ASTN1

Summary

ASTN1 (astrotactin 1, HGNC:773) is a protein-coding gene on chromosome 1q25.2, encoding Astrotactin-1 (O14525). Neuronal adhesion molecule that is required for normal migration of young postmitotic neuroblasts along glial fibers, especially in the cerebellum.

Astrotactin is a neuronal adhesion molecule required for glial-guided migration of young postmitotic neuroblasts in cortical regions of developing brain, including cerebrum, hippocampus, cerebellum, and olfactory bulb (Fink et al., 1995).

Source: NCBI Gene 460 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cerebral malformation (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 200 total — 2 likely-pathogenic
• MANE Select transcript: NM_004319

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:773
Approved symbol	ASTN1
Name	astrotactin 1
Location	1q25.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000152092
Ensembl biotype	protein_coding
OMIM	600904
Entrez	460

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000281881, ENST00000361833, ENST00000367657, ENST00000424564, ENST00000473640, ENST00000850957, ENST00000915515

RefSeq mRNA: 4 — MANE Select: NM_004319 NM_001286164, NM_001364856, NM_004319, NM_207108

CCDS: CCDS1319, CCDS44280, CCDS65732

Canonical transcript exons

ENST00000361833 — 23 exons

Exon	Start	End
ENSE00001067466	176882859	176882994
ENSE00001067467	176888071	176888204
ENSE00001067469	176884339	176884490
ENSE00001067470	176894562	176894830
ENSE00001067474	176934152	176934340
ENSE00001067481	176876537	176876637
ENSE00001067483	176868844	176869027
ENSE00001067484	176936266	176936370
ENSE00001817191	177164394	177164712
ENSE00001953722	176861067	176864521
ENSE00003477652	176965163	176965237
ENSE00003491697	177030806	177030952
ENSE00003492199	176945926	176946120
ENSE00003496616	177029634	177029741
ENSE00003526655	177023404	177023571
ENSE00003543161	177014791	177014875
ENSE00003568200	176957678	176957828
ENSE00003602566	177032456	177032849
ENSE00003611074	177061078	177061265
ENSE00003626895	176949185	176949351
ENSE00003629401	177024583	177024732
ENSE00003638084	176958345	176958482
ENSE00003664497	176943891	176944018

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 95.12.

FANTOM5 (CAGE): breadth broad, TPM avg 6.8742 / max 208.1936, expressed in 399 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16021	4.0509	328
16025	1.2215	224
16024	0.4307	150
16026	0.2362	109
16030	0.2205	70
16027	0.1808	80
16023	0.1268	67
16022	0.0920	59
16020	0.0828	58
16031	0.0796	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
postcentral gyrus	UBERON:0002581	95.12	gold quality
entorhinal cortex	UBERON:0002728	94.66	gold quality
superior frontal gyrus	UBERON:0002661	94.60	gold quality
parietal lobe	UBERON:0001872	93.95	gold quality
middle temporal gyrus	UBERON:0002771	93.41	gold quality
orbitofrontal cortex	UBERON:0004167	93.01	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.53	gold quality
cortical plate	UBERON:0005343	92.06	gold quality
prefrontal cortex	UBERON:0000451	91.66	gold quality
frontal cortex	UBERON:0001870	91.32	gold quality
ventricular zone	UBERON:0003053	91.22	gold quality
temporal lobe	UBERON:0001871	90.86	gold quality
neocortex	UBERON:0001950	90.80	gold quality
cerebral cortex	UBERON:0000956	90.46	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.29	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.87	gold quality
nucleus accumbens	UBERON:0001882	89.66	gold quality
telencephalon	UBERON:0001893	89.64	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.34	gold quality
right frontal lobe	UBERON:0002810	89.30	gold quality
CA1 field of hippocampus	UBERON:0003881	89.21	gold quality
Brodmann (1909) area 10	UBERON:0013541	89.12	gold quality
cingulate cortex	UBERON:0003027	89.10	gold quality
anterior cingulate cortex	UBERON:0009835	89.00	gold quality
occipital lobe	UBERON:0002021	88.77	gold quality
amygdala	UBERON:0001876	88.61	gold quality
Ammon’s horn	UBERON:0001954	88.58	gold quality
forebrain	UBERON:0001890	88.50	gold quality
primary visual cortex	UBERON:0002436	88.37	gold quality
caudate nucleus	UBERON:0001873	87.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

189 targeting ASTN1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4645-5P	99.98	65.81	1284

Literature-anchored findings (GeneRIF, showing 2)

• Family-based association analysis shows the ASTN1 gene significantly associated with alcohol dependence. (PMID:22488871)
• ASTN1 is associated with immune infiltrates in hepatocellular carcinoma, and inhibits the migratory and invasive capacity of liver cancer via the Wnt/betacatenin signaling pathway. (PMID:32945491)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	astn1	ENSDARG00000068323
mus_musculus	Astn1	ENSMUSG00000026587
rattus_norvegicus	Astn1	ENSRNOG00000005667

Paralogs (1): ASTN2 (ENSG00000148219)

Protein

Protein identifiers

Astrotactin-1 — O14525 (reviewed: O14525)

All UniProt accessions (2): O14525, B1AJS1

UniProt curated annotations — full annotation on UniProt →

Function. Neuronal adhesion molecule that is required for normal migration of young postmitotic neuroblasts along glial fibers, especially in the cerebellum. Required for normal rate of migration of granule cells during brain development and for normal cerebellum development.

Subunit / interactions. Interacts with ASTN2; the interaction is not calcium-dependent.

Subcellular location. Cell membrane. Perikaryon. Endosome. Cytoplasmic vesicle. Clathrin-coated vesicle.

Similarity. Belongs to the astrotactin family.

Isoforms (3)

UniProt ID	Names	Canonical?
O14525-1	2	yes
O14525-2	1
O14525-3	3

RefSeq proteins (4): NP_001273093, NP_001351785, NP_004310, NP_996991 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR020864	MACPF	Domain
IPR026995	Astrotactin	Family
IPR036116	FN3_sf	Homologous_superfamily
IPR040685	Annexin-like	Domain
IPR045574	ASTN1_2_Fn3	Domain
IPR045575	ASTN_1_2_N	Domain

Pfam: PF18411, PF19441, PF19743

UniProt features (46 total): disulfide bond 17, glycosylation site 6, domain 4, sequence variant 4, topological domain 3, sequence conflict 3, modified residue 2, transmembrane region 2, splice variant 2, signal peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14525-F1	64.88	0.19

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 (2): 227, 337

Disulfide bonds (17): 463–475, 471–490, 492–506, 612–625, 619–636, 638–651, 660–672, 668–692, 694–707, 785–951, 876–941, 947–954, 1000–1011, 1013–1026, 1101–1121, 1153–1240, 1261–1284

Glycosylation sites (6): 115, 453, 729, 742, 804, 984

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 161 (showing top): AGGAAGC_MIR5163P, GNF2_RTN1, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, MAZ_Q6, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS, GOBP_CELL_CELL_ADHESION, MORF_ZNF10, GOCC_COATED_VESICLE, GOBP_NEURON_MIGRATION, GOBP_NEURON_CELL_CELL_ADHESION, MORF_EPHA7, MORF_RAB3A, MORF_BMPR2

GO Biological Process (6): neuron migration (GO:0001764), neuron cell-cell adhesion (GO:0007158), locomotory behavior (GO:0007626), cell adhesion (GO:0007155), cell migration (GO:0016477), cell-cell adhesion (GO:0098609)

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

GO Cellular Component (7): endosome (GO:0005768), external side of plasma membrane (GO:0009897), membrane (GO:0016020), clathrin-coated vesicle (GO:0030136), perikaryon (GO:0043204), plasma membrane (GO:0005886), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell migration	1
generation of neurons	1
cell-cell adhesion	1
behavior	1
cellular process	1
cell motility	1
cell adhesion	1
binding	1
endomembrane system	1
cytoplasmic vesicle	1
plasma membrane	1
cell surface	1
side of membrane	1
coated vesicle	1
neuronal cell body	1
membrane	1
cell periphery	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1970 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASTN1	ZNF671	Q8TAW3	582
ASTN1	BRINP1	O60477	530
ASTN1	RXFP3	Q9NSD7	506
ASTN1	C2orf80	Q0P641	488
ASTN1	RELN	P78509	458
ASTN1	BRINP2	Q9C0B6	447
ASTN1	CNTN2	P78432	433
ASTN1	LAMB1	P07942	427
ASTN1	LAMA2	P24043	415
ASTN1	JAG1	P78504	413
ASTN1	RALGPS2	Q86X27	410
ASTN1	LAMC1	P11047	409
ASTN1	EBLN2	Q6P2I7	406
ASTN1	BRINP3	Q76B58	405
ASTN1	AP4E1	Q9UPM8	401

IntAct

8 interactions, top by confidence:

A	B	Type	Score
ASTN1	HSPA9	psi-mi:“MI:0915”(physical association)	0.400
LAMP1	HAX1	psi-mi:“MI:0914”(association)	0.350
CACNA1C	CACNB4	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POM121C	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
DSCAM	ASTN1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): ASTN1 (Affinity Capture-MS), HSPA9 (Proximity Label-MS), ASTN1 (Proximity Label-MS), ASTN1 (Proximity Label-MS), ASTN1 (Proximity Label-MS), ASTN1 (Protein-peptide), KEAP1 (Protein-peptide), KEAP1 (Reconstituted Complex), ASTN1 (Two-hybrid), ASTN1 (Affinity Capture-MS), ASTN1 (Co-fractionation), ASTN1 (Proximity Label-MS)

ESM2 similar proteins: A0A088MLT8, A0JPH4, A2A8U2, A2ATD1, A6QLD2, B1AKI9, B1AL88, B3KU38, O14525, O35757, O75129, P0DPB3, P0DPB4, P12755, P17863, P27424, P49140, P55001, P55002, P85299, P97953, Q3V1G4, Q58CS8, Q5EGE1, Q5QQ56, Q5QQ57, Q60698, Q61137, Q68BL8, Q6DVA0, Q6L8S8, Q6L9W6, Q6S5C2, Q6ZWB6, Q80U62, Q80Z10, Q812A5, Q86Y38, Q8CCS2, Q8JG33

Diamond homologs: O14525, O75129, Q61137, Q80Z10

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ASTN2	“down-regulates quantity”	ASTN1	binding
ASTN1	up-regulates	Neuron_migration

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	164
Likely benign	14
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
3064662	NM_004319.3(ASTN1):c.3334C>T (p.Arg1112Ter)	Likely pathogenic
402149	NM_004319.3(ASTN1):c.2224G>C (p.Gly742Arg)	Likely pathogenic

SpliceAI

5004 predictions. Top by Δscore:

Variant	Effect	Δscore
1:176868845:TGGG:T	donor_gain	1.0000
1:176868854:A:C	donor_gain	1.0000
1:176868858:AT:A	donor_gain	1.0000
1:176869023:TATTT:T	acceptor_gain	1.0000
1:176869025:TTT:T	acceptor_gain	1.0000
1:176869026:TT:T	acceptor_gain	1.0000
1:176869027:TC:T	acceptor_loss	1.0000
1:176869028:C:CA	acceptor_loss	1.0000
1:176869028:C:CC	acceptor_gain	1.0000
1:176876532:CTTA:C	donor_loss	1.0000
1:176876533:TTAC:T	donor_loss	1.0000
1:176876534:TAC:T	donor_loss	1.0000
1:176876638:C:CA	acceptor_loss	1.0000
1:176876639:T:A	acceptor_loss	1.0000
1:176882853:ACT:A	donor_loss	1.0000
1:176882854:CTC:C	donor_loss	1.0000
1:176882854:CTCA:C	donor_gain	1.0000
1:176882855:TCA:T	donor_loss	1.0000
1:176882856:CAC:C	donor_loss	1.0000
1:176882857:A:AC	donor_gain	1.0000
1:176882858:C:CA	donor_gain	1.0000
1:176882858:CA:C	donor_gain	1.0000
1:176882858:CAT:C	donor_gain	1.0000
1:176882858:CATG:C	donor_gain	1.0000
1:176882858:CATGT:C	donor_gain	1.0000
1:176882990:TGTTT:T	acceptor_gain	1.0000
1:176882992:TTT:T	acceptor_gain	1.0000
1:176882995:C:CC	acceptor_gain	1.0000
1:176883000:C:CT	acceptor_gain	1.0000
1:176883000:C:T	acceptor_gain	1.0000

AlphaMissense

8538 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000006158 (1:177124504 C>A,T), RS1000009331 (1:177103770 G>C), RS1000024736 (1:176991481 C>A,T), RS1000026233 (1:177059902 T>C), RS1000040308 (1:176898124 C>G,T), RS1000057265 (1:177039937 A>G), RS1000058554 (1:177100068 G>A,T), RS1000058809 (1:176865218 T>C), RS1000059983 (1:176879869 T>C), RS1000078609 (1:177033549 A>G), RS1000084067 (1:177116925 G>A), RS1000086126 (1:176886526 T>A), RS1000098187 (1:176862724 G>A), RS1000098517 (1:177145315 G>A), RS1000106184 (1:177051225 C>A)

Disease associations

OMIM: gene MIM:600904 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
cerebral malformation	Strong	Autosomal recessive

Mondo (1): (MONDO:0016054)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005174_2	Coronary artery calcified atherosclerotic plaque score in type 2 diabetes	8.000000e-06
GCST90020028_270	Hip circumference adjusted for BMI	4.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
trichostatin A	decreases expression, affects cotreatment	3
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Panobinostat	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
belinostat	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Ethanol	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects response to substance	1
Diethylhexyl Phthalate	decreases expression	1
Smoke	increases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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