatment, increases expression	2
Doxorubicin	decreases expression, increases expression	2
Estradiol	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	increases methylation	2
Cadmium Chloride	increases abundance, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
propionaldehyde	increases expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
arsenite	increases methylation	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	increases methylation	1
nitazoxanide	affects response to substance	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05213676	PHASE4	RECRUITING	De-implementing Inhaled Nitric Oxide for Congenital Diaphragmatic Hernia
NCT07247240	PHASE4	NOT_YET_RECRUITING	Efficacy of Inhaled Nitric Oxide in Congenital Diaphragmatic Hernia
NCT00257946	PHASE3	TERMINATED	Type of Material in Repair of Congenital Diaphragmatic Hernia
NCT03861182	PHASE3	TERMINATED	Contribution of PRF in CDH in Children With Prothetic Patch Closure
NCT06946576	PHASE3	NOT_YET_RECRUITING	Safety and Efficacy of Fetoscopic Endoluminal Tracheal Occlusion in Congenital Diaphragmatic Hernia
NCT07187206	PHASE3	RECRUITING	Safety and Efficacy of FETO in CDH Phase III
NCT00373438	PHASE2	UNKNOWN	Fetoscopic Tracheal Balloon Occlusion in Left Diaphragmatic Hernia
NCT00966823	PHASE2	TERMINATED	Fetal Tracheal Balloon Study in Diaphragmatic Hernia
NCT01302977	PHASE2	UNKNOWN	Fetal Tracheal Occlusion in Severe Diaphragmatic Hernia: a Randomized Trial
NCT01731509	PHASE2	UNKNOWN	Early FETO for Severe Congenital Diaphragmatic Hernia
NCT02875860	PHASE2	COMPLETED	‘TOTAL’ (Tracheal Occlusion To Accelerate Lung Growth) Trial
NCT02951130	PHASE2	COMPLETED	Milrinone in Congenital Diaphragmatic Hernia
NCT05201144	PHASE2	RECRUITING	A Trial of Phosphodiesterase-5 Inhibitor in Neonatal Congenital Diaphragmatic Hernia (TOP-CDH)
NCT04115345	PHASE1	COMPLETED	A Study of a Renal Autologous Cell Therapy (REACT) in Patients With Chronic Kidney Disease (CKD) From Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).
NCT05694169	PHASE1	TERMINATED	A Study of Participants With Chronic Kidney Disease Previously Treated With REACT
NCT03526588	PHASE1	TERMINATED	Umbilical Cord Blood Mononuclear Cells for Hypoxic Neurologic Injury in Infants With Congenital Diaphragmatic Hernia (CDH)
NCT04537364	Not specified	COMPLETED	Prediction of Renal Parenchymal Damage of CAKUT
NCT06921733	Not specified	RECRUITING	Ultrasound Localization Microscopy in Patient With Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
NCT01240057	PHASE2/PHASE3	COMPLETED	Tracheal Occlusion To Accelerate Lung Growth (TOTAL) Trial for Severe Pulmonary Hypoplasia
NCT00371241	Not specified	COMPLETED	Antibody Secreting Cell and Cyotokine Profiles in Neonates on ECMO
NCT00373763	Not specified	WITHDRAWN	Fetoscopic Tracheal Balloon Occlusion in Unborns With Severe Congenital Diaphragmatic Hernia - EUROTRIAL I
NCT00763737	Not specified	COMPLETED	Fetal Surgery for Moderate Left Sided Congenital Diaphragmatic Hernia.
NCT00881660	Not specified	COMPLETED	Fetal Endotracheal Occlusion (FETO) in Severe and Extremely Severe Congenital Diaphragmatic Hernia
NCT00950118	Not specified	RECRUITING	Diaphragmatic Hernia Research & Exploration, Advancing Molecular Science
NCT01098929	Not specified	UNKNOWN	Gene Mutations and Rescue in Human Congenital Diaphragmatic Hernia
NCT01155830	Not specified	COMPLETED	Inflammatory Cytokine Quantification in Infants
NCT01243229	Not specified	COMPLETED	Genetic Analysis of Congenital Diaphragmatic Disorders
NCT01467245	Not specified	COMPLETED	Open or Keyhole Surgery Through the Chest for Newborn Babies: Effect on Blood Gases
NCT01921309	Not specified	UNKNOWN	Trinity™ BIOLOX Delta™ CoC THR Multi-center Study
NCT02033772	Not specified	COMPLETED	Prospective Data Collection of Patients < 6 Months of Age Undergoing Thoracoscopic Surgery
NCT02364843	Not specified	TERMINATED	A Physiological Study to Determine the Enteral Threonine Requirements in Infants Aged 1 to 6 Months
NCT02453750	Not specified	COMPLETED	Airway Inflammation in Congenital Diaphragmatic Hernia Patients
NCT02466451	Not specified	COMPLETED	Study in Children With the Diagnosis of Congenital Diaphragmatic Hernia (CDH) and Oesophageal Atresia (EA)
NCT02530073	Not specified	RECRUITING	Trial of Fetoscopic Endoluminal Tracheal Occlusion (FETO) for CDH
NCT02549820	Not specified	ACTIVE_NOT_RECRUITING	Fetoscopic Endoluminal Tracheal Occlusion in Severe Left Congenital Diaphragmatic Hernia
NCT02596802	Not specified	ACTIVE_NOT_RECRUITING	Fetoscopic Endoluminal Tracheal Occlusion (FETO) for Congenital Diaphragm Hernia
NCT02710968	Not specified	ACTIVE_NOT_RECRUITING	Fetoscopic Endoluminal Tracheal Occlusion (FETO) for Severe Left Diaphragmatic Hernia (CDH)
NCT02849054	Not specified	UNKNOWN	CDH - Optimisation of Neonatal Ventilation
NCT02986087	Not specified	RECRUITING	Feto-Endoscopic Tracheal Occlusion (FETO) for Severe Congenital Diaphragmatic Hernia
NCT03094039	Not specified	WITHDRAWN	Initiation of Resuscitation While Attached to the Cord With Congenital Diaphragmatic Hernia