ANK3

Summary

ANK3 (ankyrin 3, HGNC:494) is a protein-coding gene on chromosome 10q21.2, encoding Ankyrin-3 (Q12955). Membrane-cytoskeleton linker.

Ankyrins are a family of proteins that are believed to link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact, and the maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. Ankyrin 3 is an immunologically distinct gene product from ankyrins 1 and 2, and was originally found at the axonal initial segment and nodes of Ranvier of neurons in the central and peripheral nervous systems. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 288 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability-hypotonia-spasticity-sleep disorder syndrome (Strong, GenCC) — +4 more curated relationships
• GWAS associations: 34
• Clinical variants (ClinVar): 1,863 total — 16 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 18
• MANE Select transcript: NM_020987

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:494
Approved symbol	ANK3
Name	ankyrin 3
Location	10q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000151150
Ensembl biotype	protein_coding
OMIM	600465
Entrez	288

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 26 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000280772, ENST00000355288, ENST00000373815, ENST00000373820, ENST00000373827, ENST00000459732, ENST00000460468, ENST00000465749, ENST00000467420, ENST00000469721, ENST00000474360, ENST00000480699, ENST00000486349, ENST00000489505, ENST00000502769, ENST00000503366, ENST00000503925, ENST00000506635, ENST00000508449, ENST00000510382, ENST00000511043, ENST00000513049, ENST00000514197, ENST00000610321, ENST00000610901, ENST00000612776, ENST00000613207, ENST00000616444, ENST00000617800, ENST00000618080, ENST00000621739, ENST00000622427, ENST00000850961, ENST00000870520

RefSeq mRNA: 5 — MANE Select: NM_020987 NM_001149, NM_001204403, NM_001204404, NM_001320874, NM_020987

CCDS: CCDS55711, CCDS55712, CCDS7258, CCDS7259

Canonical transcript exons

ENST00000280772 — 44 exons

Exon	Start	End
ENSE00000997921	60068637	60076448
ENSE00000997958	60166591	60166653
ENSE00001671026	60067935	60068009
ENSE00001698969	60064157	60064288
ENSE00001736354	60080537	60080618
ENSE00001784875	60063111	60063254
ENSE00001804622	60082150	60082176
ENSE00002433170	60278774	60278872
ENSE00002439064	60279538	60279639
ENSE00002442133	60213412	60213510
ENSE00002464646	60279050	60279148
ENSE00002466964	60208036	60208233
ENSE00002494227	60263835	60264020
ENSE00002496568	60059340	60059430
ENSE00002505030	60270131	60270229
ENSE00002514748	60261859	60261957
ENSE00002724313	60389425	60389875
ENSE00003228681	60055658	60056036
ENSE00003243449	60084602	60084830
ENSE00003245801	60196145	60196243
ENSE00003250824	60200129	60200227
ENSE00003258471	60172900	60172998
ENSE00003262936	60114225	60114331
ENSE00003308778	60082615	60082737
ENSE00003338886	60105905	60106059
ENSE00003344568	60205792	60205890
ENSE00003357067	60203002	60203100
ENSE00003361820	60172308	60172403
ENSE00003369360	60186715	60186912
ENSE00003370097	60085157	60085253
ENSE00003371478	60086677	60086884
ENSE00003383580	60196527	60196625
ENSE00003393611	60173088	60173186
ENSE00003397271	60198340	60198537
ENSE00003406141	60181329	60181427
ENSE00003432083	60166824	60166896
ENSE00003440301	60088147	60088358
ENSE00003564421	60042672	60042759
ENSE00003570080	60083492	60083617
ENSE00003641362	60138964	60139087
ENSE00003705532	60026298	60029826
ENSE00003784812	60134271	60134373
ENSE00003790866	60108830	60109054
ENSE00003790898	60234688	60234786

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 99.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.3008 / max 1334.8861, expressed in 1226 samples.

FANTOM5 promoters (46 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109520	3.4318	169
109553	2.9180	487
109543	2.4487	340
109521	2.2585	150
109538	1.0812	249
109541	0.9206	142
109498	0.8472	287
109513	0.8446	215
109545	0.8182	310
109500	0.7707	316

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.84	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.74	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.68	gold quality
middle temporal gyrus	UBERON:0002771	99.58	gold quality
CA1 field of hippocampus	UBERON:0003881	99.44	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.42	gold quality
inferior olivary complex	UBERON:0002127	99.37	gold quality
postcentral gyrus	UBERON:0002581	99.33	gold quality
cerebellar vermis	UBERON:0004720	99.32	gold quality
substantia nigra pars compacta	UBERON:0001965	99.23	gold quality
parietal lobe	UBERON:0001872	99.19	gold quality
corpus epididymis	UBERON:0004359	99.19	gold quality
heart right ventricle	UBERON:0002080	99.18	gold quality
orbitofrontal cortex	UBERON:0004167	99.16	gold quality
seminal vesicle	UBERON:0000998	99.15	gold quality
paraflocculus	UBERON:0005351	99.12	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.08	gold quality
pons	UBERON:0000988	99.07	gold quality
lateral globus pallidus	UBERON:0002476	99.04	gold quality
entorhinal cortex	UBERON:0002728	99.03	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.02	gold quality
nephron tubule	UBERON:0001231	98.97	gold quality
bronchial epithelial cell	CL:0002328	98.96	gold quality
jejunal mucosa	UBERON:0000399	98.96	gold quality
parotid gland	UBERON:0001831	98.96	gold quality
corpus callosum	UBERON:0002336	98.93	gold quality
middle frontal gyrus	UBERON:0002702	98.77	gold quality
primary visual cortex	UBERON:0002436	98.74	gold quality
occipital lobe	UBERON:0002021	98.70	gold quality
cortical plate	UBERON:0005343	98.61	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	3784.28
E-HCAD-35	yes	80.70
E-MTAB-7316	yes	39.31
E-CURD-119	yes	27.46
E-GEOD-135922	yes	22.58
E-HCAD-11	yes	21.73
E-MTAB-8410	yes	21.29
E-GEOD-137537	yes	20.69
E-GEOD-93593	yes	14.92
E-CURD-46	yes	14.66
E-HCAD-5	yes	11.98
E-GEOD-130148	yes	8.76
E-GEOD-81608	yes	7.51
E-GEOD-84465	yes	6.62
E-MTAB-10553	yes	5.16

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
SCN5A	Activation

Upstream regulators (CollecTRI, top): HNF4A, TCF12

miRNA regulators (miRDB)

204 targeting ANK3, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-548AW	99.99	72.57	3559
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-4775	99.98	75.00	6394
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593

Literature-anchored findings (GeneRIF, showing 40)

• The ankyrin-B C-terminal domain determines activity of ankyrin-B/G chimeras (PMID:11781319)
• Ankyrin G, a key protein of membrane remodeling after axonal injury, colocalizes with voltage gated sodium channels in human neuroma. (PMID:11950515)
• A propensity to overexpress ankyrin G after peripheral nerve trauma may turn out to be a factor in the development of painful neuromas and neuropathic pain. (PMID:12507143)
• ankyrin-G plays a pleiotropic role in assembly of lateral membranes of bronchial epithelial cells (PMID:14757759)
• Altered expression is associated with therapy failure and death in patients with multiple types of cancer. (PMID:15931389)
• ankyrin-G regulates neuronal excitability not only through clustering Nav channels but also by directly modifying their channel gating. (PMID:16775201)
• Ankyrin G may have a role in Hutchinson-Gilford progeria syndrome (PMID:17033732)
• ankyrin-G and beta(2)-spectrin are functional partners in biogenesis of the lateral membrane of epithelial cells (PMID:17074766)
• E-cadherin requires both ankyrin-G and beta-2-spectrin for its cellular localization in early embryos as well as cultured epithelial cells. (PMID:17620337)
• Significant association with late-onset Alzheimer’s disease for 4 SNPs: rs1881747 near DKK1, rs2279420 in ANK3, rs2306402 in CTNNA3, and rs5030882 in CXXC6 in 1,160 cases and 1,389 controls. (PMID:18163421)
• Phosphorylation and ankyrin-G binding of the C-terminal domain regulate targeting and function of the ammonium transporter RhBG (PMID:18635543)
• To identify susceptibility loci for bipolar disorder, we tested 1.8 million variants in 4,387 cases and 6,209 controls and identified a region of strong association (rs10994336, P = 9.1 x 10(-9)) in ANK3 (ankyrin G). (PMID:18711365)
• Ankyrin facilitates intracellular trafficking of alpha1-Na+-K+-ATPase in polarized cells. (PMID:18768923)
• This study strongly support ANK3 as a bipolar disorder susceptibility gene and suggest true allelic heterogeneity. (PMID:19088739)
• The association of ANK3 with schizophrenia is intriguing in light of recent associations of ANK3 with bipolar disorder, thereby supporting the hypothesis of an overlap in genetic susceptibility between these psychopathological entities. (PMID:20185149)
• there is genetic variation local to ANK3 gene affecting its expression, but that this variation is not responsible for increasing risk of bipolar disorder. (PMID:20636642)
• results suggest that allelic variation in ANK3 impacts cognitive processes associated with signal detection and this mechanism may relate to risk for Bipolar Disorder (PMID:21304963)
• we did not find evidence for association between the bipolar disorder risk polymorphisms rs10994336 in the ANK3 gene and rs1006737 in the CACNA1C gene in migraine (PMID:21395576)
• These findings supported the association between ANK3 and bipolar disorder, and also suggested the genomic region around rs1938526 as a common risk locus across ethnicities. (PMID:21438140)
• This study demonistreated that ANK3 genotype was associated with proneness to anhedonia. (PMID:21676128)
• results support a specific genetic contribution of ANK3 to bipolar disorder though failed to replicate findings for schizophrenia. (PMID:21702894)
• association of SNPs rs10994336 and rs9804190 with bipolar disorders and psychosis subphenotype (PMID:21767209)
• The ANK3 rs9804190 C allele increases the risk for schizophrenia by affecting ANK3 expression levels (PMID:21893642)
• These results further support that ANK3 is a susceptibility gene specific to bipolar disorder and that more than one risk locus is involved. (PMID:21972176)
• loss of AnkG expression may prevent the arrival of Cx43 to its final destination. (PMID:22180603)
• DNA sequencing revealed a novel low frequency (0.007) ANK3 SNP (ss469104599) which causes a non-conservative amino acid change at position 794 in the shorter isoforms of the ankyrin G protein. (PMID:22328486)
• Individuals carrying the bipolar disorder risk T-allele of ANK3 showed significantly reduced sensitivity in target detection, increased errors of commission, and atypical response latency variability. (PMID:22498896)
• The findings of this study do not support a strong genetic link between bipolar disorder and major depressive disorder for ANK3 genes. (PMID:22647524)
• data established a role for ankG in the human adaptive immune response against resident brain proteins, and they show that ankG immunization reduces brain beta-amyloid and its related neuropathology (PMID:22688190)
• These findings suggest a brain-specific cis-regulatory transcriptional effect of ANK3 that may be relevant to BD pathophysiology. (PMID:22850628)
• An association between ANK3 mutations and autism spectrum disorder susceptibility. (PMID:22865819)
• show novel expression of genes near regions of significantly associated SNPS, including TMEM26 and FOXA1 in airway epithelium and lung parenchyma, and ANK3 in alveolar macrophages in COPD (PMID:22986903)
• study concludes that ANK3 gene has a major influence on susceptibility to schizophrenia across populations (PMID:23109352)
• Cysteine 70 of ankyrin-G is S-palmitoylated and is required for function of ankyrin-G in membrane domain assembly. (PMID:23129772)
• inactivating mutations in the Ankyrin 3 (ANK3) gene in patients with severe cognitive deficits. (PMID:23390136)
• haplotype associated with bipolar disorder in Latino populations (PMID:23715300)
• A role of ANK3 in risk of stress-related and externalizing disorders, beyond its previous associations with bipolar disorder and schizophrenia. (PMID:23796624)
• ANK3 risk allele rs1938526 appears to be associated with general cognitive impairment and widespread cortical thinning in patients with first-episode psychosis (PMID:24016415)
• ANK3 SNP associated with brain connectivity changes in bipolar disorder. (PMID:24108394)
• results indicated that genetic variation within ANK3 may exert gene-specific modulating effects onworking memory deficits in schizophrenia. (PMID:24361380)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ank3a	ENSDARG00000061736
danio_rerio	ank3b	ENSDARG00000077582
danio_rerio		ENSDARG00000110151
danio_rerio		ENSDARG00000111362
mus_musculus	Ank3	ENSMUSG00000069601
rattus_norvegicus	Ank3	ENSRNOG00000053288

Paralogs (3): ANK1 (ENSG00000029534), ANK2 (ENSG00000145362), ASB7 (ENSG00000183475)

Protein

Protein identifiers

Ankyrin-3 — Q12955 (reviewed: Q12955)

Alternative names: Ankyrin-G

All UniProt accessions (23): Q12955, A0A087WTE8, A0A087WTF3, A0A087WTP5, A0A087WVC2, A0A087WWI5, A0A087WX55, A0A087WY90, A0A087WZ26, A0A087WZ65, A0A087X0B4, A0A087X0L3, B1AQT1, D6RBY7, D6RF31, D6RFK6, D6RHY3, H0Y3A4, H0Y8Z4, H0Y951, H0Y9E9, H0YA66, H0YAH5

UniProt curated annotations — full annotation on UniProt →

Function. Membrane-cytoskeleton linker. May participate in the maintenance/targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments. In skeletal muscle, required for costamere localization of DMD and betaDAG1. Regulates KCNA1 channel activity in function of dietary Mg(2+) levels, and thereby contributes to the regulation of renal Mg(2+) reabsorption. Required for intracellular adhesion and junctional conductance in myocytes, potentially via stabilization of GJA1/CX43 protein abundance and promotion of PKP2, GJA1/CX43, and SCN5A/Nav1.5 localization to cell-cell junctions. May be part of a Golgi-specific membrane cytoskeleton in association with beta-spectrin.

Subunit / interactions. Directly interacts with DMD and betaDAG1. This interaction does not interfere with binding between DMD and betaDAG1. It is also required for DMD and betaDAG1 retention at costameres. Interacts (via N-terminal ANK repeats) with SCHIP1 isoform 5 (via C-terminus); this interaction is required for the localization at axon initial segments (AISs) and nodes of Ranvier (NRs). May be a constituent of a NFASC/NRCAM/ankyrin G complex. Interacts with RHBG. Interacts with PLEC and FLNC. Interacts with KCNA1; this inhibits channel activity. Interacts (via ANK repeats) with IQCJ-SCHIP1; required for IQCJ-SCHIP1 localization at axon initial segments (AIS) and nodes of Ranvier. Interacts with SCHIP1. Interacts with SCN5A. Interacts with PKP2 and GJA1/CX43. Interacts with PRICKLE2; the interaction is necessary for correct microtubule bundling.

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Axon. Cell membrane. Sarcolemma. Postsynaptic cell membrane. Lysosome. T-tubule Cytoplasm. Golgi apparatus.

Tissue specificity. Expressed in brain, neurons, muscles and other tissues.

Disease relevance. Genetic variations in ANK3 may be associated with autism spectrum disorders susceptibility. Intellectual developmental disorder, autosomal recessive 37 (MRT37) [MIM:615493] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT37 patients manifest delayed global development with speech delay, hypotonia, spasticity, and a sleep disorder. Severe behavioral abnormalities include aggression, hyperactivity, and grinding of the teeth. The disease is caused by variants affecting the gene represented in this entry. A homozygous deletion in ANK3 predicted to result in frameshift and premature truncation, has been shown to be the cause of moderate intellectual disability, an ADHD-like phenotype and behavioral problems in a consanguineous family.

Domain organisation. The tandem configuration of the two ZU5 and the UPA domains forms a structural supramodule termed ZZU. ZU5-1 mediates interaction with beta-spectrin, and the ZU5-1/UPA interface is required for ankyrin’s function other than binding to spectrin.

Miscellaneous. Avidly binds beta spectrin.

Isoforms (5)

UniProt ID	Names	Canonical?
Q12955-3	1	yes
Q12955-4	2
Q12955-5	3
Q12955-6	4
Q12955-7	5, AnkG119, Golgi ankyrin

RefSeq proteins (5): NP_001140, NP_001191332, NP_001191333, NP_001307803, NP_066267* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000488	Death_dom	Domain
IPR000906	ZU5_dom	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR037971	Ank3_Death	Domain
IPR040745	Ankyrin_UPA	Domain
IPR051165	Multifunctional_ANK_Repeat	Family

Pfam: PF00023, PF00531, PF00791, PF12796, PF13637, PF17809

UniProt features (164 total): modified residue 32, compositionally biased region 32, repeat 23, region of interest 20, sequence conflict 18, splice variant 16, sequence variant 10, helix 9, domain 3, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4O6X	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

No AlphaFold model available for Q12955 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (32): 4229, 4290, 4298, 4350, 1632, 1658, 1625, 1651, 765, 791, 468, 39, 623, 847, 861, 867, 913, 916, 922, 957 …

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-445095	Interaction between L1 and Ankyrins
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-9768727	Regulation of CDH1 posttranslational processing and trafficking to plasma membrane
R-HSA-1266738	Developmental Biology
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-373760	L1CAM interactions
R-HSA-392499	Metabolism of proteins
R-HSA-422475	Axon guidance
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5653656	Vesicle-mediated transport
R-HSA-597592	Post-translational protein modification
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-9675108	Nervous system development

MSigDB gene sets: 573 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, GOBP_MITOTIC_CYTOKINESIS, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, JI_RESPONSE_TO_FSH_UP, MODULE_274, GOBP_NEGATIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, GOBP_MEMBRANE_BIOGENESIS, FISCHER_G1_S_CELL_CYCLE, JAEGER_METASTASIS_DN, NKX25_02, GOBP_MEMBRANE_DEPOLARIZATION_DURING_ACTION_POTENTIAL, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN

GO Biological Process (25): mitotic cytokinesis (GO:0000281), plasma membrane organization (GO:0007009), signal transduction (GO:0007165), axonogenesis (GO:0007409), neuromuscular junction development (GO:0007528), positive regulation of gene expression (GO:0010628), positive regulation of cell communication by electrical coupling (GO:0010650), positive regulation of sodium ion transport (GO:0010765), magnesium ion homeostasis (GO:0010960), neuronal action potential (GO:0019228), positive regulation of homotypic cell-cell adhesion (GO:0034112), Golgi to plasma membrane protein transport (GO:0043001), regulation of potassium ion transport (GO:0043266), establishment of protein localization (GO:0045184), positive regulation of membrane potential (GO:0045838), cellular response to magnesium ion (GO:0071286), membrane assembly (GO:0071709), protein localization to plasma membrane (GO:0072659), maintenance of protein location in plasma membrane (GO:0072660), positive regulation of protein targeting to membrane (GO:0090314), protein localization to axon (GO:0099612), positive regulation of membrane depolarization during cardiac muscle cell action potential (GO:1900827), negative regulation of delayed rectifier potassium channel activity (GO:1902260), cytoskeleton organization (GO:0007010), Golgi vesicle transport (GO:0048193)

GO Molecular Function (10): structural constituent of cytoskeleton (GO:0005200), cytoskeletal protein binding (GO:0008092), cytoskeletal adaptor activity (GO:0008093), sodium channel regulator activity (GO:0017080), spectrin binding (GO:0030507), protein-macromolecule adaptor activity (GO:0030674), transmembrane transporter binding (GO:0044325), cadherin binding (GO:0045296), channel activator activity (GO:0099103), protein binding (GO:0005515)

GO Cellular Component (30): lysosome (GO:0005764), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), cell surface (GO:0009986), intercalated disc (GO:0014704), spectrin-associated cytoskeleton (GO:0014731), basolateral plasma membrane (GO:0016323), lateral plasma membrane (GO:0016328), sarcoplasmic reticulum (GO:0016529), Z disc (GO:0030018), T-tubule (GO:0030315), dendrite (GO:0030425), neuromuscular junction (GO:0031594), node of Ranvier (GO:0033268), sarcolemma (GO:0042383), neuron projection (GO:0043005), costamere (GO:0043034), axon initial segment (GO:0043194), postsynaptic membrane (GO:0045211), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), bicellular tight junction (GO:0005923), membrane (GO:0016020), axon (GO:0030424), cell projection (GO:0042995), organelle (GO:0043226), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
L1CAM interactions	1
ER to Golgi Anterograde Transport	1
Regulation of CDH1 Expression and Function	1
Membrane Trafficking	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Axon guidance	1
Nervous system development	1
Post-translational protein modification	1
Metabolism of proteins	1
Asparagine N-linked glycosylation	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
protein binding	3
cytoplasm	3
membrane organization	2
protein localization to plasma membrane	2
cytoskeleton	2
cytoskeletal protein binding	2
endomembrane system	2
intracellular membrane-bounded organelle	2
plasma membrane region	2
plasma membrane	2
mitotic cell cycle	1
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
endomembrane system organization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
synapse organization	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
cell communication by electrical coupling	1
positive regulation of cell communication	1
regulation of cell communication by electrical coupling	1
regulation of sodium ion transport	1
sodium ion transport	1
positive regulation of monoatomic ion transport	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
action potential	1
transmission of nerve impulse	1
positive regulation of cell-cell adhesion	1
homotypic cell-cell adhesion	1
regulation of homotypic cell-cell adhesion	1

Protein interactions and networks

STRING

5794 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANK3	EPB41	P11171	996
ANK3	SPTBN4	Q9H254	996
ANK3	NFASC	O94856	993
ANK3	ADD1	P35611	983
ANK3	SCN5A	Q14524	982
ANK3	ADD3	Q9UEY8	978
ANK3	ADD2	P35612	957
ANK3	L1CAM	P32004	946
ANK3	SCN2A	Q99250	937
ANK3	SLC4A1	P02730	928
ANK3	TTN	Q8WZ42	923
ANK3	SCN8A	Q9UQD0	914
ANK3	KCNQ2	O43526	910
ANK3	NRCAM	Q92823	897
ANK3	SPTAN1	Q13813	889

IntAct

113 interactions, top by confidence:

A	B	Type	Score
MAPK8IP1	MAPK8	psi-mi:“MI:0914”(association)	0.770
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HIF1AN	GMDS	psi-mi:“MI:0914”(association)	0.640
SMAD2	ANK3	psi-mi:“MI:0915”(physical association)	0.570
PCNA	POM121C	psi-mi:“MI:0914”(association)	0.550
AP3B1	ANK3	psi-mi:“MI:0407”(direct interaction)	0.530
AP3B1	ANK3	psi-mi:“MI:0915”(physical association)	0.530
CHL1	LGALS1	psi-mi:“MI:0914”(association)	0.530
PWP1	ANK3	psi-mi:“MI:0914”(association)	0.530
MAPK8IP1	HOXC8	psi-mi:“MI:0914”(association)	0.530
PHAF1	PSMG1	psi-mi:“MI:0914”(association)	0.530
RAPGEF5	ANK3	psi-mi:“MI:0915”(physical association)	0.500
SCN5A	ANK3	psi-mi:“MI:0407”(direct interaction)	0.440
NEDD4	ANK3	psi-mi:“MI:0407”(direct interaction)	0.440
YAP1	ANK3	psi-mi:“MI:0407”(direct interaction)	0.440
ANK3	CCT3	psi-mi:“MI:0915”(physical association)	0.400
ANK3	HMGN1	psi-mi:“MI:0915”(physical association)	0.400
ANK3	H1-10	psi-mi:“MI:0915”(physical association)	0.400
SMAD3	ANK3	psi-mi:“MI:0915”(physical association)	0.370
KIF11	ILVBL	psi-mi:“MI:0914”(association)	0.350
Cry1	NFIB	psi-mi:“MI:0914”(association)	0.350
Dennd6a	IFT88	psi-mi:“MI:0914”(association)	0.350
Tmed10	NDUFS8	psi-mi:“MI:0914”(association)	0.350
	VWA8	psi-mi:“MI:0914”(association)	0.350
PB1	HAX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (238): ANK3 (Affinity Capture-MS), ANK3 (Affinity Capture-MS), ANK3 (Affinity Capture-MS), ANK3 (Affinity Capture-MS), ANK3 (Affinity Capture-Western), ANK3 (Biochemical Activity), ANK3 (Proximity Label-MS), ANK3 (Affinity Capture-MS), ANK3 (Affinity Capture-MS), ANK3 (Affinity Capture-MS), ANK3 (Affinity Capture-MS), ANK3 (Affinity Capture-MS), ANK3 (Affinity Capture-MS), ANK3 (Proximity Label-MS), ANK3 (Proximity Label-MS)

ESM2 similar proteins: A0PJZ0, A6NGH8, A7E2S9, B2RR83, B7U179, B9DHT4, C7B178, D3J162, D3J163, F4IDQ6, G5E8K5, O22161, O44997, O70511, P16157, P53355, Q01484, Q02357, Q05921, Q08E43, Q12955, Q3EC11, Q4R3S3, Q4R544, Q52T38, Q5R6D7, Q5RCK5, Q5TYM7, Q5VYY1, Q60772, Q641X1, Q7T163, Q80YE7, Q8C8R3, Q91ZT9, Q91ZU0, Q92527, Q94B55, Q9BGT9, Q9CQM6

Diamond homologs: G5E8K5, O70511, P16157, Q01484, Q02357, Q12955, Q8C8R3, Q8IV45

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
ANK3	“up-regulates activity”	CDH1	binding
ANK3	“up-regulates activity”	SPTBN1	binding
GLDN	“up-regulates quantity”	ANK3	relocalization
ELAVL3	“down-regulates quantity”	ANK3	“post transcriptional regulation”
ANK3	“up-regulates activity”	GABARAP	binding
ANK3	“up-regulates quantity”	DAG1	relocalization
ANK3	“up-regulates quantity”	DMD	relocalization
NFASC	“up-regulates quantity”	ANK3	relocalization
NRCAM	“up-regulates quantity”	ANK3	relocalization
CHL1	“up-regulates quantity”	ANK3	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

1863 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	15
Uncertain significance	1142
Likely benign	455
Benign	66

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1334683	NM_020987.5(ANK3):c.5843_5844dup (p.Glu1949Ter)	Pathogenic
1455955	NM_020987.5(ANK3):c.93del (p.Ser32fs)	Pathogenic
1802532	NM_020987.5(ANK3):c.7068dup (p.Glu2357fs)	Pathogenic
2065855	NM_020987.5(ANK3):c.12059del (p.Lys4020fs)	Pathogenic
2603741	NM_020987.5(ANK3):c.855dup (p.Leu286fs)	Pathogenic
3340968	NM_020987.5(ANK3):c.2948+1G>A	Pathogenic
3776524	NM_020987.5(ANK3):c.9349dup (p.Ile3117fs)	Pathogenic
3781159	NM_020987.5(ANK3):c.8433dup (p.Gln2812fs)	Pathogenic
4071789	NM_020987.5(ANK3):c.12487C>T (p.Arg4163Ter)	Pathogenic
4082355	NM_020987.5(ANK3):c.3589del (p.Ala1197fs)	Pathogenic
4097617	NM_020987.5(ANK3):c.3526C>T (p.Arg1176Ter)	Pathogenic
4531485	NM_020987.5(ANK3):c.3163C>T (p.Gln1055Ter)	Pathogenic
802576	NM_020987.5(ANK3):c.2659C>T (p.Gln887Ter)	Pathogenic
815348	GRCh37/hg19 10q21.1-21.2(chr10:55589950-63990649)x1	Pathogenic
88648	NM_020987.5(ANK3):c.10995del (p.Thr3666fs)	Pathogenic
918004	NM_020987.5(ANK3):c.11033del (p.Pro3678fs)	Pathogenic
1050844	NM_020987.5(ANK3):c.2125C>T (p.Arg709Ter)	Likely pathogenic
1180617	NM_020987.5(ANK3):c.3327del (p.Glu1110fs)	Likely pathogenic
2430260	NM_020987.5(ANK3):c.631C>T (p.Arg211Ter)	Likely pathogenic
2433810	NM_020987.5(ANK3):c.1863_1864del (p.Ala622fs)	Likely pathogenic
3256665	NM_020987.5(ANK3):c.4867C>T (p.Arg1623Ter)	Likely pathogenic
3378111	NM_020987.5(ANK3):c.212_216+1del	Likely pathogenic
3390421	NM_020987.5(ANK3):c.10645C>T (p.Arg3549Ter)	Likely pathogenic
3393908	NM_020987.5(ANK3):c.2706C>G (p.Tyr902Ter)	Likely pathogenic
3776409	NM_020987.5(ANK3):c.217-2A>G	Likely pathogenic
3893318	NM_020987.5(ANK3):c.2093T>C (p.Leu698Pro)	Likely pathogenic
402146	NM_020987.5(ANK3):c.9652C>T (p.Leu3218Phe)	Likely pathogenic
442208	GRCh37/hg19 10q21.1-21.2(chr10:57587928-64212007)x1	Likely pathogenic
4846809	NM_020987.5(ANK3):c.12910C>T (p.Gln4304Ter)	Likely pathogenic
817450	NM_020987.5(ANK3):c.3810del (p.Asp1271fs)	Likely pathogenic

SpliceAI

7592 predictions. Top by Δscore:

Variant	Effect	Δscore
10:60044263:A:AC	donor_gain	1.0000
10:60044264:C:CC	donor_gain	1.0000
10:60044264:CTTTT:C	donor_gain	1.0000
10:60063143:T:C	donor_gain	1.0000
10:60063251:TCAG:T	acceptor_gain	1.0000
10:60063252:CAG:C	acceptor_gain	1.0000
10:60063252:CAGC:C	acceptor_gain	1.0000
10:60063255:C:CC	acceptor_gain	1.0000
10:60064155:A:AC	donor_gain	1.0000
10:60064156:C:CC	donor_gain	1.0000
10:60064289:C:CC	acceptor_gain	1.0000
10:60080535:A:AC	donor_gain	1.0000
10:60080536:C:CC	donor_gain	1.0000
10:60080536:CT:C	donor_gain	1.0000
10:60080539:ATT:A	donor_gain	1.0000
10:60082196:T:TC	acceptor_gain	1.0000
10:60082214:T:C	acceptor_gain	1.0000
10:60082214:T:TC	acceptor_gain	1.0000
10:60082225:A:T	acceptor_gain	1.0000
10:60082227:C:CT	acceptor_gain	1.0000
10:60082228:A:T	acceptor_gain	1.0000
10:60083487:TTTAC:T	donor_loss	1.0000
10:60083488:TTAC:T	donor_loss	1.0000
10:60083489:TA:T	donor_loss	1.0000
10:60083490:ACCTT:A	donor_loss	1.0000
10:60083617:CCTTT:C	acceptor_gain	1.0000
10:60083626:G:GC	acceptor_gain	1.0000
10:60084597:GGTAC:G	donor_loss	1.0000
10:60084600:A:AG	donor_loss	1.0000
10:60084601:C:G	donor_loss	1.0000

AlphaMissense

28762 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:60063197:A:G	L4170P	1.000
10:60063200:A:G	L4169P	1.000
10:60063209:A:C	I4166R	1.000
10:60063209:A:T	I4166K	1.000
10:60063212:T:A	D4165V	1.000
10:60063212:T:C	D4165G	1.000
10:60063212:T:G	D4165A	1.000
10:60063213:C:G	D4165H	1.000
10:60063218:C:G	R4163P	1.000
10:60063219:G:C	R4163G	1.000
10:60063233:A:C	L4158W	1.000
10:60063233:A:G	L4158S	1.000
10:60063245:A:G	L4154S	1.000
10:60064162:G:T	A4149D	1.000
10:60064185:C:A	W4141C	1.000
10:60064185:C:G	W4141C	1.000
10:60064187:A:G	W4141R	1.000
10:60064187:A:T	W4141R	1.000
10:60064195:A:G	L4138S	1.000
10:60064198:A:G	L4137S	1.000
10:60064206:G:C	S4134R	1.000
10:60064206:G:T	S4134R	1.000
10:60064208:T:G	S4134R	1.000
10:60064209:C:A	Q4133H	1.000
10:60064209:C:G	Q4133H	1.000
10:60064240:C:G	R4123P	1.000
10:60064241:G:C	R4123G	1.000
10:60064241:G:T	R4123S	1.000
10:60064243:A:T	I4122K	1.000
10:60064252:A:C	I4119S	1.000

dbSNP variants (sampled 300 via entrez): RS1000003011 (10:60669682 C>G,T), RS1000005848 (10:60414094 G>A,T), RS1000006665 (10:60451345 A>G), RS1000012580 (10:60611196 C>T), RS1000014310 (10:60323232 T>C,G), RS1000015055 (10:60328180 A>G), RS1000016854 (10:60701861 C>A), RS1000031998 (10:60400458 A>G,T), RS1000033118 (10:60112317 A>C), RS1000034128 (10:60106223 C>T), RS1000036671 (10:60125224 TAGC>T), RS1000045032 (10:60611408 A>G), RS1000052555 (10:60029539 A>C), RS1000056371 (10:60327718 C>G,T), RS1000066923 (10:60334893 G>C,T)

Disease associations

OMIM: gene MIM:600465 | disease phenotypes: MIM:615493, MIM:618221, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability-hypotonia-spasticity-sleep disorder syndrome	Strong	Autosomal recessive
neurodevelopmental disorder	Strong	Semidominant
coloboma	Moderate	Autosomal dominant
intellectual disability	Limited	Autosomal dominant
Tourette syndrome	Limited	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
intellectual disability	Moderate	AR

Mondo (10): intellectual disability-hypotonia-spasticity-sleep disorder syndrome (MONDO:0014210), congenital nervous system disorder (MONDO:0002320), intellectual disability, autosomal recessive 66 (MONDO:0032605), classic medulloblastoma (MONDO:0016712), intellectual disability (MONDO:0001071), complex neurodevelopmental disorder (MONDO:0100038), neurodevelopmental disorder (MONDO:0700092), autism (MONDO:0005260), Tourette syndrome (MONDO:0007661), coloboma (MONDO:0001476)

Orphanet (4): ANK3-related intellectual disability-sleep disturbance syndrome (Orphanet:356996), Classic medulloblastoma (Orphanet:251867), Non-specific syndromic intellectual disability (Orphanet:528084), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

18 total (19 of 18 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001520	Large for gestational age
HP:0002342	Moderate intellectual disability
HP:0002360	Sleep disturbance
HP:0003763	Bruxism
HP:0000717	Autism

GWAS associations

34 associations (top):

Study	Trait	p-value
GCST000220_2	Bipolar disorder	9.000000e-09
GCST000607_3	Schizophrenia	8.000000e-06
GCST000641_7	Bipolar disorder or major depressive disorder	5.000000e-07
GCST001241_10	Bipolar disorder	3.000000e-07
GCST001358_5	Bipolar disorder	4.000000e-10
GCST001877_39	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	7.000000e-09
GCST001877_66	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	3.000000e-09
GCST002337_89	Amyotrophic lateral sclerosis (sporadic)	3.000000e-07
GCST002359_2	Plasma amyloid beta peptide concentrations (ABx-42)	1.000000e-06
GCST002385_1	Bipolar disorder	7.000000e-11
GCST002866_1	Behavioral disturbance or psychiatric symptoms and prion disease	1.000000e-06
GCST003962_5	Bipolar disorder	1.000000e-09
GCST004068_8	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	4.000000e-06
GCST005173_81	Coronary artery calcified atherosclerotic plaque (130 HU threshold) in type 2 diabetes	3.000000e-06
GCST006627_39	Diastolic blood pressure	1.000000e-11
GCST006865_10	Bipolar disorder	9.000000e-09
GCST006979_587	Heel bone mineral density	2.000000e-16
GCST007324_150	Adventurousness	3.000000e-09
GCST007576_110	Chronotype	2.000000e-08
GCST008103_15	Bipolar disorder	7.000000e-09
GCST008115_7	Bipolar I disorder	2.000000e-08
GCST008491_8	Voxel-wise structural brain imaging measurements in Alzheimer’s disease	6.000000e-08
GCST008491_9	Voxel-wise structural brain imaging measurements in Alzheimer’s disease	3.000000e-07
GCST008839_354	Height	4.000000e-11
GCST008895_1	Psychotic experience	3.000000e-08
GCST009214_5	Third ventricle volume	2.000000e-06
GCST009391_1652	Metabolite levels	1.000000e-06
GCST009544_4	Cleft lip with or without cleft palate x maternal periconceptional smoking interaction (parent of origin effect)	3.000000e-06
GCST010002_289	Refractive error	3.000000e-18
GCST010703_134	Brain morphology (MOSTest)	4.000000e-08

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0005660	plasma beta-amyloid 1-42 measurement
EFO:0004723	coronary artery calcification
EFO:0006336	diastolic blood pressure
EFO:0009270	heel bone mineral density
EFO:0008579	risk-taking behaviour
EFO:0008328	chronotype measurement
EFO:0009963	bipolar I disorder
EFO:0004346	neuroimaging measurement
EFO:0005940	psychotic symptoms
EFO:0010469	carnitine measurement
EFO:0003959	cleft lip
EFO:0005939	parental genotype effect measurement
EFO:0009115	tobacco smoke exposure measurement
EFO:0004980	appendicular lean mass
EFO:0009885	frailty measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D003103	Coloboma	C11.250.110; C11.270.147; C16.131.384.282
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs143414470	ANK3		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects cotreatment, increases expression, affects expression	6
bisphenol A	decreases methylation, increases expression	3
trichostatin A	affects cotreatment, increases expression	3
(+)-JQ1 compound	affects cotreatment, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Estradiol	decreases expression, increases reaction, affects cotreatment	3
Silicon Dioxide	decreases expression, increases expression	3
sodium arsenite	affects methylation, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	increases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
Particulate Matter	decreases expression, increases abundance	2
sotorasib	affects cotreatment, decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
apocarotenal	increases expression	1
triphenyl phosphate	affects expression	1
methylselenic acid	decreases expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
afimoxifene	decreases expression, decreases reaction	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	increases expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
clothianidin	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D6B9	HyCyte HCT 116 KO-hANK3	Cancer cell line	Male

Clinical trials (associated diseases)

400 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
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	PHASE3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	PHASE3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	PHASE3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	PHASE3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	PHASE3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	PHASE3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	PHASE3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00004393	PHASE2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	PHASE2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	PHASE2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	PHASE2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	PHASE2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	PHASE2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome