NTN4

Summary

NTN4 (netrin 4, HGNC:13658) is a protein-coding gene on chromosome 12q22, encoding Netrin-4 (Q9HB63). May play an important role in neural, kidney and vascular development.

This gene encodes a member of the netrin family of proteins, which function in various biological processes including axon guidance, tumorogenesis, and angiogenesis. Netrins are laminin-related proteins that have an N-terminal laminin-type domain, epidermal growth factor-like repeat domain, and a positively charged heparin-binding domain at the C-terminus. The protein encoded by this gene is involved in processes including neurite growth and migration, angiogenesis and mural cell adhesion to endothelial cells. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 59277 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 86 total
• MANE Select transcript: NM_021229

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13658
Approved symbol	NTN4
Name	netrin 4
Location	12q22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000074527
Ensembl biotype	protein_coding
OMIM	610401
Entrez	59277

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 14 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000343702, ENST00000344911, ENST00000538383, ENST00000547980, ENST00000552603, ENST00000553059, ENST00000674345, ENST00000674466, ENST00000890156, ENST00000890157, ENST00000890158, ENST00000890159, ENST00000890160, ENST00000967951, ENST00000967952, ENST00000967953

RefSeq mRNA: 4 — MANE Select: NM_021229 NM_001329700, NM_001329701, NM_001329702, NM_021229

CCDS: CCDS86324, CCDS86325, CCDS9054

Canonical transcript exons

ENST00000343702 — 10 exons

Exon	Start	End
ENSE00000497539	95665810	95665980
ENSE00000753420	95670078	95670146
ENSE00000937627	95713212	95713338
ENSE00001098588	95710441	95710629
ENSE00001192786	95682707	95682822
ENSE00001192793	95683498	95683711
ENSE00001192808	95790255	95790764
ENSE00001366762	95657807	95659222
ENSE00003459352	95737866	95738144
ENSE00003673418	95786939	95787468

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 98.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.0836 / max 344.2161, expressed in 1199 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132747	4.0766	746
132748	2.2538	840
132745	1.7878	714
132746	0.8558	526
132749	0.0811	37
132750	0.0285	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	98.56	gold quality
epithelial cell of pancreas	CL:0000083	98.27	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.51	gold quality
seminal vesicle	UBERON:0000998	97.13	gold quality
epithelium of mammary gland	UBERON:0003244	97.04	gold quality
mammary duct	UBERON:0001765	97.02	gold quality
spleen	UBERON:0002106	96.86	gold quality
left ventricle myocardium	UBERON:0006566	96.85	gold quality
synovial joint	UBERON:0002217	96.76	gold quality
right coronary artery	UBERON:0001625	96.23	gold quality
palpebral conjunctiva	UBERON:0001812	95.86	gold quality
renal medulla	UBERON:0000362	95.45	gold quality
myocardium	UBERON:0002349	95.18	gold quality
thoracic mammary gland	UBERON:0005200	95.15	gold quality
mammary gland	UBERON:0001911	95.14	gold quality
layer of synovial tissue	UBERON:0007616	95.03	gold quality
germinal epithelium of ovary	UBERON:0001304	94.96	gold quality
visceral pleura	UBERON:0002401	94.90	gold quality
metanephros cortex	UBERON:0010533	94.70	gold quality
heart right ventricle	UBERON:0002080	94.56	gold quality
adult mammalian kidney	UBERON:0000082	94.38	gold quality
lower lobe of lung	UBERON:0008949	94.15	gold quality
left coronary artery	UBERON:0001626	93.94	gold quality
kidney	UBERON:0002113	93.88	gold quality
right uterine tube	UBERON:0001302	93.77	gold quality
cardiac atrium	UBERON:0002081	93.25	gold quality
popliteal artery	UBERON:0002250	93.16	gold quality
decidua	UBERON:0002450	93.16	gold quality
tibial artery	UBERON:0007610	93.16	gold quality
descending thoracic aorta	UBERON:0002345	93.14	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-8530	yes	187.25
E-MTAB-10553	yes	46.91
E-ANND-3	yes	22.91
E-HCAD-9	yes	17.70
E-ENAD-27	yes	6.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

134 targeting NTN4, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-98-3P	100.00	74.08	3907
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-381-3P	99.93	71.87	2854

Literature-anchored findings (GeneRIF, showing 34)

• NTN4, TRA1, and STC2 have roles in progression of breast cancer (PMID:17545519)
• Knockdown of Netrin-4 expression in EC increased their ability to form tubular structures; Netrin-4 bound only to neogenin but not to Unc5B or Unc5C receptors (PMID:18719102)
• A potential role for netrin-4 in regulating tumor growth. (PMID:19094984)
• Loss of NTN4 by methylation is associated with breast cancer. (PMID:19859801)
• Netrin-4, at physiologic doses, induces proliferation, migration, adhesion, tube formation and survival of human lymphatic endothelial cells. (PMID:20407033)
• Netrin-4 is upregulated in breast carcinoma effusions compared to corresponding solid tumors (PMID:20730893)
• NT-4 overexpression decreases tumor growth and carcinomatosis, probably via an antiangiogenic effect (PMID:21406174)
• The alpha6beta1 integrin is a netrin-4 receptor in endothelial cells. (PMID:21799154)
• glioma cells reduce netrin-4 expression to decrease its inhibitory effects. (PMID:22496621)
• pattern of distribution suggests that a functional netrin-4-neogenin pathway might be restricted to syncytiotrophoblasts, mesenchymal cells, and villous endothelial cells (PMID:22705235)
• GWAS study found two new SNPs associated with nickel dermatitis; SNPs are located in the NTN4 and PELI1 genes (PMID:23921680)
• NTN4 expression was downregulated in cervical cancer tissues compared to normal controls, and in vivo mRNA level of NTN4 inversely correlated with miR-196a expression. (PMID:24120501)
• NETRIN-4 protects glioblastoma cells FROM temozolomide induced senescence. (PMID:24265816)
• Increased maternal netrin-4 levels in IUGR neonates may reflect in utero hypoxia, while the negative correlations between fetal netrin-1 and -4 levels may exert the dynamic balance between their angio- and anti-angiogenic properties. (PMID:24716747)
• Increased expression of miR-20a may play an important role in the pathogenesis of ovarian endometriosis by suppressing NTN4 expression. (PMID:24972566)
• NTN4 acts as a positive regulator for TC axon branching through activity-dependent expression (PMID:25288737)
• 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)
• inhibits placental microvascular endothelial cells proliferation, tube-like formation, migration and spheroid sprouting (PMID:26390805)
• We found statistically significant association with AAO for three genes (WRN, NTN4 and LAMC3) with common associated variants. (PMID:26394601)
• Data indicate that OR3A4 upregulation contributes to metastasis and tumorigenesis in gastric cancer by regulating the activation of PDLIM2, MACC1, NTN4, and GNB2L1. (PMID:26863570)
• NTN4 is reduced in breast cancer tissues and NTN4 is associated with breast cancer cell migration and invasion via regulation of epithelial mesenchymal transition (EMT)-related biomarkers. (PMID:27840993)
• Endogenous NTN4/NEO1 maintain neuroblastoma growth via both pro-survival and pro-migratory molecular signaling. (PMID:28038459)
• Findings indicate that activation of notch receptor 1 (Notch1) signalling significantly up-regulated Netrin4 (NTN4) mRNA and protein expressions. (PMID:30784178)
• this paper shows that NTN4 gene polymorphism is associated with IgA nephropathy risk in Chinese Han population (PMID:30928649)
• Enrichment of damaging missense variants in genes related with axonal guidance signalling in sporadic Meniere’s disease. (PMID:31494579)
• silencing of UNC5B, an NTN4 receptor, abrogated the NTN4-induced cellular activities of SEPCs in vitro and blood-flow recovery and neovascularization in vivo in ischemic muscle by reducing EPC homing and incorporation. (PMID:31914695)
• eQTL Colocalization Analyses Identify NTN4 as a Candidate Breast Cancer Risk Gene. (PMID:32871102)
• Netrin-4 expression by human endothelial cells inhibits endothelial inflammation and senescence. (PMID:33636396)
• Anti-Inflammatory Role of Netrin-4 in Diabetic Retinopathy. (PMID:33923095)
• The Interaction of NTN4 and miR-17-92 Polymorphisms on Breast Cancer Susceptibility in a Chinese Population. (PMID:35232666)
• NTN4 as a prognostic marker and a hallmark for immune infiltration in breast cancer. (PMID:35732855)
• Netrin-4: Focus on Its Role in Axon Guidance, Tissue Stability, Angiogenesis and Tumors. (PMID:36350538)
• RNA-binding protein quaking 5 inhibits the progression of non-small cell lung cancer by upregulating netrin-4 expression. (PMID:37800632)
• Hepatic Expression of NTN4 and Its Receptors in Patients with Hepatocellular Carcinoma. (PMID:38156865)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ntn4	ENSDARG00000102066
mus_musculus	Ntn4	ENSMUSG00000020019
rattus_norvegicus	Ntn4	ENSRNOG00000005573

Paralogs (27): USH2A (ENSG00000042781), LAMC3 (ENSG00000050555), LAMA3 (ENSG00000053747), LAMC2 (ENSG00000058085), NTN1 (ENSG00000065320), 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-4 — Q9HB63 (reviewed: Q9HB63)

Alternative names: Beta-netrin, Hepar-derived netrin-like protein

All UniProt accessions (3): Q9HB63, A0A6I8PS14, F8W0I7

UniProt curated annotations — full annotation on UniProt →

Function. May play an important role in neural, kidney and vascular development. Promotes neurite elongation from olfactory bulb explants.

Subunit / interactions. May form a homodimer.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Basement membrane.

Tissue specificity. Expressed in kidney, spleen, mammary gland, aorta, heart, ovary, prostate and fetal spleen.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9HB63-1	1	yes
Q9HB63-2	2
Q9HB63-3	3, Hetrin

RefSeq proteins (4): NP_001316629, NP_001316630, NP_001316631, NP_067052* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001134	Netrin_domain	Domain
IPR002049	LE_dom	Domain
IPR008211	Laminin_N	Domain
IPR008993	TIMP-like_OB-fold	Homologous_superfamily
IPR018933	Netrin_module_non-TIMP	Domain
IPR035811	Netrin-4_NTR	Domain
IPR050440	Laminin/Netrin_ECM	Family
IPR056863	LMN_ATRN_NET-like_EGF	Domain

Pfam: PF00053, PF00055, PF01759, PF24973

UniProt features (36 total): disulfide bond 14, sequence conflict 8, domain 5, glycosylation site 4, splice variant 2, signal peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HB63-F1	84.02	0.61

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 (14): 262–271, 264–293, 295–304, 307–329, 332–341, 334–359, 362–371, 374–392, 395–413, 397–420, 422–431, 434–446, 506–576, 520–627

Glycosylation sites (4): 483, 56, 163, 353

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-3000171	Non-integrin membrane-ECM interactions
R-HSA-373752	Netrin-1 signaling
R-HSA-1266738	Developmental Biology
R-HSA-1474244	Extracellular matrix organization
R-HSA-422475	Axon guidance
R-HSA-9675108	Nervous system development

MSigDB gene sets: 213 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_GLAND_MORPHOGENESIS, GOBP_REGULATION_OF_MORPHOGENESIS_OF_A_BRANCHING_STRUCTURE, GOBP_SALIVARY_GLAND_DEVELOPMENT, GCANCTGNY_MYOD_Q6, GOBP_NEURON_MATURATION, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOBP_NEUROGENESIS, GOBP_EXTRACELLULAR_MATRIX_ASSEMBLY, GGGTGGRR_PAX4_03, SREBP1_02, HERNANDEZ_ABERRANT_MITOSIS_BY_DOCETACEL_2NM_UP, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, EVI1_05

GO Biological Process (8): axon guidance (GO:0007411), animal organ morphogenesis (GO:0009887), tissue development (GO:0009888), neuron remodeling (GO:0016322), cell migration (GO:0016477), substrate adhesion-dependent cell spreading (GO:0034446), regulation of branching involved in salivary gland morphogenesis by extracellular matrix-epithelial cell signaling (GO:0060668), basement membrane assembly (GO:0070831)

GO Molecular Function (2): laminin-1 binding (GO:0043237), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), laminin trimer (GO:0043256), extracellular region (GO:0005576), basement membrane (GO:0005604)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Extracellular matrix organization	1
Axon guidance	1
Nervous system development	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
axonogenesis	1
neuron projection guidance	1
anatomical structure morphogenesis	1
animal organ development	1
anatomical structure development	1
neuron maturation	1
cell motility	1
cell-substrate adhesion	1
extracellular matrix-cell signaling	1
regulation of branching involved in salivary gland morphogenesis	1
basement membrane organization	1
extracellular matrix assembly	1
laminin binding	1
binding	1
membrane	1
cell periphery	1
laminin network	1
extracellular protein-containing complex	1
cellular anatomical structure	1
extracellular matrix	1

Protein interactions and networks

STRING

748 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NTN4	NEO1	Q92859	949
NTN4	UNC5B	Q8IZJ1	937
NTN4	DSCAM	O60469	794
NTN4	DCC	P43146	742
NTN4	UNC5C	O95185	736
NTN4	UNC5A	Q6ZN44	702
NTN4	ALOX12	P18054	555
NTN4	ROBO4	Q8WZ75	553
NTN4	ADORA2B	P29275	552
NTN4	UNC5D	Q6UXZ4	545
NTN4	PTK2	Q05397	464
NTN4	EBF1	Q9UH73	453
NTN4	PLXNA1	Q9UIW2	450
NTN4	NRP2	O60462	422
NTN4	FYN	P06241	410

IntAct

60 interactions, top by confidence:

A	B	Type	Score
KRTAP5-9	NTN4	psi-mi:“MI:0915”(physical association)	0.670
CYSRT1	NTN4	psi-mi:“MI:0915”(physical association)	0.560
CASK	NTN4	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	NTN4	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	NTN4	psi-mi:“MI:0915”(physical association)	0.560
KPRP	NTN4	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	NTN4	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	NTN4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	NTN4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP21-2	NTN4	psi-mi:“MI:0915”(physical association)	0.560
NTN4	PECAM1	psi-mi:“MI:0915”(physical association)	0.560
NTN4	BRAF	psi-mi:“MI:2364”(proximity)	0.470
NTN4	BRAF	psi-mi:“MI:0915”(physical association)	0.470
DCC	NTN4	psi-mi:“MI:0407”(direct interaction)	0.440
	NTN4	psi-mi:“MI:0407”(direct interaction)	0.440
NEO1	NTN4	psi-mi:“MI:0915”(physical association)	0.400
	NTN4	psi-mi:“MI:0915”(physical association)	0.370
ECE1	NTN4	psi-mi:“MI:0915”(physical association)	0.370
PLSCR1	NTN4	psi-mi:“MI:0915”(physical association)	0.370
ADAMTSL4	NTN4	psi-mi:“MI:0915”(physical association)	0.370
	CCN1	psi-mi:“MI:0914”(association)	0.350
C1orf54	QSOX1	psi-mi:“MI:0914”(association)	0.350
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
CDH5	MYO1C	psi-mi:“MI:2364”(proximity)	0.270
SPOP	NTN4	psi-mi:“MI:2364”(proximity)	0.270
NTN4	SPOP	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (25): NTN4 (Two-hybrid), NTN4 (Affinity Capture-RNA), NTN4 (Affinity Capture-RNA), NTN4 (Affinity Capture-RNA), NTN4 (Affinity Capture-RNA), NTN4 (Two-hybrid), NTN4 (Two-hybrid), NTN4 (Two-hybrid), NTN4 (Positive Genetic), HOXA1 (Two-hybrid), MEOX2 (Two-hybrid), CASK (Two-hybrid), KRTAP21-2 (Two-hybrid), KRTAP10-8 (Two-hybrid), LCE1C (Two-hybrid)

ESM2 similar proteins: A0A6I8RMG7, A0JP86, A4D0S4, O54890, O70309, P02468, P02469, P05106, P0CY46, P11046, P11047, P13387, P13388, P15215, P15800, P18084, P18563, P18564, P19137, P24043, P25391, P35555, P55268, P80747, P98133, Q07441, Q18823, Q1LVF0, Q1RPR6, Q2KIT5, Q5RB89, Q60675, Q61220, Q61292, Q61526, Q61554, Q61555, Q62918, Q6AYF4, Q6UXH1

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

3 interactions.

A	Effect	B	Mechanism
NTN4	“up-regulates activity”	NEO1	binding
NTN4	“up-regulates activity”	UNC5	binding
NTN4	up-regulates	UNC5A	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 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
positive regulation of cell migration	5	13.4×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2520 predictions. Top by Δscore:

Variant	Effect	Δscore
12:95682823:C:CC	acceptor_gain	1.0000
12:95694597:T:C	donor_gain	1.0000
12:95710435:ACTT:A	donor_loss	1.0000
12:95710437:TTA:T	donor_loss	1.0000
12:95710438:TACGT:T	donor_loss	1.0000
12:95710439:A:AC	donor_gain	1.0000
12:95710440:C:CG	donor_gain	1.0000
12:95710440:CG:C	donor_gain	1.0000
12:95710440:CGT:C	donor_gain	1.0000
12:95710440:CGTT:C	donor_gain	1.0000
12:95710440:CGTTT:C	donor_gain	1.0000
12:95710626:CAGG:C	acceptor_gain	1.0000
12:95710630:C:CC	acceptor_gain	1.0000
12:95710636:A:C	acceptor_gain	1.0000
12:95713206:ACTT:A	donor_loss	1.0000
12:95713207:CTT:C	donor_loss	1.0000
12:95713208:TTAC:T	donor_loss	1.0000
12:95713209:TACTT:T	donor_loss	1.0000
12:95713210:A:AC	donor_gain	1.0000
12:95713210:A:T	donor_loss	1.0000
12:95713211:C:CC	donor_gain	1.0000
12:95713211:CTT:C	donor_gain	1.0000
12:95738141:TAAC:T	acceptor_gain	1.0000
12:95738142:AACC:A	acceptor_loss	1.0000
12:95738145:C:CA	acceptor_loss	1.0000
12:95738145:C:CC	acceptor_gain	1.0000
12:95738146:T:C	acceptor_loss	1.0000
12:95790676:T:TA	donor_gain	1.0000
12:95790677:C:A	donor_gain	1.0000
12:95665932:T:TG	acceptor_gain	0.9900

AlphaMissense

4140 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:95710545:C:G	C359S	0.997
12:95710546:A:T	C359S	0.997
12:95713292:C:G	C304S	0.997
12:95713293:A:T	C304S	0.997
12:95683575:C:A	W439C	0.996
12:95683575:C:G	W439C	0.996
12:95710500:C:G	C374S	0.996
12:95710501:A:T	C374S	0.996
12:95710620:C:G	C334S	0.996
12:95710621:A:T	C334S	0.996
12:95713255:C:A	W316C	0.996
12:95713255:C:G	W316C	0.996
12:95683591:C:G	C434S	0.995
12:95683592:A:T	C434S	0.995
12:95710446:C:G	C392S	0.995
12:95710447:A:T	C392S	0.995
12:95710508:G:C	C371W	0.995
12:95710509:C:G	C371S	0.995
12:95710510:A:T	C371S	0.995
12:95713319:C:G	C295S	0.995
12:95713320:A:T	C295S	0.995
12:95659155:G:C	S606R	0.994
12:95659155:G:T	S606R	0.994
12:95659157:T:G	S606R	0.994
12:95683528:C:T	C455Y	0.994
12:95683600:C:G	C431S	0.994
12:95683601:A:T	C431S	0.994
12:95713217:C:G	C329S	0.994
12:95713218:A:T	C329S	0.994
12:95713283:C:G	C307S	0.994

dbSNP variants (sampled 300 via entrez): RS1000018974 (12:95736441 A>T), RS1000036802 (12:95737387 C>T), RS1000055589 (12:95780202 A>G), RS1000079648 (12:95691114 C>T), RS1000092144 (12:95736083 C>T), RS1000099198 (12:95692487 T>C), RS1000125810 (12:95772646 A>G), RS1000128866 (12:95778773 T>C), RS1000151025 (12:95737046 C>G,T), RS1000157791 (12:95708796 C>T), RS1000165095 (12:95680945 T>A), RS1000203880 (12:95763948 A>C), RS1000239304 (12:95773962 T>C), RS1000281670 (12:95686225 T>C), RS1000282650 (12:95729846 G>A,T)

Disease associations

OMIM: gene MIM:610401 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression, increases expression	4
Estradiol	increases expression, decreases expression, affects expression, affects binding	4
Acetaminophen	increases expression, decreases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation, affects expression	3
Cyclosporine	decreases expression, increases expression	3
graphene oxide	increases expression	2
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Doxorubicin	decreases expression, affects expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression	2
Valproic Acid	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
Aflatoxin B1	affects expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
bisphenol A	decreases expression	1
hydroxyhydroquinone	increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	increases abundance, increases expression	1
rutecarpine	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
mercuric bromide	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F1UL	HyCyte U-118MG KO-hNTN4	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer