ADAMTS6

Summary

ADAMTS6 (ADAM metallopeptidase with thrombospondin type 1 motif 6, HGNC:222) is a protein-coding gene on chromosome 5q12.3, encoding A disintegrin and metalloproteinase with thrombospondin motifs 6 (Q9UKP5).

This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature enzyme. Expression of this gene may be regulated by the cytokine TNF-alpha.

Source: NCBI Gene 11174 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (Limited, GenCC)
• GWAS associations: 33
• Clinical variants (ClinVar): 138 total — 4 pathogenic, 3 likely-pathogenic
• MANE Select transcript: NM_197941

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:222
Approved symbol	ADAMTS6
Name	ADAM metallopeptidase with thrombospondin type 1 motif 6
Location	5q12.3
Locus type	gene with protein product
Status	Approved
Aliases	ADAM-TS6
Ensembl gene	ENSG00000049192
Ensembl biotype	protein_coding
OMIM	605008
Entrez	11174

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 3 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding

ENST00000314351, ENST00000381052, ENST00000381055, ENST00000417396, ENST00000464680, ENST00000470597, ENST00000502886, ENST00000504282

RefSeq mRNA: 1 — MANE Select: NM_197941 NM_197941

CCDS: CCDS3983

Canonical transcript exons

ENST00000381055 — 25 exons

Exon	Start	End
ENSE00001487392	65473577	65473952
ENSE00001895037	65481343	65481920
ENSE00002049900	65148738	65151945
ENSE00003467873	65197022	65197151
ENSE00003489762	65226086	65226219
ENSE00003496268	65242104	65242206
ENSE00003533012	65460170	65460338
ENSE00003536457	65452133	65452216
ENSE00003541168	65224924	65225047
ENSE00003542340	65170617	65170773
ENSE00003542979	65299985	65300131
ENSE00003569559	65334042	65334085
ENSE00003575447	65224320	65224400
ENSE00003576329	65260600	65260663
ENSE00003577653	65451475	65451620
ENSE00003595993	65452707	65452918
ENSE00003610073	65172832	65173008
ENSE00003640811	65214794	65214932
ENSE00003641141	65188016	65188220
ENSE00003643886	65329378	65329483
ENSE00003644348	65291329	65291470
ENSE00003654109	65262817	65262962
ENSE00003670140	65273340	65273447
ENSE00003672448	65470778	65471142
ENSE00003686937	65215324	65215487

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 93.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.2301 / max 274.7869, expressed in 1187 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61947	2.2051	671
61948	1.5573	669
61949	1.3436	671
61946	0.8211	379
61945	0.1991	84
61943	0.1039	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	93.33	gold quality
calcaneal tendon	UBERON:0003701	88.33	gold quality
mucosa of stomach	UBERON:0001199	85.02	gold quality
stromal cell of endometrium	CL:0002255	83.56	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.52	gold quality
placenta	UBERON:0001987	80.91	gold quality
tendon	UBERON:0000043	79.97	gold quality
ventricular zone	UBERON:0003053	79.12	gold quality
adrenal tissue	UBERON:0018303	78.72	gold quality
right uterine tube	UBERON:0001302	77.10	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.41	gold quality
gall bladder	UBERON:0002110	76.23	gold quality
buccal mucosa cell	CL:0002336	75.06	gold quality
sperm	CL:0000019	74.29	silver quality
endometrium	UBERON:0001295	72.60	gold quality
right lung	UBERON:0002167	72.55	gold quality
male germ cell	CL:0000015	72.34	silver quality
ascending aorta	UBERON:0001496	72.14	gold quality
ganglionic eminence	UBERON:0004023	72.10	gold quality
thoracic aorta	UBERON:0001515	72.09	gold quality
tibial artery	UBERON:0007610	71.92	gold quality
popliteal artery	UBERON:0002250	71.90	gold quality
aorta	UBERON:0000947	71.89	gold quality
epithelium of nasopharynx	UBERON:0001951	70.16	gold quality
visceral pleura	UBERON:0002401	69.77	gold quality
cortical plate	UBERON:0005343	69.49	gold quality
pleura	UBERON:0000977	69.05	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	68.68	gold quality
body of uterus	UBERON:0009853	68.53	gold quality
parietal pleura	UBERON:0002400	68.17	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	304.05
E-CURD-119	yes	11.15
E-ANND-3	yes	5.67
E-GEOD-124858	no	469.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

265 targeting ADAMTS6, 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-5692A	100.00	74.40	6850
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-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-7110-3P	100.00	73.18	2486
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-4500	99.99	72.72	2367
HSA-MIR-4531	99.99	69.70	3181

Literature-anchored findings (GeneRIF, showing 9)

• Study shows that the ADAMTS6 transcript contains unusually large untranslated regions (UTRs) at both the 5’ and 3’end, and the 5’UTR contains 11 AUG codons upstream of the predicted ADAMTS6 start codon. (PMID:16129570)
• The gain of function studies indicated that ADAM metallopeptidase with thrombospondin type 1 motif 6 activate NR5A1 gene expression. (PMID:18579725)
• Novel inguinal hernia susceptibility genes are identified as EFEMP1, WT1, EBF2 and ADAMTS6. (PMID:26686553)
• ADAMTS6 inhibits breast tumor development by regulating the ERK pathway via binding of miR-221-3p (PMID:27542224)
• Using siRNA, over-expression and mutagenesis, it was found ADAMTS6 inhibits and ADAMTS10 is required for focal adhesions, epithelial cell-cell junction formation, and microfibril deposition. (PMID:27779234)
• High ADAMTS-6 expression is a marker of poor prognosis in patients with esophageal squamous cell carcinoma. (PMID:29475036)
• Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6. (PMID:30012220)
• Identified a disintegrin and metalloproteinase with thrombospondin motifs 6 serve as a novel gastric cancer prognostic biomarker by bioinformatics analysis. (PMID:33851708)
• The role of ADAMTS6 and ADAMTS17 polymorphisms in susceptibility to lumbar disc herniation in Chinese Han population. (PMID:36810712)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adamts6	ENSDARG00000041982
mus_musculus	Adamts6	ENSMUSG00000046169
rattus_norvegicus	Adamts6	ENSRNOG00000012655

Paralogs (25): ADAMTS2 (ENSG00000087116), PAPLN (ENSG00000100767), ADAMTS8 (ENSG00000134917), ADAMTS7 (ENSG00000136378), ADAMTS14 (ENSG00000138316), ADAMTS17 (ENSG00000140470), ADAMTS18 (ENSG00000140873), ADAMTS10 (ENSG00000142303), ADAMTSL4 (ENSG00000143382), ADAMTS16 (ENSG00000145536), ADAMTS19 (ENSG00000145808), ADAMTS12 (ENSG00000151388), ADAMTS1 (ENSG00000154734), ADAMTS5 (ENSG00000154736), ADAMTS3 (ENSG00000156140), ADAMTSL3 (ENSG00000156218), ADAMTS4 (ENSG00000158859), ADAMTS13 (ENSG00000160323), ADAMTS9 (ENSG00000163638), ADAMTS15 (ENSG00000166106), ADAMTS20 (ENSG00000173157), ADAMTSL1 (ENSG00000178031), ADAMTSL5 (ENSG00000185761), THSD4 (ENSG00000187720), ADAMTSL2 (ENSG00000197859)

Protein

Protein identifiers

A disintegrin and metalloproteinase with thrombospondin motifs 6 — Q9UKP5 (reviewed: Q9UKP5)

All UniProt accessions (1): Q9UKP5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed at low levels in placenta and barely detectable in a number of other tissues.

Post-translational modifications. The precursor is cleaved by a furin endopeptidase. Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.

Induction. Isoform 1 and isoform 2 expressions are up-regulated by TNF in retinal pigment epithelial cells.

Miscellaneous. Contains critical point mutations in the region encoding the catalytic domain as well as 2 point mutations compared with genomic sequence. May either be a rare polymorphism or may have arisen through a combination of aberrant RNA editing and point mutation/sequencing error.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UKP5-1	1, Variant 2	yes
Q9UKP5-2	2, Variant 1
Q9UKP5-3	3, Variant 3
Q9UKP5-4	4, Variant 4

RefSeq proteins (1): NP_922932* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000884	TSP1_rpt	Repeat
IPR001590	Peptidase_M12B	Domain
IPR002870	Peptidase_M12B_N	Domain
IPR010294	ADAMTS_spacer1	Domain
IPR010909	PLAC	Domain
IPR013273	ADAMTS/ADAMTS-like	Family
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR036383	TSP1_rpt_sf	Homologous_superfamily
IPR041645	ADAMTS_CR_2	Domain
IPR045371	ADAMTS_CR_3	Domain
IPR050439	ADAMTS_ADAMTS-like	Family

Pfam: PF00090, PF01421, PF01562, PF05986, PF08686, PF17771, PF19030, PF19236

UniProt features (51 total): disulfide bond 14, domain 8, sequence conflict 8, splice variant 7, glycosylation site 6, binding site 3, signal peptide 1, propeptide 1, region of interest 1, active site 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKP5-F1	77.45	0.20

Functional residue map

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

Catalytic / active sites (1): 404

Ligand- & substrate-binding residues (3): 403; 407; 413

Disulfide bonds (14): 326–387, 362–369, 381–463, 420–447, 490–512, 501–519, 507–542, 532–547, 570–607, 574–612, 585–597, 911–954, 915–959, 926–943

Glycosylation sites (6): 99, 172, 222, 234, 724, 956

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-5083635	Defective B3GALTL causes PpS
R-HSA-5173214	O-glycosylation of TSR domain-containing proteins
R-HSA-1643685	Disease
R-HSA-3781865	Diseases of glycosylation
R-HSA-3906995	Diseases associated with O-glycosylation of proteins
R-HSA-392499	Metabolism of proteins
R-HSA-5173105	O-linked glycosylation
R-HSA-5668914	Diseases of metabolism
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 305 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_CORONARY_VASCULATURE_DEVELOPMENT, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_ARTERY_DEVELOPMENT, GOBP_AORTA_DEVELOPMENT, CDP_01, GGGCATT_MIR365, CATTTCA_MIR203, MODULE_206, TGANTCA_AP1_C, GATA1_03, STONER_ESOPHAGEAL_CARCINOGENESIS_UP

GO Biological Process (7): kidney development (GO:0001822), cardiac septum development (GO:0003279), proteolysis (GO:0006508), extracellular matrix organization (GO:0030198), aorta development (GO:0035904), coronary vasculature development (GO:0060976), heart development (GO:0007507)

GO Molecular Function (5): metalloendopeptidase activity (GO:0004222), metallopeptidase activity (GO:0008237), metal ion binding (GO:0046872), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (2): extracellular matrix (GO:0031012), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Diseases associated with O-glycosylation of proteins	1
O-linked glycosylation	1
Diseases of metabolism	1
Diseases of glycosylation	1
Post-translational protein modification	1
Disease	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	2
renal system development	1
cardiac chamber development	1
anatomical structure development	1
protein metabolic process	1
extracellular structure organization	1
external encapsulating structure organization	1
artery development	1
blood vessel development	1
heart development	1
circulatory system development	1
endopeptidase activity	1
metallopeptidase activity	1
peptidase activity	1
cation binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
external encapsulating structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

690 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAMTS6	FURIN	P09958	710
ADAMTS6	FBN2	P35556	648
ADAMTS6	FBN1	P35555	611
ADAMTS6	LTBP1	P22064	561
ADAMTS6	KRTAP20-3	Q3LI60	474
ADAMTS6	PPWD1	Q96BP3	473
ADAMTS6	SDC4	P31431	464
ADAMTS6	FBN3	Q75N90	440
ADAMTS6	LOX	P28300	434
ADAMTS6	LCN12	Q6JVE5	433
ADAMTS6	COMP	P49747	431
ADAMTS6	GLT8D2	Q9H1C3	399
ADAMTS6	MFAP4	P55083	398
ADAMTS6	TMEM248	Q9NWD8	397
ADAMTS6	C6orf132	Q5T0Z8	338

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ADAMTS6	ERP29	psi-mi:“MI:0915”(physical association)	0.400
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): ADAMTS6 (Affinity Capture-MS), ADAMTS6 (Affinity Capture-MS), ADAMTS6 (Proximity Label-MS), ADAMTS6 (Affinity Capture-MS), ADAMTS6 (Proximity Label-MS), ADAMTS6 (Affinity Capture-RNA), ADAMTS6 (Negative Genetic), ADAMTS6 (Cross-Linking-MS (XL-MS)), USP25 (Cross-Linking-MS (XL-MS)), ADAMTS6 (Co-fractionation), ADAMTS6 (Co-fractionation), ADAMTS6 (Affinity Capture-MS), ADAMTS6 (Affinity Capture-RNA), ADAMTS6 (Protein-peptide)

ESM2 similar proteins: A2A863, A5Z1X6, A8X3A7, B0FYY4, G5ECE3, O14672, O35598, O77633, P05107, P05556, P07228, P08069, P09055, P11046, P11584, P11835, P12606, P12607, P16144, P18563, P24348, P26007, P32592, P33434, P33436, P34446, P49134, P53712, P53713, P53714, Q00174, Q10741, Q10743, Q19267, Q1RPR6, Q21313, Q27591, Q27874, Q2VJ42, Q3UV74

Diamond homologs: A2VEC9, A6QNY1, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, O08721, O08722, O08747, O14514, O15072, O55225, O60241, O60242, O75173, O88783, O95185, O95450, P04275, P07358, P07996, P27918, P35441, P35442, P35448, P55314, P57110, P58397, P58459, P59384, P79331, P80012, P97857, P98088, P98092, P98160, P98164

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	110
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1456117	NC_000005.9:g.(?63256278)(65374358_?)del	Pathogenic
1527167	GRCh37/hg19 5q12.3-13.2(chr5:64049692-70306646)	Pathogenic
3024635	GRCh37/hg19 5q12.3-13.1(chr5:64111112-67101123)x1	Pathogenic
3148880	GRCh37/hg19 5q12.3-13.2(chr5:64364710-72835471)x1	Pathogenic
151651	GRCh38/hg38 5q12.3(chr5:65413763-66430722)x1	Likely pathogenic
442344	GRCh37/hg19 5q12.1-13.2(chr5:58966132-68847066)x4	Likely pathogenic
929750	NM_197941.4(ADAMTS6):c.2840G>A (p.Arg947Gln)	Likely pathogenic

SpliceAI

5429 predictions. Top by Δscore:

Variant	Effect	Δscore
5:65170612:CTCA:C	donor_loss	1.0000
5:65170613:TCA:T	donor_loss	1.0000
5:65170614:CA:C	donor_loss	1.0000
5:65170615:A:AC	donor_gain	1.0000
5:65170616:C:CC	donor_gain	1.0000
5:65170616:C:CT	donor_loss	1.0000
5:65170616:CCTT:C	donor_gain	1.0000
5:65170640:CTG:C	donor_gain	1.0000
5:65170641:TGT:T	donor_gain	1.0000
5:65170769:GAACA:G	acceptor_gain	1.0000
5:65170770:AACA:A	acceptor_gain	1.0000
5:65170771:ACA:A	acceptor_gain	1.0000
5:65170772:CA:C	acceptor_gain	1.0000
5:65170772:CAC:C	acceptor_gain	1.0000
5:65170772:CACT:C	acceptor_gain	1.0000
5:65170773:ACTA:A	acceptor_gain	1.0000
5:65170774:C:CC	acceptor_gain	1.0000
5:65170781:C:CT	acceptor_gain	1.0000
5:65170781:C:T	acceptor_gain	1.0000
5:65170782:A:T	acceptor_gain	1.0000
5:65170787:C:CT	acceptor_gain	1.0000
5:65172826:CCTTA:C	donor_loss	1.0000
5:65172827:CTTA:C	donor_loss	1.0000
5:65172828:TTA:T	donor_loss	1.0000
5:65172829:TA:T	donor_loss	1.0000
5:65172830:A:C	donor_loss	1.0000
5:65172831:CCTGG:C	donor_gain	1.0000
5:65172911:T:A	donor_gain	1.0000
5:65173004:GTACA:G	acceptor_gain	1.0000
5:65173005:TACA:T	acceptor_gain	1.0000

AlphaMissense

7416 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:65151848:G:C	C1114W	1.000
5:65151849:C:G	C1114S	1.000
5:65151849:C:T	C1114Y	1.000
5:65151850:A:G	C1114R	1.000
5:65151850:A:T	C1114S	1.000
5:65151860:A:C	C1110W	1.000
5:65151861:C:A	C1110F	1.000
5:65151861:C:G	C1110S	1.000
5:65151861:C:T	C1110Y	1.000
5:65151862:A:G	C1110R	1.000
5:65151862:A:T	C1110S	1.000
5:65151872:G:C	F1106L	1.000
5:65151872:G:T	F1106L	1.000
5:65151873:A:C	F1106C	1.000
5:65151873:A:G	F1106S	1.000
5:65151874:A:G	F1106L	1.000
5:65151876:T:C	Y1105C	1.000
5:65151887:G:C	C1101W	1.000
5:65151888:C:A	C1101F	1.000
5:65151888:C:G	C1101S	1.000
5:65151888:C:T	C1101Y	1.000
5:65151889:A:G	C1101R	1.000
5:65151889:A:T	C1101S	1.000
5:65151890:G:C	F1100L	1.000
5:65151890:G:T	F1100L	1.000
5:65151891:A:C	F1100C	1.000
5:65151892:A:G	F1100L	1.000
5:65151909:A:G	L1094P	1.000
5:65151914:G:C	C1092W	1.000
5:65151915:C:A	C1092F	1.000

dbSNP variants (sampled 300 via entrez): RS1000001800 (5:65423603 G>A), RS1000012046 (5:65336145 A>G), RS1000014382 (5:65448137 T>C), RS1000016559 (5:65302687 G>T), RS1000018503 (5:65310067 G>A), RS1000026716 (5:65148590 G>C), RS1000041660 (5:65188594 G>A), RS1000044443 (5:65446067 A>G), RS1000063810 (5:65291591 C>T), RS1000070690 (5:65309693 T>A,C), RS1000072974 (5:65188959 T>C), RS1000078240 (5:65367893 T>C), RS1000081961 (5:65284524 T>C), RS1000110745 (5:65375954 G>A,C), RS1000116324 (5:65205010 C>G)

Disease associations

OMIM: gene MIM:605008 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	Limited	Unknown

Mondo (2): primary ovarian failure (MONDO:0005387), Tourette syndrome (MONDO:0007661)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

33 associations (top):

Study	Trait	p-value
GCST001757_2	Schizophrenia	1.000000e-06
GCST001806_6	Corneal structure	6.000000e-11
GCST002056_6	Osteosarcoma	5.000000e-07
GCST003198_2	Inguinal hernia	4.000000e-09
GCST003804_4	Non-response to bupropion and depression	7.000000e-07
GCST005580_219	Intraocular pressure	4.000000e-21
GCST005580_221	Intraocular pressure	5.000000e-20
GCST005667_32	Central corneal thickness	6.000000e-14
GCST006366_3	Central corneal thickness	3.000000e-12
GCST006394_54	Intraocular pressure	7.000000e-11
GCST006412_46	Intraocular pressure	5.000000e-12
GCST006952_20	Feeling tense	3.000000e-09
GCST006979_103	Heel bone mineral density	8.000000e-10
GCST008839_434	Height	9.000000e-20
GCST008839_592	Height	8.000000e-35
GCST009220_2	Corpus callosum anterior volume	9.000000e-07
GCST009414_17	Central corneal thickness	6.000000e-09
GCST009414_30	Central corneal thickness	4.000000e-11
GCST010396_305	Gut microbiota (bacterial taxa, hurdle binary method)	6.000000e-06
GCST010701_121	Cortical surface area (MOSTest)	6.000000e-11
GCST010702_62	Subcortical volume (MOSTest)	6.000000e-12
GCST010703_77	Brain morphology (MOSTest)	2.000000e-16
GCST012226_251	Waist circumference adjusted for body mass index	1.000000e-08
GCST012324_9	LDL levels x SSRI defined daily dose interaction in schizophrenia or bipolar disorder	2.000000e-09
GCST90000654_19	Central corneal thickness	5.000000e-23
GCST90020024_912	A body shape index	4.000000e-08
GCST90020024_913	A body shape index	2.000000e-08
GCST90020024_914	A body shape index	4.000000e-09
GCST90020029_1532	Waist circumference adjusted for body mass index	3.000000e-09
GCST90020029_1533	Waist circumference adjusted for body mass index	5.000000e-08

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004345	corneal topography
EFO:0004695	intraocular pressure measurement
EFO:0005213	central corneal thickness
EFO:0009596	feeling tense measurement
EFO:0009270	heel bone mineral density
EFO:0007874	gut microbiome measurement
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0005658	response to selective serotonin reuptake inhibitor

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
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)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — M12: Astacin/Adamalysin

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	4
Benzo(a)pyrene	decreases expression, increases methylation	3
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	3
trichostatin A	increases expression	2
(+)-JQ1 compound	affects cotreatment, decreases expression	2
8-Bromo Cyclic Adenosine Monophosphate	increases expression	2
bisphenol F	increases methylation	1
TAK-243	increases sumoylation	1
sotorasib	affects cotreatment, increases expression	1
aminomethylphosphonic acid (AMPA)	increases expression	1
methyleugenol	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
arsenite	affects binding, decreases reaction	1
sulforaphane	decreases expression	1
cupric chloride	increases expression	1
pentanal	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dimethylarsinous acid	increases expression	1
abrine	increases expression	1
mirdametinib	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1

Clinical trials (associated diseases)

258 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
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
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
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
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