NTN1

Summary

NTN1 (netrin 1, HGNC:8029) is a protein-coding gene on chromosome 17p13.1, encoding Netrin-1 (O95631). Netrins control guidance of CNS commissural axons and peripheral motor axons.

Netrin is included in a family of laminin-related secreted proteins. The function of this gene has not yet been defined; however, netrin is thought to be involved in axon guidance and cell migration during development. Mutations and loss of expression of netrin suggest that variation in netrin may be involved in cancer development.

Source: NCBI Gene 9423 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mirror movements 4 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 20
• Clinical variants (ClinVar): 127 total — 3 pathogenic
• Phenotypes (HPO): 17
• Druggable target: yes
• MANE Select transcript: NM_004822

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8029
Approved symbol	NTN1
Name	netrin 1
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	NTN1L, NET1
Ensembl gene	ENSG00000065320
Ensembl biotype	protein_coding
OMIM	601614
Entrez	9423

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000173229, ENST00000436734, ENST00000962853

RefSeq mRNA: 1 — MANE Select: NM_004822 NM_004822

CCDS: CCDS11148

Canonical transcript exons

ENST00000173229 — 7 exons

Exon	Start	End
ENSE00000423960	9221168	9221242
ENSE00001104530	9162813	9163001
ENSE00001104535	9179807	9179956
ENSE00001104539	9182916	9182969
ENSE00001126297	9239640	9244000
ENSE00001284677	9021510	9021585
ENSE00001284696	9022311	9023391

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 96.91.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8863 / max 56.2992, expressed in 799 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159537	1.0144	501
159538	0.5695	306
159539	0.5527	303
159540	0.4030	242
159536	0.1874	85
159543	0.0952	54
159542	0.0641	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	96.91	gold quality
right atrium auricular region	UBERON:0006631	94.09	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.53	gold quality
lower esophagus	UBERON:0013473	93.49	gold quality
cardiac atrium	UBERON:0002081	91.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.64	gold quality
descending thoracic aorta	UBERON:0002345	91.33	gold quality
thoracic aorta	UBERON:0001515	89.08	gold quality
ascending aorta	UBERON:0001496	88.67	gold quality
aorta	UBERON:0000947	87.72	gold quality
esophagus	UBERON:0001043	87.71	gold quality
popliteal artery	UBERON:0002250	86.71	gold quality
tibial artery	UBERON:0007610	86.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.71	gold quality
apex of heart	UBERON:0002098	85.15	gold quality
parotid gland	UBERON:0001831	84.04	silver quality
esophagus mucosa	UBERON:0002469	82.94	gold quality
nipple	UBERON:0002030	82.86	gold quality
lower esophagus mucosa	UBERON:0035834	82.29	gold quality
heart right ventricle	UBERON:0002080	81.96	gold quality
urethra	UBERON:0000057	81.93	gold quality
heart	UBERON:0000948	81.45	gold quality
bronchial epithelial cell	CL:0002328	81.20	gold quality
synovial joint	UBERON:0002217	81.15	gold quality
muscle layer of sigmoid colon	UBERON:0035805	80.84	gold quality
body of stomach	UBERON:0001161	80.43	gold quality
vena cava	UBERON:0004087	80.43	gold quality
mucosa of paranasal sinus	UBERON:0005030	80.24	silver quality
heart left ventricle	UBERON:0002084	79.86	gold quality
cardiac ventricle	UBERON:0002082	79.79	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-56	yes	637.73
E-MTAB-9154	yes	299.75
E-HCAD-25	yes	8.68
E-ANND-3	yes	4.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A, NFKB

miRNA regulators (miRDB)

129 targeting NTN1, 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-5193	100.00	67.26	1744
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-378G	99.71	64.90	1106

Literature-anchored findings (GeneRIF, showing 40)

• Netrin binds discrete subdomains of DCC and UNC5 and mediates interactions between DCC and heparin (PMID:12810718)
• Data demonstrate that alpha6beta4 integrin mediates pancreatic epithelial cell adhesion to Netrin-1, whereas recruitment of alpha6beta4 and alpha3beta1 regulate the migration of putative pancreatic progenitors on Netrin-1. (PMID:14602071)
• DCC/netrin-1 signaling may commit cells to the transition of endometrial gland architecture or function from a proliferating to a secretory phase. (PMID:15491747)
• Binding of netrin-1 to its receptors inhibits tumour suppressor p53-dependent apoptosis (review) (PMID:15573119)
• Netrin binds through multiple domains to both DCC and Unc5c. (PMID:15574733)
• Raft localization of DCC is required for netrin-1-induced DCC-dependent ERK activation, and netrin-1-mediated axon outgrowth requires lipid raft integrity. (PMID:15811950)
• Review suggests possible roles of netrin-1 in nervous system development, neovascularisation, adhesion and tumorigenesis. (PMID:16158190)
• Ligand-mediated down-regulation of deleted in colorectal cancer might participate in loss of netrin-responsiveness in developing nervous system. (PMID:16181408)
• Endothelial expression of netrin-1 may inhibit basal cell migration into tissues and its down-regulation with the onset of sepsis/inflammation may facilitate leukocyte recruitment. (PMID:16203981)
• Both deleted in colorectal cancer (DCC) and neogenin become tyrosine phosphorylated in cortical neurons in response to netrin-1. (PMID:18253061)
• Netrin-1 expression observed in a large fraction of human metastatic breast tumors confers a selective advantage for tumor cell survival. (PMID:18353983)
• Although cAMP can alter response of axons to netrin-1, we conclude that netrin-1 does not alter cAMP levels in axons attracted by this cue and that soluble adenyl cyclase is not required for axon attraction to netrin-1. (PMID:18400890)
• Data show that Netrin-1 expressing cells inhibited angiogenic sprouting of unc5b expressing blood vessels, but had no pro-angiogenic activity at any stage of development examined. (PMID:18439993)
• In adults, decreased expression within the spinal cord injury lesion; likely an inhibitor of regenerating neural progenitors (PMID:18455953)
• PIKE-L acts as a downstream survival effector for netrin-1 through UNC5B in the nervous system (PMID:18469807)
• Netrin 1, through its receptor DCC, inhibits RhoA in embryonic spinal commissural neurons. (PMID:18653556)
• NF-kappaB activation that occurs in response to inflammation confers a selective advantage for tumor development through NF-kappaB-mediated netrin-1 up-regulation (PMID:18692059)
• netrin-1 is not only an attractive cue for developing commissural axons but also promotes their survival (PMID:18796601)
• the transcriptionally active TAp73alpha tumor suppressor is implicated in the apoptosis induced by netrin-1 in a p53-independent and DCC/ubiquitin-proteasome dependent manner. (PMID:18922894)
• HIF-1alpha-dependent induction of netrin-1 attenuates hypoxia-elicited inflammation at mucosal surfaces (PMID:19122655)
• High levels of netrin-1 found in 43 of the 92 NSCLC tumor samples. Interference with netrin-1 in human lung cancer cell lines was associated with UNC5H-mediated cell death in vitro and with tumor growth inhibition and/or regression in xenografted mice. (PMID:19211441)
• Netrin-1 up-regulation is a potential marker for poor prognosis in stage 4 neueroblastoma in infants. (PMID:19349462)
• Netrin-1 inhibited migration of synovial fibroblasts from patients with rheumatoid arthritis and osteoarthitis. (PMID:19822088)
• Netrin-1 protein functions might vary with its localization in the placenta and probably with time of gestation. (PMID:19826074)
• Study suggests that Netrin-1 promotes melanoma cell invasion and migration and therefore has an important role in the progression of malignant melanoma. (PMID:19940358)
• Netrin-1 is an early, predictive biomarker of acute kidney injury after cardiopulmnoary bypass. (PMID:20007677)
• Netrin-1 has a role in cardioprotection (PMID:20036673)
• Pulmonary netrin-1 levels are repressed during acute lung injury. (PMID:20075388)
• Netrin-1 might be an important regulator of pancreatic tumor growth that functions in tumor and endothelial cells. (PMID:20080097)
• Data propose that induction of netrin-1 expression via NFkappaB in inflammatory bowel diseases patients could affect colorectal tumor promotion and progression (PMID:20305387)
• our findings might indicate also an important role for DCC and netrin-1 in human foetal central nervous system development (PMID:20609112)
• Urinary netrin-1 levels are increased in patients with various forms of acute kidney injury, and may therefore serve as a biomarker. (PMID:20620466)
• Netrin-1 may regulate the development of placental vessels and plays a key role in the pathogenesis of fetal growth restriction. (PMID:21193949)
• Plasma netrin-1 can be used as diagnostic biomarker of many human cancers. (PMID:21303223)
• Netrin-1 enhanced the viability, migration and tube formation of human placental microvascular endothelial cells. (PMID:21505994)
• Gene silencing of netrin-1 could inhibit viability, proliferation, migration, and tubal formation of HUVECs, and placental angiogenesis. (PMID:21733374)
• Properties and perspectives of uNGAL and Netrin-1 for their appropriate clinical utilization. (PMID:21740336)
• overexpression is predictive of ovarian malignancies (PMID:21789787)
• an autocrine function for netrin-1 and netrin-3 in U87 and U373 cells that slows migration (PMID:21980448)
• It was shown that netrin-1 was secreted by macrophages in human and mouse atheroma, where it inactivated macrophage migration out of atherosclerotic plaques. (PMID:22231519)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ntn1b	ENSDARG00000022531
mus_musculus	Ntn1	ENSMUSG00000020902
rattus_norvegicus	Ntn1	ENSRNOG00000003947
drosophila_melanogaster	NetA	FBGN0015773
drosophila_melanogaster	NetB	FBGN0015774
caenorhabditis_elegans		WBGENE00006746

Paralogs (27): USH2A (ENSG00000042781), LAMC3 (ENSG00000050555), LAMA3 (ENSG00000053747), LAMC2 (ENSG00000058085), NTN4 (ENSG00000074527), ATRN (ENSG00000088812), LAMB4 (ENSG00000091128), LAMB1 (ENSG00000091136), LAMA1 (ENSG00000101680), MEGF8 (ENSG00000105429), MEGF9 (ENSG00000106780), ATRNL1 (ENSG00000107518), LAMA4 (ENSG00000112769), LAMA5 (ENSG00000130702), LAMC1 (ENSG00000135862), NTN5 (ENSG00000142233), HSPG2 (ENSG00000142798), TMEFF2 (ENSG00000144339), NTN3 (ENSG00000162068), NTNG1 (ENSG00000162631), EGFLAM (ENSG00000164318), LAMB2 (ENSG00000172037), AGRN (ENSG00000188157), NTNG2 (ENSG00000196358), LAMA2 (ENSG00000196569), LAMB3 (ENSG00000196878), TMEFF1 (ENSG00000241697)

Protein

Protein identifiers

Netrin-1 — O95631 (reviewed: O95631)

Alternative names: Epididymis tissue protein Li 131P

All UniProt accessions (2): O95631, H7BZF4

UniProt curated annotations — full annotation on UniProt →

Function. Netrins control guidance of CNS commissural axons and peripheral motor axons. Its association with either DCC or some UNC5 receptors will lead to axon attraction or repulsion, respectively. Binding to UNC5C might cause dissociation of UNC5C from polymerized TUBB3 in microtubules and thereby lead to increased microtubule dynamics and axon repulsion. Involved in dorsal root ganglion axon projection towards the spinal cord. It also serves as a survival factor via its association with its receptors which prevent the initiation of apoptosis. Involved in tumorigenesis by regulating apoptosis.

Subunit / interactions. Binds to its receptors; DCC, UNC5A, UNC5B, UNC5C and probably UNC5D. Binds to its receptor; DSCAM. Interacts with DCC. Interacts with APP.

Subcellular location. Secreted. Cytoplasm.

Tissue specificity. Widely expressed in normal adult tissues with highest levels in heart, small intestine, colon, liver and prostate. Reduced expression in brain tumors and neuroblastomas. Expressed in epididymis (at protein level).

Disease relevance. Mirror movements 4 (MRMV4) [MIM:618264] A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities. MRMV4 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_004813* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001134	Netrin_domain	Domain
IPR002049	LE_dom	Domain
IPR008211	Laminin_N	Domain
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR008993	TIMP-like_OB-fold	Homologous_superfamily
IPR018933	Netrin_module_non-TIMP	Domain
IPR050440	Laminin/Netrin_ECM	Family
IPR056863	LMN_ATRN_NET-like_EGF	Domain

Pfam: PF00053, PF00055, PF01759, PF24973

UniProt features (76 total): strand 27, disulfide bond 15, helix 9, turn 7, domain 5, sequence variant 5, glycosylation site 4, signal peptide 1, chain 1, sequence conflict 1, short sequence motif 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6FKQ	X-RAY DIFFRACTION	3.07
4URT	X-RAY DIFFRACTION	3.1
7NE1	X-RAY DIFFRACTION	3.15
7NE0	X-RAY DIFFRACTION	3.25
7NDG	ELECTRON MICROSCOPY	5.98

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95631-F1	89.10	0.70

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 (15): 119–152, 285–294, 287–304, 306–315, 318–338, 341–350, 343–368, 371–380, 383–401, 404–416, 406–423, 425–434, 437–451, 472–544, 491–601

Glycosylation sites (4): 131, 417, 95, 116

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-373752	Netrin-1 signaling
R-HSA-376172	DSCAM interactions
R-HSA-418885	DCC mediated attractive signaling
R-HSA-418886	Netrin mediated repulsion signals
R-HSA-418890	Role of second messengers in netrin-1 signaling
R-HSA-428542	Regulation of commissural axon pathfinding by SLIT and ROBO
R-HSA-1266738	Developmental Biology
R-HSA-376176	Signaling by ROBO receptors
R-HSA-422475	Axon guidance
R-HSA-9675108	Nervous system development

MSigDB gene sets: 632 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_MAMMARY_GLAND_MORPHOGENESIS, BENPORATH_ES_WITH_H3K27ME3, GOBP_GLAND_MORPHOGENESIS, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_NEGATIVE_REGULATION_OF_AXON_EXTENSION, GOBP_SYNAPSE_ASSEMBLY, JAEGER_METASTASIS_DN, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, PEREZ_TP63_TARGETS, PID_NETRIN_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH

GO Biological Process (25): regulation of transcription by RNA polymerase II (GO:0006357), apoptotic process (GO:0006915), substrate-dependent cell migration, cell extension (GO:0006930), nuclear migration (GO:0007097), Ras protein signal transduction (GO:0007265), glial cell proliferation (GO:0014009), negative regulation of axon extension (GO:0030517), Cdc42 protein signal transduction (GO:0032488), anterior/posterior axon guidance (GO:0033564), inner ear morphogenesis (GO:0042472), positive regulation of axon extension (GO:0045773), regulation of synapse assembly (GO:0051963), positive regulation of glial cell proliferation (GO:0060252), mammary gland duct morphogenesis (GO:0060603), chemorepulsion of axon (GO:0061643), motor neuron migration (GO:0097475), cell-cell adhesion (GO:0098609), regulation of glial cell migration (GO:1903975), positive regulation of cell motility (GO:2000147), neuron migration (GO:0001764), axonogenesis (GO:0007409), axon guidance (GO:0007411), cell population proliferation (GO:0008283), regulation of cell migration (GO:0030334), mammary gland development (GO:0030879)

GO Molecular Function (3): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), protein binding (GO:0005515)

GO Cellular Component (8): extracellular region (GO:0005576), basement membrane (GO:0005604), nucleoplasm (GO:0005654), cytosol (GO:0005829), actin cytoskeleton (GO:0015629), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Netrin-1 signaling	4
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
cellular anatomical structure	4
regulation of axon extension	2
axon extension	2
axon guidance	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
substrate-dependent cell migration	1
plasma membrane bounded cell projection assembly	1
intracellular transport	1
nucleus localization	1
establishment of organelle localization	1
small GTPase-mediated signal transduction	1
cell population proliferation	1
gliogenesis	1
negative regulation of cell growth	1
negative regulation of developmental growth	1
negative regulation of axonogenesis	1
Rho protein signal transduction	1
ear morphogenesis	1
embryonic morphogenesis	1
inner ear development	1
positive regulation of cell growth	1
positive regulation of developmental growth	1
positive regulation of axonogenesis	1
synapse assembly	1
regulation of synapse organization	1
regulation of cell junction assembly	1
positive regulation of cell population proliferation	1
glial cell proliferation	1
positive regulation of gliogenesis	1
regulation of glial cell proliferation	1
mammary gland morphogenesis	1
epithelial tube morphogenesis	1
mammary gland epithelium development	1
negative chemotaxis	1
cellular response to chemical stimulus	1

Protein interactions and networks

STRING

2006 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NTN1	UNC5C	O95185	999
NTN1	DCC	P43146	999
NTN1	UNC5B	Q8IZJ1	999
NTN1	UNC5A	Q6ZN44	998
NTN1	NEO1	Q92859	998
NTN1	DSCAM	O60469	995
NTN1	SLIT3	O75094	890
NTN1	UNC5D	Q6UXZ4	860
NTN1	ROBO2	Q9HCK4	858
NTN1	ROBO1	Q9Y6N7	815
NTN1	SLIT2	O94813	803
NTN1	ADORA2B	P29275	797
NTN1	SLIT1	O75093	789
NTN1	SEMA3A	Q14563	737
NTN1	ROBO3	Q96MS0	729

IntAct

42 interactions, top by confidence:

A	B	Type	Score
DCC	NTN1	psi-mi:“MI:0915”(physical association)	0.700
DCC	NTN1	psi-mi:“MI:0407”(direct interaction)	0.700
DCC	NTN1	psi-mi:“MI:0914”(association)	0.700
NEUROG3	GXYLT2	psi-mi:“MI:0914”(association)	0.640
DRAXIN	NTN1	psi-mi:“MI:0407”(direct interaction)	0.540
DRAXIN	NTN1	psi-mi:“MI:0915”(physical association)	0.540
OS9	AGRN	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
NTN1	Unc5b	psi-mi:“MI:0407”(direct interaction)	0.440
APP	NTN1	psi-mi:“MI:0407”(direct interaction)	0.440
UNC5B	NTN1	psi-mi:“MI:0915”(physical association)	0.400
draxin	NTN1	psi-mi:“MI:0915”(physical association)	0.400
NEO1	NTN1	psi-mi:“MI:0915”(physical association)	0.400
UNC5C	NTN1	psi-mi:“MI:0915”(physical association)	0.400
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
OS9	GXYLT2	psi-mi:“MI:0914”(association)	0.350
RPS19	ZNF320	psi-mi:“MI:0914”(association)	0.350

BioGRID (24): NTN1 (Affinity Capture-MS), NTN1 (Affinity Capture-RNA), NTN1 (Affinity Capture-RNA), NTN1 (Reconstituted Complex), NTN1 (Reconstituted Complex), DCC (Reconstituted Complex), NTN1 (Affinity Capture-MS), NTN1 (Affinity Capture-MS), NTN1 (Affinity Capture-MS), NTN1 (Affinity Capture-MS), NTN1 (Affinity Capture-MS), NTN1 (Affinity Capture-MS), NTN1 (Affinity Capture-MS), NTN1 (Affinity Capture-MS), NTN1 (Affinity Capture-MS)

ESM2 similar proteins: A5Z1X6, B0FYY4, G5ECE3, O09118, O15230, O75445, O95631, P05556, P07228, P08069, P09055, P11046, P11584, P11835, P12606, P12607, P15215, P19137, P24043, P24062, P24348, P25391, P34710, P41413, P49134, P53712, P53713, P53714, P98160, Q00174, Q05793, Q06561, Q16787, Q18823, Q21313, Q27591, Q27874, Q2HXW4, Q2QI47, Q5RCA9

Diamond homologs: A0JP86, A2ASQ1, G5ECE3, O00468, O00634, O09118, O15230, O75445, O75882, O95631, P02468, P11047, P15215, P19137, P24043, P25304, P25391, P31696, P34710, P97927, Q00174, Q01635, Q13751, Q13753, Q16363, Q16787, Q18823, Q19981, Q1LVF0, Q24567, Q24568, Q27262, Q2HXW4, Q2QI47, Q5RB89, Q5VV63, Q60675, Q61001, Q61087, Q61092

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
NTN1	“up-regulates activity”	DCC	binding
NTN1	“up-regulates activity”	NEO1	binding
NTN1	“up-regulates activity”	UNC5	binding
NTN1	up-regulates	UNC5C	binding
NTN1	“up-regulates activity”	DSCAM	binding
NTN1	“up-regulates quantity”	ACTB	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 34 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.

GO biological processes:

GO term	Partners	Fold	FDR
axon guidance	5	16.2×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	89
Likely benign	18
Benign	6

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
599324	NM_004822.3(NTN1):c.1801T>C (p.Cys601Arg)	Pathogenic
599325	NM_004822.3(NTN1):c.1549ATC[1] (p.Ile518del)	Pathogenic
599326	NM_004822.3(NTN1):c.1802G>C (p.Cys601Ser)	Pathogenic

SpliceAI

3377 predictions. Top by Δscore:

Variant	Effect	Δscore
17:9060269:G:GG	donor_gain	1.0000
17:9162807:CTGCA:C	acceptor_loss	1.0000
17:9162808:T:A	acceptor_gain	1.0000
17:9162808:TGCA:T	acceptor_loss	1.0000
17:9162809:GCA:G	acceptor_loss	1.0000
17:9162810:CA:C	acceptor_loss	1.0000
17:9162811:A:AG	acceptor_gain	1.0000
17:9162811:A:C	acceptor_loss	1.0000
17:9162811:AGCCT:A	acceptor_gain	1.0000
17:9162812:G:GT	acceptor_gain	1.0000
17:9162812:GC:G	acceptor_gain	1.0000
17:9162812:GCC:G	acceptor_gain	1.0000
17:9162812:GCCT:G	acceptor_gain	1.0000
17:9162812:GCCTG:G	acceptor_gain	1.0000
17:9162988:G:GT	donor_gain	1.0000
17:9162997:CAAAG:C	donor_loss	1.0000
17:9162998:AAAG:A	donor_loss	1.0000
17:9163002:GT:G	donor_loss	1.0000
17:9163003:T:G	donor_loss	1.0000
17:9179801:CTGCA:C	acceptor_loss	1.0000
17:9179802:TGCAG:T	acceptor_loss	1.0000
17:9179803:GCAGC:G	acceptor_loss	1.0000
17:9179804:CA:C	acceptor_loss	1.0000
17:9179805:A:AG	acceptor_gain	1.0000
17:9179805:A:C	acceptor_loss	1.0000
17:9179805:AGCCT:A	acceptor_gain	1.0000
17:9179806:G:GG	acceptor_gain	1.0000
17:9179806:G:T	acceptor_loss	1.0000
17:9179806:GC:G	acceptor_gain	1.0000
17:9179806:GCCT:G	acceptor_gain	1.0000

AlphaMissense

3994 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:9022524:T:A	C51S	1.000
17:9022524:T:C	C51R	1.000
17:9022525:G:C	C51S	1.000
17:9022536:T:C	F55L	1.000
17:9022537:T:G	F55C	1.000
17:9022538:T:A	F55L	1.000
17:9022538:T:G	F55L	1.000
17:9022731:T:A	W120R	1.000
17:9022731:T:C	W120R	1.000
17:9022733:G:C	W120C	1.000
17:9022733:G:T	W120C	1.000
17:9022819:T:C	L149P	1.000
17:9022840:C:A	P156H	1.000
17:9022862:G:C	K163N	1.000
17:9022862:G:T	K163N	1.000
17:9022863:T:C	S164P	1.000
17:9022864:C:T	S164F	1.000
17:9022886:G:C	W171C	1.000
17:9022886:G:T	W171C	1.000
17:9022906:C:T	S178F	1.000
17:9022980:T:A	C203S	1.000
17:9022980:T:C	C203R	1.000
17:9022981:G:A	C203Y	1.000
17:9022981:G:C	C203S	1.000
17:9022982:C:G	C203W	1.000
17:9023094:T:A	W241R	1.000
17:9023094:T:C	W241R	1.000
17:9023096:G:C	W241C	1.000
17:9023096:G:T	W241C	1.000
17:9023221:G:A	G283D	1.000

dbSNP variants (sampled 300 via entrez): RS1000003702 (17:9048973 T>C), RS1000016110 (17:9225670 G>T), RS1000038149 (17:9196168 C>T), RS1000038687 (17:9166330 C>G,T), RS1000043591 (17:9124097 G>A), RS1000054052 (17:9085914 C>T), RS1000055230 (17:9022235 A>G), RS1000058181 (17:9042752 A>G), RS1000067529 (17:9161318 G>A), RS1000079571 (17:9225968 G>A), RS1000092261 (17:9191226 C>A,T), RS1000095144 (17:9048814 A>G), RS1000097146 (17:9001221 C>G,T), RS1000102275 (17:9124441 G>A), RS1000119906 (17:9231077 C>T)

Disease associations

OMIM: gene MIM:601614 | disease phenotypes: MIM:119530, MIM:618264, MIM:157600

GenCC curated gene-disease

Disease	Classification	Inheritance
mirror movements 4	Strong	Autosomal dominant
familial congenital mirror movements	Supportive	Autosomal dominant
multiple congenital anomalies/dysmorphic syndrome	Limited	Autosomal dominant

Mondo (5): orofacial cleft 1 (MONDO:0007335), mirror movements 4 (MONDO:0032641), mirror movements 1 (MONDO:0008002), multiple congenital anomalies/dysmorphic syndrome (MONDO:0019042), familial congenital mirror movements (MONDO:0016558)

Orphanet (1): Familial congenital mirror movements (Orphanet:238722)

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000044	Hypogonadotropic hypogonadism
HP:0001256	Mild intellectual disability
HP:0001274	Agenesis of corpus callosum
HP:0001328	Specific learning disability
HP:0001335	Bimanual synkinesia
HP:0002312	Clumsiness
HP:0002492	Abnormal corticospinal tract morphology
HP:0002949	Fused cervical vertebrae
HP:0003326	Myalgia
HP:0003388	Easy fatigability
HP:0003593	Infantile onset
HP:0003829	Typified by incomplete penetrance
HP:0007010	Poor fine motor coordination
HP:0025101	Dysgenesis of the hippocampus
HP:0100021	Cerebral palsy
HP:0100022	Abnormality of movement

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST001816_5	Breast cancer (prognosis)	8.000000e-06
GCST002811_4	Nonsyndromic cleft lip with or without cleft palate	5.000000e-19
GCST002942_13	Percentage gas trapping	1.000000e-06
GCST004166_21	Nonsyndromic cleft lip with cleft palate	9.000000e-12
GCST006288_284	Heel bone mineral density	8.000000e-11
GCST006288_355	Heel bone mineral density	4.000000e-07
GCST006585_2089	Blood protein levels	5.000000e-53
GCST006585_2184	Blood protein levels	7.000000e-48
GCST006951_10	Feeling hurt	4.000000e-08
GCST006979_804	Heel bone mineral density	3.000000e-13
GCST006979_805	Heel bone mineral density	5.000000e-16
GCST006979_806	Heel bone mineral density	1.000000e-36
GCST008097_7	Bisphosphonate-associated atypical femoral fracture	3.000000e-08
GCST009197_9	Cortex volume	7.000000e-06
GCST009202_9	Rostral middle frontal gyrus volume	2.000000e-07
GCST009263_12	Total grey matter volume	1.000000e-06
GCST010703_159	Brain morphology (MOSTest)	3.000000e-09
GCST011088_4	Orofacial clefts	4.000000e-08
GCST012337_12	Nonsyndromic cleft lip with or without cleft palate	9.000000e-10
GCST90000025_122	Appendicular lean mass	2.000000e-11

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0003959	cleft lip
EFO:0007628	gas trapping measurement
EFO:0009270	heel bone mineral density
EFO:0009599	feeling emotionally hurt measurement
EFO:0009958	response to bisphosphonate
EFO:0009960	atypical femoral fracture
EFO:0005420	grey matter volume measurement
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566121	Orofacial Cleft 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1741307 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	3
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
Acetaminophen	increases expression	2
Doxorubicin	decreases expression, increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Valproic Acid	increases expression, increases methylation	2
Aflatoxin B1	decreases expression, affects methylation	2
bisphenol F	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
trichostatin A	increases expression	1
butyraldehyde	increases expression	1
bisphenol A diglycidyl ether	decreases expression, decreases reaction, decreases response to substance	1
benzo(e)pyrene	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
pentanal	increases expression	1
CGP 52608	increases reaction, affects binding	1
nutlin 3	affects cotreatment, increases expression, increases secretion	1
abrine	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Aldehydes	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases expression	1
Camptothecin	increases expression	1
Cisplatin	increases expression, affects cotreatment	1
Dactinomycin	affects cotreatment, increases expression, increases secretion	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5164177	Binding	Inhibition of human NET at 10 uM relative to control	Overcoming undesirable hERG affinity by incorporating fluorine atoms: A case of MAO-B inhibitors derived from 1 H-pyrrolo-[3,2-c]quinolines. — Eur J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E8G1	Abcam MCF-7 NTN1 KO	Cancer cell line	Female
CVCL_E8G2	U2OS NTN1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02073604	Not specified	COMPLETED	Role of the SMA During Unimanual and Bimanual Movements Preparation: the Mirror Movements Paradigm