SLIT1

Summary

SLIT1 (slit guidance ligand 1, HGNC:11085) is a protein-coding gene on chromosome 10q24.1, encoding Slit homolog 1 protein (O75093). Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors.

Enables Roundabout binding activity. Involved in axon extension involved in axon guidance; motor neuron axon guidance; and negative chemotaxis. Predicted to be located in extracellular region. Predicted to be active in extracellular space.

Source: NCBI Gene 6585 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital diaphragmatic hernia (Moderate, GenCC)
• GWAS associations: 26
• Clinical variants (ClinVar): 510 total — 2 likely-pathogenic
• MANE Select transcript: NM_003061

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11085
Approved symbol	SLIT1
Name	slit guidance ligand 1
Location	10q24.1
Locus type	gene with protein product
Status	Approved
Aliases	MEGF4, Slit-1, SLIT3
Ensembl gene	ENSG00000187122
Ensembl biotype	protein_coding
OMIM	603742
Entrez	6585

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000266058, ENST00000314867, ENST00000371041, ENST00000371070, ENST00000456008, ENST00000494968, ENST00000497714

RefSeq mRNA: 1 — MANE Select: NM_003061 NM_003061

CCDS: CCDS7453

Canonical transcript exons

ENST00000266058 — 37 exons

Exon	Start	End
ENSE00003460056	97002158	97002369
ENSE00003463531	97018586	97018683
ENSE00003471590	97046654	97046797
ENSE00003483290	97046991	97047065
ENSE00003483520	97013741	97013834
ENSE00003485402	97047690	97047834
ENSE00003497644	97031606	97031677
ENSE00003502173	97018983	97019107
ENSE00003504378	97063455	97063618
ENSE00003505380	96998038	97001350
ENSE00003512172	97006483	97006720
ENSE00003516414	97163380	97163451
ENSE00003531592	97060087	97060158
ENSE00003560692	97004068	97004222
ENSE00003568712	97002704	97002992
ENSE00003570454	97010993	97011130
ENSE00003571339	97039988	97040120
ENSE00003576180	97047973	97047996
ENSE00003580522	97064168	97064239
ENSE00003586995	97030757	97030828
ENSE00003592612	97164819	97164890
ENSE00003592782	97021250	97021413
ENSE00003595711	97004693	97004823
ENSE00003600524	97056321	97056464
ENSE00003600705	97057210	97057281
ENSE00003604633	97064805	97064876
ENSE00003620162	97042901	97043067
ENSE00003622573	97060640	97060787
ENSE00003627715	97048955	97049118
ENSE00003636312	97043370	97043513
ENSE00003654925	97014019	97014158
ENSE00003662139	97157818	97157889
ENSE00003673152	97066015	97066086
ENSE00003677425	97059460	97059531
ENSE00003691228	97034471	97034542
ENSE00003784764	97037698	97037766
ENSE00003846267	97185478	97185959

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 97.41.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5380 / max 109.5274, expressed in 296 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110913	0.4945	156
110916	0.4582	126
110914	0.2919	113
110917	0.2108	109
110915	0.0351	19
110918	0.0328	23
110912	0.0148	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.41	gold quality
middle temporal gyrus	UBERON:0002771	95.77	gold quality
orbitofrontal cortex	UBERON:0004167	95.73	gold quality
CA1 field of hippocampus	UBERON:0003881	95.02	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.57	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.35	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.05	gold quality
entorhinal cortex	UBERON:0002728	93.91	gold quality
superior frontal gyrus	UBERON:0002661	93.84	gold quality
pancreatic ductal cell	CL:0002079	93.01	gold quality
frontal pole	UBERON:0002795	92.85	gold quality
postcentral gyrus	UBERON:0002581	91.17	gold quality
prefrontal cortex	UBERON:0000451	91.09	gold quality
parietal lobe	UBERON:0001872	90.36	gold quality
temporal lobe	UBERON:0001871	90.01	gold quality
frontal lobe	UBERON:0016525	89.86	gold quality
frontal cortex	UBERON:0001870	89.85	gold quality
neocortex	UBERON:0001950	89.10	gold quality
cerebral cortex	UBERON:0000956	89.09	gold quality
cingulate cortex	UBERON:0003027	88.64	gold quality
anterior cingulate cortex	UBERON:0009835	88.61	gold quality
Ammon’s horn	UBERON:0001954	88.47	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.99	gold quality
amygdala	UBERON:0001876	87.64	gold quality
telencephalon	UBERON:0001893	87.33	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.87	gold quality
caudate nucleus	UBERON:0001873	86.68	gold quality
endothelial cell	CL:0000115	86.63	silver quality
forebrain	UBERON:0001890	86.35	gold quality
nucleus accumbens	UBERON:0001882	85.86	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	5.35
E-ANND-3	yes	4.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting SLIT1, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-302B-5P	99.50	69.49	1857

Literature-anchored findings (GeneRIF, showing 8)

• Analysis of alternative splicing and conserved domains in human and mouse slit genes (PMID:12141424)
• evidence showing that Slit1 and Slit2 proteins are selective inhibitors and repellents for dorsally projecting, but not for ventrally projecting, cranial motor axons (PMID:16162649)
• In fetal and embryonic stem cell cultures Slit-1 inhibited neurite outgrowth. (PMID:16840550)
• 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)
• Slits are negative regulators of Sdf1 and Cxcr4 in breast cancer cells. (PMID:18829537)
• Findings show that SLIT1 is a direct target of SUV39H2 which binds to its promoter and catalyzes H3K9 tri-methylation to silence SLIT1 expression. (PMID:29458143)
• SLIT1-mutated hematopoietic stem cells have a role in clonal hematopoiesis in acquired aplastic anemia (PMID:31186493)
• Micro RNA-640 Targeting SLIT1 Enhances Glioma Radiosensitivity by Restraining the Activation of Wnt/beta-Catenin Signaling Pathway. (PMID:35996510)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	slit1a	ENSDARG00000044954
danio_rerio	slit1b	ENSDARG00000099446
mus_musculus	Slit1	ENSMUSG00000025020
rattus_norvegicus	Slit1	ENSRNOG00000026065

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), SLIT3 (ENSG00000184347), SLITRK6 (ENSG00000184564), SLITRK2 (ENSG00000185985), LRRC70 (ENSG00000186105), TLR9 (ENSG00000239732), TPBGL (ENSG00000261594)

Protein

Protein identifiers

Slit homolog 1 protein — O75093 (reviewed: O75093)

Alternative names: Multiple epidermal growth factor-like domains protein 4

All UniProt accessions (4): O75093, Q5T0V0, Q5T0V2, Q5T0V4

UniProt curated annotations — full annotation on UniProt →

Function. Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors. During neural development involved in axonal navigation at the ventral midline of the neural tube and projection of axons to different regions. SLIT1 and SLIT2 together seem to be essential for midline guidance in the forebrain by acting as repulsive signal preventing inappropriate midline crossing by axons projecting from the olfactory bulb.

Subunit / interactions. Interacts with ROBO1 and GREM1.

Subcellular location. Secreted.

Tissue specificity. Predominantly expressed in adult forebrain. Expressed in fetal brain, lung and kidney.

Isoforms (2)

UniProt ID	Names	Canonical?
O75093-1	1	yes
O75093-2	2, B

RefSeq proteins (1): NP_003052* (*=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
IPR003645	Fol_N	Domain
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 (101 total): disulfide bond 39, repeat 20, domain 19, glycosylation site 13, sequence conflict 4, splice variant 3, signal peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75093-F1	80.28	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 (39): 286–295, 443–466, 445–487, 513–519, 517–526, 675–698, 677–719, 929–940, 934–950, 952–961, 968–979, 973–991, 993–1002, 1009–1020, 1014–1029, 1031–1040, 1047–1060, 1054–1069, 1071–1080, 1087–1098 …

Glycosylation sites (13): 72, 192, 406, 571, 630, 762, 801, 806, 1026, 1079, 1189, 1259, 1306

Function

Pathways and Gene Ontology

Reactome pathways

8 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-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: 394 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_FOREBRAIN_NEURON_DEVELOPMENT, RNGTGGGC_UNKNOWN, BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, GOBP_OLFACTORY_BULB_INTERNEURON_DIFFERENTIATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_VENTRICULAR_SEPTUM_MORPHOGENESIS, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_FOREBRAIN_MORPHOGENESIS, GOBP_NEGATIVE_REGULATION_OF_AXON_EXTENSION, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN

GO Biological Process (18): nuclear migration (GO:0007097), axon guidance (GO:0007411), motor neuron axon guidance (GO:0008045), spinal cord development (GO:0021510), tangential migration from the subventricular zone to the olfactory bulb (GO:0022028), retinal ganglion cell axon guidance (GO:0031290), dorsal/ventral axon guidance (GO:0033563), negative regulation of axon extension involved in axon guidance (GO:0048843), axon extension involved in axon guidance (GO:0048846), forebrain morphogenesis (GO:0048853), negative chemotaxis (GO:0050919), negative regulation of synapse assembly (GO:0051964), nervous system development (GO:0007399), axonogenesis (GO:0007409), olfactory bulb development (GO:0021772), telencephalon cell migration (GO:0022029), cell differentiation (GO:0030154), neuron projection morphogenesis (GO:0048812)

GO Molecular Function (5): calcium ion binding (GO:0005509), heparin binding (GO:0008201), heparan sulfate proteoglycan binding (GO:0043395), Roundabout binding (GO:0048495), protein binding (GO:0005515)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Signaling by ROBO receptors	3
Axon guidance	2
Nervous system development	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
axon guidance	4
anatomical structure development	2
intracellular transport	1
nucleus localization	1
establishment of organelle localization	1
axonogenesis	1
neuron projection guidance	1
central nervous system development	1
olfactory bulb development	1
telencephalon cell migration	1
negative regulation of axon extension	1
regulation of axon extension involved in axon guidance	1
axon extension involved in axon guidance	1
negative regulation of chemotaxis	1
axon extension	1
anatomical structure morphogenesis	1
forebrain development	1
brain morphogenesis	1
chemotaxis	1
synapse assembly	1
negative regulation of nervous system development	1
regulation of synapse assembly	1
negative regulation of cell junction assembly	1
negative regulation of synapse organization	1
system development	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
olfactory lobe development	1
telencephalon development	1
forebrain cell migration	1
cellular developmental process	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
metal ion binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
proteoglycan binding	1
signaling receptor binding	1
binding	1

Protein interactions and networks

STRING

2350 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLIT1	ROBO1	Q9Y6N7	999
SLIT1	ROBO2	Q9HCK4	998
SLIT1	ROBO4	Q8WZ75	979
SLIT1	ROBO3	Q96MS0	944
SLIT1	SRGAP1	Q7Z6B7	836
SLIT1	NTN1	O95631	789
SLIT1	SRGAP2	O75044	726
SLIT1	NKX6-1	P78426	722
SLIT1	NKX6-2	Q9C056	721
SLIT1	SRGAP3	O43295	704
SLIT1	DCC	P43146	620
SLIT1	UNC5B	Q8IZJ1	611
SLIT1	PAX6	P26367	596
SLIT1	RELN	P78509	585
SLIT1	SEMA3A	Q14563	581

IntAct

44 interactions, top by confidence:

A	B	Type	Score
SLIT1	HOXA1	psi-mi:“MI:0915”(physical association)	0.670
SLIT1	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.560
SLIT1	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	SLIT1	psi-mi:“MI:0915”(physical association)	0.560
SLIT1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
SLIT1	TRIM42	psi-mi:“MI:0915”(physical association)	0.560
SLIT1	FHL5	psi-mi:“MI:0915”(physical association)	0.560
SLIT1	KRTAP13-3	psi-mi:“MI:0915”(physical association)	0.560
SLIT1	ZNF620	psi-mi:“MI:0915”(physical association)	0.560
SLIT1	CHRDL2	psi-mi:“MI:0915”(physical association)	0.560
SLIT1	KRTAP13-2	psi-mi:“MI:0915”(physical association)	0.560
SLIT1	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
SLIT1	FXR1	psi-mi:“MI:0915”(physical association)	0.370
SLIT1		psi-mi:“MI:0915”(physical association)	0.370
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350
MTNR1A	SLIT1	psi-mi:“MI:0915”(physical association)	0.000
DISC1	SLIT1	psi-mi:“MI:0915”(physical association)	0.000
SLIT1	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.000
SLIT1	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.000
SLIT1	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
SLIT1	HOXA1	psi-mi:“MI:0915”(physical association)	0.000
SLIT1	KRTAP13-2	psi-mi:“MI:0915”(physical association)	0.000
SLIT1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.000
SLIT1	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): SLIT1 (Two-hybrid), SLIT1 (Two-hybrid), SLIT1 (Two-hybrid), SLIT1 (Two-hybrid), SLIT1 (Two-hybrid), SLIT1 (Two-hybrid), SLIT1 (Two-hybrid), SLIT1 (Two-hybrid), SLIT1 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP1-1 (Two-hybrid), CYSRT1 (Two-hybrid), KRTAP13-3 (Two-hybrid), SLIT1 (Affinity Capture-MS), SLIT1 (Affinity Capture-RNA)

ESM2 similar proteins: A1A5Y0, A1KZ92, A2AJ76, B0S5N4, D3YXG0, D3ZPX4, F1MMS9, O00187, O55005, O60500, O75093, O88279, O88280, P11627, P17852, P26006, P32004, P51805, P57110, P59511, P70208, P85171, Q05695, Q0PMG2, Q13219, Q3UH53, Q4KMG0, Q62470, Q62918, Q7Z5N4, Q80TR4, Q8AV58, Q8AXZ4, Q8CIY2, Q8HZK2, Q8HZK3, Q8NDA2, Q8R4K8, Q8TE57, Q91WP0

Diamond homologs: A1A4H9, B4F7C5, D3ZAL8, D4A6D8, D4A7P2, O43300, O75093, P58874, Q5R6B1, Q80XG9, Q86UE6, Q86VH4, Q86VH5, Q8BGA3, Q8BZ81, Q8C2S7, Q8K377, Q920A0, Q9BGP6, Q9UBM4, A3KNN3, A4IIW9, A6H789, A6H793, A6NJW4, A8WHP9, E9Q7T7, O46379, O75094, O88280, O94769, P21793, P24014, P51884, P51885, P51886, P59034, P59035, P83503, Q05443

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
SLIT1	up-regulates	ROBO	binding
SLIT1	up-regulates	GPC1	binding
NFIA	“up-regulates quantity”	SLIT1	“transcriptional regulation”
NFIB	“up-regulates quantity”	SLIT1	“transcriptional regulation”
NFIX	“up-regulates quantity”	SLIT1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	400
Likely benign	47
Benign	15

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2500146	NM_003061.3(SLIT1):c.2276T>A (p.Ile759Asn)	Likely pathogenic
992921	NM_003062.4(SLIT3):c.1528C>T (p.Arg510Cys)	Likely pathogenic

SpliceAI

14908 predictions. Top by Δscore:

Variant	Effect	Δscore
10:97002702:A:AC	donor_gain	1.0000
10:97002703:C:CC	donor_gain	1.0000
10:97002843:AG:A	donor_gain	1.0000
10:97002864:T:TA	donor_gain	1.0000
10:97002988:CATCC:C	acceptor_gain	1.0000
10:97002990:TCC:T	acceptor_gain	1.0000
10:97002991:CC:C	acceptor_gain	1.0000
10:97002991:CCC:C	acceptor_gain	1.0000
10:97002991:CCCTG:C	acceptor_loss	1.0000
10:97002992:CC:C	acceptor_gain	1.0000
10:97002992:CCTGG:C	acceptor_loss	1.0000
10:97002993:C:CA	acceptor_loss	1.0000
10:97002993:C:CC	acceptor_gain	1.0000
10:97002994:T:C	acceptor_loss	1.0000
10:97004062:CCTCA:C	donor_loss	1.0000
10:97004063:CTCA:C	donor_loss	1.0000
10:97004064:TCACC:T	donor_loss	1.0000
10:97004065:CACCT:C	donor_loss	1.0000
10:97004066:A:AT	donor_loss	1.0000
10:97004066:ACCTC:A	donor_gain	1.0000
10:97004067:C:G	donor_loss	1.0000
10:97004067:CCTCC:C	donor_gain	1.0000
10:97004069:T:TA	donor_gain	1.0000
10:97004070:C:A	donor_gain	1.0000
10:97006721:C:CC	acceptor_gain	1.0000
10:97013736:CTCA:C	donor_loss	1.0000
10:97013737:TCAC:T	donor_loss	1.0000
10:97013738:CACC:C	donor_loss	1.0000
10:97013835:C:CC	acceptor_gain	1.0000
10:97014015:TTAC:T	donor_loss	1.0000

AlphaMissense

10080 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:97034537:A:G	L791P	1.000
10:97042972:C:G	C698S	1.000
10:97042973:A:G	C698R	1.000
10:97042973:A:T	C698S	1.000
10:97049022:A:C	C466W	1.000
10:97049023:C:G	C466S	1.000
10:97049024:A:G	C466R	1.000
10:97049024:A:T	C466S	1.000
10:97049091:G:C	C443W	1.000
10:97049092:C:T	C443Y	1.000
10:97049093:A:G	C443R	1.000
10:97049103:G:C	N439K	1.000
10:97049103:G:T	N439K	1.000
10:97049113:A:G	L436P	1.000
10:97056321:A:G	L434P	1.000
10:97056377:G:C	N415K	1.000
10:97056377:G:T	N415K	1.000
10:97056378:T:A	N415I	1.000
10:97056387:A:G	L412P	1.000
10:97056391:A:G	S411P	1.000
10:97056393:A:G	L410P	1.000
10:97056396:A:G	L409P	1.000
10:97056449:G:C	N391K	1.000
10:97056449:G:T	N391K	1.000
10:97056455:A:C	N389K	1.000
10:97056455:A:T	N389K	1.000
10:97056462:A:G	L387P	1.000
10:97057210:A:G	L386P	1.000
10:97057213:A:G	L385P	1.000
10:97057266:G:C	N367K	1.000

dbSNP variants (sampled 300 via entrez): RS1000009477 (10:97065284 G>A), RS1000032250 (10:97106586 G>A), RS1000036980 (10:97000808 T>C), RS1000046143 (10:97042068 T>G), RS1000055406 (10:97148392 G>A), RS1000069802 (10:97130681 T>C,G), RS1000074416 (10:97081906 A>G), RS1000081978 (10:96999834 G>A), RS1000090041 (10:97165119 T>C), RS1000101940 (10:97048598 C>G,T), RS1000114301 (10:97099577 G>A), RS1000117679 (10:97141354 G>A,C,T), RS1000127888 (10:97104478 C>T), RS1000131194 (10:97066695 C>T), RS1000135990 (10:97116185 A>G)

Disease associations

OMIM: gene MIM:603742 | disease phenotypes: MIM:602440

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital diaphragmatic hernia	Moderate	Autosomal recessive

Mondo (2): monomelic amyotrophy (MONDO:0011224), congenital diaphragmatic hernia (MONDO:0005711)

Orphanet (1): Monomelic amyotrophy (Orphanet:65684)

HPO phenotypes

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

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST000817_76	Height	7.000000e-16
GCST001762_817	Obesity-related traits	6.000000e-06
GCST002308_7	Mean arterial pressure (alcohol consumption interaction)	2.000000e-07
GCST002309_2	Diastolic blood pressure (alcohol consumption interaction)	1.000000e-06
GCST002541_19	Menarche (age at onset)	2.000000e-09
GCST002647_126	Height	4.000000e-24
GCST002702_119	Height	4.000000e-08
GCST002740_70	Inflammatory skin disease	1.000000e-08
GCST003854_10	Gut microbiota (functional units)	4.000000e-09
GCST004139_11	Bipolar disorder	7.000000e-07
GCST006414_137	Atrial fibrillation	3.000000e-09
GCST007478_20	Non-word reading	2.000000e-06
GCST007665_2	Treatment resistant depression	6.000000e-07
GCST008025_3	Body mass index	8.000000e-09
GCST008163_160	Height	7.000000e-08
GCST008839_145	Height	2.000000e-21
GCST009532_21	Circulating leptin levels in high cardiovascular risk	2.000000e-06
GCST009533_1	Circulating leptin levels x sex interaction in high cardiovascular risk	1.000000e-08
GCST009846_6	Hallux valgus	2.000000e-06
GCST010423_3	Diastolic blood pressure x educational attainment (graduated college) interaction (2df)	5.000000e-08
GCST012227_196	Hip circumference adjusted for BMI	3.000000e-09
GCST012307_7	Bipolar disorder x sex interaction	8.000000e-06
GCST012318_4	Total cholesterol levels x SSRI levels (escitalopram or citalopram) interaction in schizophrenia or bipolar disorder	1.000000e-05
GCST90000025_25	Appendicular lean mass	5.000000e-41
GCST90020028_1002	Hip circumference adjusted for BMI	1.000000e-08
GCST90020028_1003	Hip circumference adjusted for BMI	2.000000e-09

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0005134	amino acid measurement
EFO:0004329	alcohol drinking
EFO:0006340	mean arterial pressure
EFO:0006336	diastolic blood pressure
EFO:0004703	age at menarche
EFO:0007874	gut microbiome measurement
EFO:0005299	non-word reading
EFO:0009854	treatment resistant depression
EFO:0004340	body mass index
EFO:0005000	leptin measurement
EFO:0008343	sex interaction measurement
EFO:0004784	self reported educational attainment
EFO:0008039	BMI-adjusted hip circumference
EFO:0004574	total cholesterol measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065630	Hernias, Diaphragmatic, Congenital	C16.131.433; C23.300.707.960.500.116
C538253	Amyotrophy, monomelic (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	7
trichostatin A	affects cotreatment, increases expression	3
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Tretinoin	decreases expression, increases expression	2
Acrylamide	decreases expression, increases expression	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	affects methylation	1
tetrabromobisphenol A	increases expression	1
aflatoxin B2	increases methylation	1
coumarin	decreases phosphorylation	1
tetrachlorodian	increases expression	1
tebuconazole	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
theaflavin-3,3’-digallate	affects expression	1
Amphotericin B	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	decreases expression	1
Cyclophosphamide	decreases expression	1
Estradiol	decreases expression	1
Gentamicins	decreases expression	1
Lead	affects expression	1

Clinical trials (associated diseases)

87 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)
NCT03526588	PHASE1	TERMINATED	Umbilical Cord Blood Mononuclear Cells for Hypoxic Neurologic Injury in Infants With Congenital Diaphragmatic Hernia (CDH)
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
NCT03138863	Not specified	RECRUITING	Fetal Endoscopic Tracheal Occlusion for Congenital Diaphragmatic Hernia (FETO)
NCT03179371	Not specified	UNKNOWN	Proteomic Profiling for Congenital Diaphragmatic Hernia
NCT03242044	Not specified	COMPLETED	Resuscitation of Infants With Congenital Diaphragmatic Hernia With an Intact Umbilical Cord
NCT03314233	Not specified	COMPLETED	Delayed Cord Clamping for Congenital Diaphragmatic Hernia