NTN5

Summary

NTN5 (netrin 5, HGNC:25208) is a protein-coding gene on chromosome 19q13.33, encoding Netrin-5 (Q8WTR8). Plays a role in neurogenesis.

Predicted to be involved in neurogenesis. Predicted to be located in extracellular region.

Source: NCBI Gene 126147 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 138 total
• MANE Select transcript: NM_145807

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25208
Approved symbol	NTN5
Name	netrin 5
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000142233
Ensembl biotype	protein_coding
Entrez	126147

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000270235, ENST00000596844, ENST00000600468, ENST00000954299

RefSeq mRNA: 1 — MANE Select: NM_145807 NM_145807

CCDS: CCDS33068

Canonical transcript exons

ENST00000270235 — 7 exons

Exon	Start	End
ENSE00000953075	48663761	48663814
ENSE00000953076	48663463	48663543
ENSE00001116379	48672932	48673017
ENSE00001130710	48661407	48662041
ENSE00003590292	48670356	48671006
ENSE00003640438	48664143	48664292
ENSE00003691802	48664579	48664767

Expression profiles

Bgee: expression breadth ubiquitous, 150 present calls, max score 83.84.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	83.84	gold quality
pituitary gland	UBERON:0000007	74.76	gold quality
adenohypophysis	UBERON:0002196	74.14	gold quality
left ovary	UBERON:0002119	72.58	gold quality
right ovary	UBERON:0002118	71.59	gold quality
tendon of biceps brachii	UBERON:0008188	70.15	gold quality
cerebellar hemisphere	UBERON:0002245	69.60	gold quality
right hemisphere of cerebellum	UBERON:0014890	69.49	gold quality
cerebellar cortex	UBERON:0002129	69.48	gold quality
left uterine tube	UBERON:0001303	69.19	gold quality
granulocyte	CL:0000094	67.90	gold quality
endocervix	UBERON:0000458	67.79	gold quality
body of uterus	UBERON:0009853	67.55	gold quality
ovary	UBERON:0000992	67.53	gold quality
cerebellum	UBERON:0002037	67.51	gold quality
ectocervix	UBERON:0012249	67.05	gold quality
skin of abdomen	UBERON:0001416	66.74	gold quality
skin of leg	UBERON:0001511	66.41	gold quality
right frontal lobe	UBERON:0002810	66.31	gold quality
putamen	UBERON:0001874	66.12	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	65.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	65.68	gold quality
nucleus accumbens	UBERON:0001882	65.44	gold quality
left lobe of thyroid gland	UBERON:0001120	65.25	gold quality
Brodmann (1909) area 9	UBERON:0013540	65.11	gold quality
caudate nucleus	UBERON:0001873	64.96	gold quality
lower esophagus mucosa	UBERON:0035834	64.96	gold quality
stromal cell of endometrium	CL:0002255	64.87	gold quality
thyroid gland	UBERON:0002046	64.65	gold quality
prostate gland	UBERON:0002367	64.30	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	8.53
E-ENAD-17	no	3.22
E-ANND-3	no	1.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting NTN5, 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-12118	100.00	65.88	1270
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-509-3P	98.12	67.25	612
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-8057	97.64	66.54	897
HSA-MIR-6787-5P	97.54	63.85	457
HSA-MIR-10396B-5P	94.99	63.57	358
HSA-MIR-1908-5P	94.99	63.41	352
HSA-MIR-663A	94.99	63.54	378
HSA-MIR-3672	94.46	65.67	646
HSA-MIR-6864-3P	94.46	65.97	625

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ntn5	ENSMUSG00000070564
rattus_norvegicus	Ntn5	ENSRNOG00000021016

Paralogs (27): USH2A (ENSG00000042781), LAMC3 (ENSG00000050555), LAMA3 (ENSG00000053747), LAMC2 (ENSG00000058085), NTN1 (ENSG00000065320), NTN4 (ENSG00000074527), ATRN (ENSG00000088812), LAMB4 (ENSG00000091128), LAMB1 (ENSG00000091136), LAMA1 (ENSG00000101680), MEGF8 (ENSG00000105429), MEGF9 (ENSG00000106780), ATRNL1 (ENSG00000107518), LAMA4 (ENSG00000112769), LAMA5 (ENSG00000130702), LAMC1 (ENSG00000135862), 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-5 — Q8WTR8 (reviewed: Q8WTR8)

Alternative names: Netrin-1-like protein

All UniProt accessions (2): Q8WTR8, M0QXZ9

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in neurogenesis. Prevents motor neuron cell body migration out of the neural tube.

Subcellular location. Secreted.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WTR8-1	1	yes
Q8WTR8-2	2

RefSeq proteins (1): NP_665806* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001134	Netrin_domain	Domain
IPR002049	LE_dom	Domain
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, PF01759, PF24973

UniProt features (25 total): disulfide bond 15, domain 4, splice variant 2, signal peptide 1, chain 1, region of interest 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WTR8-F1	84.39	0.54

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): 177–186, 189–209, 212–221, 214–239, 242–251, 254–272, 275–287, 277–294, 296–305, 308–322, 345–418, 349–420, 364–475, 157–166, 159–175

Glycosylation sites (1): 62

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 59 (showing top): FREAC2_01, GOBP_NEUROGENESIS, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, ARGGGTTAA_UNKNOWN, GOBP_SUBSTRATE_ADHESION_DEPENDENT_CELL_SPREADING, HFH1_01, FREAC4_01, GOCC_BASEMENT_MEMBRANE, CREBP1_01, GOBP_CELL_SUBSTRATE_ADHESION, CCCNNGGGAR_OLF1_01, WGGAATGY_TEF1_Q6, WGTTNNNNNAAA_UNKNOWN, NFAT_Q6, GOMF_STRUCTURAL_MOLECULE_ACTIVITY

GO Biological Process (2): neurogenesis (GO:0022008), nervous system development (GO:0007399)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nervous system development	1
cell differentiation	1
system development	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

706 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NTN5	UNC5A	Q6ZN44	561
NTN5	UNC5C	O95185	540
NTN5	TMEM19	Q96HH6	521
NTN5	DCC	P43146	495
NTN5	KCNJ14	Q9UNX9	461
NTN5	BPIFB1	Q8TDL5	457
NTN5	GRIN2D	O15399	450
NTN5	MDGA1	Q8NFP4	441
NTN5	UNC5D	Q6UXZ4	438
NTN5	DSCAM	O60469	436
NTN5	TMEM216	Q9P0N5	436
NTN5	ADAMTS7	Q9UKP4	436
NTN5	NEO1	Q92859	435
NTN5	NTF4	P34130	433
NTN5	NPAS3	Q8IXF0	433

IntAct

3 interactions, top by confidence:

A	B	Type	Score
NTN5	LRP4	psi-mi:“MI:0914”(association)	0.350
NTN5	ZSWIM8	psi-mi:“MI:0914”(association)	0.350

BioGRID (22): VWDE (Affinity Capture-MS), FBLN5 (Affinity Capture-MS), MTMR4 (Affinity Capture-MS), ERBB2IP (Affinity Capture-MS), LTBP4 (Affinity Capture-MS), JAG2 (Affinity Capture-MS), AMER1 (Affinity Capture-MS), LGR4 (Affinity Capture-MS), APC (Affinity Capture-MS), LRP2 (Affinity Capture-MS), LRP4 (Affinity Capture-MS), SORL1 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), FRAS1 (Affinity Capture-MS), NOTCH1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTW7, A6NE52, D3Z7H8, D3ZT86, G7PWZ3, I6M4H4, O00634, O08852, O15197, O43157, O75074, O88204, O88516, O88671, O95428, O97507, P00744, P0C0K6, P0C5J5, P20863, P59222, P98140, P98161, Q04756, Q04912, Q04997, Q3UQ22, Q4TUC0, Q5IJ48, Q5JZY3, Q6EMK4, Q76LX8, Q7TQH7, Q7Z4F1, Q86T13, Q86VZ4, Q8BYG9, Q8CB67, Q8CJH3, Q8R0S6

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	118
Likely benign	6
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

924 predictions. Top by Δscore:

Variant	Effect	Δscore
19:48662042:C:CC	acceptor_gain	1.0000
19:48663812:TTC:T	acceptor_gain	1.0000
19:48663813:TCCT:T	acceptor_loss	1.0000
19:48663814:CCTG:C	acceptor_loss	1.0000
19:48663815:C:A	acceptor_loss	1.0000
19:48663815:C:CC	acceptor_gain	1.0000
19:48663824:C:CT	acceptor_gain	1.0000
19:48663824:C:T	acceptor_gain	1.0000
19:48663825:A:T	acceptor_gain	1.0000
19:48664574:CTCA:C	donor_loss	1.0000
19:48664575:TCA:T	donor_loss	1.0000
19:48664576:CACCT:C	donor_loss	1.0000
19:48664578:CCT:C	donor_gain	1.0000
19:48664763:GCAGG:G	acceptor_gain	1.0000
19:48664764:CAGG:C	acceptor_gain	1.0000
19:48664764:CAGGC:C	acceptor_gain	1.0000
19:48664765:AGG:A	acceptor_gain	1.0000
19:48664768:C:CC	acceptor_gain	1.0000
19:48662037:GAGAA:G	acceptor_gain	0.9900
19:48662038:AGAA:A	acceptor_gain	0.9900
19:48662039:GAA:G	acceptor_gain	0.9900
19:48662040:AA:A	acceptor_gain	0.9900
19:48663755:TCTTA:T	donor_loss	0.9900
19:48663756:CTTA:C	donor_loss	0.9900
19:48663758:T:TG	donor_loss	0.9900
19:48663759:A:AC	donor_gain	0.9900
19:48663759:A:AT	donor_loss	0.9900
19:48663760:C:CC	donor_gain	0.9900
19:48663811:ATTC:A	acceptor_gain	0.9900
19:48663813:TC:T	acceptor_gain	0.9900

AlphaMissense

3117 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:48664730:G:C	F223L	0.998
19:48664730:G:T	F223L	0.998
19:48664732:A:G	F223L	0.998
19:48670393:C:A	W198C	0.998
19:48670393:C:G	W198C	0.998
19:48664731:A:C	F223C	0.997
19:48664646:G:C	C251W	0.995
19:48664647:C:A	C251F	0.994
19:48664647:C:T	C251Y	0.994
19:48664647:C:G	C251S	0.993
19:48664648:A:T	C251S	0.993
19:48664716:A:C	F228C	0.993
19:48664737:C:G	C221S	0.993
19:48664738:A:T	C221S	0.993
19:48664199:C:A	C305F	0.992
19:48664199:C:T	C305Y	0.992
19:48664758:C:T	C214Y	0.992
19:48664232:C:G	C294S	0.991
19:48664233:A:T	C294S	0.991
19:48664625:G:C	F258L	0.991
19:48664625:G:T	F258L	0.991
19:48664627:A:G	F258L	0.991
19:48664674:C:G	C242S	0.991
19:48664675:A:T	C242S	0.991
19:48664683:C:T	C239Y	0.990
19:48664731:A:G	F223S	0.990
19:48664198:G:C	C305W	0.989
19:48664199:C:G	C305S	0.989
19:48664200:A:T	C305S	0.989
19:48664683:C:G	C239S	0.989

dbSNP variants (sampled 300 via entrez): RS1000063861 (19:48665096 G>A,T), RS1000497603 (19:48669056 C>T), RS1000678040 (19:48674393 C>T), RS1000713613 (19:48674388 G>C,T), RS1000733024 (19:48674660 G>A), RS1001457049 (19:48668857 A>G), RS1001537488 (19:48668067 G>A), RS1001582893 (19:48674617 G>A), RS1001691592 (19:48662617 G>A), RS1001753366 (19:48669523 C>A,T), RS1001913311 (19:48673729 A>G), RS1001966815 (19:48668331 C>T), RS1002025599 (19:48661302 C>A,T), RS1002080971 (19:48661060 A>C,T), RS1002166966 (19:48662655 A>G,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001241_6	Bipolar disorder	3.000000e-06
GCST003624_1	diarrhoeal disease at age 2 with doctor diagnosis	2.000000e-07
GCST003626_1	diarrhoeal disease at age 1	8.000000e-14
GCST004131_128	Inflammatory bowel disease	5.000000e-06
GCST004132_59	Crohn’s disease	4.000000e-11
GCST010134_4	Non-oily fish consumption	3.000000e-16
GCST010135_4	Oily fish consumption	2.000000e-16
GCST010140_48	Pork consumption	2.000000e-16
GCST010142_1	Fish- and plant-related diet	7.000000e-13
GCST010142_45	Fish- and plant-related diet	3.000000e-08
GCST90011900_166	Serum alkaline phosphatase levels	5.000000e-206

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression	3
Silicon Dioxide	increases expression, decreases expression	2
Valproic Acid	affects expression, increases methylation	2
propionaldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
abrine	decreases expression	1
Carbamazepine	affects expression	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	decreases expression	1
Methapyrilene	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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