MX2

Summary

MX2 (MX dynamin like GTPase 2, HGNC:7533) is a protein-coding gene on chromosome 21q22.3, encoding Interferon-induced GTP-binding protein Mx2 (P20592). Interferon-induced dynamin-like GTPase with potent antiviral activity against human immunodeficiency virus type 1 (HIV-1).

The protein encoded by this gene has a nuclear and a cytoplasmic form and is a member of both the dynamin family and the family of large GTPases. The nuclear form is localized in a granular pattern in the heterochromatin region beneath the nuclear envelope. A nuclear localization signal (NLS) is present at the amino terminal end of the nuclear form but is lacking in the cytoplasmic form due to use of an alternate translation start codon. This protein is upregulated by interferon-alpha but does not contain the antiviral activity of a similar myxovirus resistance protein 1.

Source: NCBI Gene 4600 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (No Known Disease Relationship, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 114 total
• MANE Select transcript: NM_002463

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7533
Approved symbol	MX2
Name	MX dynamin like GTPase 2
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	MXB
Ensembl gene	ENSG00000183486
Ensembl biotype	protein_coding
OMIM	147890
Entrez	4600

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 19 protein_coding, 9 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000330714, ENST00000398632, ENST00000416447, ENST00000418103, ENST00000435611, ENST00000436410, ENST00000474368, ENST00000481838, ENST00000482953, ENST00000493753, ENST00000494252, ENST00000495892, ENST00000496774, ENST00000680215, ENST00000680539, ENST00000680862, ENST00000681171, ENST00000681460, ENST00000910608, ENST00000910609, ENST00000910610, ENST00000910611, ENST00000910612, ENST00000910613, ENST00000940556, ENST00000965971, ENST00000965972, ENST00000965973, ENST00000965974, ENST00000965975, ENST00000965976, ENST00000965977

RefSeq mRNA: 1 — MANE Select: NM_002463 NM_002463

CCDS: CCDS13672

Canonical transcript exons

ENST00000330714 — 14 exons

Exon	Start	End
ENSE00001290756	41376836	41377155
ENSE00001306785	41380017	41380151
ENSE00001328894	41382410	41382564
ENSE00001813213	41362027	41362055
ENSE00002502168	41377789	41377981
ENSE00002506138	41390565	41390703
ENSE00003461072	41399196	41399337
ENSE00003483351	41403267	41403343
ENSE00003486071	41401970	41402128
ENSE00003494762	41406744	41406998
ENSE00003548437	41407991	41409393
ENSE00003625443	41397613	41397691
ENSE00003659722	41398897	41399019
ENSE00003670439	41395587	41395785

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 96.82.

FANTOM5 (CAGE): breadth broad, TPM avg 17.0637 / max 1022.1200, expressed in 806 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189243	15.6958	698
189247	1.0277	250
189249	0.1773	78
189251	0.0807	32
189248	0.0689	38
209331	0.0132	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	96.82	gold quality
monocyte	CL:0000576	96.17	gold quality
leukocyte	CL:0000738	96.07	gold quality
mononuclear cell	CL:0000842	96.03	gold quality
granulocyte	CL:0000094	95.44	gold quality
pancreatic ductal cell	CL:0002079	93.68	gold quality
spleen	UBERON:0002106	93.68	gold quality
lower esophagus mucosa	UBERON:0035834	90.42	gold quality
gall bladder	UBERON:0002110	90.18	gold quality
bone marrow cell	CL:0002092	89.33	gold quality
vermiform appendix	UBERON:0001154	88.81	gold quality
decidua	UBERON:0002450	87.97	gold quality
periodontal ligament	UBERON:0008266	87.03	gold quality
lymph node	UBERON:0000029	86.97	gold quality
omental fat pad	UBERON:0010414	86.95	gold quality
peritoneum	UBERON:0002358	86.89	gold quality
adipose tissue of abdominal region	UBERON:0007808	86.27	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.21	gold quality
mucosa of urinary bladder	UBERON:0001259	85.87	gold quality
apex of heart	UBERON:0002098	85.82	gold quality
palpebral conjunctiva	UBERON:0001812	85.55	gold quality
colonic epithelium	UBERON:0000397	85.46	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.95	gold quality
right lung	UBERON:0002167	84.73	gold quality
epithelium of nasopharynx	UBERON:0001951	84.64	gold quality
bone marrow	UBERON:0002371	84.63	gold quality
calcaneal tendon	UBERON:0003701	84.60	gold quality
right atrium auricular region	UBERON:0006631	84.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.08	gold quality
left uterine tube	UBERON:0001303	83.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.00
E-GEOD-93593	no	22.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DNMT1, SP1

miRNA regulators (miRDB)

40 targeting MX2, 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-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-12136	99.98	72.81	5713
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-4483	98.09	64.12	1642

Literature-anchored findings (GeneRIF, showing 40)

• the MX2 gene to be significantly less expressed in comparison with normal subjects in the white blood cells of narcoleptic patients (PMID:17702266)
• The expression level of the MX2 gene tended to be downregulated in subjects carrying HLA-DQB1*0602, compared with that of the control subjects without this allele. (PMID:18517045)
• In MS, Mx proteins are detectable in plaques suggesting endogenous synthesis of type I IFNs as part of the acute inflammatory process. (PMID:19236454)
• The MX2 promoter is activated by Trichostatin A (TSA) treatment and by serum depletion according to promoter reporter assays in HEK 293 cells. (PMID:20494980)
• MX2 is therefore a cell-autonomous, anti-HIV-1 resistance factor whose purposeful mobilization may represent a new therapeutic approach for the treatment of HIV/AIDS (PMID:24048477)
• Taken together, it is concluded that human MxB protein inhibits HIV-1 DNA integration by a CypA-dependent mechanism. (PMID:24055605)
• findings indicate that MX2 is an effector of the anti-HIV-1 activity of type-I IFN, and suggest that MX2 inhibits HIV-1 infection by inhibiting capsid-dependent nuclear import of subviral complexes (PMID:24121441)
• Through a combination of in vitro evolution and unbiased mutagenesis, authors further map the determinants of sensitivity to Mx2 and reveal that multiple capsid (CA) surfaces define sensitivity to Mx2. (PMID:24760893)
• To identify protein domains of MX2 that specify HIV-1 inhibition. (PMID:24899177)
• Study analyzed the evolutionary history of MX2 at the inter- and intraspecific level and use this information to identify a haplotype that associates with natural resistance to HIV-1 infection in humans; the ancestral (G) allele of rs2074560 protects from HIV-1 infection with a recessive effect. (PMID:24930137)
• MxB binding to the HIV-1 capsid. (PMID:25123063)
• MxB inhibits HIV-1 by interfering with minimally two steps of infection, nuclear entry and post-nuclear trafficking and/or integration, without destabilizing the inherent catalytic activity of viral preintegration complexes. (PMID:25348155)
• The amino-terminal domain of Mx2/MxB-dependent interaction with the HIV-1 capsid has been characterized. (PMID:25363729)
• structural analysis of assembly of human anti-HIV dynamin-like protein MxB/Mx2 (PMID:25446123)
• HIV-seronegative women who use Depo-Provera have the highest levels of Mx2 expression, highlighting a possible mechanism for hormonal modulation of HIV resistance. (PMID:25562491)
• MxB oligomerization is important for the ability of MxB to bind to the HIV-1 core proteins. (PMID:25568212)
• The high prevalence of MxB-resistant mutations in the CypA-binding loop indicates the significant selective pressure of MxB on HIV-1 replication in vivo. (PMID:25571928)
• A triple-arginine motif in the amino-terminal domain and oligomerization are required for HIV-1 inhibition by human MX2. (PMID:25673704)
• We propose that lower-order oligomerization of MX2 is sufficient for the effective inhibition of human immunodeficiency virus type 1. (PMID:26446602)
• Together, the data demonstrate that interferon-beta inhibits foamy virus early in infection and that MxB is not a restriction factor of foamy virus. (PMID:26609934)
• These experiments suggested that MxB does not contribute to the HIV-1 restriction observed in IFN-alpha-treated human cells. (PMID:26719253)
• MxB dimers form higher order oligomers that restrict retroviral replication by binding to the viral capsid. [review] (PMID:27492442)
• Study identifies MxB as a potent pan-herpesvirus restriction factor which blocks the uncoating of viral DNA from the incoming viral capsid. (PMID:29773792)
• Therefore, these results demonstrate the importance of MxB in alpha interferon-mediated inhibition of HIV-1 infection. (PMID:29925663)
• The dynamin-like MxB GTPase serves as a broadly acting intracellular restriction factor that controls retrovirus as well as herpesvirus infections. (PMID:29950411)
• These data demonstrate that human MXB but not other human or murine MX proteins inhibit murine cytomegalovirus propagation. Evidently, the viral protein expression was delayed and the viral DNA amount in nucleus was diminished in MXB expressing cells indicating an obstruction of nuclear entry. (PMID:30032029)
• Here, the authors show that HIV-1 capsid can bind multiple nucleoporins that impacts HIV-1 infection in a manner that is strikingly dependent on cell-type, cell-cycle, and cyclophilin A (CypA). They also show that nucleoporins mediate the function of the antiviral protein MX2, and that MX2 can variably inhibit non-viral nuclear localization signal function. (PMID:30084827)
• Authors propose a model whereby multiple components of the nuclear import machinery and nuclear pore complex help position MX2 at the nuclear envelope to promote MX2-mediated restriction of HIV-1. (PMID:30496303)
• SAMHD1 restriction of HIV-1 was found to be defective in non-dividing cells that did not express MxB. (PMID:30959264)
• Study shows that MxB is targeting the HIV capsid by recognizing the region created at the intersection of three CA hexamers, and allos to map this interaction to a few CA residues, located in a negatively charged well at the interface between the three CA hexamers. (PMID:31155311)
• Overexpression of human MX2 gene suppresses cell proliferation, migration, and invasion via ERK/P38/NF-kappaB pathway in glioblastoma cells. (PMID:31265172)
• MX 2 is a novel regulator of cell cycle in melanoma cells. (PMID:31660681)
• The GTPase Domain of MX2 Interacts with the HIV-1 Capsid, Enabling Its Short Isoform to Moderate Antiviral Restriction. (PMID:31722207)
• Interferon-inducible MX2 is a host restriction factor of hepatitis B virus replication. (PMID:31863794)
• MxB is an inner mitochondrial membrane GTPase that plays an important role in the maintenance of mitochondrial cristae and DNA stability of this organelle. (PMID:32102993)
• Pro-515 of the dynamin-like GTPase MxB contributes to HIV-1 inhibition by regulating MxB oligomerization and binding to HIV-1 capsid. (PMID:32217692)
• Massively parallel reporter assays of melanoma risk variants identify MX2 as a gene promoting melanoma. (PMID:32483191)
• MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface. (PMID:32553106)
• MxB impedes the NUP358-mediated HIV-1 pre-integration complex nuclear import and viral replication cooperatively with CPSF6. (PMID:32600399)
• HIV-1 resists MxB inhibition of viral Rev protein. (PMID:32873191)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	shi	FBGN0003392
caenorhabditis_elegans		WBGENE00001130

Paralogs (6): DNM2 (ENSG00000079805), DNM1L (ENSG00000087470), DNM1 (ENSG00000106976), MX1 (ENSG00000157601), DNM3 (ENSG00000197959), OPA1 (ENSG00000198836)

Protein

Protein identifiers

Interferon-induced GTP-binding protein Mx2 — P20592 (reviewed: P20592)

Alternative names: Interferon-regulated resistance GTP-binding protein MxB, Myxovirus resistance protein 2, p78-related protein

All UniProt accessions (6): A0A7P0Z4E8, C9J9T4, C9JEL4, C9JS04, C9JZQ9, P20592

UniProt curated annotations — full annotation on UniProt →

Function. Interferon-induced dynamin-like GTPase with potent antiviral activity against human immunodeficiency virus type 1 (HIV-1). Acts by targeting the viral capsid and affects the nuclear uptake and/or stability of the HIV-1 replication complex and the subsequent chromosomal integration of the proviral DNA. Exhibits antiviral activity also against simian immunodeficiency virus (SIV-mnd). May play a role in regulating nucleocytoplasmic transport and cell-cycle progression.

Subcellular location. Cytoplasm. Nucleus. Nuclear pore complex.

Induction. By type I and type III interferons.

Similarity. Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.

Isoforms (2)

UniProt ID	Names	Canonical?
P20592-1	1	yes
P20592-2	2

RefSeq proteins (1): NP_002454* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000375	Dynamin_stalk	Domain
IPR001401	Dynamin_GTPase	Domain
IPR003130	GED	Domain
IPR019762	Dynamin_GTPase_CS	Conserved_site
IPR020850	GED_dom	Domain
IPR022812	Dynamin	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030381	G_DYNAMIN_dom	Domain
IPR045063	Dynamin_N	Domain

Pfam: PF00350, PF01031, PF02212

UniProt features (49 total): helix 19, strand 12, region of interest 5, binding site 3, splice variant 3, domain 2, mutagenesis site 2, turn 2, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4X0R	X-RAY DIFFRACTION	2.9
4WHJ	X-RAY DIFFRACTION	3.2
5UOT	ELECTRON MICROSCOPY	4.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20592-F1	78.21	0.36

Functional residue map

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

Ligand- & substrate-binding residues (3): 294–297; 125–132; 225–229

Mutagenesis-validated functional residues (2):

Position	Phenotype
131	loss of gtp-binding and localization to nuclear pore. disruption of nuclear import.
151	defective gtp-hydrolysis. disruption of nuclear import and cell-cycle progression.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-909733	Interferon alpha/beta signaling
R-HSA-1169410	Antimicrobial mechanism of IFN-stimulated genes
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
R-HSA-913531	Interferon Signaling

MSigDB gene sets: 452 (showing top): GOBP_SYNAPTIC_VESICLE_LOCALIZATION, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_VESICLE_LOCALIZATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, BROWNE_HCMV_INFECTION_8HR_UP, GOBP_VESICLE_ORGANIZATION, MODULE_45, MODULE_418, HOEGERKORP_CD44_TARGETS_TEMPORAL_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_SYNAPTIC_VESICLE_RECYCLING, GOBP_RESPONSE_TO_INTERFERON_ALPHA, CHANG_IMMORTALIZED_BY_HPV31_DN, GOBP_NUCLEAR_TRANSPORT

GO Biological Process (11): defense response (GO:0006952), response to virus (GO:0009615), protein transport (GO:0015031), synaptic vesicle budding from presynaptic endocytic zone membrane (GO:0016185), response to interferon-alpha (GO:0035455), innate immune response (GO:0045087), regulation of nucleocytoplasmic transport (GO:0046822), mRNA transport (GO:0051028), defense response to virus (GO:0051607), regulation of cell cycle (GO:0051726), immune system process (GO:0002376)

GO Molecular Function (5): GTPase activity (GO:0003924), GTP binding (GO:0005525), microtubule binding (GO:0008017), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), nuclear pore (GO:0005643), cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule (GO:0005874), plasma membrane (GO:0005886), synapse (GO:0045202), presynapse (GO:0098793), nuclear envelope (GO:0005635)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Interferon Signaling	2
Antimicrobial mechanism of IFN-stimulated genes	1
Immune System	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
response to stress	1
response to other organism	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
synaptic vesicle endocytosis	1
synaptic vesicle budding	1
response to cytokine	1
immune response	1
defense response to symbiont	1
nucleocytoplasmic transport	1
regulation of intracellular transport	1
RNA transport	1
defense response	1
response to virus	1
cell cycle	1
regulation of cellular process	1
biological_process	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
tubulin binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear envelope	1
nuclear protein-containing complex	1
intracellular anatomical structure	1
cytoplasm	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
cell junction	1
synapse	1
nucleus	1
endomembrane system	1
organelle envelope	1

Protein interactions and networks

STRING

2169 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MX2	GPKOW	Q92917	922
MX2	ISG15	P05161	879
MX2	RSAD2	Q8WXG1	846
MX2	IFIT1	P09914	828
MX2	SAMHD1	Q9Y3Z3	790
MX2	RIGI	O95786	735
MX2	IFNA13	P01562	732
MX2	OAS2	P29728	730
MX2	TRIM5	Q9C035	729
MX2	OAS1	P00973	727
MX2	IFI6	P09912	714
MX2	IFIT3	O14879	710
MX2	IFIT2	P09913	707
MX2	BST2	Q10589	703
MX2	CXCL10	P02778	701

IntAct

18 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
MX2	EHMT2	psi-mi:“MI:0915”(physical association)	0.560
MX2	PIAS2	psi-mi:“MI:0915”(physical association)	0.560
ATRIP	MX2	psi-mi:“MI:0915”(physical association)	0.560
EHMT2	MX2	psi-mi:“MI:0915”(physical association)	0.560
PIAS2	MX2	psi-mi:“MI:0915”(physical association)	0.560
MX2	ATRIP	psi-mi:“MI:0915”(physical association)	0.560
	MX2	psi-mi:“MI:0407”(direct interaction)	0.410
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
MX2	EHMT2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (30): PIAS2 (Two-hybrid), EHMT2 (Two-hybrid), ATRIP (Two-hybrid), MX2 (Affinity Capture-MS), MX2 (Affinity Capture-MS), AK2 (Co-fractionation), FXN (Co-fractionation), PRDX5 (Co-fractionation), RHOA (Co-fractionation), TXN2 (Co-fractionation), MX2 (Co-fractionation), MX2 (Co-fractionation), EHMT2 (Two-hybrid), MX2 (Affinity Capture-Western), MX2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JDV3, A0MWD1, A1E2I4, A4UUI3, A6QQL3, A7VK00, B0BNF1, B0KWP7, B1H120, B1MTN8, B2KIE9, B3GNI6, B5FW69, P20591, P20592, P32455, P32456, Q01514, Q0VCP4, Q14141, Q1MT80, Q28379, Q2KTC2, Q3SZN0, Q4R555, Q5D1D6, Q5I2P5, Q5R5G3, Q5R9T9, Q5RBE1, Q61107, Q63663, Q642H3, Q6AXA6, Q6IRQ5, Q6ZN66, Q6ZU15, Q8C1B7, Q8C650, Q8CFB4

Diamond homologs: A0MWD1, A1E2I4, A1E2I5, A6H7I5, A7VK00, G0SGC7, O00429, O35303, O60313, P09922, P18588, P18589, P18590, P20591, P20592, P20593, P21575, P27594, P27619, P32266, P33237, P33238, P39052, P39053, P39054, P39055, P42697, P50570, P54861, P58281, P79135, P87320, Q000A9, Q05193, Q08877, Q08DF4, Q28379, Q2KIA5, Q2KTC2, Q3UD61

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	94
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2075 predictions. Top by Δscore:

Variant	Effect	Δscore
21:41362053:GCG:G	donor_gain	1.0000
21:41377979:GCG:G	donor_gain	1.0000
21:41377981:GGTA:G	donor_loss	1.0000
21:41377982:G:C	donor_loss	1.0000
21:41377982:G:GG	donor_gain	1.0000
21:41382398:T:A	acceptor_gain	1.0000
21:41382399:G:A	acceptor_gain	1.0000
21:41382562:CAGGT:C	donor_loss	1.0000
21:41382565:G:GA	donor_loss	1.0000
21:41382566:T:A	donor_loss	1.0000
21:41390548:C:CA	acceptor_gain	1.0000
21:41390556:T:A	acceptor_gain	1.0000
21:41390712:A:T	donor_gain	1.0000
21:41391246:A:T	donor_gain	1.0000
21:41395579:T:G	acceptor_gain	1.0000
21:41395585:A:AC	acceptor_loss	1.0000
21:41395723:GC:G	donor_gain	1.0000
21:41397692:G:GG	donor_gain	1.0000
21:41398892:TTTA:T	acceptor_loss	1.0000
21:41398893:TTAG:T	acceptor_loss	1.0000
21:41398894:TAG:T	acceptor_loss	1.0000
21:41398895:A:AC	acceptor_loss	1.0000
21:41398895:A:AG	acceptor_gain	1.0000
21:41398896:G:A	acceptor_loss	1.0000
21:41398896:G:GA	acceptor_gain	1.0000
21:41398896:GA:G	acceptor_gain	1.0000
21:41398896:GAA:G	acceptor_gain	1.0000
21:41398896:GAAA:G	acceptor_gain	1.0000
21:41398896:GAAAT:G	acceptor_gain	1.0000
21:41399016:TGAGG:T	donor_loss	1.0000

AlphaMissense

4771 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:41382494:T:C	L221P	0.994
21:41402038:T:C	F495L	0.994
21:41402040:T:A	F495L	0.994
21:41402040:T:G	F495L	0.994
21:41408004:G:C	R640P	0.993
21:41397675:T:C	L378P	0.992
21:41377859:T:C	L107P	0.991
21:41397663:T:C	L374P	0.991
21:41399304:T:A	W461R	0.988
21:41399304:T:C	W461R	0.988
21:41406982:T:C	L630P	0.988
21:41390696:G:C	R288S	0.986
21:41390696:G:T	R288S	0.986
21:41402018:G:C	R488P	0.986
21:41402056:T:C	F501L	0.986
21:41402058:T:A	F501L	0.986
21:41402058:T:G	F501L	0.986
21:41377895:C:A	P119Q	0.984
21:41380044:T:C	L157P	0.984
21:41382464:T:C	L211P	0.984
21:41382509:T:C	L226P	0.984
21:41377847:T:C	L103P	0.983
21:41406828:T:C	F579L	0.983
21:41406830:T:A	F579L	0.983
21:41406830:T:G	F579L	0.983
21:41408007:T:C	L641P	0.983
21:41408181:T:C	L699P	0.983
21:41377904:C:A	A122D	0.981
21:41406987:G:C	A632P	0.981
21:41408189:G:C	A702P	0.981

dbSNP variants (sampled 300 via entrez): RS1000050224 (21:41396067 T>C), RS1000139920 (21:41387015 T>C), RS1000146829 (21:41360764 C>T), RS1000233627 (21:41405301 A>G), RS1000276357 (21:41391251 A>G), RS1000312570 (21:41385975 C>T), RS1000324739 (21:41385714 TAG>T), RS1000469689 (21:41364567 C>T), RS1000662745 (21:41374589 G>T), RS1000748303 (21:41375856 G>A), RS1000796355 (21:41382150 A>G), RS1000830442 (21:41366407 A>G), RS1000944527 (21:41366658 T>C,G), RS1000977471 (21:41382393 C>T), RS1001034341 (21:41389783 G>T)

Disease associations

OMIM: gene MIM:147890 | 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

7 associations (top):

Study	Trait	p-value
GCST001267_1	Melanoma	3.000000e-09
GCST002778_3	Parkinson disease and lewy body pathology	3.000000e-07
GCST004142_18	Melanoma	3.000000e-08
GCST007505_19	Nevus count or cutaneous melanoma	4.000000e-10
GCST010303_19	Nevus count or cutaneous melanoma	1.000000e-17
GCST010304_23	Cutaneous malignant melanoma	1.000000e-32
GCST011624_11	Tau burden	9.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004632	nevus count
EFO:0004760	t-tau measurement

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects expression	4
Benzo(a)pyrene	affects methylation, increases expression	3
Nickel	decreases expression, increases expression	3
Plant Extracts	affects reaction, affects cotreatment, increases expression, affects expression	3
Cadmium Chloride	decreases expression, increases abundance	3
Lipopolysaccharides	affects expression, increases expression, affects reaction, decreases reaction	2
Tretinoin	affects expression, increases expression	2
testosterone enanthate	affects expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	decreases expression	1
tofacitinib	decreases expression	1
abrine	decreases expression	1
N4-(2,2-dimethyl-3-oxo-4H-pyrid(1,4)oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
Irinotecan	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1

Cellosaurus cell lines

6 cell lines: 4 cancer cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1GI	Abcam A-549 MX2 KO 2	Cancer cell line	Male
CVCL_B2P1	Abcam A-549 MX2 KO 1	Cancer cell line	Male
CVCL_D5HE	Vero MxB clone VB33	Spontaneously immortalized cell line	Female
CVCL_D5HF	Vero MxB clone VB72	Spontaneously immortalized cell line	Female
CVCL_SZ52	HAP1 MX2 (-) 1	Cancer cell line	Male
CVCL_XQ79	HAP1 MX2 (-) 2	Cancer cell line	Male

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