MX1

Summary

MX1 (MX dynamin like GTPase 1, HGNC:7532) is a protein-coding gene on chromosome 21q22.3, encoding Interferon-induced GTP-binding protein Mx1 (P20591). Interferon-induced dynamin-like GTPase with antiviral activity against a wide range of RNA viruses and some DNA viruses.

This gene encodes a guanosine triphosphate (GTP)-metabolizing protein that participates in the cellular antiviral response. The encoded protein is induced by type I and type II interferons and antagonizes the replication process of several different RNA and DNA viruses. There is a related gene located adjacent to this gene on chromosome 21, and there are multiple pseudogenes located in a cluster on chromosome 4. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 4599 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 123 total
• MANE Select transcript: NM_002462

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7532
Approved symbol	MX1
Name	MX dynamin like GTPase 1
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	IFI-78K, MxA, lncMX1-215
Ensembl gene	ENSG00000157601
Ensembl biotype	protein_coding
OMIM	147150
Entrez	4599

Gene structure

Transcript identifiers

Ensembl transcripts: 103 — 91 protein_coding, 11 retained_intron, 1 nonsense_mediated_decay

ENST00000288383, ENST00000398598, ENST00000398600, ENST00000413778, ENST00000417963, ENST00000419044, ENST00000424365, ENST00000441677, ENST00000455164, ENST00000467510, ENST00000468506, ENST00000478268, ENST00000484465, ENST00000486275, ENST00000491110, ENST00000619682, ENST00000679386, ENST00000679408, ENST00000679445, ENST00000679464, ENST00000679528, ENST00000679543, ENST00000679626, ENST00000679705, ENST00000679911, ENST00000680176, ENST00000680182, ENST00000680347, ENST00000680364, ENST00000680536, ENST00000680629, ENST00000680637, ENST00000680760, ENST00000680776, ENST00000680942, ENST00000680980, ENST00000681039, ENST00000681191, ENST00000681266, ENST00000681382, ENST00000681415, ENST00000681607, ENST00000681671, ENST00000681849, ENST00000681857, ENST00000681867, ENST00000681896, ENST00000681944, ENST00000896022, ENST00000896023, ENST00000896024, ENST00000896025, ENST00000896026, ENST00000896027, ENST00000896028, ENST00000896029, ENST00000896030, ENST00000896031, ENST00000896032, ENST00000896033, ENST00000896034, ENST00000896035, ENST00000896036, ENST00000896037, ENST00000896038, ENST00000896039, ENST00000896040, ENST00000896041, ENST00000896042, ENST00000896043, ENST00000896044, ENST00000896045, ENST00000896046, ENST00000896047, ENST00000896048, ENST00000915290, ENST00000915291, ENST00000915292, ENST00000915293, ENST00000915294, ENST00000967462, ENST00000967463, ENST00000967464, ENST00000967465, ENST00000967466, ENST00000967467, ENST00000967468, ENST00000967469, ENST00000967470, ENST00000967471, ENST00000967472, ENST00000967473, ENST00000967474, ENST00000967475, ENST00000967476, ENST00000967477, ENST00000967478, ENST00000967479, ENST00000967480, ENST00000967481, ENST00000967482, ENST00000967483, ENST00000967484

RefSeq mRNA: 4 — MANE Select: NM_002462 NM_001144925, NM_001178046, NM_001282920, NM_002462

CCDS: CCDS13673, CCDS74796

Canonical transcript exons

ENST00000398598 — 17 exons

Exon	Start	End
ENSE00001033780	41449137	41449295
ENSE00001033785	41441716	41441914
ENSE00001033788	41443788	41443866
ENSE00001033791	41452621	41452869
ENSE00001033793	41445448	41445570
ENSE00001033794	41437015	41437152
ENSE00001225085	41451167	41451243
ENSE00001534036	41430533	41430608
ENSE00001534038	41427755	41427866
ENSE00001534040	41427206	41427304
ENSE00001784904	41426239	41426263
ENSE00002440210	41440887	41441025
ENSE00002459117	41435837	41436029
ENSE00003640572	41446000	41446141
ENSE00003785790	41439694	41439848
ENSE00003795097	41432050	41432175
ENSE00003850052	41458528	41459212

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 97.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.3132 / max 862.2353, expressed in 1329 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189258	12.8159	777
189257	2.9527	569
189256	1.0085	333
189252	0.6616	289
189255	0.6196	358
189262	0.4788	305
189259	0.2789	166
189261	0.1867	53
189253	0.1631	53
189260	0.1474	86

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trigeminal ganglion	UBERON:0001675	97.71	gold quality
dorsal root ganglion	UBERON:0000044	97.11	gold quality
nasal cavity epithelium	UBERON:0005384	96.88	gold quality
palpebral conjunctiva	UBERON:0001812	96.84	gold quality
monocyte	CL:0000576	96.52	gold quality
leukocyte	CL:0000738	96.38	gold quality
mononuclear cell	CL:0000842	96.35	gold quality
decidua	UBERON:0002450	96.11	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.01	gold quality
granulocyte	CL:0000094	95.82	gold quality
spleen	UBERON:0002106	95.51	gold quality
nasal cavity mucosa	UBERON:0001826	95.45	gold quality
penis	UBERON:0000989	95.38	gold quality
right uterine tube	UBERON:0001302	95.19	gold quality
gall bladder	UBERON:0002110	95.12	gold quality
gingiva	UBERON:0001828	94.80	gold quality
pericardium	UBERON:0002407	94.73	gold quality
gingival epithelium	UBERON:0001949	94.47	gold quality
lymph node	UBERON:0000029	94.41	gold quality
epithelium of nasopharynx	UBERON:0001951	94.33	gold quality
nasopharynx	UBERON:0001728	94.31	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.76	gold quality
calcaneal tendon	UBERON:0003701	93.67	gold quality
thymus	UBERON:0002370	93.38	gold quality
tonsil	UBERON:0002372	93.15	gold quality
adenohypophysis	UBERON:0002196	93.12	gold quality
vermiform appendix	UBERON:0001154	93.09	gold quality
caecum	UBERON:0001153	92.64	gold quality
mucosa of stomach	UBERON:0001199	92.64	gold quality
right lung	UBERON:0002167	92.53	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-ENAD-20	yes	2387.41
E-CURD-53	yes	1566.50
E-MTAB-7037	yes	1160.39
E-GEOD-139324	yes	1123.73
E-MTAB-8559	yes	742.71
E-MTAB-10662	yes	716.52
E-CURD-95	yes	517.87
E-ANND-3	yes	13.33
E-MTAB-3929	no	341.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB5, HNF4A, IRF6, MXD1, POU2F3, PTPN22, STAT1, STAT2

miRNA regulators (miRDB)

15 targeting MX1, 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-4283	100.00	66.42	2097
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-558	97.50	67.16	977
HSA-MIR-4475	97.36	66.95	761

Literature-anchored findings (GeneRIF, showing 40)

• The MxA promoter nt -88 G/T SNP may be useful to predict the response of chronic hepatitis C patients to interferon therapy. (PMID:10971132)
• The MxA promoter with haplotype -88T/-123A confers greater expression of MxA in vitro, as well as a better treatment outcome for chronic hepatitis C patients treated with interferon in vivo, as compared to the MxA promoter with haplotype -88G/-123C. (PMID:11805446)
• Self-assembly of human MxA GTPase into highly ordered dynamin-like oligomers (PMID:11847228)
• MxA promoted cell death induced by apoptotic stimuli as well as influenza virus infection (PMID:11911186)
• The antiviral dynamin family member, MxA, tubulates lipids and localizes to the smooth endoplasmic reticulum (PMID:11916975)
• Lipopolysaccharide stimulates p38-dependent induction of antiviral genes , such as myxovirus resistance-1 (MX1) in neutrophils independently of paracrine factors. (PMID:12595530)
• down regulated by HBV preC/C proteins interacting directly with the MxA promoter, as shown by electrophoretic mobility shift (PMID:12867637)
• Polymorphisms in the MxA gene is associated with outcome of hepatitis C virus infection (PMID:12944978)
• the reduction of Dugbe(DUGV) viral antigen expression and N protein accumulation, together with the decrease in viral genomic RNA and the decrease in viral titre in the presence of MxA, suggest a role for MxA in the inhibition of DUGV replication (PMID:14687945)
• nuclear MxA suppresses the influenza virus transcription by interacting not only with RNA polymerase subunit PB2 but also with influenza NP (PMID:14752052)
• MxA promoter -88 G/T SNP may confer host genetic susceptibility to SSPE in Japanese individuals. The MxA protein promotes the establishment of persistent measles virus infection of neural cells. (PMID:14872030)
• MxA, by interacting with a component of the nucleocapsid, prevents replication of Crimean-Congo hemorrhagic fever virus viral RNA and thereby inhibits the production of new infectious virus particles. (PMID:15047845)
• SNP of the MxA gene is one of the important host factors that independently influences the response to IFN in patients with chronic HCV infection, especially those with a low viral load. (PMID:15117331)
• not responsible for the strong inhibitory effect of interferon-beta against SARS-CoV in cell culture (PMID:15135736)
• induced 16 hr after HUVEC ( human umbilical vein endothelial cells) infection with Tula virus ; in contrast, Hantaan virus-infected HUVECs showed no expression of MxA until 48 h postinfection. (PMID:15163707)
• HCV core protein clearly inhibited the nuclear import of MxA protein expression (PMID:15221897)
• Upregulation in epithelial cells in response to andes virus infection. (PMID:15602733)
• MxA is a new regulatory protein involved in Ca2+ signaling (PMID:15757897)
• polymorphisms of two interferon-inducible genes 2’,5’-oligoadenylate synthetase 1 and MxA might affect susceptibility to the disease and progression of severe acute respiratory syndrome at each level (PMID:15766558)
• IL-28A and IL-29 induced mRNA expression of the antiviral proteins 2’,5’-OAS and MxA was abolished by overexpression of SOCS-1 (PMID:15850793)
• MxA reduces Hepatitis B virus expression augments the antiviral activity interferon alpha against HBV. (PMID:16168514)
• mxA promoter-88G/T SNP might be confered to host genetic susceptibility to SARS in Chinese Han population. (PMID:16390004)
• MxA was the most sensitive gene to detect decreased bioavailability due to betaferon theapy in multiple sclerosis. (PMID:16459719)
• Pretreatment of Huh-7 cells with 0.5-1 mM H2O2 resulted in the suppression of the IFN-alpha-induced antiviral protein MxA and of IRF-9 mRNA expression. (PMID:16595158)
• In the case of cell death after in vitro influenza viral infection, both C-terminal and N-terminal regions of MxA were shown to be involved in cell death promotion. (PMID:16704297)
• Immunostaining for Mx proteins was positive in the hepatocytes of all newborns with biliary atresia. Intrahepatic bile ducts were positive in all but one. (PMID:16769349)
• Polymorphisms within the MxA gene are associated with susceptibility to severe acute respiratory syndrome. (PMID:16824203)
• A significantly higher frequency of the haplotype with -88T and -123A, which correlates with over-expression of MxA, was observed in MS. SNPs on MxA promoter region may play an important role in the pathophysiology of MS. (PMID:16843495)
• Results demonstrate that MxA is an interferon-induced antiviral effector protein that resembles the constitutively expressed large GTPase family members in its capacity to localize to and reorganize intracellular membranes. (PMID:16978069)
• MxA mRNA expression was also significantly higher in early stage of biliary atresia (BA) and in choledochal cyst than in late stage of BA (PMID:17075576)
• No significant association was found between the MXA genotype and promoter region single nucleotide polymorphisms (rs2071430 and rs17000900) and the gene expression responses, clinical and MRI phenotypes in IFN-beta treated multiple sclerosis patients. (PMID:17126411)
• the effects of MxA on the replication cycle of parainfluenza virus type 5 (PMID:17307214)
• MxA targets two double-stranded RNA viruses, Infectious bursal disease virus and a mammalian reovirus (PMID:17374778)
• Chronic hepatitis B patients with GT genotype at MxA promoter -88 responded well to IFN treatment. (PMID:17407708)
• A highly significant difference in the distribution of MxA -88 G/T was observed between those with persistent and self-limiting HBV infections. (PMID:17845304)
• Pretreatment of A549 cells with IFN-alpha lead to increased expression of MxA, which contributed to inhibition of WNV(KUN) replication and secretion. (PMID:17947524)
• significantly higher levels of MxA in stable patients with primary progressive multiple sclerosis treated with interferon beta compared with progressing patients (PMID:18549400)
• GTPase activity is not essential for MxA protein to inhibit HBV replication. (PMID:18668195)
• HIV replication unresponsive to antiretroviral treatment in perinatal-infected patients with advanced disease and plasmacytoid dendritic cell depletion may lead to interferon-alpha expression and subsequent induction of MxA mRNA (PMID:18782441)
• induction of MxA expression in some patients with systemic sclerosis, correlating with the presence of ischemic ulcers and other signs of worse disease, suggests a potential role of Type I IFN in the pathogenesis of this disease and/or its complications (PMID:18843779)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mx1	ENSMUSG00000000386
mus_musculus	Mx2	ENSMUSG00000023341
rattus_norvegicus	Mx1	ENSRNOG00000001959
rattus_norvegicus	Mx2	ENSRNOG00000001963

Paralogs (6): DNM2 (ENSG00000079805), DNM1L (ENSG00000087470), DNM1 (ENSG00000106976), MX2 (ENSG00000183486), DNM3 (ENSG00000197959), OPA1 (ENSG00000198836)

Protein

Protein identifiers

Interferon-induced GTP-binding protein Mx1 — P20591 (reviewed: P20591)

Alternative names: Interferon-induced protein p78, Interferon-regulated resistance GTP-binding protein MxA, Myxoma resistance protein 1, Myxovirus resistance protein 1

All UniProt accessions (9): P20591, A0A7P0T9I6, A0A7P0T9R0, A0A7P0Z4E0, F8W8T1, H9KVC3, H9KVC7, H9KVC9, H9KVD0

UniProt curated annotations — full annotation on UniProt →

Function. Interferon-induced dynamin-like GTPase with antiviral activity against a wide range of RNA viruses and some DNA viruses. Its target viruses include negative-stranded RNA viruses and HBV through binding and inactivation of their ribonucleocapsid. May also antagonize reoviridae and asfarviridae replication. Inhibits thogoto virus (THOV) replication by preventing the nuclear import of viral nucleocapsids. Inhibits La Crosse virus (LACV) replication by sequestering viral nucleoprotein in perinuclear complexes, preventing genome amplification, budding, and egress. Inhibits influenza A virus (IAV) replication by decreasing or delaying NP synthesis and by blocking endocytic traffic of incoming virus particles. Enhances ER stress-mediated cell death after influenza virus infection. May regulate the calcium channel activity of TRPCs.

Subunit / interactions. Homotetramer. Oligomerizes into multimeric filamentous or ring-like structures by virtue of its stalk domain. Oligomerization is critical for GTPase activity, protein stability, and recognition of viral target structures. Interacts with TRPC1, TRPC3, TRPC4, TRPC5, TRPC6 and TRPC7. Interacts with HSPA5. Interacts with DDX39A and DDX39B. Interacts with TUBB/TUBB5. The GTP-bound form interacts (via C-terminus) with THOV P5 protein. The GTP-bound form interacts with LACV protein N. Interacts with CCHFV protein N.

Subcellular location. Cytoplasm. Endoplasmic reticulum membrane. Perinuclear region Cytoplasm. Nucleus.

Post-translational modifications. ISGylated.

Domain organisation. The C-terminal GTPase effector domain (GED) is involved in oligomerization and viral target recognition. The middle domain mediates self-assembly and oligomerization.

Induction. By type I and type III interferons. Isoform 2 is induced by HSV-1.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P20591-1	1	yes
P20591-2	2, 56-kda, varMxA

RefSeq proteins (4): NP_001138397, NP_001171517, NP_001269849, NP_002453* (*=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

Enzyme classification (BRENDA):

• EC 3.6.5.5 — dynamin GTPase (BRENDA: 23 organisms, 104 substrates, 250 inhibitors, 42 Km, 26 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GTP	0.0034–2.115	37
ATP	0.2	1

UniProt features (84 total): helix 25, strand 17, mutagenesis site 12, region of interest 9, sequence conflict 5, binding site 3, sequence variant 3, turn 3, chain 2, domain 2, initiator methionine 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
4P4U	X-RAY DIFFRACTION	1.9
4P4T	X-RAY DIFFRACTION	2.3
3LJB	X-RAY DIFFRACTION	2.4
5GTM	X-RAY DIFFRACTION	2.9
4P4S	X-RAY DIFFRACTION	3.3
3SZR	X-RAY DIFFRACTION	3.5
3ZYS	ELECTRON MICROSCOPY	12.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20591-F1	83.72	0.48

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): 77–84; 178–182; 247–250

Post-translational modifications (1): 1

Mutagenesis-validated functional residues (12):

Position	Phenotype
81	no effect on gtp-binding, nor on viral infection.
83	loss of gtp-binding. loss of potentiation of trpc6 activity. loss of protection against viral infection.
83	loss of gtp-binding. loss of protection against viral infection.
103	loss of gtp-binding. loss of potentiation of trpc6 activity. loss of protection against viral infection.
554	strong liposome-binding reduction.
555	strong liposome-binding reduction.
556	strong liposome-binding reduction.
557	strong liposome-binding reduction.
612	loss of gtp-hydrolysis. no effect on gtp-binding, nor on potentiation of trpc6 activity.
632	reduced antiviral activity.
640	fails to sequester viral nucleoproteins, no antiviral activity.
645	loss of antiviral activity towards cchfv and lacv.

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: 455 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_SYNAPTIC_VESICLE_LOCALIZATION, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, HONMA_DOCETAXEL_RESISTANCE, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_VESICLE_LOCALIZATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, PEREZ_TP63_TARGETS, CHIARETTI_T_ALL_REFRACTORY_TO_THERAPY, GOBP_VESICLE_ORGANIZATION, BECKER_TAMOXIFEN_RESISTANCE_UP, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS

GO Biological Process (12): apoptotic process (GO:0006915), defense response (GO:0006952), signal transduction (GO:0007165), response to virus (GO:0009615), synaptic vesicle budding from presynaptic endocytic zone membrane (GO:0016185), response to type I interferon (GO:0034340), negative regulation of viral genome replication (GO:0045071), innate immune response (GO:0045087), defense response to virus (GO:0051607), interleukin-27-mediated signaling pathway (GO:0070106), antiviral innate immune response (GO:0140374), immune system process (GO:0002376)

GO Molecular Function (6): GTPase activity (GO:0003924), GTP binding (GO:0005525), microtubule binding (GO:0008017), identical protein binding (GO:0042802), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (13): nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), microtubule (GO:0005874), plasma membrane (GO:0005886), nuclear membrane (GO:0031965), synapse (GO:0045202), perinuclear region of cytoplasm (GO:0048471), presynapse (GO:0098793), nuclear envelope (GO:0005635), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

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	5
cytoplasm	3
innate immune response	2
intracellular membrane-bounded organelle	2
organelle membrane	2
nucleus	2
endomembrane system	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
response to stress	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
response to other organism	1
synaptic vesicle endocytosis	1
synaptic vesicle budding	1
response to cytokine	1
viral genome replication	1
regulation of viral genome replication	1
negative regulation of viral process	1
immune response	1
defense response to symbiont	1
defense response	1
response to virus	1
cytokine-mediated signaling pathway	1
defense response to virus	1
biological_process	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
tubulin binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular anatomical structure	1
nuclear outer membrane-endoplasmic reticulum membrane network	1

Protein interactions and networks

STRING

3494 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MX1	ISG15	P05161	932
MX1	OAS1	P00973	922
MX1	IFIT1	P09914	918
MX1	RSAD2	Q8WXG1	888
MX1	OAS2	P29728	878
MX1	EIF2AK2	P19525	876
MX1	IFNA13	P01562	871
MX1	IFIT3	O14879	870
MX1	IFIT2	P09913	856
MX1	OASL	Q15646	852
MX1	IFIH1	Q9BYX4	851
MX1	IFI44	Q8TCB0	849
MX1	IFI44L	Q53G44	841
MX1	IRF9	Q00978	835
MX1	OAS3	Q9Y6K5	825

IntAct

75 interactions, top by confidence:

A	B	Type	Score
MX1	MX1	psi-mi:“MI:0915”(physical association)	0.870
MX1	MX1	psi-mi:“MI:0407”(direct interaction)	0.870
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
MX1	BCS1L	psi-mi:“MI:0915”(physical association)	0.590
TRPC6	MX1	psi-mi:“MI:0915”(physical association)	0.580
MX1	TRPC6	psi-mi:“MI:0915”(physical association)	0.580
SIAH1	MX1	psi-mi:“MI:0915”(physical association)	0.560
CAB39L	MX1	psi-mi:“MI:0915”(physical association)	0.560
MX1	CAB39L	psi-mi:“MI:0915”(physical association)	0.560
MX1	SIAH1	psi-mi:“MI:0915”(physical association)	0.560
MX1	GCD7	psi-mi:“MI:0915”(physical association)	0.560
MX1	TAE1	psi-mi:“MI:0915”(physical association)	0.560
MX1	SRP1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (73): MX1 (Two-hybrid), SIAH1 (Two-hybrid), CAB39L (Two-hybrid), MX1 (Affinity Capture-MS), DAXX (Two-hybrid), RELA (Two-hybrid), SUMO1 (Two-hybrid), EPM2AIP1 (Two-hybrid), MX1 (Two-hybrid), ZBTB16 (Two-hybrid), UBE2I (Two-hybrid), KIF26B (Two-hybrid), ZNF251 (Two-hybrid), CASP8AP2 (Two-hybrid), ZNF623 (Two-hybrid)

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

1 interactions.

A	Effect	B	Mechanism
CREB5	“up-regulates quantity by expression”	MX1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 39 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
TRP channels	6	97.9×	2e-09

GO biological processes:

GO term	Partners	Fold	FDR
regulation of cytosolic calcium ion concentration	6	74.1×	4e-08
calcium ion transmembrane transport	6	40.8×	8e-07
calcium ion transport	5	29.2×	6e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	5
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

3424 predictions. Top by Δscore:

Variant	Effect	Δscore
21:41432048:A:G	acceptor_gain	1.0000
21:41432172:CTCGG:C	donor_loss	1.0000
21:41432175:GGT:G	donor_loss	1.0000
21:41432176:G:A	donor_loss	1.0000
21:41432177:TAAGT:T	donor_loss	1.0000
21:41435834:CAGGT:C	acceptor_loss	1.0000
21:41435835:A:AC	acceptor_loss	1.0000
21:41435835:A:AG	acceptor_gain	1.0000
21:41435835:AG:A	acceptor_gain	1.0000
21:41435835:AGGT:A	acceptor_gain	1.0000
21:41435835:AGGTG:A	acceptor_gain	1.0000
21:41435836:G:GA	acceptor_gain	1.0000
21:41435836:GG:G	acceptor_gain	1.0000
21:41435836:GGT:G	acceptor_gain	1.0000
21:41435836:GGTG:G	acceptor_gain	1.0000
21:41435836:GGTGG:G	acceptor_gain	1.0000
21:41436027:GCG:G	donor_gain	1.0000
21:41436028:CGGTA:C	donor_loss	1.0000
21:41436029:GGTAA:G	donor_loss	1.0000
21:41436030:G:GC	donor_loss	1.0000
21:41436030:G:GG	donor_gain	1.0000
21:41436031:T:A	donor_loss	1.0000
21:41439692:A:AG	acceptor_gain	1.0000
21:41439692:AGCCC:A	acceptor_loss	1.0000
21:41439693:G:GT	acceptor_gain	1.0000
21:41439693:GC:G	acceptor_gain	1.0000
21:41439693:GCCC:G	acceptor_gain	1.0000
21:41439693:GCCCA:G	acceptor_gain	1.0000
21:41439844:ATAAG:A	donor_loss	1.0000
21:41439845:TAAG:T	donor_loss	1.0000

AlphaMissense

4393 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:41439793:T:C	L179P	0.998
21:41443838:T:C	L327P	0.998
21:41435961:G:A	G77E	0.997
21:41439778:T:C	L174P	0.997
21:41435960:G:T	G77W	0.996
21:41435968:G:C	Q79H	0.996
21:41435968:G:T	Q79H	0.996
21:41439784:T:C	L176P	0.996
21:41439790:A:G	D178G	0.996
21:41439791:C:A	D178E	0.996
21:41439791:C:G	D178E	0.996
21:41443850:T:C	L331P	0.996
21:41435895:T:C	L55P	0.995
21:41435952:C:A	A74D	0.995
21:41435969:A:C	S80R	0.995
21:41435971:C:A	S80R	0.995
21:41435971:C:G	S80R	0.995
21:41435978:A:C	K83Q	0.995
21:41435979:A:T	K83M	0.995
21:41439799:G:A	G181D	0.995
21:41441018:G:C	R241S	0.995
21:41441018:G:T	R241S	0.995
21:41441818:T:A	V278D	0.995
21:41449205:T:C	F448L	0.995
21:41449207:T:A	F448L	0.995
21:41449207:T:G	F448L	0.995
21:41435949:T:A	I73N	0.994
21:41435960:G:A	G77R	0.994
21:41435960:G:C	G77R	0.994
21:41435961:G:T	G77V	0.994

dbSNP variants (sampled 300 via entrez): RS1000016089 (21:41420301 G>GGCGCGA), RS1000057424 (21:41434550 A>G), RS1000127540 (21:41433183 C>T), RS1000171103 (21:41455854 T>C), RS1000225902 (21:41419386 A>G,T), RS1000273491 (21:41422423 G>A), RS1000359148 (21:41424126 G>A), RS1000419710 (21:41424742 T>C), RS1000434796 (21:41437912 C>T), RS1000466615 (21:41418984 T>G), RS1000533253 (21:41434879 A>G), RS1000546629 (21:41457354 G>A), RS1000625469 (21:41421031 C>T), RS1000629909 (21:41458832 G>A,T), RS1000706839 (21:41425671 C>T)

Disease associations

OMIM: gene MIM:147150 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Silicon Dioxide	increases expression	4
Cyclosporine	decreases expression, increases expression	4
sodium arsenite	decreases expression, increases abundance	3
2,2’,4,4’-tetrabromodiphenyl ether	increases expression, decreases expression	3
Decitabine	affects cotreatment, affects expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation, decreases reaction	3
Lipopolysaccharides	affects reaction, affects cotreatment, decreases reaction, affects expression, increases expression	3
Nickel	decreases reaction, affects expression, increases expression	3
Poly I-C	decreases reaction, increases expression	3
Smoke	decreases expression, increases abundance	3
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
epigallocatechin gallate	decreases expression, affects cotreatment	2
chromium hexavalent ion	affects expression, decreases expression, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Arsenic	affects expression, increases abundance, decreases expression	2
Benzene	increases expression, decreases expression	2
Estradiol	affects cotreatment, decreases expression	2
Plant Extracts	affects expression, affects reaction, increases expression	2
Triclosan	affects cotreatment, increases expression	2
Valproic Acid	decreases expression, increases expression	2
Asbestos, Serpentine	decreases expression, increases expression	2
testosterone enanthate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
chlorophyllin	decreases reaction, increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization	1
decabromobiphenyl ether	increases expression	1
trichostatin A	affects expression, decreases reaction	1
cinnamaldehyde	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1

Cellosaurus cell lines

3 cell lines: 2 spontaneously immortalized cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1GH	Abcam A-549 MX1 KO	Cancer cell line	Male
CVCL_D5HC	Vero MxA clone VA8	Spontaneously immortalized cell line	Female
CVCL_D5HD	Vero MxA clone VA9	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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