ASTN2

Summary

ASTN2 (astrotactin 2, HGNC:17021) is a protein-coding gene on chromosome 9q33.1, encoding Astrotactin-2 (O75129). Mediates recycling of the neuronal cell adhesion molecule ASTN1 to the anterior pole of the cell membrane in migrating neurons.

This gene encodes a protein that is expressed in the brain and may function in neuronal migration, based on functional studies of the related astrotactin 1 gene in human and mouse. A deletion at this locus has been associated with schizophrenia. Multiple transcript variants encoding different proteins have been found for this locus.

Source: NCBI Gene 23245 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Moderate, GenCC) — +2 more curated relationships
• GWAS associations: 83
• Clinical variants (ClinVar): 1,124 total — 49 pathogenic, 23 likely-pathogenic
• Phenotypes (HPO): 4
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001365068

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17021
Approved symbol	ASTN2
Name	astrotactin 2
Location	9q33.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0634
Ensembl gene	ENSG00000148219
Ensembl biotype	protein_coding
OMIM	612856
Entrez	23245

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000288520, ENST00000313400, ENST00000341734, ENST00000358637, ENST00000361209, ENST00000361477, ENST00000373986, ENST00000417725, ENST00000882685

RefSeq mRNA: 8 — MANE Select: NM_001365068 NM_001184734, NM_001184735, NM_001365068, NM_001365069, NM_014010, NM_198186, NM_198187, NM_198188

CCDS: CCDS48009, CCDS55334, CCDS6814, CCDS6815, CCDS6816

Canonical transcript exons

ENST00000313400 — 23 exons

Exon	Start	End
ENSE00001597889	116487359	116487500
ENSE00001625659	116442453	116442553
ENSE00001691779	116618324	116618472
ENSE00001697604	116620310	116620443
ENSE00001714268	117141326	117141478
ENSE00001793095	116440609	116440792
ENSE00002248961	116423112	116426088
ENSE00003466819	117039819	117039965
ENSE00003478504	116725771	116725950
ENSE00003480367	117214358	117214742
ENSE00003500722	116820617	116820783
ENSE00003506443	116976701	116976785
ENSE00003534800	116733399	116733523
ENSE00003548124	116805632	116805820
ENSE00003558128	116728992	116729096
ENSE00003567870	116651528	116651793
ENSE00003575259	117291326	117291513
ENSE00003583848	116863583	116863733
ENSE00003596862	116976114	116976188
ENSE00003663230	117096044	117096151
ENSE00003666550	117008092	117008259
ENSE00003679242	116975208	116975345
ENSE00003913301	117414497	117415057

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 94.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.7920 / max 263.2010, expressed in 1485 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102254	3.7606	526
102248	3.2569	1393
102255	0.6779	255
102253	0.0966	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	94.34	gold quality
trigeminal ganglion	UBERON:0001675	91.12	gold quality
dorsal root ganglion	UBERON:0000044	91.05	gold quality
cortical plate	UBERON:0005343	89.47	gold quality
secondary oocyte	CL:0000655	89.22	gold quality
bronchial epithelial cell	CL:0002328	87.29	gold quality
ventral tegmental area	UBERON:0002691	87.24	gold quality
prefrontal cortex	UBERON:0000451	87.01	gold quality
right atrium auricular region	UBERON:0006631	86.73	gold quality
lateral nuclear group of thalamus	UBERON:0002736	86.69	gold quality
paraflocculus	UBERON:0005351	86.66	gold quality
endometrium epithelium	UBERON:0004811	86.36	silver quality
pons	UBERON:0000988	86.29	gold quality
superior vestibular nucleus	UBERON:0007227	86.27	gold quality
cardiac atrium	UBERON:0002081	86.10	gold quality
sperm	CL:0000019	86.06	gold quality
hypothalamus	UBERON:0001898	85.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.81	gold quality
cerebellar vermis	UBERON:0004720	85.76	gold quality
cerebellum	UBERON:0002037	85.65	gold quality
prostate gland	UBERON:0002367	85.64	gold quality
male germ cell	CL:0000015	85.51	gold quality
cerebellar cortex	UBERON:0002129	85.50	gold quality
cerebellar hemisphere	UBERON:0002245	85.38	gold quality
midbrain	UBERON:0001891	85.25	gold quality
substantia nigra	UBERON:0002038	85.18	gold quality
epithelium of bronchus	UBERON:0002031	84.89	gold quality
dorsal plus ventral thalamus	UBERON:0001897	84.79	gold quality
putamen	UBERON:0001874	84.63	gold quality
testis	UBERON:0000473	84.36	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	49.94
E-HCAD-25	yes	16.93
E-MTAB-5061	yes	13.68
E-MTAB-7249	yes	10.86
E-MTAB-6379	no	189.25
E-ENAD-20	no	117.40
E-MTAB-4850	no	38.17
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting ASTN2, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-5011-3P	98.63	64.81	638
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-5007-5P	97.95	64.71	614
HSA-MIR-9851-5P	97.57	67.49	1067
HSA-MIR-4662A-3P	97.02	67.77	941

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 13)

• Single nucleotide polymorphism in ASTN2 gene is associated with cognition disorders. (PMID:22504421)
• 3’ terminal ASTN2 deletions are significantly enriched in males with neurodevelopmental disorders, but not in females. (PMID:24381304)
• Study found a significant association of ASTN2 genetic variants with age at onset in Alzheimer’s disease in two independent samples together with in silico analysis that demonstrated potential role of ASTN2 in the pathogenesis of the disease (PMID:25410587)
• rs4836732 may contribute to hip OA susceptibility by altering proximal femur shape. (PMID:25939412)
• The expression of coding and non-coding genes with SAFB1 cross-link sites was altered by SAFB1 knockdown. The isoform-specific expression of neural cell adhesion molecule (NCAM1) and ASTN2 was influenced by SAFB1. (PMID:26694817)
• The findings of this study do not support a major role of ASTN2 variants in ADHD or its comorbid disorders respective aADHD associated personality traits. (PMID:27138430)
• Results present the structure of ASTN-2 consisting of a combination of polypeptide folds: a perforin-like domain, a minimal epidermal growth factor-like module, a unique form of fibronectin type III domain and an annexin-like domain. Structural and biophysical data show that ASTN-2 binds inositol triphosphates, suggesting a mechanism for membrane recognition or secondary messenger regulation of its activity. (PMID:27249642)
• Our study suggests that the MEF2D, PRDM16 and ASTN2 genes from GWAS are associated with migraine susceptibility, especially migraine without aura , among Chinese patients. It appears that there is no association with serotonin receptor related genes. (PMID:28058730)
• ASTN2 localizes primarily to endocytic and autophagocytic vesicles in the cell soma and in subsets of dendritic spines (PMID:30242134)
• Chimeric RNA ASTN2-PAPPAas aggravates tumor progression and metastasis in human esophageal cancer. (PMID:33388371)
• Effects of rs958804 and rs7858836 single-nucleotide polymorphisms of the ASTN2 gene on pain-related phenotypes in patients who underwent laparoscopic colectomy and mandibular sagittal split ramus osteotomy. (PMID:33476460)
• Rare copy number variants in ASTN2 gene in patients with neurodevelopmental disorders. (PMID:34412080)
• Genetic Variation in the ASTN2 Locus in Cardiovascular, Metabolic and Psychiatric Traits: Evidence for Pleiotropy Rather Than Shared Biology. (PMID:34440368)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000105924
mus_musculus	Astn2	ENSMUSG00000028373
rattus_norvegicus	Astn2	ENSRNOG00000060105

Paralogs (1): ASTN1 (ENSG00000152092)

Protein

Protein identifiers

Astrotactin-2 — O75129 (reviewed: O75129)

All UniProt accessions (5): O75129, A0A0A0MRH9, H0Y3A8, H7C3I6, X6R5P2

UniProt curated annotations — full annotation on UniProt →

Function. Mediates recycling of the neuronal cell adhesion molecule ASTN1 to the anterior pole of the cell membrane in migrating neurons. Promotes ASTN1 internalization and intracellular transport of endocytosed ASTN1. Selectively binds inositol-4,5-bisphosphate, inositol-3,4,5-trisphosphate and inositol-1,3,4,5-tetrakisphosphate, suggesting it is recruited to membranes that contain lipids with a phosphoinositide headgroup (Ref.6).

Subunit / interactions. Interacts with ASTN1; the interaction is not calcium-dependent.

Subcellular location. Membrane. Perikaryon. Cytoplasm. Cell cortex. Early endosome. Late endosome. Cytoplasmic vesicle. Clathrin-coated vesicle.

Domain organisation. The C-terminal region after the fibronectin type-III domain presents structural similarity to annexin domains and binds calcium ions.

Similarity. Belongs to the astrotactin family.

Isoforms (5)

UniProt ID	Names	Canonical?
O75129-1	1	yes
O75129-2	2
O75129-3	3
O75129-4	4
O75129-6	6

RefSeq proteins (8): NP_001171663, NP_001171664, NP_001351997, NP_001351998, NP_054729, NP_937829, NP_937830, NP_937831 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR020864	MACPF	Domain
IPR026995	Astrotactin	Family
IPR036116	FN3_sf	Homologous_superfamily
IPR040510	ASTN_2_hairpin	Domain
IPR040685	Annexin-like	Domain
IPR045574	ASTN1_2_Fn3	Domain
IPR045575	ASTN_1_2_N	Domain

Pfam: PF01823, PF18411, PF18577, PF19441, PF19743

UniProt features (99 total): strand 28, disulfide bond 17, helix 16, turn 7, splice variant 6, sequence variant 6, domain 4, glycosylation site 4, topological domain 3, region of interest 2, transmembrane region 2, signal peptide 1, chain 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5J67	X-RAY DIFFRACTION	3.16
5J69	X-RAY DIFFRACTION	3.63
5J68	X-RAY DIFFRACTION	5.22

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75129-F1	64.93	0.31

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 (17): 514–526, 522–533, 535–549, 655–668, 662–679, 681–694, 703–715, 711–735, 737–750, 825–987, 916–977, 983–990, 1036–1047, 1049–1062, 1136–1158, 1190–1277, 1298–1321

Glycosylation sites (4): 168, 770, 783, 1020

Mutagenesis-validated functional residues (1):

Position	Phenotype
1175	abolishes inositol-4,5-bisphosphate binding. strongly reduces affinity for inositol-3,4,5-trisphosphate.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 140 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, WANG_CLIM2_TARGETS_UP, BENPORATH_ES_WITH_H3K27ME3, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_CELL_CELL_ADHESION, ONKEN_UVEAL_MELANOMA_UP, GOBP_REGULATION_OF_PROTEIN_LOCALIZATION_TO_CELL_SURFACE, THEODOROU_MAMMARY_TUMORIGENESIS, GOCC_COATED_VESICLE, GOBP_NEURON_MIGRATION, GOBP_NEURON_CELL_CELL_ADHESION, GOBP_PROTEIN_LOCALIZATION_TO_CELL_SURFACE

GO Biological Process (6): neuron migration (GO:0001764), neuron cell-cell adhesion (GO:0007158), protein transport (GO:0015031), protein localization to cell surface (GO:0034394), establishment of body hair planar orientation (GO:0048105), negative regulation of protein localization to cell surface (GO:2000009)

GO Molecular Function (4): calcium ion binding (GO:0005509), inositol 1,3,4,5 tetrakisphosphate binding (GO:0043533), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (10): endosome (GO:0005768), early endosome (GO:0005769), late endosome (GO:0005770), cell cortex (GO:0005938), membrane (GO:0016020), clathrin-coated vesicle (GO:0030136), perikaryon (GO:0043204), cell pole (GO:0060187), cytoplasm (GO:0005737), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular protein localization	2
endosome	2
cytoplasm	2
cell migration	1
generation of neurons	1
cell-cell adhesion	1
transport	1
establishment of protein localization	1
establishment of body hair or bristle planar orientation	1
protein localization to cell surface	1
negative regulation of protein localization	1
regulation of protein localization to cell surface	1
metal ion binding	1
anion binding	1
alcohol binding	1
binding	1
cation binding	1
endomembrane system	1
cytoplasmic vesicle	1
cell periphery	1
coated vesicle	1
neuronal cell body	1
intracellular anatomical structure	1
intracellular vesicle	1

Protein interactions and networks

STRING

1596 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASTN2	FBXO40	Q9UH90	763
ASTN2	CNTN4	Q8IWV2	763
ASTN2	COP1	Q8NHY2	722
ASTN2	NLGN1	Q8N2Q7	709
ASTN2	NLGN4X	Q8N0W4	703
ASTN2	CDH9	Q9ULB4	676
ASTN2	NRXN1	Q9ULB1	667
ASTN2	CDH10	Q9Y6N8	661
ASTN2	NLGN3	Q9NZ94	660
ASTN2	DLGAP2	Q9P1A6	648
ASTN2	TAS2R1	Q9NYW7	635
ASTN2	ATP1A2	P50993	631
ASTN2	PTCHD1	Q96NR3	626
ASTN2	SEMA5A	Q13591	609
ASTN2	TRPM8	Q7Z2W7	582

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ASTN2	CHRM5	psi-mi:“MI:0915”(physical association)	0.370
ASTN2	ALDH3B1	psi-mi:“MI:0914”(association)	0.350
DYRK1A	ASTN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): CCT6B (Affinity Capture-MS), ASTN2 (Affinity Capture-MS), CCT4 (Affinity Capture-MS), ASTN2 (Affinity Capture-RNA), ASTN2 (Two-hybrid), ASTN2 (Affinity Capture-MS), ALDH3B1 (Affinity Capture-MS), RAD50 (Affinity Capture-MS), ASTN2 (Protein-RNA), ASTN2 (Two-hybrid)

ESM2 similar proteins: A0A5F9C6I2, A1L3F5, A2BDA5, A3KGS3, A8E4X8, D3ZXK7, F1R7R1, O75129, P21359, P51593, P97526, Q04690, Q1JPG0, Q2PPJ7, Q3SZD5, Q4QQM5, Q4R5A4, Q5RC14, Q5XPI3, Q5XPI4, Q62717, Q66K64, Q6GLR7, Q6NXD8, Q6P4S8, Q6PFH3, Q6VNB8, Q7L4E1, Q7TMY8, Q7Z6Z7, Q80TJ1, Q86UW7, Q8BHR8, Q8BK03, Q8BYR5, Q8CDG3, Q8CF97, Q8CID0, Q8IY22, Q8IZQ1

Diamond homologs: O14525, O75129, Q61137, Q80Z10

SIGNOR signaling

2 interactions.

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

Disease & clinical

Clinical variants and AI predictions

ClinVar

1124 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	49
Likely pathogenic	23
Uncertain significance	663
Likely benign	272
Benign	28

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069572	NC_000009.11:g.(?119380583)(119495822_?)del	Pathogenic
1072407	NM_012210.4(TRIM32):c.1185dup (p.Gln396fs)	Pathogenic
1076771	NM_012210.4(TRIM32):c.542_543insAAAGGTA (p.Tyr181Ter)	Pathogenic
1391008	NM_012210.4(TRIM32):c.476_477dup (p.Met160fs)	Pathogenic
1424414	NM_012210.4(TRIM32):c.1518_1530del (p.Lys506fs)	Pathogenic
1454351	NM_012210.4(TRIM32):c.868C>T (p.Gln290Ter)	Pathogenic
1460307	NC_000009.11:g.(?119460155)(119508439_?)del	Pathogenic
2127373	NM_012210.4(TRIM32):c.928G>T (p.Glu310Ter)	Pathogenic
2157886	NM_012210.4(TRIM32):c.484del (p.Glu162fs)	Pathogenic
2425778	NC_000009.11:g.(?119461613)(119523251_?)del	Pathogenic
2499117	GRCh37/hg19 9q33.1(chr9:119448976-119461984)x1	Pathogenic
2730382	NM_012210.4(TRIM32):c.885del (p.Lys296fs)	Pathogenic
2739417	NM_012210.4(TRIM32):c.699_700delinsCT (p.Gln234Ter)	Pathogenic
2750372	NM_012210.4(TRIM32):c.921G>A (p.Trp307Ter)	Pathogenic
2750667	NM_012210.4(TRIM32):c.341del (p.Ser114fs)	Pathogenic
2753423	NM_012210.4(TRIM32):c.1188del (p.Val397fs)	Pathogenic
2755842	NM_012210.4(TRIM32):c.741_745dup (p.Ala249fs)	Pathogenic
2768571	NM_012210.4(TRIM32):c.920G>A (p.Trp307Ter)	Pathogenic
2784570	NM_012210.4(TRIM32):c.190del (p.Cys64fs)	Pathogenic
2785051	NM_012210.4(TRIM32):c.1505C>G (p.Ser502Ter)	Pathogenic
2804891	NM_012210.4(TRIM32):c.763G>T (p.Glu255Ter)	Pathogenic
2811384	NM_012210.4(TRIM32):c.201del (p.Thr68fs)	Pathogenic
2813433	NM_012210.4(TRIM32):c.498del (p.Lys167fs)	Pathogenic
2815889	NM_012210.4(TRIM32):c.1563dup (p.Asp522Ter)	Pathogenic
2870901	NM_012210.4(TRIM32):c.1087del (p.Ala363fs)	Pathogenic
2908560	NM_012210.4(TRIM32):c.826C>T (p.Gln276Ter)	Pathogenic
291222	NM_012210.4(TRIM32):c.509T>A (p.Leu170Ter)	Pathogenic
291311	NM_012210.4(TRIM32):c.1365_1366dup (p.Thr456fs)	Pathogenic
3063064	GRCh37/hg19 9q33.1(chr9:119431587-119475882)x1	Pathogenic
3245164	NC_000009.11:g.(?119460022)(119495822_?)del	Pathogenic

SpliceAI

5908 predictions. Top by Δscore:

Variant	Effect	Δscore
9:116440608:C:CA	donor_loss	1.0000
9:116440623:AT:A	donor_gain	1.0000
9:116440624:T:TA	donor_gain	1.0000
9:116440629:A:AC	donor_gain	1.0000
9:116440630:C:CC	donor_gain	1.0000
9:116440630:CTT:C	donor_gain	1.0000
9:116487357:A:AC	donor_gain	1.0000
9:116487358:C:CC	donor_gain	1.0000
9:116613443:ATATC:A	donor_gain	1.0000
9:116613445:ATC:A	donor_gain	1.0000
9:116613447:C:A	donor_gain	1.0000
9:116618322:A:AC	donor_gain	1.0000
9:116618322:ACCTG:A	donor_loss	1.0000
9:116618323:C:CC	donor_gain	1.0000
9:116618469:CAGC:C	acceptor_gain	1.0000
9:116618470:AGC:A	acceptor_gain	1.0000
9:116618471:GC:G	acceptor_gain	1.0000
9:116618471:GCCT:G	acceptor_loss	1.0000
9:116618472:CC:C	acceptor_gain	1.0000
9:116618472:CCTA:C	acceptor_loss	1.0000
9:116618473:C:CC	acceptor_gain	1.0000
9:116618473:CT:C	acceptor_loss	1.0000
9:116618482:A:AC	acceptor_gain	1.0000
9:116651522:GCTCA:G	donor_loss	1.0000
9:116651523:CTCAC:C	donor_loss	1.0000
9:116651524:TCA:T	donor_loss	1.0000
9:116651525:CACC:C	donor_loss	1.0000
9:116651526:A:AG	donor_loss	1.0000
9:116651526:ACCT:A	donor_gain	1.0000
9:116651527:CCTC:C	donor_gain	1.0000

AlphaMissense

8715 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:116440618:A:G	L1258P	1.000
9:116440635:C:A	W1252C	1.000
9:116440635:C:G	W1252C	1.000
9:116440637:A:G	W1252R	1.000
9:116440637:A:T	W1252R	1.000
9:116440737:C:A	Q1218H	1.000
9:116440737:C:G	Q1218H	1.000
9:116618420:A:G	W1087R	1.000
9:116618420:A:T	W1087R	1.000
9:116651640:C:T	C987Y	1.000
9:116651641:A:G	C987R	1.000
9:116651653:A:G	C983R	1.000
9:116725787:C:A	W930C	1.000
9:116725787:C:G	W930C	1.000
9:116725791:A:G	L929P	1.000
9:116725831:A:G	C916R	1.000
9:116729049:A:G	W857R	1.000
9:116729049:A:T	W857R	1.000
9:116733445:G:C	C825W	1.000
9:116733446:C:G	C825S	1.000
9:116733447:A:G	C825R	1.000
9:116733447:A:T	C825S	1.000
9:116805780:A:G	C750R	1.000
9:116820679:G:C	C715W	1.000
9:116820680:C:G	C715S	1.000
9:116820681:A:G	C715R	1.000
9:116820681:A:T	C715S	1.000
9:116820715:G:C	C703W	1.000
9:116820716:C:G	C703S	1.000
9:116820717:A:G	C703R	1.000

dbSNP variants (sampled 300 via entrez): RS1000000125 (9:117381793 C>T), RS1000008110 (9:116674295 G>A,T), RS1000012959 (9:116512616 A>C,G), RS1000013618 (9:117200187 C>A,T), RS1000015499 (9:117189000 T>A), RS1000027570 (9:116609145 G>A,C), RS1000030423 (9:116832753 T>C), RS1000035249 (9:117295457 T>A,C), RS1000035506 (9:116881090 G>A,T), RS1000037988 (9:116915140 C>T), RS1000039852 (9:116710504 G>A), RS1000043099 (9:116422742 G>A,C), RS1000045938 (9:116909118 G>A,C), RS1000049535 (9:117371954 A>C), RS1000050387 (9:116703749 T>C,G)

Disease associations

OMIM: gene MIM:612856 | disease phenotypes: MIM:254110, MIM:615988, MIM:209900, MIM:253600, MIM:209850, MIM:181500, MIM:192600

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Moderate	Semidominant
intellectual disability	Limited	Autosomal dominant
autism spectrum disorder	Limited	Autosomal dominant

Mondo (15): autosomal recessive limb-girdle muscular dystrophy type 2H (MONDO:0009683), Bardet-Biedl syndrome 11 (MONDO:0014439), Bardet-Biedl syndrome (MONDO:0015229), cerebral palsy (MONDO:0006497), autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152), inherited retinal dystrophy (MONDO:0019118), primary ovarian failure (MONDO:0005387), limb-girdle muscular dystrophy (MONDO:0016971), autism (MONDO:0005260), schizophrenia (MONDO:0005090), myopathy (MONDO:0005336), familial hypertrophic cardiomyopathy (MONDO:0024573), intellectual disability (MONDO:0001071), autism spectrum disorder (MONDO:0005258), neurodevelopmental disorder (MONDO:0700092)

Orphanet (9): Bardet-Biedl syndrome (Orphanet:110), TRIM32-related limb-girdle muscular dystrophy R8 (Orphanet:1878), Autosomal recessive limb-girdle muscular dystrophy (Orphanet:102015), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Limb-girdle muscular dystrophy (Orphanet:263), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0100021	Cerebral palsy
HP:0000556	Retinal dystrophy
HP:0000717	Autism
HP:0100753	Schizophrenia

GWAS associations

83 associations (top):

Study	Trait	p-value
GCST000246_5	Attention deficit hyperactivity disorder	1.000000e-07
GCST000618_36	Response to antipsychotic treatment	3.000000e-07
GCST000821_27	Bipolar disorder and schizophrenia	6.000000e-09
GCST001112_4	Lifetime average cigarettes per day in chronic obstructive pulmonary disease	1.000000e-06
GCST001485_5	Hippocampal volume	1.000000e-07
GCST001513_6	Economic and political preferences (fairness)	6.000000e-06
GCST001547_3	Immune response to anthrax vaccine	6.000000e-06
GCST001563_6	Migraine	4.000000e-08
GCST001762_452	Obesity-related traits	2.000000e-06
GCST001784_22	Pulmonary function (smoking interaction)	5.000000e-07
GCST002078_2	Migraine without aura	1.000000e-07
GCST002079_12	Migraine - clinic-based	1.000000e-09
GCST002726_38	Glucose homeostasis traits	9.000000e-06
GCST003720_32	Migraine	1.000000e-12
GCST003721_5	Migraine without aura	1.000000e-10
GCST003918_7	Idiopathic osteonecrosis of the femoral head	7.000000e-06
GCST003986_19	Migraine	2.000000e-08
GCST004185_56	Lung function (FEV1/FVC)	4.000000e-07
GCST004292_21	Glomerular filtration rate (creatinine)	2.000000e-08
GCST004485_14	Survival in pancreatic cancer	9.000000e-07
GCST004557_14	Body mass index	1.000000e-08
GCST004557_199	Body mass index	2.000000e-06
GCST004557_228	Body mass index	1.000000e-08
GCST004557_98	Body mass index	9.000000e-07
GCST004558_11	Body mass index (joint analysis main effects and physical activity interaction)	2.000000e-08
GCST004558_148	Body mass index (joint analysis main effects and physical activity interaction)	2.000000e-08
GCST004558_170	Body mass index (joint analysis main effects and physical activity interaction)	3.000000e-06
GCST004558_96	Body mass index (joint analysis main effects and physical activity interaction)	3.000000e-06
GCST004559_129	Body mass index in physically active individuals	6.000000e-06
GCST004559_49	Body mass index in physically active individuals	9.000000e-06

EFO canonical traits (29, from GWAS)

EFO ID	Trait name
EFO:0005035	hippocampal volume
EFO:0004827	economic and social preference
EFO:0004645	response to vaccine
EFO:0004736	aspartate aminotransferase measurement
EFO:0003892	pulmonary function measurement
EFO:0004314	forced expiratory volume
EFO:0006831	acute insulin response measurement
EFO:1001930	idiopathic osteonecrosis of the femoral head
EFO:0004713	FEV/FVC ratio
EFO:0000638	overall survival
EFO:0004340	body mass index
EFO:0008002	physical activity measurement
EFO:0009396	hippocampal CA4 volume
EFO:0004685	hip geometry
EFO:0009595	guilt measurement
EFO:0009270	heel bone mineral density
EFO:0009707	fractures, ununited
EFO:0009718	peak expiratory flow
EFO:0009939	Antimigraine preparation use measurement
EFO:0010100	multisite chronic pain
EFO:0009658	adverse effect
EFO:0010448	3-hydroxyphenylacetic acid measurement
EFO:0004462	PR interval
EFO:0004346	neuroimaging measurement
EFO:0007918	response to anti-tuberculosis drug
EFO:0008039	BMI-adjusted hip circumference
EFO:0004531	urate measurement
EFO:0004980	appendicular lean mass
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (12)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D020788	Bardet-Biedl Syndrome	C10.228.140.617.200; C11.270.684.624; C16.131.077.245.125; C16.320.184.125
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D002547	Cerebral Palsy	C10.228.140.140.254
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D049288	Muscular Dystrophies, Limb-Girdle	C05.651.534.500.280; C10.668.491.175.500.149; C16.320.577.280
D065886	Neurodevelopmental Disorders	F03.625
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
D058499	Retinal Dystrophies	C11.768.585.658
C565920	Bardet-Biedl Syndrome 11 (supp.)
C538640	Limb-girdle muscular dystrophy autosomal recessive (supp.)
C535897	Limb-girdle muscular dystrophy type 2H (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs7858836	Dosage	3	fentanyl	Pain;Postoperative
rs958804	Dosage	3	fentanyl	Pain;Postoperative

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6478241	ASTN2		0.00	0
rs117491755	ASTN2		0.00	0
rs958804	ASTN2	3	3.25	1	fentanyl
rs7858836	ASTN2	3	3.25	1	fentanyl

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	9
Benzo(a)pyrene	affects expression, affects methylation, decreases expression	5
Aflatoxin B1	affects expression, decreases methylation, increases expression, increases methylation	4
Cisplatin	affects expression, decreases expression, increases expression	3
bisphenol A	affects methylation, affects cotreatment, increases methylation, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Nickel	decreases expression	2
Cyclosporine	affects expression, decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
testosterone enanthate	affects expression	1
chloroacetaldehyde	increases expression	1
propionaldehyde	increases expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
sodium arsenite	affects methylation	1
benzo(e)pyrene	increases methylation	1
rutecarpine	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Arsenicals	increases methylation	1

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_VK73	PNUi001-A	Induced pluripotent stem cell	Male
CVCL_VK74	PNUi001-B	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00154830	PHASE4	COMPLETED	Alterations of Functional Activities and Leg Stiffness After Hamstring Lengthening in Cerebral Palsy Children
NCT00432055	PHASE4	COMPLETED	Effects of Botulinum Toxin Type A in Adults With Cerebral Palsy
NCT00549471	PHASE4	TERMINATED	Improvement After Botulinum Toxin Injections to the Arms in Children With Cerebral Palsy
NCT00752934	PHASE4	TERMINATED	Does Oral Baclofen Improve Care and Comfort in Spastic Children in Nursing Homes?
NCT00964639	PHASE4	COMPLETED	Postoperative Pain in Children With Cerebral Palsy After Pelvic and Femoral Osteotomies
NCT01386255	PHASE4	WITHDRAWN	Placebo Controlled Study of Baclofen for GERD in Children With Cerebral Palsy
NCT02546999	PHASE4	COMPLETED	Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?
NCT02633241	PHASE4	COMPLETED	A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic Resonance Imaging
NCT03117322	PHASE4	COMPLETED	Synbiotic, Prebiotics and Probiotics in Children With Cerebral Palsy and Constipation
NCT03648658	PHASE4	UNKNOWN	Paracetamol Study in Patients With Low Muscle Mass
NCT04074265	PHASE4	COMPLETED	Peri-operative Use of a Pain Injection in Pediatric Patients With Cerebral Palsy
NCT04273737	PHASE4	TERMINATED	Amantadine in Treating Cognitive & Motor Impairments in Adolescents and Adults With Cerebral Palsy
NCT04523935	PHASE4	COMPLETED	Excessive Crying in Children With Cerebral Palsy and Communication Deficits
NCT05887765	PHASE4	COMPLETED	Effect of Systematic Dexamethasone on the Duration of Popliteal Nerve Block for Anesthesia After Pediatric Ankle Surgery
NCT06176430	PHASE4	UNKNOWN	Comparison of Twice Weekly Versus Daily Iron Therapy in Treating Anemia in Children With Cerebral Palsy