DRAXIN

Summary

DRAXIN (dorsal inhibitory axon guidance protein, HGNC:25054) is a protein-coding gene on chromosome 1p36.22, encoding Draxin (Q8NBI3). Chemorepulsive axon guidance protein required for the development of spinal cord and forebrain commissures.

Enables molecular adaptor activity. Predicted to be involved in negative regulation of canonical Wnt signaling pathway and nervous system development. Predicted to act upstream of or within negative regulation of axon extension and negative regulation of hippocampal neuron apoptotic process. Predicted to be active in extracellular region.

Source: NCBI Gene 374946 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_198545

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25054
Approved symbol	DRAXIN
Name	dorsal inhibitory axon guidance protein
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Aliases	FLJ34999, Neucrin
Ensembl gene	ENSG00000162490
Ensembl biotype	protein_coding
OMIM	612682
Entrez	374946

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000294485, ENST00000855916, ENST00000911391, ENST00000911392, ENST00000911393

RefSeq mRNA: 1 — MANE Select: NM_198545 NM_198545

CCDS: CCDS135

Canonical transcript exons

ENST00000294485 — 7 exons

Exon	Start	End
ENSE00001065722	11712340	11712429
ENSE00001145592	11715119	11715208
ENSE00001235382	11711851	11711965
ENSE00001235387	11709275	11709465
ENSE00001297775	11719584	11725857
ENSE00001413796	11706249	11706709
ENSE00001471247	11691710	11691853

Expression profiles

Bgee: expression breadth broad, 53 present calls, max score 92.59.

FANTOM5 (CAGE): breadth broad, TPM avg 6.7571 / max 466.8610, expressed in 621 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
633	6.3008	607
632	0.1930	69
634	0.1469	67
631	0.1164	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	92.59	gold quality
ganglionic eminence	UBERON:0004023	88.65	gold quality
granulocyte	CL:0000094	74.68	gold quality
cerebellar vermis	UBERON:0004720	73.27	gold quality
buccal mucosa cell	CL:0002336	72.00	silver quality
cartilage tissue	UBERON:0002418	70.32	gold quality
ventricular zone	UBERON:0003053	70.00	gold quality
pharyngeal mucosa	UBERON:0000355	66.61	gold quality
thymus	UBERON:0002370	66.28	silver quality
secondary oocyte	CL:0000655	65.79	gold quality
cardia of stomach	UBERON:0001162	65.54	gold quality
gingival epithelium	UBERON:0001949	65.31	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	64.81	gold quality
saphenous vein	UBERON:0007318	64.66	gold quality
synovial joint	UBERON:0002217	64.44	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	64.36	gold quality
pericardium	UBERON:0002407	64.35	gold quality
sperm	CL:0000019	64.28	gold quality
nipple	UBERON:0002030	64.20	gold quality
lateral globus pallidus	UBERON:0002476	64.11	gold quality
inferior vagus X ganglion	UBERON:0005363	64.05	gold quality
ventral tegmental area	UBERON:0002691	64.04	gold quality
superior surface of tongue	UBERON:0007371	63.89	gold quality
substantia nigra pars reticulata	UBERON:0001966	63.88	gold quality
dorsal root ganglion	UBERON:0000044	63.85	gold quality
trigeminal ganglion	UBERON:0001675	63.85	gold quality
pylorus	UBERON:0001166	63.79	gold quality
tongue	UBERON:0001723	63.74	gold quality
body of tongue	UBERON:0011876	63.74	gold quality
vena cava	UBERON:0004087	63.73	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	14.53
E-ANND-3	yes	4.37
E-MTAB-7008	no	73.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting DRAXIN, 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-1184	99.99	68.19	1458
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-376C-3P	97.63	68.88	1263
HSA-MIR-3616-3P	96.96	65.45	983
HSA-MIR-6888-5P	95.89	63.78	831
HSA-MIR-24-1-5P	95.57	65.85	492
HSA-MIR-24-2-5P	95.57	66.16	484
HSA-MIR-659-5P	95.36	65.00	300
HSA-MIR-2861	95.24	65.47	1056
HSA-MIR-431-3P	88.20	62.12	40

Literature-anchored findings (GeneRIF, showing 4)

• Neucrin is a unique secreted Wnt antagonist that is predominantly expressed in developing neural tissues. (PMID:19857465)
• results suggest that draxin functions as a repulsive guidance cue for PCN migration. However, we observed no significant differences in PCN distribution between draxin(-/-) and wild type embryos. (PMID:24832731)
• DRAXIN regulates interhemispheric fissure remodelling to influence the extent of corpus callosum formation. (PMID:33945466)
• DRAXIN as a Novel Diagnostic Marker to Predict the Poor Prognosis of Glioma Patients. (PMID:36040678)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	draxina	ENSDARG00000058256
danio_rerio	draxinb	ENSDARG00000087681
mus_musculus	Draxin	ENSMUSG00000029005
rattus_norvegicus	Draxin	ENSRNOG00000077899

Protein

Protein identifiers

Draxin — Q8NBI3 (reviewed: Q8NBI3)

Alternative names: Dorsal inhibitory axon guidance protein, Dorsal repulsive axon guidance protein, Neucrin

All UniProt accessions (1): Q8NBI3

UniProt curated annotations — full annotation on UniProt →

Function. Chemorepulsive axon guidance protein required for the development of spinal cord and forebrain commissures. Acts as a chemorepulsive guidance protein for commissural axons during development. Able to inhibit or repel neurite outgrowth from dorsal spinal cord. Inhibits the stabilization of cytosolic beta-catenin (CTNNB1) via its interaction with LRP6, thereby acting as an antagonist of Wnt signaling pathway.

Subunit / interactions. Interacts with LRP6.

Subcellular location. Secreted.

Similarity. Belongs to the draxin family.

RefSeq proteins (1): NP_940947* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029094	Draxin	Family

Pfam: PF15550

UniProt features (13 total): region of interest 3, compositionally biased region 3, signal peptide 1, chain 1, sequence conflict 1, strand 1, helix 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6FKQ	X-RAY DIFFRACTION	3.07

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NBI3-F1	58.78	0.16

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 264

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 105 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_NEGATIVE_REGULATION_OF_AXON_EXTENSION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_GROWTH, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_CELL_DIFFERENTIATION_IN_SPINAL_CORD, GOBP_FOREBRAIN_DEVELOPMENT

GO Biological Process (12): axon guidance (GO:0007411), Wnt signaling pathway (GO:0016055), dorsal spinal cord development (GO:0021516), commissural neuron differentiation in spinal cord (GO:0021528), anterior commissure morphogenesis (GO:0021960), negative regulation of axon extension (GO:0030517), forebrain development (GO:0030900), negative regulation of canonical Wnt signaling pathway (GO:0090090), hippocampal neuron apoptotic process (GO:0110088), negative regulation of hippocampal neuron apoptotic process (GO:0110091), negative regulation of neuron projection development (GO:0010977), neuron apoptotic process (GO:0051402)

GO Molecular Function (2): molecular adaptor activity (GO:0060090), 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
anatomical structure development	2
binding	2
axonogenesis	1
neuron projection guidance	1
cell surface receptor signaling pathway	1
spinal cord development	1
cell differentiation in spinal cord	1
central nervous system neuron differentiation	1
telencephalon development	1
central nervous system projection neuron axonogenesis	1
negative regulation of cell growth	1
regulation of axon extension	1
negative regulation of developmental growth	1
axon extension	1
negative regulation of axonogenesis	1
brain development	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
neuron apoptotic process	1
negative regulation of neuron apoptotic process	1
hippocampal neuron apoptotic process	1
regulation of hippocampal neuron apoptotic process	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
apoptotic process	1
molecular_function	1
cellular anatomical structure	1

Protein interactions and networks

STRING

594 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DRAXIN	NEO1	Q92859	732
DRAXIN	DSCAM	O60469	729
DRAXIN	NTN1	O95631	603
DRAXIN	LRP6	O75581	579
DRAXIN	LRP5	O75197	500
DRAXIN	UNC5A	Q6ZN44	487
DRAXIN	SLIT3	O75094	452
DRAXIN	SLIT1	O75093	450
DRAXIN	PMFBP1	Q8TBY8	443
DRAXIN	MAD2L1BP	Q15013	440
DRAXIN	RNF10	Q8N5U6	427
DRAXIN	SMCO4	Q9NRQ5	427
DRAXIN	BICDL1	Q6ZP65	422
DRAXIN	EPHA1	P21709	420
DRAXIN	COQ5	Q5HYK3	409

IntAct

7 interactions, top by confidence:

A	B	Type	Score
DRAXIN	NTN1	psi-mi:“MI:0407”(direct interaction)	0.540
DRAXIN	NTN1	psi-mi:“MI:0915”(physical association)	0.540
ntn1a	DRAXIN	psi-mi:“MI:0915”(physical association)	0.400
DRAXIN	NTN3	psi-mi:“MI:0915”(physical association)	0.400
NTN3	DRAXIN	psi-mi:“MI:0915”(physical association)	0.400

ESM2 similar proteins: A0A1B0GV85, A2ALI5, A2APT9, B0BN44, B1ARY8, B6ZI38, O14836, O35188, O55145, O60279, O60667, P07141, P09603, P0C8S2, P28906, P40225, P40226, P42705, P78423, Q06154, Q08DV9, Q13261, Q1ERP8, Q28270, Q2TB54, Q3UY90, Q4V9H3, Q4W8E7, Q5F267, Q5R770, Q60819, Q64314, Q6PAL1, Q6PCP7, Q6UXB8, Q80XI1, Q8BLK9, Q8CAE9, Q8CBC4, Q8JZQ0

Diamond homologs: B5X1Q3, B5X216, B6ZI38, P0C8S2, Q4V9H3, Q6PAL1, Q8NBI3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1741 predictions. Top by Δscore:

Variant	Effect	Δscore
1:11706669:G:GT	donor_gain	1.0000
1:11706688:G:T	donor_gain	1.0000
1:11709464:AGGTA:A	donor_loss	1.0000
1:11709465:GGTA:G	donor_loss	1.0000
1:11709466:GT:G	donor_loss	1.0000
1:11709467:T:A	donor_loss	1.0000
1:11711840:AC:A	acceptor_gain	1.0000
1:11711841:C:CA	acceptor_gain	1.0000
1:11711849:A:AG	acceptor_gain	1.0000
1:11711850:G:GA	acceptor_gain	1.0000
1:11711850:GCA:G	acceptor_gain	1.0000
1:11711961:GAAAG:G	donor_gain	1.0000
1:11711966:G:GA	donor_loss	1.0000
1:11711966:G:GG	donor_gain	1.0000
1:11711967:T:G	donor_loss	1.0000
1:11712338:A:AG	acceptor_gain	1.0000
1:11712338:AGAGA:A	acceptor_loss	1.0000
1:11712339:G:GG	acceptor_gain	1.0000
1:11712339:GA:G	acceptor_gain	1.0000
1:11712339:GAGA:G	acceptor_gain	1.0000
1:11712339:GAGAA:G	acceptor_gain	1.0000
1:11712426:CCAGG:C	donor_loss	1.0000
1:11712427:CAGG:C	donor_loss	1.0000
1:11712429:GGTAC:G	donor_loss	1.0000
1:11713426:A:AG	acceptor_gain	1.0000
1:11715113:T:A	acceptor_gain	1.0000
1:11715113:TGGCA:T	acceptor_loss	1.0000
1:11715114:GGCA:G	acceptor_loss	1.0000
1:11715115:GCA:G	acceptor_loss	1.0000
1:11715116:CAGGG:C	acceptor_loss	1.0000

AlphaMissense

2263 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:11719643:T:A	C333S	0.999
1:11719644:G:C	C333S	0.999
1:11711913:G:C	W235C	0.998
1:11711913:G:T	W235C	0.998
1:11715181:T:A	C304S	0.998
1:11715182:G:C	C304S	0.998
1:11715183:C:G	C304W	0.998
1:11715199:T:A	C310S	0.998
1:11715199:T:C	C310R	0.998
1:11715200:G:C	C310S	0.998
1:11715201:T:G	C310W	0.998
1:11719592:T:A	C316S	0.998
1:11719592:T:C	C316R	0.998
1:11719593:G:C	C316S	0.998
1:11719594:C:G	C316W	0.998
1:11719643:T:C	C333R	0.998
1:11711905:T:C	F233L	0.997
1:11711907:C:A	F233L	0.997
1:11711907:C:G	F233L	0.997
1:11715127:T:A	C286S	0.997
1:11715128:G:C	C286S	0.997
1:11715148:T:A	C293S	0.997
1:11715149:G:C	C293S	0.997
1:11715181:T:C	C304R	0.997
1:11715200:G:A	C310Y	0.997
1:11711906:T:G	F233C	0.996
1:11715128:G:A	C286Y	0.996
1:11715150:C:G	C293W	0.996
1:11715193:T:A	C308S	0.996
1:11715194:G:A	C308Y	0.996

dbSNP variants (sampled 300 via entrez): RS1000014483 (1:11696728 C>A), RS1000017364 (1:11722999 G>A), RS1000049956 (1:11722632 A>G), RS1000063516 (1:11707782 T>C), RS1000118155 (1:11701844 C>T), RS1000234007 (1:11699798 G>A), RS1000286240 (1:11699981 G>A), RS1000356790 (1:11712865 T>C), RS1000464027 (1:11705583 G>A,T), RS1000516242 (1:11706174 G>T), RS1000562604 (1:11716531 T>C), RS1000589930 (1:11705810 C>T), RS1000619067 (1:11701419 C>T), RS1000633058 (1:11707347 G>A,C), RS1000642176 (1:11711194 AC>A,ACC)

Disease associations

OMIM: gene MIM:612682 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004703_8	Obsessive-compulsive disorder or autism spectrum disorder	7.000000e-06
GCST010654_5	Arterial stiffness (brachial-femoral pulse wave velocity)	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004517	arterial stiffness measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	5
Benzo(a)pyrene	affects methylation, increases expression	3
Aflatoxin B1	increases expression	3
methylmercuric chloride	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
GSK-J4	decreases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
tobacco tar	decreases reaction, increases expression	1
benzo(e)pyrene	increases methylation	1
diallyl disulfide	decreases reaction, increases expression	1
allyl sulfide	decreases reaction, increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
nutlin 3	affects cotreatment, increases expression, increases secretion	1
dorsomorphin	decreases expression, affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression, increases secretion	1
Ethyl Methanesulfonate	increases expression	1
Folic Acid	decreases expression	1
Formaldehyde	increases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Methapyrilene	increases methylation	1

Clinical trials (associated diseases)

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