NEO1

Summary

NEO1 (neogenin 1, HGNC:7754) is a protein-coding gene on chromosome 15q24.1, encoding Neogenin (Q92859). Multi-functional cell surface receptor regulating cell adhesion in many diverse developmental processes, including neural tube and mammary gland formation, myogenesis and angiogenesis.

This gene encodes a cell surface protein that is a member of the immunoglobulin superfamily. The encoded protein consists of four N-terminal immunoglobulin-like domains, six fibronectin type III domains, a transmembrane domain and a C-terminal internal domain that shares homology with the tumor suppressor candidate gene DCC. This protein may be involved in cell growth and differentiation and in cell-cell adhesion. Defects in this gene are associated with cell proliferation in certain cancers. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 4756 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 249 total
• MANE Select transcript: NM_002499

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7754
Approved symbol	NEO1
Name	neogenin 1
Location	15q24.1
Locus type	gene with protein product
Status	Approved
Aliases	NGN, HsT17534, IGDCC2, NTN1R2
Ensembl gene	ENSG00000067141
Ensembl biotype	protein_coding
OMIM	601907
Entrez	4756

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 19 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000261908, ENST00000339362, ENST00000558485, ENST00000558807, ENST00000558886, ENST00000558964, ENST00000560262, ENST00000560328, ENST00000560352, ENST00000560407, ENST00000560808, ENST00000881911, ENST00000881912, ENST00000881913, ENST00000881914, ENST00000881915, ENST00000881916, ENST00000881917, ENST00000881918, ENST00000881919, ENST00000881920, ENST00000916988, ENST00000916989, ENST00000916990, ENST00000944648

RefSeq mRNA: 4 — MANE Select: NM_002499 NM_001172623, NM_001172624, NM_001419531, NM_002499

CCDS: CCDS10247, CCDS53957, CCDS58378

Canonical transcript exons

ENST00000261908 — 29 exons

Exon	Start	End
ENSE00003546140	73293390	73293548
ENSE00003598339	73298348	73298611
ENSE00003599158	73249060	73249208
ENSE00003664487	73244344	73244498
ENSE00003686996	73236347	73236506
ENSE00003692986	73301321	73301457
ENSE00003841280	73052463	73052805
ENSE00003889077	73258766	73258876
ENSE00003890295	73273811	73274005
ENSE00003890875	73116540	73116857
ENSE00003891018	73253400	73253449
ENSE00003891721	73302613	73305205
ENSE00003891853	73260271	73260465
ENSE00003891960	73272455	73272562
ENSE00003892287	73176403	73176557
ENSE00003892637	73282964	73283111
ENSE00003893049	73274692	73274724
ENSE00003893579	73178307	73178427
ENSE00003893724	73270316	73270454
ENSE00003894460	73289146	73289238
ENSE00003894572	73122525	73122800
ENSE00003894727	73266316	73266411
ENSE00003894758	73135891	73136027
ENSE00003894802	73288313	73288551
ENSE00003894835	73126417	73126570
ENSE00003895636	73270010	73270233
ENSE00003895850	73254682	73254829
ENSE00003895995	73249583	73249721
ENSE00003896044	73278131	73278199

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 97.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.7207 / max 164.1850, expressed in 1415 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147595	9.2172	1348
147593	0.8648	470
147596	0.4747	251
147597	0.1641	78

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.37	gold quality
ventricular zone	UBERON:0003053	97.35	gold quality
medial globus pallidus	UBERON:0002477	97.04	gold quality
globus pallidus	UBERON:0001875	96.72	gold quality
inferior vagus X ganglion	UBERON:0005363	96.56	gold quality
rectum	UBERON:0001052	96.11	gold quality
colonic epithelium	UBERON:0000397	95.60	gold quality
subthalamic nucleus	UBERON:0001906	95.45	gold quality
corpus callosum	UBERON:0002336	95.07	gold quality
ventral tegmental area	UBERON:0002691	94.88	gold quality
superior vestibular nucleus	UBERON:0007227	94.40	gold quality
pylorus	UBERON:0001166	94.36	gold quality
lateral globus pallidus	UBERON:0002476	94.24	gold quality
nipple	UBERON:0002030	93.98	gold quality
transverse colon	UBERON:0001157	93.93	gold quality
oocyte	CL:0000023	93.86	gold quality
ganglionic eminence	UBERON:0004023	93.86	gold quality
islet of Langerhans	UBERON:0000006	93.64	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.41	gold quality
right coronary artery	UBERON:0001625	92.98	gold quality
skin of abdomen	UBERON:0001416	92.96	gold quality
skin of leg	UBERON:0001511	92.84	gold quality
thoracic aorta	UBERON:0001515	92.83	gold quality
ascending aorta	UBERON:0001496	92.82	gold quality
substantia nigra pars compacta	UBERON:0001965	92.52	gold quality
dorsal plus ventral thalamus	UBERON:0001897	92.43	gold quality
pons	UBERON:0000988	92.30	gold quality
mucosa of transverse colon	UBERON:0004991	92.30	gold quality
descending thoracic aorta	UBERON:0002345	92.19	gold quality
secondary oocyte	CL:0000655	91.99	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.28

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F3

miRNA regulators (miRDB)

162 targeting NEO1, 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-5692A	100.00	74.40	6850
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562

Literature-anchored findings (GeneRIF, showing 37)

• neogenin and restin have roles in proproliferation/survival action on ovarian cancer cells (PMID:12833147)
• neogenin may play a role in mammary carcinogenesis as well as morphogenesis (PMID:16324219)
• results show that different isoforms of hemojuvelin may play unique physiological roles through defined interactions with distinct signaling proteins such as BMP2 and neogenin, and demonstrate that some of these interactions are defective. (PMID:18287331)
• HJV-induced BMP signaling and hepcidin expression are not altered by neogenin overexpression or by inhibition of endogenous neogenin expr (PMID:18326817)
• the neogenin intracellular domain regulates gene transcription via nuclear translocation (PMID:18391016)
• neogenin-mediated HJV release occurs after the HJV-neogenin complex is internalized from the cell surface (PMID:18445598)
• Results show that the serine/threonine kinase death-associated protein kinase (DAPK) is involved in the signal transduction of neogenin. (PMID:18583991)
• Results support that hepatic neogenin possesses two functions, mediation of cellular HJV release, and stimulation of HJV-enhanced hepcidin expression. (PMID:19564337)
• Netrin-1 can promote the potential of proliferation and invasion of extravillous trophoblasts in vitro through its receptors neogenin and UNC5B. (PMID:19570425)
• This study supports the hypothesis that, as in the embryo, neogenin regulates fundamental signalling pathways important for neurogenesis in the adult mouse and human forebrain. (PMID:20575069)
• Neogenin FN5, which does not bind hemojuvelin in isolation, exhibits a highly electropositive surface, which may be involved in interactions with negatively-charged polysaccharides or phospholipids in the membrane bilayer. (PMID:20971194)
• neogenin negatively regulates the functions of BMP and that this effect of neogenin is mediated by the activation of RhoA. (PMID:21149453)
• identification of neogenin-binding site on the repulsive guidance molecule A (PMID:22396795)
• the proposed role of neogenin as a tumor suppressor in gliomas (PMID:22666451)
• pattern of distribution suggests that a functional netrin-4-neogenin pathway might be restricted to syncytiotrophoblasts, mesenchymal cells, and villous endothelial cells (PMID:22705235)
• neogenin forms a ternary complex with both MT2 and HJV at the plasma membrane. The complex facilitates HJV cleavage by MT2, and release of the cleaved HJV from the cell occurs after a retrograde trafficking through the TGN/Golgi compartments. (PMID:22893705)
• two RGMB ectodomains conformationally stabilize the juxtamembrane regions of two NEO1 receptors in a pH-dependent manner. (PMID:23744777)
• these results highlight Neogenin1 as a novel downstream effector of the Sonic Hedgehog pathway in medulloblastoma (PMID:23775842)
• miR-18a may regulate biological behavior of human glioblastoma cells by targeting neogenin. (PMID:24657544)
• high-expression of neogenin-1 promotes gastric cancer proliferation and motility (PMID:24930499)
• Neogenin expression is inversely associated with breast cancer grade. (PMID:25416629)
• Ntn4 promotes the proliferation and motility of gastric cancer cells which is mediated by its receptor Neo and through further activation of multi-oncogenic pathways (PMID:25909166)
• These results show how repulsive guidance molecule acts as the central hub that links BMP2 and NEO1 and physically connects these fundamental signaling pathways. (PMID:25938661)
• The present study demonstrates that neogenin may be a tumor suppressor in breast cancer. Neogenin may serve as a potential diagnostic marker and therapeutic target for breast cancer. (PMID:25998984)
• The hemizygous 15q deletion unmasks the recessive functional polymorphism in NEO1 which plays a pivotal role in cortical interneuron development; study provides the first evidence linking NEO1 with autism spectrum disorders in humans (PMID:26518331)
• Neogenin influences both cadherin dynamics and junctional tension. (PMID:27029596)
• these results suggested that GD3 recruits gamma-secretase to lipid/rafts, allowing efficient cleavage of neogenin. (PMID:27288875)
• Environmental and endogenous proteases may contribute to cancer development by depleting DCC and neogenin. (PMID:27716118)
• Endogenous NTN4/NEO1 maintain neuroblastoma growth via both pro-survival and pro-migratory molecular signaling. (PMID:28038459)
• Overexpression of Neo1 significantly reduced the GC cell sensitivity to cisplatin and increased the cell viability, motility and adhesion ability, and while silencing of Neo1 showed contrary results. (PMID:30064133)
• Together, these findings identify a crucial role for Neo1 in regulating tissue regeneration and resolution of inflammation, and determined Neo1 to be a predictor of morbidity and mortality in critically ill children affected by clinical inflammation. (PMID:30222138)
• Loss of Neogenin1 in human colorectal carcinoma cells causes a partial EMT and wound-healing response. (PMID:30858446)
• Netrin-1 promotes naive pluripotency through Neo1 and Unc5b co-regulation of Wnt and MAPK signaling. (PMID:32231305)
• Neogenin is highly expressed in diffuse intrinsic pontine glioma and influences tumor invasion. (PMID:33571520)
• Hippocampal astrocytic neogenin regulating glutamate uptake, a critical pathway for preventing epileptic response. (PMID:33850017)
• Netrin-1 Stimulates Migration of Neogenin Expressing Aggressive Melanoma Cells. (PMID:36361539)
• Hepatic Expression of NTN4 and Its Receptors in Patients with Hepatocellular Carcinoma. (PMID:38156865)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	neo1b	ENSDARG00000075100
danio_rerio		ENSDARG00000102069
danio_rerio	neo1a	ENSDARG00000102855
mus_musculus	Neo1	ENSMUSG00000032340
rattus_norvegicus	Neo1	ENSRNOG00000006490

Paralogs (36): CNTN1 (ENSG00000018236), CDON (ENSG00000064309), 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), ROBO1 (ENSG00000169855), DSCAM (ENSG00000171587), IGDCC3 (ENSG00000174498), VSIG10 (ENSG00000176834), DSCAML1 (ENSG00000177103), CNTN2 (ENSG00000184144), ROBO2 (ENSG00000185008), VSIG10L (ENSG00000186806), DCC (ENSG00000187323), L1CAM (ENSG00000198910)

Protein

Protein identifiers

Neogenin — Q92859 (reviewed: Q92859)

Alternative names: Immunoglobulin superfamily DCC subclass member 2

All UniProt accessions (2): Q92859, Q59FP8

UniProt curated annotations — full annotation on UniProt →

Function. Multi-functional cell surface receptor regulating cell adhesion in many diverse developmental processes, including neural tube and mammary gland formation, myogenesis and angiogenesis. Receptor for members of the BMP, netrin, and repulsive guidance molecule (RGM) families. Netrin-Neogenin interactions result in a chemoattractive axon guidance response and cell-cell adhesion, the interaction between NEO1/Neogenin and RGMa and RGMb induces a chemorepulsive response.

Subunit / interactions. Interacts with MYO10. Interacts with RGMA and RGMB. Interacts with BMP2, BMP4, BMP6, and BMP7.

Subcellular location. Cell membrane.

Tissue specificity. Widely expressed and also in cancer cell lines.

Domain organisation. The Fibronectin repeats 5 and 6 mediate interaction with RGM family molecules.

Miscellaneous. Knockdown of NEO1 in C2C12 cells results in the enhancement of the BMP-2-induced processes of osteoblastic differentiation and phosphorylation of Smad1, Smad5, and Smad8. Conversely, overexpression suppresses these processes.

Similarity. Belongs to the immunoglobulin superfamily. DCC family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q92859-1	1	yes
Q92859-2	2
Q92859-3	3
Q92859-4	4

RefSeq proteins (4): NP_001166094, NP_001166095, NP_001406460, NP_002490* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR010560	Neogenin_C	Domain
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF00041, PF06583, PF07679, PF13895, PF13927

UniProt features (100 total): strand 46, domain 10, modified residue 8, glycosylation site 8, compositionally biased region 6, region of interest 5, disulfide bond 4, splice variant 3, topological domain 2, helix 2, signal peptide 1, chain 1, transmembrane region 1, sequence variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
3P4L	X-RAY DIFFRACTION	1.8
4UI2	X-RAY DIFFRACTION	3.15
1X5F	SOLUTION NMR
1X5G	SOLUTION NMR
1X5H	SOLUTION NMR
1X5I	SOLUTION NMR
1X5J	SOLUTION NMR
1X5K	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92859-F1	68.50	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.

Post-translational modifications (8): 1178, 1194, 1198, 1401, 1404, 1432, 1434, 1435

Disulfide bonds (4): 74–129, 173–221, 270–320, 362–410

Glycosylation sites (8): 73, 210, 326, 470, 489, 639, 715, 909

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-373752	Netrin-1 signaling
R-HSA-525793	Myogenesis
R-HSA-1266738	Developmental Biology
R-HSA-422475	Axon guidance
R-HSA-9675108	Nervous system development

MSigDB gene sets: 316 (showing top): MODULE_92, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, HNF3ALPHA_Q6, RORA1_01, NKX25_02, SP3_Q3, MODULE_64, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOCC_CELL_SURFACE, TATTATA_MIR374, GOBP_REGENERATION, GOBP_NEUROGENESIS, MODULE_453, GOBP_RESPONSE_TO_AXON_INJURY

GO Biological Process (14): neuron migration (GO:0001764), regulation of DNA-templated transcription (GO:0006355), intracellular iron ion homeostasis (GO:0006879), cell adhesion (GO:0007155), axon guidance (GO:0007411), myoblast fusion (GO:0007520), protein secretion (GO:0009306), positive regulation of BMP signaling pathway (GO:0030513), negative regulation of axon regeneration (GO:0048681), negative regulation of protein secretion (GO:0050709), multicellular organismal-level iron ion homeostasis (GO:0060586), cell-cell adhesion (GO:0098609), trans-synaptic signaling, modulating synaptic transmission (GO:0099550), regulation of axon regeneration (GO:0048679)

GO Molecular Function (5): signaling receptor activity (GO:0038023), co-receptor binding (GO:0039706), cadherin binding (GO:0045296), BMP receptor binding (GO:0070700), protein binding (GO:0005515)

GO Cellular Component (10): nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), cell surface (GO:0009986), growth cone (GO:0030426), intracellular vesicle (GO:0097708), plasma membrane protein complex (GO:0098797), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Developmental Biology	2
Axon guidance	1
Nervous system development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
inorganic ion homeostasis	2
axon regeneration	2
intracellular membrane-bounded organelle	2
cell migration	1
generation of neurons	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
intracellular monoatomic cation homeostasis	1
cellular process	1
axonogenesis	1
neuron projection guidance	1
syncytium formation by cell-cell fusion	1
myotube differentiation	1
protein transport	1
secretion by cell	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of response to external stimulus	1
regulation of axon regeneration	1
negative regulation of neuron projection regeneration	1
negative regulation of response to wounding	1
protein secretion	1
regulation of protein secretion	1
negative regulation of protein transport	1
negative regulation of secretion by cell	1
monoatomic cation homeostasis	1
multicellular organismal-level chemical homeostasis	1
cell adhesion	1
chemical synaptic transmission	1
modulation of chemical synaptic transmission	1
trans-synaptic signaling	1
regulation of response to external stimulus	1
regulation of neuron projection regeneration	1
regulation of response to wounding	1
molecular transducer activity	1

Protein interactions and networks

STRING

1340 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEO1	RGMA	Q96B86	999
NEO1	NTN1	O95631	998
NEO1	HJV	Q6ZVN8	995
NEO1	UNC5B	Q8IZJ1	990
NEO1	TMPRSS6	Q8IU80	955
NEO1	NTN4	Q9HB63	949
NEO1	RGMB	Q6NW40	909
NEO1	NTN3	O00634	885
NEO1	UNC5A	Q6ZN44	808
NEO1	UNC5C	O95185	776
NEO1	FAM107B	Q9H098	763
NEO1	DRAXIN	Q8NBI3	732
NEO1	BMP6	P22004	702
NEO1	TFR2	Q9UP52	685
NEO1	UNC5D	Q6UXZ4	673

IntAct

49 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HJV	NEO1	psi-mi:“MI:0407”(direct interaction)	0.620
BMP2	HJV	psi-mi:“MI:0915”(physical association)	0.540
IGLL5	IGLC7	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
TNF	B4GALT5	psi-mi:“MI:0914”(association)	0.530
LGALS1	LAMA5	psi-mi:“MI:0914”(association)	0.530
ANKH	FAM234B	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
ICAM5	NEO1	psi-mi:“MI:0407”(direct interaction)	0.440
NEO1	LTF	psi-mi:“MI:0407”(direct interaction)	0.440
NEO1	IGFBPL1	psi-mi:“MI:0407”(direct interaction)	0.440
IGFBP7	NEO1	psi-mi:“MI:0407”(direct interaction)	0.440
NEO1	NTN4	psi-mi:“MI:0915”(physical association)	0.400
UNC5B	NEO1	psi-mi:“MI:0915”(physical association)	0.400
NEO1	NTN1	psi-mi:“MI:0915”(physical association)	0.400
	NEO1	psi-mi:“MI:2364”(proximity)	0.380
	NEO1	psi-mi:“MI:0403”(colocalization)	0.380
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CACNA1C	CACNB4	psi-mi:“MI:0914”(association)	0.350

BioGRID (76): NEO1 (Affinity Capture-MS), NEO1 (Affinity Capture-MS), NEO1 (Proximity Label-MS), NEO1 (Affinity Capture-RNA), NEO1 (Proximity Label-MS), NEO1 (Proximity Label-MS), NEO1 (Protein-RNA), NEO1 (Affinity Capture-MS), NEO1 (Affinity Capture-MS), NEO1 (Affinity Capture-MS), NEO1 (Proximity Label-MS), NEO1 (Proximity Label-MS), NEO1 (Proximity Label-MS), NEO1 (Proximity Label-MS), NEO1 (Proximity Label-MS)

ESM2 similar proteins: D3ZB51, E9PZ19, M0RAS4, O60245, O70472, P13591, P13596, P24503, P24786, P31836, P33150, P39038, P55283, P55290, P58365, P69849, P78539, P97798, Q0ZM14, Q15155, Q16288, Q3B7N0, Q3UQ28, Q5H8C1, Q5IFJ9, Q5IS37, Q5IS82, Q5JPE7, Q5R5W6, Q5VV63, Q63769, Q6A051, Q6AZB0, Q6GQT9, Q6VNS1, Q7TNR6, Q8TDF5, Q91044, Q91987, Q92545

Diamond homologs: A0A1Y9G8H0, A0A452E9Y6, A1KZ92, A2A8L5, A2AJ76, A4IGL7, A5JUY8, A7MBJ4, A8WQH2, B3A0Q8, B3MH43, B3NS99, B4HNW4, B4P5Q9, B4QC63, D3YXG0, G5EBF1, G5EG78, H2A0M7, O01761, O15146, O35158, O55005, O89026, O94779, P05164, P05548, P07202, P09933, P0C5H6, P10586, P11247, P11678, P14650, P16621, P20241, P22079, P28685, P35419, P43146

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
NTN1	“up-regulates activity”	NEO1	binding
NTN4	“up-regulates activity”	NEO1	binding
NTN3	“up-regulates activity”	NEO1	binding
Netrin	“up-regulates activity”	NEO1	binding
RGMA	“down-regulates activity”	NEO1	binding
NEO1	up-regulates	Chemoattraction_of_axon

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 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	34.0×	8e-05
Extracellular matrix organization	5	7.9×	8e-03
Axon guidance	6	6.8×	8e-03
Nervous system development	6	6.4×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	185
Likely benign	19
Benign	15

Top pathogenic / likely-pathogenic (0)

SpliceAI

5125 predictions. Top by Δscore:

Variant	Effect	Δscore
15:73116530:A:AG	acceptor_gain	1.0000
15:73116535:T:TA	acceptor_gain	1.0000
15:73116537:TA:T	acceptor_loss	1.0000
15:73116537:TAGG:T	acceptor_gain	1.0000
15:73116538:A:AG	acceptor_gain	1.0000
15:73116538:A:T	acceptor_loss	1.0000
15:73116538:AG:A	acceptor_gain	1.0000
15:73116538:AGGA:A	acceptor_gain	1.0000
15:73116539:G:GT	acceptor_gain	1.0000
15:73116539:GG:G	acceptor_gain	1.0000
15:73116539:GGA:G	acceptor_gain	1.0000
15:73116539:GGAG:G	acceptor_gain	1.0000
15:73116539:GGAGC:G	acceptor_gain	1.0000
15:73116854:GCAG:G	donor_gain	1.0000
15:73116855:CAG:C	donor_gain	1.0000
15:73116855:CAGG:C	donor_loss	1.0000
15:73116856:AGGTA:A	donor_loss	1.0000
15:73116857:GGTA:G	donor_loss	1.0000
15:73116858:G:GG	donor_gain	1.0000
15:73116858:GTA:G	donor_loss	1.0000
15:73119699:T:G	donor_gain	1.0000
15:73135884:A:AG	acceptor_gain	1.0000
15:73135888:C:G	acceptor_gain	1.0000
15:73135889:A:AG	acceptor_gain	1.0000
15:73135890:G:GA	acceptor_gain	1.0000
15:73135890:GC:G	acceptor_gain	1.0000
15:73135890:GCT:G	acceptor_gain	1.0000
15:73135890:GCTCT:G	acceptor_gain	1.0000
15:73136023:GCAAG:G	donor_gain	1.0000
15:73136025:AAGG:A	donor_loss	1.0000

AlphaMissense

9540 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:73116665:T:A	W86R	1.000
15:73116665:T:C	W86R	1.000
15:73116667:G:C	W86C	1.000
15:73116667:G:T	W86C	1.000
15:73122629:T:A	W185R	1.000
15:73122629:T:C	W185R	1.000
15:73122631:G:C	W185C	1.000
15:73122631:G:T	W185C	1.000
15:73126536:T:A	W282R	1.000
15:73126536:T:C	W282R	1.000
15:73126538:G:C	W282C	1.000
15:73126538:G:T	W282C	1.000
15:73176507:T:A	W374R	1.000
15:73176507:T:C	W374R	1.000
15:73176509:G:C	W374C	1.000
15:73176509:G:T	W374C	1.000
15:73249123:T:A	V557D	1.000
15:73249128:T:A	W559R	1.000
15:73249128:T:C	W559R	1.000
15:73116666:G:C	W86S	0.999
15:73116794:T:C	C129R	0.999
15:73116796:T:G	C129W	0.999
15:73116846:T:C	L146P	0.999
15:73122630:G:C	W185S	0.999
15:73122693:T:C	L206P	0.999
15:73122731:T:G	Y219D	0.999
15:73126502:T:G	C270W	0.999
15:73126537:G:C	W282S	0.999
15:73135926:T:C	L305P	0.999
15:73135964:T:G	Y318D	0.999

dbSNP variants (sampled 300 via entrez): RS1000015975 (15:73061543 A>G,T), RS1000016100 (15:73139991 A>G), RS1000020828 (15:73221991 T>C), RS1000035827 (15:73147160 C>G), RS1000049062 (15:73300160 A>G), RS1000062771 (15:73144718 T>C), RS1000070741 (15:73127118 C>T), RS1000110660 (15:73268925 G>A), RS1000113355 (15:73226590 G>A), RS1000119713 (15:73280516 C>A,G), RS1000121187 (15:73238834 GT>G,GTTTTTT), RS1000125157 (15:73184875 C>G), RS1000129350 (15:73050598 G>A,C), RS1000154163 (15:73213482 A>G), RS1000166397 (15:73102761 A>C,G)

Disease associations

OMIM: gene MIM:601907 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST002928_15	Nickel levels	3.000000e-06
GCST003818_78	Resting heart rate	1.000000e-32
GCST004732_7	Heart rate variability traits (pvRSA/HF)	3.000000e-06
GCST004733_16	Heart rate variability traits (RMSSD)	5.000000e-10
GCST004733_3	Heart rate variability traits (RMSSD)	5.000000e-10
GCST004734_13	Heart rate variability traits (SDNN)	2.000000e-08
GCST006585_1072	Blood protein levels	9.000000e-13
GCST007324_36	Adventurousness	3.000000e-08
GCST008295_31	Number of decayed, missing and filled tooth surfaces or use of dentures	3.000000e-10
GCST008306_5	Dentures	9.000000e-09
GCST008971_103	Urate levels	6.000000e-09
GCST008972_243	Urate levels	2.000000e-08
GCST009309_9	Face memory	7.000000e-06
GCST010703_184	Brain morphology (MOSTest)	5.000000e-11
GCST90000025_222	Appendicular lean mass	1.000000e-16
GCST90002390_421	Mean corpuscular hemoglobin	1.000000e-16
GCST90002392_433	Mean corpuscular volume	8.000000e-13
GCST90002404_368	Red cell distribution width	5.000000e-12

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0008003	heart rate variability measurement
EFO:0008579	risk-taking behaviour
EFO:0010078	dentures
EFO:0004531	urate measurement
EFO:0004874	memory performance
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass
EFO:0004527	mean corpuscular hemoglobin
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases methylation	5
bisphenol A	increases expression, increases methylation	2
sodium arsenite	decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
4-hydroxy-2-nonenal	decreases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
N-butyrylglucosamine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
Dasatinib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Ethanol	increases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Folic Acid	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Lead	affects splicing	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1TP	Abcam U-87MG NEO1 KO	Cancer cell line	Male
CVCL_D8R7	Ubigene HCT 116 NEO1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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