KBTBD8

Summary

KBTBD8 (kelch repeat and BTB domain containing 8, HGNC:30691) is a protein-coding gene on chromosome 3p14.1, encoding Kelch repeat and BTB domain-containing protein 8 (Q8NFY9). Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of neural crest specification.

Predicted to enable ubiquitin-like ligase-substrate adaptor activity. Involved in neural crest cell development; neural crest formation; and protein monoubiquitination. Part of Cul3-RING ubiquitin ligase complex.

Source: NCBI Gene 84541 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (No Known Disease Relationship, GenCC)
• GWAS associations: 14
• Clinical variants (ClinVar): 71 total
• Druggable target: yes
• MANE Select transcript: NM_032505

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30691
Approved symbol	KBTBD8
Name	kelch repeat and BTB domain containing 8
Location	3p14.1
Locus type	gene with protein product
Status	Approved
Aliases	TA-KRP, KIAA1842
Ensembl gene	ENSG00000163376
Ensembl biotype	protein_coding
OMIM	616607
Entrez	84541

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000417314, ENST00000460576, ENST00000460784, ENST00000469661, ENST00000484414

RefSeq mRNA: 1 — MANE Select: NM_032505 NM_032505

CCDS: CCDS2906

Canonical transcript exons

ENST00000417314 — 4 exons

Exon	Start	End
ENSE00001073932	67007922	67011210
ENSE00001073934	67003195	67004309
ENSE00003472474	66998981	66999191
ENSE00003553634	66998307	66998371

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 94.51.

FANTOM5 (CAGE): breadth broad, TPM avg 2.6352 / max 124.7403, expressed in 854 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37197	2.3016	760
202804	0.2992	142
37196	0.0344	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	94.51	gold quality
oocyte	CL:0000023	88.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.46	gold quality
ileal mucosa	UBERON:0000331	82.58	gold quality
lymph node	UBERON:0000029	81.47	gold quality
left ventricle myocardium	UBERON:0006566	80.31	gold quality
epithelium of nasopharynx	UBERON:0001951	79.59	gold quality
bone marrow	UBERON:0002371	79.09	gold quality
sperm	CL:0000019	79.08	gold quality
superficial temporal artery	UBERON:0001614	78.32	gold quality
vermiform appendix	UBERON:0001154	77.83	gold quality
epithelial cell of pancreas	CL:0000083	77.06	silver quality
bone marrow cell	CL:0002092	76.11	gold quality
tonsil	UBERON:0002372	75.92	gold quality
leukocyte	CL:0000738	75.82	gold quality
monocyte	CL:0000576	75.72	gold quality
adrenal tissue	UBERON:0018303	74.30	gold quality
cortical plate	UBERON:0005343	73.47	gold quality
deltoid	UBERON:0001476	73.46	silver quality
caecum	UBERON:0001153	72.93	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.58	gold quality
spleen	UBERON:0002106	72.15	gold quality
islet of Langerhans	UBERON:0000006	71.90	gold quality
placenta	UBERON:0001987	71.76	gold quality
granulocyte	CL:0000094	71.56	gold quality
esophagus squamous epithelium	UBERON:0006920	71.53	gold quality
myocardium	UBERON:0002349	71.51	silver quality
mucosa of sigmoid colon	UBERON:0004993	71.38	gold quality
amniotic fluid	UBERON:0000173	71.29	gold quality
parietal pleura	UBERON:0002400	70.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.62
E-MTAB-6075	no	171.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

234 targeting KBTBD8, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6856-5P	100.00	65.47	1298
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-3162-3P	100.00	65.37	363
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-485-3P	99.98	70.68	1585

Literature-anchored findings (GeneRIF, showing 2)

• The authors found that CUL3 complexed with KBTBD8 monoubiquitylates its essential targets only after these have been phosphorylated in multiple motifs by CK2, a kinase whose levels gradually increase during embryogenesis. (PMID:29999490)
• Downregulation of the ubiquitin ligase KBTBD8 prevented epithelial ovarian cancer progression. (PMID:33109073)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	kbtbd8	ENSDARG00000070698
mus_musculus	Kbtbd8	ENSMUSG00000030031
rattus_norvegicus	Kbtbd8	ENSRNOG00000013390

Paralogs (54): KLHL13 (ENSG00000003096), KLHL20 (ENSG00000076321), KEAP1 (ENSG00000079999), KLHL42 (ENSG00000087448), KLHL22 (ENSG00000099910), KLHL4 (ENSG00000102271), KLHL2 (ENSG00000109466), KLHL5 (ENSG00000109790), BACH2 (ENSG00000112182), KLHL18 (ENSG00000114648), KLHL24 (ENSG00000114796), IVNS1ABP (ENSG00000116679), KLHL12 (ENSG00000117153), KLHL29 (ENSG00000119771), KBTBD7 (ENSG00000120696), KLHL7 (ENSG00000122550), KLHL31 (ENSG00000124743), KLHDC7B (ENSG00000130487), KLHL36 (ENSG00000135686), KLHL8 (ENSG00000145332), KLHL3 (ENSG00000146021), KLHL35 (ENSG00000149243), KLHL1 (ENSG00000150361), BACH1 (ENSG00000156273), KLHL40 (ENSG00000157119), KLHL10 (ENSG00000161594), KLHL21 (ENSG00000162413), KLHDC8A (ENSG00000162873), KBTBD6 (ENSG00000165572), KLHL26 (ENSG00000167487), KLHL30 (ENSG00000168427), KBTBD2 (ENSG00000170852), KLHL6 (ENSG00000172578), KLHL15 (ENSG00000174010), KLHL38 (ENSG00000175946), KBTBD11 (ENSG00000176595), KLHDC7A (ENSG00000179023), KLHL28 (ENSG00000179454), KBTBD3 (ENSG00000182359), KLHL33 (ENSG00000185271)

Protein

Protein identifiers

Kelch repeat and BTB domain-containing protein 8 — Q8NFY9 (reviewed: Q8NFY9)

Alternative names: T-cell activation kelch repeat protein

All UniProt accessions (3): C9J331, C9JAA6, Q8NFY9

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of neural crest specification. The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and TCOF1: monoubiquitination promotes the formation of a NOLC1-TCOF1 complex that acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification.

Subunit / interactions. Component of the BCR(KBTBD8) E3 ubiquitin ligase complex, at least composed of CUL3, KBTBD8 and RBX1.

Subcellular location. Cytoplasm. Cytoskeleton. Spindle. Golgi apparatus.

Similarity. Belongs to the KBTBD8 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NFY9-1	1	yes
Q8NFY9-2	2

RefSeq proteins (1): NP_115894* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR006652	Kelch_1	Repeat
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR011705	BACK	Domain
IPR015915	Kelch-typ_b-propeller	Homologous_superfamily
IPR017096	BTB-kelch_protein	Family
IPR028764	BTB/POZ_KBTBD8	Domain

Pfam: PF00651, PF01344, PF07707

UniProt features (16 total): repeat 5, sequence variant 3, domain 2, mutagenesis site 2, chain 1, splice variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NFY9-F1	88.48	0.70

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (2):

Position	Phenotype
74	abolishes cul3-binding and ability to mediate monoubiquitination of nolc1 and tcof1.
579	abolishes substrate-binding and ability to mediate monoubiquitination of nolc1 and tcof1.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-8951664	Neddylation
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 256 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, TGGTGCT_MIR29A_MIR29B_MIR29C, MODULE_97, AP1_01, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, ATACCTC_MIR202, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, AACYNNNNTTCCS_UNKNOWN, MODULE_182, CTATGCA_MIR153, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, GOBP_TRANSLATION

GO Biological Process (5): regulation of translation (GO:0006417), protein monoubiquitination (GO:0006513), neural crest formation (GO:0014029), neural crest cell development (GO:0014032), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

GO Molecular Function (2): ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), spindle (GO:0005819), cytosol (GO:0005829), Cul3-RING ubiquitin ligase complex (GO:0031463), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Post-translational protein modification	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Metabolism of proteins	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	2
intracellular membraneless organelle	2
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
protein ubiquitination	1
epithelial to mesenchymal transition	1
chordate embryonic development	1
anatomical structure formation involved in morphogenesis	1
neural crest cell differentiation	1
stem cell development	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
enzyme-substrate adaptor activity	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
microtubule cytoskeleton	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

814 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KBTBD8	CUL3	Q13618	907
KBTBD8	NOLC1	Q14978	636
KBTBD8	TCOF1	Q13428	537
KBTBD8	LRRC19	Q9H756	476
KBTBD8	BRD2	P25440	469
KBTBD8	ELOC	Q15369	457
KBTBD8	BTBD7	Q9P203	446
KBTBD8	HSD17B11	Q8NBQ5	425
KBTBD8	GULP1	Q9UBP9	404
KBTBD8	BCL2L13	Q9BXK5	395
KBTBD8	RIPK4	P57078	390
KBTBD8	CDYL2	Q8N8U2	387
KBTBD8	CORO7	P57737	383
KBTBD8	CAMKMT	Q7Z624	381
KBTBD8	SLF1	Q9BQI6	364

IntAct

25 interactions, top by confidence:

A	B	Type	Score
KBTBD8	KBTBD7	psi-mi:“MI:0915”(physical association)	0.740
KBTBD8	KBTBD7	psi-mi:“MI:0914”(association)	0.740
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
SOCS7	NCK2	psi-mi:“MI:0914”(association)	0.670
KBTBD8	CUL3	psi-mi:“MI:0915”(physical association)	0.620
CUL3	RHOBTB1	psi-mi:“MI:0914”(association)	0.530
KBTBD8	FBXL17	psi-mi:“MI:0915”(physical association)	0.500
MOG	KBTBD8	psi-mi:“MI:0915”(physical association)	0.400
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
ZNF692	NSD2	psi-mi:“MI:0914”(association)	0.350
GAN	ZMYM3	psi-mi:“MI:0914”(association)	0.350
KLHL29	NPHP3	psi-mi:“MI:0914”(association)	0.350
FBXL17	ENC1	psi-mi:“MI:0914”(association)	0.350
KBTBD8	TCOF1	psi-mi:“MI:0914”(association)	0.350
CD6	CIBAR1	psi-mi:“MI:0914”(association)	0.350
AGO4	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
GAN	CACNB1	psi-mi:“MI:0914”(association)	0.350

BioGRID (55): TCOF1 (Affinity Capture-Western), NOLC1 (Affinity Capture-Western), ARRB1 (Affinity Capture-Western), ARRB2 (Affinity Capture-Western), PKN1 (Affinity Capture-Western), CUL3 (Affinity Capture-Western), TCOF1 (Reconstituted Complex), NOLC1 (Reconstituted Complex), CUL3 (Reconstituted Complex), KBTBD8 (Affinity Capture-Western), KBTBD8 (Affinity Capture-Western), KBTBD8 (Affinity Capture-Western), KBTBD8 (Affinity Capture-MS), KBTBD8 (Affinity Capture-MS), KBTBD8 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B8YAB1, B1H285, B3DIV9, E9QIN8, E9QJ30, F1QEG2, O88879, Q08CL3, Q08CY1, Q0D2A9, Q13939, Q28068, Q3UQV5, Q3ZCT8, Q503R4, Q5F3N5, Q5R4S6, Q5R663, Q5RG82, Q5XHZ6, Q5XI58, Q5ZI33, Q69ZK5, Q6DFF7, Q6DFU2, Q6Q7X9, Q6V595, Q7ZVQ8, Q86V97, Q8BHI4, Q8BUL5, Q8BWA5, Q8CA72, Q8CDE2, Q8CE33, Q8IXQ5, Q8NAB2, Q8NFY9, Q8R179, Q8WVZ9

Diamond homologs: A0A1B8YAB1, A1YPR0, B0WWP2, B1H285, B3M9V8, B3NDN0, B4GRJ2, B4HIK1, B4J045, B4L0G9, B4LIG6, B4MXW3, B4PD06, B4QLQ2, C9JR72, D3Z8N4, E0CZ16, G3X9X1, O15062, O88939, O93567, O95365, P28575, P41182, P41183, Q08CL3, Q08DK3, Q13105, Q16RL8, Q2M0J9, Q3UQV5, Q52KB5, Q5EXX3, Q5R7B8, Q5RDY3, Q5TC79, Q5ZI33, Q5ZKD9, Q5ZM39, Q60821

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 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
proteasome-mediated ubiquitin-dependent protein catabolic process	7	16.6×	2e-05
protein ubiquitination	6	11.3×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

723 predictions. Top by Δscore:

Variant	Effect	Δscore
3:67003193:A:AG	acceptor_gain	1.0000
3:67003194:G:GG	acceptor_gain	1.0000
3:67003194:GATCC:G	acceptor_gain	1.0000
3:67004308:GG:G	donor_gain	1.0000
3:67004309:GG:G	donor_gain	1.0000
3:66999187:TTCAG:T	donor_loss	0.9900
3:66999188:TCAG:T	donor_loss	0.9900
3:66999190:AG:A	donor_loss	0.9900
3:66999191:GG:G	donor_loss	0.9900
3:66999192:G:A	donor_loss	0.9900
3:66999193:T:G	donor_loss	0.9900
3:67003191:TTA:T	acceptor_loss	0.9900
3:67003191:TTAGA:T	acceptor_gain	0.9900
3:67003192:TAGAT:T	acceptor_gain	0.9900
3:67003194:G:GA	acceptor_loss	0.9900
3:67003194:GATC:G	acceptor_gain	0.9900
3:67007918:TTA:T	acceptor_loss	0.9900
3:67007919:TA:T	acceptor_loss	0.9900
3:67007920:A:AG	acceptor_gain	0.9900
3:67007921:G:GA	acceptor_loss	0.9900
3:67007921:G:GG	acceptor_gain	0.9900
3:67007921:GGA:G	acceptor_gain	0.9900
3:67007921:GGAGA:G	acceptor_gain	0.9900
3:66998370:AGGT:A	donor_loss	0.9800
3:66998371:GGT:G	donor_loss	0.9800
3:66998372:G:A	donor_loss	0.9800
3:66998373:T:G	donor_loss	0.9800
3:66999124:G:GT	donor_gain	0.9800
3:67003193:AGA:A	acceptor_gain	0.9800
3:67003194:GA:G	acceptor_gain	0.9800

AlphaMissense

4013 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:66999080:T:C	L39P	1.000
3:66999169:G:C	A69P	1.000
3:66999178:A:C	S72R	1.000
3:66999180:C:A	S72R	1.000
3:66999180:C:G	S72R	1.000
3:67003203:T:C	F79S	1.000
3:67003554:T:C	L196P	1.000
3:67003803:G:C	R279T	1.000
3:67003804:G:C	R279S	1.000
3:67003804:G:T	R279S	1.000
3:67003989:G:A	G341E	1.000
3:67003992:G:A	G342E	1.000
3:67004075:T:A	W370R	1.000
3:67004075:T:C	W370R	1.000
3:67004077:G:C	W370C	1.000
3:67004077:G:T	W370C	1.000
3:67004106:G:C	R380T	1.000
3:67004107:A:C	R380S	1.000
3:67004107:A:T	R380S	1.000
3:67004154:G:A	G396E	1.000
3:67004228:T:A	W421R	1.000
3:67004228:T:C	W421R	1.000
3:67008281:T:A	W568R	1.000
3:67008281:T:C	W568R	1.000
3:66999112:G:C	D50H	0.999
3:66999113:A:T	D50V	0.999
3:66999151:T:C	C63R	0.999
3:66999153:T:G	C63W	0.999
3:66999154:C:G	H64D	0.999
3:66999155:A:G	H64R	0.999

dbSNP variants (sampled 300 via entrez): RS1000038680 (3:67011274 T>A,C), RS1000092257 (3:67011006 G>T), RS1000194199 (3:67003834 A>G), RS1000317369 (3:67011025 C>T), RS1000345519 (3:67011267 T>TA), RS1000905470 (3:66998737 T>TGCCGGGCTC), RS1001668595 (3:67002263 T>A), RS1001708994 (3:67009774 T>C), RS1002103206 (3:67007741 A>G), RS1002240130 (3:67005473 C>G,T), RS1002296048 (3:67001355 C>A,T), RS1002405547 (3:67000720 A>G), RS1002636511 (3:67008547 T>C), RS1003106333 (3:67001336 T>C,G), RS1003507033 (3:67007008 A>G,T)

Disease associations

OMIM: gene MIM:616607 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (1): Tourette syndrome (MONDO:0007661)

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001610_10	Renal function-related traits (BUN)	1.000000e-19
GCST002806_3	Type 2 diabetes	4.000000e-06
GCST003542_190	Night sleep phenotypes	4.000000e-06
GCST005411_10	Thrombin-activatable fibrinolysis inhibitor activation peptide	1.000000e-08
GCST005580_258	Intraocular pressure	2.000000e-10
GCST005986_33	Blood urea nitrogen levels	1.000000e-29
GCST006412_34	Intraocular pressure	3.000000e-18
GCST007600_77	Alzheimer’s disease	3.000000e-06
GCST009391_1154	Metabolite levels	8.000000e-07
GCST009391_2064	Metabolite levels	3.000000e-06
GCST009724_31	Vertical cup-disc ratio (multi-trait analysis)	2.000000e-08
GCST009725_25	Intraocular pressure	9.000000e-15
GCST009959_12	Retinal detachment or retinal break	9.000000e-07
GCST010002_428	Refractive error	5.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0010459	aminoadipic acid measurement
EFO:0010346	cholesteryl ester 18:3 measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0010698	retinal break

MeSH disease descriptors (1)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6196112 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	7
bisphenol A	decreases expression, increases expression	3
Benzo(a)pyrene	affects expression, decreases expression, increases expression	3
Tetrachlorodibenzodioxin	decreases expression, affects expression	3
entinostat	increases expression, affects cotreatment	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Estradiol	increases expression	2
Folic Acid	increases expression, decreases expression, affects cotreatment	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
propionaldehyde	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
butyraldehyde	increases expression	1
cupric oxide	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
chloropicrin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
licochalcone B	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
Fulvestrant	decreases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL6094273	Binding	Binding affinity to KBTBD8 (unknown origin) at 10 uM by thermal shift assay	Structure-Guided Conformational Restriction Leading to High-Affinity, Selective, and Cell-Active Tetrahydroisoquinoline-Based Noncovalent Keap1-Nrf2 Inhibitors. — J Med Chem

Clinical trials (associated diseases)

183 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
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
NCT03325010	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03444038	PHASE2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome