SLITRK1

Summary

SLITRK1 (SLIT and NTRK like family member 1, HGNC:20297) is a protein-coding gene on chromosome 13q31.1, encoding SLIT and NTRK-like protein 1 (Q96PX8). It is involved in synaptogenesis and promotes excitatory synapse differentiation.

This gene encodes a member of the SLITRK protein family. Members of this family are integral membrane proteins that are characterized by two N-terminal leucine-rich repeat (LRR) domains and a C-terminal region that shares homology with trk neurotrophin receptors. However, the protein encoded by this gene lacks the region of homology to neurotrophin receptors. This protein is thought to be involved in neurite outgrowth. Mutations in this gene may be associated with Tourette syndrome. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 114798 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 176 total — 2 pathogenic
• Phenotypes (HPO): 12
• MANE Select transcript: NM_001281503

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20297
Approved symbol	SLITRK1
Name	SLIT and NTRK like family member 1
Location	13q31.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1910
Ensembl gene	ENSG00000178235
Ensembl biotype	protein_coding
OMIM	609678
Entrez	114798

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000377084, ENST00000674365

RefSeq mRNA: 2 — MANE Select: NM_001281503 NM_001281503, NM_052910

CCDS: CCDS9464

Canonical transcript exons

ENST00000674365 — 2 exons

Exon	Start	End
ENSE00003898164	83877205	83881560
ENSE00003898571	83882004	83882474

Expression profiles

Bgee: expression breadth broad, 86 present calls, max score 89.87.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6909 / max 1119.5819, expressed in 281 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137757	1.0397	145
137761	0.7981	112
137765	0.6030	100
137758	0.3296	95
137760	0.3153	79
137759	0.2807	89
137763	0.1810	75
137762	0.0853	52
137764	0.0583	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 46	UBERON:0006483	89.87	gold quality
prefrontal cortex	UBERON:0000451	86.75	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.65	gold quality
endothelial cell	CL:0000115	85.26	gold quality
superior frontal gyrus	UBERON:0002661	85.13	gold quality
cortical plate	UBERON:0005343	84.88	gold quality
entorhinal cortex	UBERON:0002728	84.81	gold quality
postcentral gyrus	UBERON:0002581	84.63	gold quality
middle temporal gyrus	UBERON:0002771	84.06	gold quality
frontal cortex	UBERON:0001870	83.49	gold quality
parietal lobe	UBERON:0001872	83.32	gold quality
primary visual cortex	UBERON:0002436	82.71	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.10	gold quality
neocortex	UBERON:0001950	82.03	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.76	gold quality
occipital lobe	UBERON:0002021	81.61	gold quality
cerebral cortex	UBERON:0000956	81.40	gold quality
temporal lobe	UBERON:0001871	79.03	gold quality
Ammon’s horn	UBERON:0001954	77.64	gold quality
anterior cingulate cortex	UBERON:0009835	77.49	gold quality
right frontal lobe	UBERON:0002810	77.39	gold quality
lateral nuclear group of thalamus	UBERON:0002736	76.72	gold quality
amygdala	UBERON:0001876	75.13	gold quality
corpus callosum	UBERON:0002336	75.01	gold quality
forebrain	UBERON:0001890	73.86	gold quality
hypothalamus	UBERON:0001898	73.36	gold quality
ventral tegmental area	UBERON:0002691	72.40	gold quality
brain	UBERON:0000955	71.97	gold quality
dorsal plus ventral thalamus	UBERON:0001897	71.87	gold quality
substantia nigra	UBERON:0002038	71.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	8.51
E-ANND-3	yes	2.95
E-ENAD-17	no	231.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

143 targeting SLITRK1, 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-3924	100.00	72.09	2394
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505

Literature-anchored findings (GeneRIF, showing 21)

• findings support the association of rare SLITRK1 sequence variants with Tourette’s syndrome (PMID:16224024)
• SLITRK1 trouble in Tourette’s syndrome. (PMID:16323357)
• No variation in patients susceptible to obsessive-compulsive disorder.( (PMID:16936762)
• Rare variations in SLITRK1 result in disorders of the obsessive-complusive disease spectrum (PMID:17003809)
• negative results of the SLITRK1 analysis point to genetic heterogeneity in Tourette syndrome (PMID:17712845)
• identified four new variants for Gilles de la Tourette syndrome (PMID:18004766)
• Genetic screening in the Slit and Trk-like 1 gene for the recently identified mutations does not appear to be of utility in the diagnosis of Tourette syndrome. (PMID:18021920)
• Observed transmission is lacking of SLITRK1 var321 from an affected parent to a child with Tourette syndrome in two families segregating this variant. (PMID:18413575)
• These findings provide the first support for the original finding indicating SLITRK1 as a susceptibility gene for Gilles de la Tourette Syndrome (PMID:18698576)
• We report the psychopathological features in a large Italian family with Gilles de la Tourette syndrome not linked to the SLITRK1 gene. (PMID:18722020)
• results provide no evidence for SLITRK1 playing a major role in Tourette disease (PMID:19018236)
• The study of this study support that SLITRK1 var321 is association to Tourette syndrome. (PMID:20351724)
• DM1 motoneuron/muscle cell cocultures showed alterations that are consistent with the known role of SLITRK genes in neurite outgrowth, neuritogenesis, and synaptogenesis; functional defects can be directly attributed to SLITRK misexpression. (PMID:21458401)
• The study of chromosomal aberrations in Tourette syndrome etiology has implicated multiple genes, with SLITRK1 being the most prominent example. (PMID:23333760)
• One of the few genes that has been linked to TS is the SLITRK1 (Slit and Trk-like 1) gene, where four variations have been suggested as possible disease-associated changes (PMID:23528612)
• the N400I variant of SLITRK1 may have a role in obsessive-compulsive disorder (PMID:23990902)
• Data provide partial support for the implication of SLITRK1 in the pathogenesis of Tourette syndrome. (PMID:26317387)
• Altogether, these results demonstrate that Slitrk family proteins regulate synapse formation. (PMID:27273464)
• Our results indicate an important influence of the neurodevelopment genes, PBX1, LMX1A, and SLITRK1 in obsessive-compulsive disorder susceptibility (PMID:30377043)
• Genomic Alterations of NTRK, POLE, ERBB2, and Microsatellite Instability Status in Chinese Patients with Colorectal Cancer. (PMID:32627883)
• In Silico Analysis Identified Putative Pathogenic Missense nsSNPs in Human SLITRK1 Gene. (PMID:35456478)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Slitrk1	ENSMUSG00000075478
rattus_norvegicus	Slitrk1	ENSRNOG00000009209

Paralogs (25): SLITRK3 (ENSG00000121871), LRFN3 (ENSG00000126243), LRFN1 (ENSG00000128011), SLIT2 (ENSG00000145147), LRFN2 (ENSG00000156564), LRRC38 (ENSG00000162494), SLITRK5 (ENSG00000165300), LRFN5 (ENSG00000165379), LRTM2 (ENSG00000166159), LINGO1 (ENSG00000169783), LRRN2 (ENSG00000170382), LRRN3 (ENSG00000173114), LRFN4 (ENSG00000173621), LINGO2 (ENSG00000174482), LRRN1 (ENSG00000175928), GP5 (ENSG00000178732), SLITRK4 (ENSG00000179542), LRRC55 (ENSG00000183908), SLIT3 (ENSG00000184347), SLITRK6 (ENSG00000184564), SLITRK2 (ENSG00000185985), LRRC70 (ENSG00000186105), SLIT1 (ENSG00000187122), TLR9 (ENSG00000239732), TPBGL (ENSG00000261594)

Protein

Protein identifiers

SLIT and NTRK-like protein 1 — Q96PX8 (reviewed: Q96PX8)

Alternative names: Leucine-rich repeat-containing protein 12

All UniProt accessions (1): Q96PX8

UniProt curated annotations — full annotation on UniProt →

Function. It is involved in synaptogenesis and promotes excitatory synapse differentiation. Enhances neuronal dendrite outgrowth.

Subunit / interactions. Can form homodimers; homodimerization requires repeat LRR 2. Interacts with YWHAB, YWHAE, YWHAG, YWHAH, SFN, YWHAQ and YWHAZ.

Subcellular location. Membrane. Secreted. Synapse.

Tissue specificity. Expressed predominantly in the frontal lobe of the cerebral cortex of the brain. Also expressed in some astrocytic brain tumors such as astrocytomas, oligodendrogliomas, glioblastomas, gangliogliomas and primitive neuroectodermal tumors.

Post-translational modifications. Undergoes proteolytic cleavage that results in shedding of the ectodomain and cleavage of the C-terminal cytoplasmic tail. Glycosylated. Phosphorylation at Ser-695 is necessary for proper function in promoting neurite outgrowth.

Disease relevance. Trichotillomania (TTM) [MIM:613229] A neuropsychiatric disorder characterized by chronic, repetitive, or compulsive hair pulling resulting in noticeable hair loss. Affected individuals may develop physical complications and often have overlapping psychological disorders, such as Gilles de la Tourette syndrome or obsessive-compulsive disorder. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the SLITRK family.

RefSeq proteins (2): NP_001268432, NP_443142 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000483	Cys-rich_flank_reg_C	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily

Pfam: PF13855

UniProt features (77 total): strand 23, helix 13, repeat 12, turn 10, sequence variant 5, domain 4, mutagenesis site 3, topological domain 2, signal peptide 1, chain 1, region of interest 1, modified residue 1, transmembrane region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4RCA	X-RAY DIFFRACTION	2.99
4RCW	X-RAY DIFFRACTION	3.19

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PX8-F1	77.43	0.54

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 (1): 695

Mutagenesis-validated functional residues (3):

Position	Phenotype
85	does not affect surface expression.
695	loss of phosphorylation. not able to promote neurite outgrowth.
695	able to promote neurite outgrowth as the wild-type.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-388844	Receptor-type tyrosine-protein phosphatases
R-HSA-112316	Neuronal System
R-HSA-6794362	Protein-protein interactions at synapses

MSigDB gene sets: 262 (showing top): AHRARNT_01, AGGAAGC_MIR5163P, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, GOBP_NEURON_PROJECTION_EXTENSION, CCAWYNNGAAR_UNKNOWN, MODULE_255, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_SYNAPSE_ASSEMBLY, GOBP_ADULT_BEHAVIOR, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_GROWTH, MODULE_317, TATTATA_MIR374

GO Biological Process (15): endocytosis (GO:0006897), axonogenesis (GO:0007409), synapse assembly (GO:0007416), gene expression (GO:0010467), adult behavior (GO:0030534), multicellular organism growth (GO:0035264), norepinephrine metabolic process (GO:0042415), homeostatic process (GO:0042592), positive regulation of axonogenesis (GO:0050772), positive regulation of synapse assembly (GO:0051965), vocalization behavior (GO:0071625), synaptic membrane adhesion (GO:0099560), regulation of presynapse assembly (GO:1905606), neuron projection extension (GO:1990138), nervous system development (GO:0007399)

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

GO Cellular Component (7): extracellular region (GO:0005576), plasma membrane (GO:0005886), synapse (GO:0045202), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein-protein interactions at synapses	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neuron projection morphogenesis	2
synapse organization	2
behavior	2
regulation of synapse assembly	2
cellular anatomical structure	2
synapse	2
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
cell morphogenesis involved in neuron differentiation	1
axon development	1
nervous system development	1
cell junction assembly	1
macromolecule biosynthetic process	1
multicellular organismal process	1
developmental growth	1
catecholamine metabolic process	1
biological_process	1
axonogenesis	1
positive regulation of cell projection organization	1
positive regulation of neurogenesis	1
regulation of axonogenesis	1
synapse assembly	1
positive regulation of nervous system development	1
positive regulation of cell junction assembly	1
cell-cell adhesion	1
presynapse assembly	1
regulation of presynapse organization	1
developmental cell growth	1
developmental growth involved in morphogenesis	1
system development	1
binding	1
membrane	1
cell periphery	1
cell junction	1
postsynaptic density	1
postsynaptic membrane	1
postsynaptic specialization membrane	1

Protein interactions and networks

STRING

2269 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLITRK1	PTPRS	Q13332	914
SLITRK1	IMMP2L	Q96T52	803
SLITRK1	DLGAP3	O95886	731
SLITRK1	SGCE	O43556	726
SLITRK1	HDC	P19113	725
SLITRK1	TOR1A	O14656	642
SLITRK1	PTPRD	P23468	626
SLITRK1	IL1RAPL1	Q9NZN1	624
SLITRK1	PTPRF	P10586	621
SLITRK1	TBCD	Q9BTW9	619
SLITRK1	DRD2	P14416	615
SLITRK1	NLGN1	Q8N2Q7	613
SLITRK1	NPTX1	Q15818	588
SLITRK1	KATNA1	O75449	580
SLITRK1	NTRK3	Q16288	578

IntAct

6 interactions, top by confidence:

A	B	Type	Score
SLITRK1	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
CACNA1C	DISP2	psi-mi:“MI:0914”(association)	0.350
YWHAB	SLITRK1	psi-mi:“MI:0914”(association)	0.350
SLITRK1	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): SLITRK1 (Affinity Capture-Western), UBQLN2 (Two-hybrid), PTPRS (Reconstituted Complex), PTPRD (Co-crystal Structure), PTPRD (Reconstituted Complex), SLITRK1 (Affinity Capture-MS), SLITRK1 (Affinity Capture-MS), SLITRK1 (Protein-peptide)

ESM2 similar proteins: A1A4H9, A2ARI4, A6NDA9, B0BLW3, B4F7C5, D3ZAL8, D3ZTV3, D4A6D8, D4A7P2, E7FE13, F1MT22, O14498, O43155, O43300, P0DM44, P83286, Q149C3, Q5NVQ6, Q5R6B1, Q5R7M3, Q5RAC4, Q6PFC5, Q6RKD8, Q80WD0, Q80XG9, Q80ZD7, Q80ZD8, Q80ZD9, Q810C0, Q810C1, Q86SJ2, Q86UE6, Q86UN2, Q86VH4, Q86VH5, Q86WK6, Q8BGA3, Q8BLU0, Q8BZ81, Q8C2S7

Diamond homologs: B1H134, B1H234, D3ZTV3, F1NUK7, G5EFX6, G5EG78, O43155, O88280, P19879, P20774, P24014, P58874, P79119, P83286, Q5R6T0, Q5RAC4, Q5RBL2, Q62000, Q6PEZ8, Q6RKD8, Q70AK3, Q810C1, Q8BGT1, Q8BLU0, Q8MJF1, Q96PX8, Q9DE65, Q9NR97, Q9NZU0, Q9NZU1, Q9UBM4, Q9W6H0, A8WGA3, D4ABX8, O42235, O55226, O60938, O75093, O88279, O94769

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
SLITRK1	up-regulates	Neurite_outgrowth
CSNK2A1	“up-regulates activity”	SLITRK1	phosphorylation
PKA	“up-regulates activity”	SLITRK1	phosphorylation
PKC	“up-regulates activity”	SLITRK1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	161
Likely benign	9
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1578	NM_001281503.2(SLITRK1):c.1264del (p.Leu422fs)	Pathogenic
1579	NM_001281503.2(SLITRK1):c.*689G>A	Pathogenic

SpliceAI

90 predictions. Top by Δscore:

Variant	Effect	Δscore
13:83881613:C:CT	acceptor_gain	0.9400
13:83881614:A:T	acceptor_gain	0.9400
13:83881485:A:T	acceptor_gain	0.8700
13:83882007:G:A	donor_gain	0.8600
13:83882156:CG:C	donor_gain	0.8200
13:83881613:C:T	acceptor_gain	0.7900
13:83881975:G:GA	donor_gain	0.7300
13:83881482:TCCA:T	acceptor_gain	0.7100
13:83881463:G:T	acceptor_gain	0.6200
13:83881997:GACT:G	donor_loss	0.6200
13:83881998:AC:A	donor_loss	0.6200
13:83881999:CTGA:C	donor_loss	0.6200
13:83882000:TGAC:T	donor_loss	0.6200
13:83882001:GA:G	donor_loss	0.6200
13:83882002:A:C	donor_loss	0.6200
13:83882003:CCTTG:C	donor_loss	0.6200
13:83882004:C:G	donor_loss	0.6200
13:83881996:GGAC:G	donor_loss	0.6100
13:83882287:CTAG:C	donor_gain	0.5800
13:83881607:C:CT	acceptor_gain	0.5600
13:83882005:T:C	donor_loss	0.5600
13:83881608:G:T	acceptor_gain	0.5100
13:83881480:TCTC:T	acceptor_gain	0.5000
13:83881481:CTCC:C	acceptor_gain	0.5000
13:83882156:CGCTG:C	donor_gain	0.5000
13:83881995:CGGA:C	donor_loss	0.4800
13:83881994:TCGGA:T	donor_loss	0.4700
13:83881460:A:T	acceptor_gain	0.4600
13:83881607:C:T	acceptor_gain	0.4600
13:83882023:G:C	donor_gain	0.4600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000693603 (13:83883534 T>G), RS1001002034 (13:83883285 A>G,T), RS1001112839 (13:83879027 T>C,G), RS1001163606 (13:83882273 C>G), RS1001384905 (13:83880031 C>T), RS1001723010 (13:83882858 A>G), RS1002252436 (13:83881903 A>G), RS1002934958 (13:83878341 C>A,T), RS1005328129 (13:83877053 A>G), RS1005681117 (13:83882137 C>T), RS1005733340 (13:83881714 C>T), RS1006281693 (13:83878890 T>G), RS1006332381 (13:83878722 G>A,C), RS1006904371 (13:83883220 C>G), RS1007353718 (13:83883533 T>C)

Disease associations

OMIM: gene MIM:609678 | disease phenotypes: MIM:613229, MIM:137580

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	Limited	Autosomal dominant
trichotillomania	Limited	Unknown

Mondo (2): trichotillomania (MONDO:0013189), Tourette syndrome (MONDO:0007661)

Orphanet (1): NON RARE IN EUROPE: Tourette syndrome (Orphanet:856)

HPO phenotypes

12 total (12 of 12 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000718	Aggressive behavior
HP:0000722	Compulsive behaviors
HP:0000742	Self-mutilation
HP:0001426	Non-Mendelian inheritance
HP:0001596	Alopecia
HP:0002360	Sleep disturbance
HP:0007018	Attention deficit hyperactivity disorder
HP:0010529	Echolalia
HP:0012167	Hair-pulling
HP:0100034	Motor tics
HP:0100035	Phonic tics

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001419_2	Temperament (bipolar disorder)	2.000000e-06
GCST001811_1	Bipolar disorder (mania)	8.000000e-06
GCST002337_34	Amyotrophic lateral sclerosis (sporadic)	2.000000e-07
GCST002579_17	Heschl’s gyrus morphology	5.000000e-06
GCST003628_2	Clozapine-induced agranulocytosis/granulocytopenia in treatment-resistant schizophrenia	2.000000e-07
GCST003945_11	Hepcidin/transferrin saturation ratio	2.000000e-06
GCST004750_4	Squamous cell lung carcinoma	3.000000e-07
GCST006904_8	Cerebral amyloid deposition (PET imaging)	4.000000e-06
GCST009391_798	Metabolite levels	9.000000e-06
GCST010151_21	Carotid intima media thickness x smoking interaction	7.000000e-07
GCST010732_4	Sensory peripheral neuropathy in microtubule targeting agent-treated breast cancer	2.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004365	personality trait
EFO:0007902	hepcidin:transferrin saturation ratio
EFO:0007707	cerebral amyloid deposition measurement
EFO:0010395	sphingomyelin 22:0 measurement
EFO:0006527	smoking status measurement
EFO:0005260	response to antimicrotubule agent

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
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
D014256	Trichotillomania	F03.080.600.625; F03.250.800

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	4
bisphenol A	decreases methylation, decreases expression	2
trichostatin A	increases expression	2
Rotenone	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
methylmercuric chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
mercuric bromide	decreases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases 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, decreases expression	1
pyrimidifen	decreases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Vorinostat	decreases expression	1
Acetaminophen	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Carbamazepine	affects expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Tretinoin	decreases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Aflatoxin B1	decreases methylation	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT00182507	PHASE4	COMPLETED	Olanzapine in the Treatment of Hair Pulling (Trichotillomania)
NCT00552266	PHASE4	UNKNOWN	Methylphenidate in ADHD With Trichotillomania
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
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
NCT01133353	PHASE2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	PHASE2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	PHASE2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	PHASE2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	PHASE2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	PHASE2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	PHASE2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	PHASE2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	PHASE2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	PHASE2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome