KLHL9

Summary

KLHL9 (kelch like family member 9, HGNC:18732) is a protein-coding gene on chromosome 9p21.3, encoding Kelch-like protein 9 (Q9P2J3). Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for mitotic progression and cytokinesis.

This gene encodes a protein that belongs to the kelch repeat-containing family, and contains an N-terminal BTB/POZ domain, a BACK domain and six C-terminal kelch repeats. The encoded protein is a component of a complex with cullin 3-based E3 ligase, which plays a role in mitosis. This protein complex is a cell cycle regulator, and functions in the organization and integrity of the spindle midzone in anaphase and the completion of cytokinesis. The complex is required for the removal of the chromosomal passenger protein aurora B from mitotic chromosomes.

Source: NCBI Gene 55958 — RefSeq curated summary.

At a glance

• Gene–disease (curated): distal myopathy (Moderate, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 208 total
• Phenotypes (HPO): 17
• MANE Select transcript: NM_018847

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18732
Approved symbol	KLHL9
Name	kelch like family member 9
Location	9p21.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1354, FLJ13568
Ensembl gene	ENSG00000198642
Ensembl biotype	protein_coding
OMIM	611201
Entrez	55958

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 nonsense_mediated_decay, 1 protein_coding

ENST00000359039, ENST00000718394, ENST00000718395

RefSeq mRNA: 1 — MANE Select: NM_018847 NM_018847

CCDS: CCDS6503

Canonical transcript exons

ENST00000359039 — 1 exons

Exon	Start	End
ENSE00004034958	21329665	21335404

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 94.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.1967 / max 155.1186, expressed in 1721 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100209	18.2922	1720
100208	0.9045	638

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	94.97	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.96	gold quality
choroid plexus epithelium	UBERON:0003911	94.92	gold quality
pericardium	UBERON:0002407	94.90	gold quality
pancreatic ductal cell	CL:0002079	94.88	gold quality
mammary duct	UBERON:0001765	94.71	gold quality
cauda epididymis	UBERON:0004360	94.57	gold quality
caput epididymis	UBERON:0004358	94.56	gold quality
pigmented layer of retina	UBERON:0001782	94.42	gold quality
trigeminal ganglion	UBERON:0001675	94.27	gold quality
germinal epithelium of ovary	UBERON:0001304	94.18	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.16	gold quality
cardia of stomach	UBERON:0001162	94.02	gold quality
epithelium of mammary gland	UBERON:0003244	93.99	gold quality
dorsal root ganglion	UBERON:0000044	93.97	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.93	gold quality
cartilage tissue	UBERON:0002418	93.71	gold quality
trabecular bone tissue	UBERON:0002483	93.68	gold quality
superior vestibular nucleus	UBERON:0007227	93.66	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.63	gold quality
middle frontal gyrus	UBERON:0002702	93.62	gold quality
pylorus	UBERON:0001166	93.61	gold quality
tongue squamous epithelium	UBERON:0006919	93.56	gold quality
renal medulla	UBERON:0000362	93.53	gold quality
colonic mucosa	UBERON:0000317	93.51	gold quality
bronchial epithelial cell	CL:0002328	93.48	gold quality
decidua	UBERON:0002450	93.48	gold quality
lower lobe of lung	UBERON:0008949	93.40	gold quality
type B pancreatic cell	CL:0000169	93.33	gold quality
epithelium of bronchus	UBERON:0002031	93.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.64
E-GEOD-124858	no	248.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

148 targeting KLHL9, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-548AE-3P	99.93	72.66	4867

Literature-anchored findings (GeneRIF, showing 1)

• A unique form of early onset autosomal dominant distal myopathy is associated with a kelch-like homologue 9 mutation and interferes with normal skeletal muscle through a novel pathogenetic mechanism. (PMID:20554658)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	klhl13	ENSDARG00000086463
danio_rerio		ENSDARG00000103786
mus_musculus	Klhl9	ENSMUSG00000070923
rattus_norvegicus	Klhl9	ENSRNOG00000081634

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), KBTBD8 (ENSG00000163376), KBTBD6 (ENSG00000165572), KLHL26 (ENSG00000167487), KLHL30 (ENSG00000168427), KBTBD2 (ENSG00000170852), KLHL6 (ENSG00000172578), KLHL15 (ENSG00000174010), KLHL38 (ENSG00000175946), KBTBD11 (ENSG00000176595), KLHDC7A (ENSG00000179023), KLHL28 (ENSG00000179454), KBTBD3 (ENSG00000182359)

Protein

Protein identifiers

Kelch-like protein 9 — Q9P2J3 (reviewed: Q9P2J3)

All UniProt accessions (2): Q9P2J3, Q58EZ4

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for mitotic progression and cytokinesis. The BCR(KLHL9-KLHL13) E3 ubiquitin ligase complex mediates the ubiquitination of AURKB and controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis.

Subunit / interactions. Component of the BCR(KLHL9-KLHL13) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL9, KLHL13 and RBX1. Interacts with AURKB.

Pathway. Protein modification; protein ubiquitination.

RefSeq proteins (1): NP_061335* (*=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

Pfam: PF00651, PF01344, PF07707, PF24681

UniProt features (10 total): repeat 6, domain 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P2J3-F1	92.00	0.86

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: 249 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_CYTOKINESIS, KOYAMA_SEMA3B_TARGETS_UP, GOBP_REGULATION_OF_CELL_CYCLE, TGTGTGA_MIR377, GOBP_REGULATION_OF_CYTOKINESIS, GOBP_REGULATION_OF_CELL_DIVISION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, PID_AURORA_B_PATHWAY, FONTAINE_PAPILLARY_THYROID_CARCINOMA_DN, KEGG_UBIQUITIN_MEDIATED_PROTEOLYSIS

GO Biological Process (3): protein ubiquitination (GO:0016567), regulation of cytokinesis (GO:0032465), cell division (GO:0051301)

GO Molecular Function (3): cullin family protein binding (GO:0097602), ubiquitin-protein transferase activity (GO:0004842), protein binding (GO:0005515)

GO Cellular Component (3): cytosol (GO:0005829), midbody (GO:0030496), Cul3-RING ubiquitin ligase complex (GO:0031463)

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
protein modification by small protein conjugation	1
cytokinesis	1
regulation of cell cycle process	1
regulation of cell division	1
cellular process	1
protein binding	1
ubiquitin-like protein transferase activity	1
binding	1
cytoplasm	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

838 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLHL9	CUL3	Q13618	993
KLHL9	AURKB	Q96GD4	822
KLHL9	KLHL13	Q9P2N7	768
KLHL9	RBX1	P62877	627
KLHL9	IFNE	Q86WN2	560
KLHL9	IFNK	Q9P0W0	507
KLHL9	MTAP	Q13126	479
KLHL9	SMAD3	P84022	444
KLHL9	MYOT	Q9UBF9	357
KLHL9	ANO5	Q75V66	352
KLHL9	KCTD6	Q8NC69	352
KLHL9	ADSS1	Q8N142	327
KLHL9	PLAA	Q9Y263	321
KLHL9	ELAVL2	Q12926	320
KLHL9	GNE	Q9Y223	320

IntAct

125 interactions, top by confidence:

A	B	Type	Score
HEXIM1	CCNT1	psi-mi:“MI:0914”(association)	0.930
CUL3	KLHL12	psi-mi:“MI:0914”(association)	0.920
INO80E	YY1	psi-mi:“MI:0914”(association)	0.900
KLHL9	CUL3	psi-mi:“MI:0915”(physical association)	0.860
KLHL9	CUL3	psi-mi:“MI:0914”(association)	0.860
KLHL12	KLHL2	psi-mi:“MI:0914”(association)	0.850
CUL3	RBX1	psi-mi:“MI:0914”(association)	0.820
KLHL13	CUL3	psi-mi:“MI:0914”(association)	0.810
FBXL17	SKP1	psi-mi:“MI:0914”(association)	0.790
HEXIM2	AHCYL1	psi-mi:“MI:0914”(association)	0.740
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
KLHL26	CUL3	psi-mi:“MI:0914”(association)	0.730
KLHL24	CUL3	psi-mi:“MI:0914”(association)	0.730
FBXL17	BACH1	psi-mi:“MI:0914”(association)	0.730
CEP170	KIF2A	psi-mi:“MI:2364”(proximity)	0.650
KLHL13	COPS2	psi-mi:“MI:0914”(association)	0.640
KLHL22	TMEM223	psi-mi:“MI:0914”(association)	0.640
KLHL21	CUL3	psi-mi:“MI:0914”(association)	0.640
KLHL25	ENC1	psi-mi:“MI:0914”(association)	0.640
KLHL22	METTL15	psi-mi:“MI:0914”(association)	0.640
ZNF414	AHCYL1	psi-mi:“MI:0914”(association)	0.640
ETV6	LRP5	psi-mi:“MI:0914”(association)	0.640
KLHL9	ENC1	psi-mi:“MI:0914”(association)	0.640
UNC119	UNC119B	psi-mi:“MI:0914”(association)	0.640

BioGRID (130): KLHL22 (Affinity Capture-MS), KLHL21 (Affinity Capture-MS), CUL3 (Affinity Capture-MS), KLHL13 (Affinity Capture-MS), KLHL9 (Affinity Capture-MS), KLHL9 (Proximity Label-MS), KLHL9 (Affinity Capture-MS), KLHL9 (Affinity Capture-MS), KLHL9 (Affinity Capture-RNA), KLHL9 (Affinity Capture-MS), KLHL9 (PCA), KLHL9 (Affinity Capture-MS), KLHL9 (Affinity Capture-MS), KLHL9 (Proximity Label-MS), KLHL9 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8Q1W5, A6QQY2, B0WWP2, B3NDN0, B4HIK1, B4L0G9, B4LIG6, B4PD06, D3Z8N4, E0CZ16, E1B932, E7F6F9, E9Q4F2, F1LZ52, O94889, P28575, P57790, P59280, Q08DK3, Q14145, Q16RL8, Q2T9Z7, Q53G59, Q5R774, Q5R7B8, Q5U374, Q5ZKD9, Q5ZLD3, Q684M4, Q6DFF6, Q6JEL2, Q6JEL3, Q6NRH0, Q6TDP3, Q6TDP4, Q6ZPT1, Q7QGL0, Q80TF4, Q8BZM0, Q8K430

Diamond homologs: A0JN76, A1L2U9, A1YEX3, A1YPR0, A2AAX3, B1WAZ8, B1WBS3, B1WBU4, B2RXF5, D3ZA50, O14867, O15062, O15156, O15209, O43167, O43298, O43829, O88282, O88939, O93567, O95365, P24278, P41182, P41183, P52739, P97302, P97303, Q08376, Q0IH98, Q0IJ29, Q0P4X6, Q0VCJ6, Q13105, Q14526, Q1H9T6, Q1L8W0, Q2T9Z7, Q3B725, Q3B7N9, Q3SWU4

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
KLHL9	“up-regulates activity”	AURKB	binding
KLHL9	“up-regulates activity”	“Cullin 3-RBX1-Skp1”	binding
KLHL9	“down-regulates quantity by destabilization”	CEBPB	binding
KLHL9	“down-regulates quantity by destabilization”	CEBPD	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 142 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
DNA Damage Recognition in GG-NER	9	28.2×	8e-09
Formation of TC-NER Pre-Incision Complex	7	16.3×	3e-05
Negative regulation of NOTCH4 signaling	6	15.7×	2e-04
NOTCH1 Intracellular Domain Regulates Transcription	5	13.1×	3e-03
GSK3B-mediated proteasomal degradation of PD-L1(CD274)	5	13.1×	3e-03
Constitutive Signaling by NOTCH1 PEST Domain Mutants	5	10.8×	5e-03
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	5	10.8×	5e-03
Neddylation	18	9.4×	4e-10

GO biological processes:

GO term	Partners	Fold	FDR
protein neddylation	7	39.3×	1e-07
regulation of protein neddylation	5	37.5×	4e-05
protein monoubiquitination	7	19.3×	2e-05
positive regulation of G1/S transition of mitotic cell cycle	5	16.1×	3e-03
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	5	15.0×	3e-03
cellular response to amino acid stimulus	5	12.3×	7e-03
cellular response to UV	5	11.8×	7e-03
positive regulation of TORC1 signaling	5	11.8×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	157
Likely benign	42
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

103 predictions. Top by Δscore:

Variant	Effect	Δscore
9:21331920:C:T	acceptor_gain	0.9100
9:21331920:C:CT	acceptor_gain	0.8600
9:21335113:G:T	donor_gain	0.8300
9:21335111:A:C	donor_gain	0.8200
9:21333000:TTAG:T	donor_gain	0.7900
9:21333001:TAG:T	donor_gain	0.7400
9:21333002:AGA:A	donor_gain	0.7400
9:21335112:TG:T	donor_gain	0.7000
9:21335120:T:C	donor_gain	0.6400
9:21331919:C:T	acceptor_gain	0.6300
9:21332967:A:AC	donor_gain	0.6100
9:21335116:CTGGT:C	donor_gain	0.5900
9:21335117:TGGTT:T	donor_gain	0.5900
9:21335122:C:T	donor_gain	0.5600
9:21331906:C:CT	acceptor_gain	0.5500
9:21335092:A:AC	donor_gain	0.5500
9:21333145:T:C	donor_gain	0.5400
9:21335091:CA:C	donor_gain	0.5300
9:21335192:A:AC	donor_gain	0.5200
9:21335193:C:CC	donor_gain	0.5200
9:21335093:TC:T	donor_gain	0.5100
9:21332981:A:AC	donor_gain	0.5000
9:21332982:C:CC	donor_gain	0.5000
9:21335090:TCATC:T	donor_gain	0.5000
9:21335094:C:T	donor_gain	0.5000
9:21334249:C:CC	acceptor_gain	0.4900
9:21331907:A:T	acceptor_gain	0.4600
9:21330917:TCTCA:T	acceptor_gain	0.4300
9:21334248:A:AC	acceptor_gain	0.4300
9:21335121:TC:T	donor_gain	0.4300

AlphaMissense

4095 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:21333140:A:G	W574R	1.000
9:21333140:A:T	W574R	1.000
9:21333205:C:T	G552E	1.000
9:21333287:A:G	W525R	1.000
9:21333287:A:T	W525R	1.000
9:21333505:C:T	G452E	1.000
9:21333584:A:G	W426R	1.000
9:21333584:A:T	W426R	1.000
9:21333725:A:G	W379R	1.000
9:21333725:A:T	W379R	1.000
9:21333881:A:G	W327R	1.000
9:21333881:A:T	W327R	1.000
9:21333949:C:T	G304E	1.000
9:21334043:C:G	A273P	1.000
9:21334111:A:G	L250P	1.000
9:21334378:G:T	A161D	1.000
9:21334474:G:T	A129D	1.000
9:21334475:C:G	A129P	1.000
9:21334533:A:C	F109L	1.000
9:21334533:A:T	F109L	1.000
9:21334535:A:G	F109L	1.000
9:21334552:A:G	L103P	1.000
9:21334618:A:G	F81S	1.000
9:21334638:A:C	S74R	1.000
9:21334638:A:T	S74R	1.000
9:21334640:T:G	S74R	1.000
9:21334666:A:T	V65D	1.000
9:21333090:A:C	C590W	0.999
9:21333138:C:A	W574C	0.999
9:21333138:C:G	W574C	0.999

dbSNP variants (sampled 300 via entrez): RS1000025937 (9:21335189 C>G,T), RS1000413361 (9:21335459 T>A), RS1000487841 (9:21330913 CCT>C), RS1000531934 (9:21337092 A>G), RS1000590957 (9:21330102 T>C), RS1000601764 (9:21335655 T>G), RS1001155182 (9:21336746 G>A), RS1001226273 (9:21331510 C>A,T), RS1001585015 (9:21335238 G>A), RS1001656293 (9:21331209 TAA>T), RS1001895990 (9:21336103 C>G), RS1002051478 (9:21336174 ATAT>A), RS1002328377 (9:21336372 T>C), RS1003004477 (9:21333299 T>A,C), RS1003042332 (9:21333913 T>C)

Disease associations

OMIM: gene MIM:611201 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
distal myopathy	Moderate	Autosomal dominant
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (2): Tourette syndrome (MONDO:0007661), distal myopathy (MONDO:0018949)

Orphanet (0):

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0001288	Gait disturbance
HP:0001430	Abnormal calf musculature morphology
HP:0002166	Impaired vibration sensation in the lower limbs
HP:0002505	Loss of ambulation
HP:0002936	Distal sensory impairment
HP:0003376	Steppage gait
HP:0003438	Absent Achilles reflex
HP:0003458	EMG: myopathic abnormalities
HP:0003477	Peripheral axonal neuropathy
HP:0006466	Ankle flexion contracture
HP:0006844	Absent patellar reflexes
HP:0006937	Impaired distal tactile sensation
HP:0008954	Intrinsic hand muscle atrophy
HP:0009005	Weakness of the intrinsic hand muscles
HP:0009031	Amyotrophy of ankle musculature
HP:0009063	Progressive distal muscle weakness
HP:0040081	Abnormal circulating creatine kinase concentration

GWAS associations

0 associations (top):

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: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Valproic Acid	affects expression, affects cotreatment, increases expression	2
Cadmium Chloride	increases expression, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
avobenzone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
NSC 689534	affects binding, increases expression	1
Temozolomide	increases expression	1
Antimycin A	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cadmium	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Copper	increases expression, affects binding	1
Dexamethasone	affects cotreatment, increases expression	1
Fluorouracil	affects response to substance	1
Hydralazine	increases expression, affects cotreatment	1
Indomethacin	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

184 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