CLSTN3

Summary

CLSTN3 (calsyntenin 3, HGNC:18371) is a protein-coding gene on chromosome 12p13.31, encoding Calsyntenin-3 (Q9BQT9). Postsynaptic adhesion molecule that binds to presynaptic neurexins to mediate both excitatory and inhibitory synapse formation.

Enables cell-cell adhesion mediator activity and neurexin family protein binding activity. Involved in L-ascorbic acid metabolic process and regulation of synapse assembly. Predicted to be located in several cellular components, including Golgi membrane; dendrite; and postsynaptic density. Predicted to be part of protein-containing complex. Predicted to be active in several cellular components, including GABA-ergic synapse; lipid droplet; and postsynaptic density membrane.

Source: NCBI Gene 9746 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 170 total
• MANE Select transcript: NM_014718

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18371
Approved symbol	CLSTN3
Name	calsyntenin 3
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	CSTN3, KIAA0726, CDHR14
Ensembl gene	ENSG00000139182
Ensembl biotype	protein_coding
OMIM	611324
Entrez	9746

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 16 protein_coding, 5 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000266546, ENST00000331148, ENST00000534830, ENST00000535313, ENST00000535452, ENST00000535668, ENST00000537408, ENST00000538933, ENST00000539982, ENST00000540931, ENST00000541667, ENST00000541770, ENST00000541953, ENST00000542663, ENST00000544584, ENST00000545663, ENST00000890357, ENST00000890358, ENST00000890359, ENST00000890360, ENST00000890361, ENST00000919283, ENST00000919284, ENST00000919285

RefSeq mRNA: 1 — MANE Select: NM_014718 NM_014718

CCDS: CCDS8575

Canonical transcript exons

ENST00000266546 — 18 exons

Exon	Start	End
ENSE00000936892	7133573	7133768
ENSE00000936901	7143163	7143311
ENSE00000936903	7149523	7149693
ENSE00000936904	7150544	7150689
ENSE00000936905	7150928	7151063
ENSE00001247211	7130371	7130712
ENSE00003487891	7141242	7141404
ENSE00003493639	7157489	7157691
ENSE00003559436	7136829	7137110
ENSE00003559676	7142086	7142139
ENSE00003560480	7148972	7149198
ENSE00003574863	7135804	7135953
ENSE00003582591	7157941	7158945
ENSE00003601094	7133024	7133146
ENSE00003624949	7136206	7136391
ENSE00003668145	7137955	7138067
ENSE00003685517	7135327	7135535
ENSE00003688100	7142869	7143026

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 98.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.3269 / max 232.5130, expressed in 1497 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123897	11.9553	1483
123901	0.1769	86
123898	0.1026	50
123896	0.0660	33
123895	0.0262	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellum	UBERON:0002037	98.96	gold quality
cerebellar cortex	UBERON:0002129	98.96	gold quality
cerebellar hemisphere	UBERON:0002245	98.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.93	gold quality
superior frontal gyrus	UBERON:0002661	98.86	gold quality
primary visual cortex	UBERON:0002436	97.92	gold quality
prefrontal cortex	UBERON:0000451	97.22	gold quality
frontal cortex	UBERON:0001870	97.11	gold quality
right frontal lobe	UBERON:0002810	96.69	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.69	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.60	gold quality
hypothalamus	UBERON:0001898	96.42	gold quality
cerebral cortex	UBERON:0000956	95.94	gold quality
cortical plate	UBERON:0005343	95.55	gold quality
anterior cingulate cortex	UBERON:0009835	95.54	gold quality
brain	UBERON:0000955	95.17	gold quality
right lobe of liver	UBERON:0001114	95.08	gold quality
pituitary gland	UBERON:0000007	95.05	gold quality
islet of Langerhans	UBERON:0000006	94.35	gold quality
adenohypophysis	UBERON:0002196	94.25	gold quality
gall bladder	UBERON:0002110	94.19	gold quality
right ovary	UBERON:0002118	94.08	gold quality
liver	UBERON:0002107	93.94	gold quality
ovary	UBERON:0000992	93.60	gold quality
left ovary	UBERON:0002119	93.53	gold quality
sural nerve	UBERON:0015488	93.35	gold quality
nucleus accumbens	UBERON:0001882	93.32	gold quality
stromal cell of endometrium	CL:0002255	93.23	gold quality
vermiform appendix	UBERON:0001154	92.61	gold quality
mucosa of stomach	UBERON:0001199	92.59	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6058	no	82.30
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting CLSTN3, 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-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-6876-5P	100.00	67.68	2126
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-2355-5P	98.83	65.51	1589

Literature-anchored findings (GeneRIF, showing 6)

• Alcadein and amyloid beta-protein precursor regulates FE65-dependent gene transactivation [alcalpha1, alcbeta, alcgamma] (PMID:15037614)
• The C-terminal fragment but not full-length Cst-3 accumulated in dystrophic neurites surrounding amyloidbeta plaques in Tg2576 mouse and Alzheimer disease brains. (PMID:23499467)
• structure of Calsyntenin 3 and its interaction with neurexin 1alpha (PMID:25352602)
• ApoE expression attenuated intracellular trafficking of APP and Alcbeta (PMID:26213366)
• CLSTN3 gene variant associates with obesity risk and contributes to dysfunction in white adipose tissue. (PMID:35753632)
• CLSTN3beta enforces adipocyte multilocularity to facilitate lipid utilization. (PMID:36477540)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	clstn3	ENSDARG00000073883
mus_musculus	Clstn3	ENSMUSG00000008153
rattus_norvegicus	Clstn3	ENSRNOG00000011156
drosophila_melanogaster	Cals	FBGN0039928
caenorhabditis_elegans		WBGENE00000403

Paralogs (2): CLSTN2 (ENSG00000158258), CLSTN1 (ENSG00000171603)

Protein

Protein identifiers

Calsyntenin-3 — Q9BQT9 (reviewed: Q9BQT9)

Alternative names: Alcadein-beta

All UniProt accessions (7): A0A3B3ISW0, F5H172, F5H5C6, F5H5D7, F5H746, F5H7C7, Q9BQT9

UniProt curated annotations — full annotation on UniProt →

Function. Postsynaptic adhesion molecule that binds to presynaptic neurexins to mediate both excitatory and inhibitory synapse formation. Promotes synapse development by acting as a cell adhesion molecule at the postsynaptic membrane, which associates with both neurexin-alpha and neurexin-beta proteins at the presynaptic membrane. Regulates the balance between excitatory and inhibitory synapses by inhibiting formation of excitatory parallel-fiber synapses and promoting formation of inhibitory synapses in the same neuron. May also be involved in ascorbate (vitamin C) uptake via its interaction with SLC23A2/SVCT2. Complex formation with APBA2 and APP, stabilizes APP metabolism and enhances APBA2-mediated suppression of beta-APP40 secretion, due to the retardation of intracellular APP maturation. Adipose-specific isoform that plays a key role in adaptive thermogenesis. Facilitates the efficient use of stored triglyceride by promoting multilocular morphology of thermogenic adipocytes: acts by inhibiting the activity of CIDEA and CIDEC on lipid droplets, thereby preventing lipid droplet fusion and facilitating lipid utilization. May also participate in adaptive thermogenesis by promoting sympathetic innervation of thermogenic adipose tissue: acts by driving secretion of neurotrophic factor S100B from brown adipocytes, stimulating neurite outgrowth from sympathetic neurons.

Subunit / interactions. Interacts (via cadherin domains) with both alpha and beta isoforms of neurexins (NRXN1, NRXN2 and NRXN3). Directly interacts with APBA2. Forms a tripartite complex with APBA2 and APP. Interacts with low affinity with KLC1. Interacts with SLC23A2/SVCT2. Interacts with CIDEA; inhibiting the lipid transferase activity of CIDEA. Interacts with CIDEC; inhibiting the lipid transferase activity of CIDEC.

Subcellular location. Postsynaptic cell membrane. Endoplasmic reticulum membrane. Golgi apparatus membrane. Cell projection. Dendrite Lipid droplet.

Tissue specificity. According to PubMed:12498782, expressed predominantly in the brain and in kidney. Low levels in heart, skeletal muscle, liver, placenta, pancreas and lung. According to PubMed:12972431, predominant expression in brain, and only marginal in kidney. In brain, present throughout all cortical layers, highest levels in GABAergic neurons (based on morphology and distribution pattern). Expression is restricted to adipose tissue, with high expression in multilocular thermogenic adipocytes (brown adipose tissue).

Post-translational modifications. Proteolytically processed under normal cellular conditions. A primary zeta-cleavage generates a large extracellular (soluble) N-terminal domain (sAlc) and a short C-terminal transmembrane fragment (CTF1). A secondary cleavage catalyzed by gamma-secretase within the transmembrane domain releases the beta-Alc-beta chain in the extracellular milieu and produces an intracellular fragment (AlcICD). This processing is strongly suppressed in the tripartite complex formed with APBA2 and APP, which seems to prevent the association with gamma-secretase. Ubiquitinated: endoplasmic reticulum-localized protein is ubiquitinated and degraded by the endoplasmic reticulum-associated degradation (ERAD) pathway.

Domain organisation. The cytoplasmic domain binds synaptic Ca(2+).

Similarity. Belongs to the calsyntenin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BQT9-1	1	yes
Q9BQT9-2	2
Q9BQT9-3	CLSTN3beta

RefSeq proteins (1): NP_055533* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002126	Cadherin-like_dom	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR015919	Cadherin-like_sf	Homologous_superfamily
IPR045588	CLSTN_C	Domain

Pfam: PF19699

UniProt features (29 total): topological domain 7, glycosylation site 5, sequence variant 3, intramembrane region 3, splice variant 2, transmembrane region 2, domain 2, compositionally biased region 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-Q9BQT9-F1	77.80	0.47

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 (5): 299, 327, 347, 507, 740

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 251 (showing top): ATF_B, GOBP_REGULATION_OF_LIPID_STORAGE, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_SYNAPSE_ASSEMBLY, GCANCTGNY_MYOD_Q6, SP3_Q3, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (26): regulation of cell growth (GO:0001558), homophilic cell-cell adhesion (GO:0007156), synapse assembly (GO:0007416), protein secretion (GO:0009306), negative regulation of lipid storage (GO:0010888), L-ascorbic acid metabolic process (GO:0019852), synaptic transmission, glutamatergic (GO:0035249), positive regulation of synaptic transmission (GO:0050806), positive regulation of lipid catabolic process (GO:0050996), synaptic transmission, GABAergic (GO:0051932), regulation of synapse assembly (GO:0051963), positive regulation of synapse assembly (GO:0051965), sympathetic neuron projection extension (GO:0097490), cold-induced thermogenesis (GO:0106106), negative regulation of lipid droplet fusion (GO:0160078), positive regulation of protein localization to synapse (GO:1902474), excitatory synapse assembly (GO:1904861), inhibitory synapse assembly (GO:1904862), regulation of excitatory synapse assembly (GO:1904889), negative regulation of excitatory synapse assembly (GO:1904890), regulation of presynapse assembly (GO:1905606), positive regulation of inhibitory synapse assembly (GO:1905704), adaptive thermogenesis (GO:1990845), cell adhesion (GO:0007155), cell-cell adhesion (GO:0098609), lipid droplet fusion (GO:0160077)

GO Molecular Function (5): enzyme inhibitor activity (GO:0004857), calcium ion binding (GO:0005509), neurexin family protein binding (GO:0042043), cell-cell adhesion mediator activity (GO:0098632), protein binding (GO:0005515)

GO Cellular Component (18): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), lipid droplet (GO:0005811), cell surface (GO:0009986), dendrite (GO:0030425), protein-containing complex (GO:0032991), organelle membrane contact site (GO:0044232), postsynaptic membrane (GO:0045211), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), membrane (GO:0016020), cell projection (GO:0042995), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
synapse assembly	4
cellular anatomical structure	4
chemical synaptic transmission	3
cell-cell adhesion	2
regulation of synapse assembly	2
excitatory synapse assembly	2
synapse	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
cell growth	1
regulation of growth	1
regulation of cellular component organization	1
nervous system development	1
cell junction assembly	1
synapse organization	1
protein transport	1
secretion by cell	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
regulation of lipid storage	1
lipid storage	1
negative regulation of cellular process	1
negative regulation of lipid localization	1
monosaccharide metabolic process	1
carboxylic acid metabolic process	1
lactone metabolic process	1
positive regulation of cell communication	1
positive regulation of signaling	1
modulation of chemical synaptic transmission	1
positive regulation of catabolic process	1
lipid catabolic process	1
positive regulation of lipid metabolic process	1
regulation of lipid catabolic process	1
regulation of synapse organization	1
regulation of cell junction assembly	1
positive regulation of nervous system development	1
positive regulation of cell junction assembly	1
neuron projection extension	1
adaptive thermogenesis	1

Protein interactions and networks

STRING

1066 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLSTN3	NRXN1	Q9ULB1	713
CLSTN3	CDH17	Q12864	690
CLSTN3	NRXN2	Q9P2S2	678
CLSTN3	NXN	Q6DKJ4	644
CLSTN3	LRRTM1	Q86UE6	595
CLSTN3	ERP27	Q96DN0	491
CLSTN3	FARP1	Q9Y4F1	465
CLSTN3	SH3BP5L	Q7L8J4	460
CLSTN3	GABBR1	Q9UBS5	455
CLSTN3	CBLN1	P02682	449
CLSTN3	IGSF21	Q96ID5	435
CLSTN3	PEX5	P50542	419
CLSTN3	MDGA1	Q8NFP4	415
CLSTN3	PLXND1	Q9Y4D7	411
CLSTN3	SHANK2	Q9UPX8	408

IntAct

100 interactions, top by confidence:

A	B	Type	Score
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
ZDHHC22	CLSTN3	psi-mi:“MI:0915”(physical association)	0.560
OLFM4	CLSTN3	psi-mi:“MI:0915”(physical association)	0.560
TMEM107	CLSTN3	psi-mi:“MI:0915”(physical association)	0.560
MAL	CLSTN3	psi-mi:“MI:0915”(physical association)	0.560
TRAM1L1	CLSTN3	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	CLSTN3	psi-mi:“MI:0915”(physical association)	0.560
CLSTN3	PGAP2	psi-mi:“MI:0915”(physical association)	0.560
TMEM97	CLSTN3	psi-mi:“MI:0915”(physical association)	0.560
TMEM54	CLSTN3	psi-mi:“MI:0915”(physical association)	0.560
NKG7	CLSTN3	psi-mi:“MI:0915”(physical association)	0.560
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
SCNN1D	ABHD16A	psi-mi:“MI:0914”(association)	0.530
CTSG	MANBA	psi-mi:“MI:0914”(association)	0.530
CMA1	MANBA	psi-mi:“MI:0914”(association)	0.530
APBA3	CLSTN1	psi-mi:“MI:0914”(association)	0.530
CLSTN3	APOE	psi-mi:“MI:0915”(physical association)	0.400
ST8SIA4	NRP1	psi-mi:“MI:0914”(association)	0.350
incE	STX7	psi-mi:“MI:0914”(association)	0.350
CACNA1C	DISP2	psi-mi:“MI:0914”(association)	0.350
HLA-DQB1	ESYT2	psi-mi:“MI:0914”(association)	0.350
TMEM106A	QSOX1	psi-mi:“MI:0914”(association)	0.350
B3GAT2	FAM20B	psi-mi:“MI:0914”(association)	0.350

BioGRID (76): CLSTN3 (Affinity Capture-RNA), CLSTN3 (Affinity Capture-MS), CLSTN3 (Affinity Capture-MS), CLSTN3 (Affinity Capture-MS), CLSTN3 (Affinity Capture-RNA), CLSTN3 (Affinity Capture-MS), CLSTN3 (Two-hybrid), CLSTN3 (Two-hybrid), CLSTN3 (Two-hybrid), CLSTN3 (Two-hybrid), PGAP2 (Two-hybrid), CMTM7 (Two-hybrid), MAL (Two-hybrid), TRAM1L1 (Two-hybrid), ZDHHC22 (Two-hybrid)

ESM2 similar proteins: A0A0R4IKU3, A0A8M9PFP2, A1A5Y0, A2A863, A2VCU8, A5A6L1, B0S5G3, L7VG99, O00622, O08841, O35118, O42493, O93512, P08163, P08833, P16042, P16144, P17668, P18406, Q07663, Q0VCN6, Q13753, Q501P1, Q53RD9, Q5R9Q9, Q61220, Q61592, Q64632, Q6DDW2, Q7T3Q2, Q7ZV46, Q7ZXL5, Q8R4Y4, Q8R553, Q8VDA1, Q91166, Q91167, Q91713, Q99JH7, Q9BQT9

Diamond homologs: A0A8M9PFP2, B0S5G3, F1R520, O02840, O55111, O88278, O94985, P30944, P33151, P55287, P55288, Q0VCN6, Q14517, Q5DRC8, Q5R9Q9, Q63418, Q6Q0N0, Q6URK6, Q6V1P9, Q86UP0, Q8BNA6, Q8R553, Q8VDA1, Q96JQ0, Q99JH7, Q9BQT9, Q9EPL2, Q9ER65, Q9H4D0, Q9HCU4, Q9NYQ6, Q9R0M0, P55289, Q5DRA8, Q5DRE0, Q6V0I7, Q967F4, Q9UN71, Q9V498, Q9VW71

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 111 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 T cell mediated cytotoxicity	5	25.5×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	135
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3434 predictions. Top by Δscore:

Variant	Effect	Δscore
12:7128235:TGTA:T	donor_loss	1.0000
12:7128236:GTAC:G	donor_loss	1.0000
12:7128237:TACCT:T	donor_loss	1.0000
12:7128238:A:C	donor_loss	1.0000
12:7128239:C:G	donor_loss	1.0000
12:7128701:A:AC	donor_gain	1.0000
12:7128702:C:CC	donor_gain	1.0000
12:7128705:A:AC	donor_gain	1.0000
12:7128705:AGGG:A	donor_gain	1.0000
12:7128706:G:C	donor_gain	1.0000
12:7130710:AAGG:A	donor_loss	1.0000
12:7133010:T:A	acceptor_gain	1.0000
12:7133012:G:GA	acceptor_gain	1.0000
12:7133015:T:TA	acceptor_gain	1.0000
12:7133148:T:G	donor_loss	1.0000
12:7133567:T:A	acceptor_gain	1.0000
12:7133569:CCAG:C	acceptor_loss	1.0000
12:7133570:CAG:C	acceptor_loss	1.0000
12:7133571:A:AG	acceptor_gain	1.0000
12:7133571:AG:A	acceptor_gain	1.0000
12:7133571:AGGT:A	acceptor_gain	1.0000
12:7133572:G:GG	acceptor_gain	1.0000
12:7133572:GG:G	acceptor_gain	1.0000
12:7133572:GGT:G	acceptor_gain	1.0000
12:7133572:GGTG:G	acceptor_gain	1.0000
12:7133572:GGTGA:G	acceptor_gain	1.0000
12:7133716:GCC:G	donor_gain	1.0000
12:7133757:G:GT	donor_gain	1.0000
12:7133766:CAAGT:C	donor_loss	1.0000
12:7133767:AAGT:A	donor_loss	1.0000

AlphaMissense

6295 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:7133039:C:A	P27Q	1.000
12:7133056:T:G	Y33D	1.000
12:7133057:A:G	Y33C	1.000
12:7133062:G:C	G35R	1.000
12:7133069:T:A	V37D	1.000
12:7133090:T:A	V44D	1.000
12:7133108:T:A	L50H	1.000
12:7133114:C:A	A52D	1.000
12:7133120:A:C	D54A	1.000
12:7133588:T:C	F68S	1.000
12:7133588:T:G	F68C	1.000
12:7133645:G:A	G87E	1.000
12:7133651:G:A	G89E	1.000
12:7133657:T:A	I91N	1.000
12:7135335:T:A	V131E	1.000
12:7135353:A:T	D137V	1.000
12:7135359:A:T	N139I	1.000
12:7135360:C:A	N139K	1.000
12:7135360:C:G	N139K	1.000
12:7135371:C:A	P143Q	1.000
12:7135371:C:G	P143R	1.000
12:7135377:T:C	F145S	1.000
12:7135377:T:G	F145C	1.000
12:7135457:G:C	D172H	1.000
12:7135458:A:C	D172A	1.000
12:7135458:A:G	D172G	1.000
12:7135458:A:T	D172V	1.000
12:7135484:T:A	C181S	1.000
12:7135484:T:C	C181R	1.000
12:7135485:G:A	C181Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000052341 (12:7155076 C>A,G,T), RS1000096304 (12:7154707 A>G), RS1000159541 (12:7144880 G>A), RS1000670307 (12:7133265 G>A,T), RS1000695341 (12:7156047 G>A), RS1000769358 (12:7157131 G>A), RS1000942577 (12:7139060 A>G), RS1000971956 (12:7138644 C>T), RS1001053488 (12:7143655 G>A,T), RS1001128776 (12:7155878 C>T), RS1001204659 (12:7145462 G>A), RS1001243568 (12:7133242 T>A,C,G), RS1001317177 (12:7143468 C>G,T), RS1001563162 (12:7157185 G>A,T), RS1001572580 (12:7155687 G>A)

Disease associations

OMIM: gene MIM:611324 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): autism spectrum disorder (MONDO:0005258)

Orphanet (1): NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003542_196	Night sleep phenotypes	5.000000e-06
GCST007201_40	Schizophrenia	1.000000e-06
GCST010002_206	Refractive error	3.000000e-62

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
aristolochic acid I	increases expression	1
uranyl acetate	affects expression	1
bisphenol A	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
cupric chloride	decreases expression	1
CGP 52608	affects binding, increases reaction	1
ON 01910	affects expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	increases expression	1
Chelating Agents	affects binding, decreases expression	1
Copper	affects binding, decreases expression	1
Dexamethasone	decreases expression	1
Lead	affects expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Niclosamide	increases expression	1
Selenomethionine	affects expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	increases expression	1
Uranium	affects expression	1
Valproic Acid	affects expression	1
Isotretinoin	decreases expression	1
Gold Compounds	increases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder