MAVS

Summary

MAVS (mitochondrial antiviral signaling protein, HGNC:29233) is a protein-coding gene on chromosome 20p13, encoding Mitochondrial antiviral-signaling protein (Q7Z434). Adapter required for innate immune defense against viruses.

This gene encodes an intermediary protein necessary in the virus-triggered beta interferon signaling pathways. It is required for activation of transcription factors which regulate expression of beta interferon and contributes to antiviral innate immunity.

Source: NCBI Gene 57506 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 95 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_020746

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29233
Approved symbol	MAVS
Name	mitochondrial antiviral signaling protein
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	VISA, KIAA1271, IPS-1, Cardif
Ensembl gene	ENSG00000088888
Ensembl biotype	protein_coding
OMIM	609676
Entrez	57506

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000416600, ENST00000428216, ENST00000883968, ENST00000883969, ENST00000883970, ENST00000883971, ENST00000972011

RefSeq mRNA: 3 — MANE Select: NM_020746 NM_001206491, NM_001385663, NM_020746

CCDS: CCDS33437, CCDS56176

Canonical transcript exons

ENST00000428216 — 7 exons

Exon	Start	End
ENSE00000858884	3857635	3857809
ENSE00001044690	3846834	3846903
ENSE00001694829	3865683	3876118
ENSE00003473192	3862254	3862413
ENSE00003506892	3861332	3861504
ENSE00003522240	3864256	3864788
ENSE00003547921	3854558	3854741

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 91.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.6769 / max 100.7770, expressed in 1813 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183234	28.6022	1813
183235	0.0747	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.96	gold quality
heart right ventricle	UBERON:0002080	91.74	gold quality
colonic mucosa	UBERON:0000317	91.58	gold quality
mammary duct	UBERON:0001765	91.26	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.23	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.05	gold quality
biceps brachii	UBERON:0001507	90.92	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.90	gold quality
gastrocnemius	UBERON:0001388	90.40	gold quality
lateral globus pallidus	UBERON:0002476	90.26	gold quality
muscle of leg	UBERON:0001383	90.14	gold quality
skeletal muscle tissue	UBERON:0001134	89.99	gold quality
muscle organ	UBERON:0001630	89.89	gold quality
epithelium of mammary gland	UBERON:0003244	89.67	gold quality
jejunum	UBERON:0002115	89.65	gold quality
left ventricle myocardium	UBERON:0006566	89.11	gold quality
jejunal mucosa	UBERON:0000399	89.04	gold quality
trabecular bone tissue	UBERON:0002483	88.63	gold quality
vastus lateralis	UBERON:0001379	88.59	gold quality
quadriceps femoris	UBERON:0001377	88.52	gold quality
mucosa of transverse colon	UBERON:0004991	88.51	gold quality
muscle tissue	UBERON:0002385	88.44	gold quality
adult organism	UBERON:0007023	88.37	gold quality
substantia nigra pars reticulata	UBERON:0001966	88.01	gold quality
superficial temporal artery	UBERON:0001614	87.95	gold quality
buccal mucosa cell	CL:0002336	87.93	gold quality
diaphragm	UBERON:0001103	87.68	gold quality
bronchial epithelial cell	CL:0002328	87.65	gold quality
stromal cell of endometrium	CL:0002255	87.64	gold quality
renal medulla	UBERON:0000362	87.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.69

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
IFNB1	Activation

Upstream regulators (CollecTRI, top): IRF3, NFKB

miRNA regulators (miRDB)

352 targeting MAVS, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4673	100.00	66.64	1490
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-5011-5P	100.00	83.46	5820
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-302E	99.96	70.74	2669

Literature-anchored findings (GeneRIF, showing 40)

• Mitochondrial antiviral signaling (MAVS) mediates the activation of NF-kappaB and IRF 3 in response to viral infection, and transmembrane domain targets MAVS to the mitochondria, implicating a new role of mitochondria in innate immunity. (PMID:16125763)
• Data suggest that VISA is critically involved in both virus-triggered TLR3-independent and TLR3-mediated antiviral interferon signaling. (PMID:16153868)
• KIAA1271 (aka Cardif, MAVS, VISA, IPS-1) has been shown to be targeted by hepatitis c virus (HCV) NS3/4A protease. This cleavage interferes with the Rig-I mediated dsRNA sensing pathway and therefore with the activation of IRF-3. (PMID:16177806)
• HCV infection transiently induces RIG-I- and IPS-1-dependent IRF-3 activation (PMID:16585524)
• HCV blocks the dsRNA signaling by an NS3/4A-independent mechanism, in addition to the NS3/4A-dependent cleavage of MAVS/IPS-1. (PMID:16707574)
• HCV NS3-4A cleavage of human MAVS/IPS-1/VISA/Cardif/K1271 results in its dissociation from the mitochondrial membrane and disrupts signaling to the antiviral immune response (PMID:16731946)
• Cardif induces interferon (IFN)alpha through a direct and specific interaction with the TRAF domain of TRAF3, implicating Cardif as the link between cytoplasmic viral receptors and TRAF3. (PMID:16858409)
• IPS-1, IRF3, and IFNbeta have critical roles in Legionella infection of lung epithelium (PMID:16984921)
• GBV-B NS3/4A protease specifically cleaves VISA and dislodges it from mitochondria, thereby disrupting its function as a RIG-I adaptor and blocking downstream activation of both interferon regulatory factor 3 and nuclear factor kappa B. (PMID:17093192)
• IPS-1 is an essential component of the pathway relevant to polyinosinic-polycytidylic acid signaling of type I interferon in intestinal epithelial cells. (PMID:17911629)
• This study uncovers MAVS splicing variants of diverse biological function. (PMID:18207245)
• Models show a very different charge profile for the equivalent surfaces compared to IPS-1/MAVS/VISA/Cardif CARD. (PMID:18307765)
• RIG-1 - MAVS interacts with cytoplasmic 100-kDa NF-kappa B2 complexes via a novel retinoic acid-inducible gene-I - NF- kappa B-inducing kinase signaling pathway (PMID:18550535)
• The role of MAVS in apoptosis was investigated. (PMID:18692023)
• This paper describes the biochemical regulation and behavior of MAVS during apoptosis. (PMID:18692023)
• Inactivation of Trif and Cardif can also occur through cellular caspases activated by various pro-apoptotic signals. (PMID:18756281)
• PKR facilitates the host innate immune response and apoptosis in virus-infected cells by mediating IRF-3 activation through the mitochondrial IPS-1 signal transduction pathway (PMID:18927075)
• Upon Sendai virus (SeV) infection, TBK1s is induced in both human and mouse cells and binds to RIG-1, disrupting the interaction between RIG-I and VISA (PMID:18977754)
• IPS-1 requires TRAF6 and MEKK1 to activate NF-kappaB and mitogen-activated protein kinases that are critical for the optimal induction of type I interferons (PMID:18984593)
• PKR, in addition to IPS-1 and IRF3 but not TRIF, was required for maximal type I IFN-beta induction and the induction of apoptosis by both transfected PRNAs and polyinosinic-polycytidylic acid. (PMID:19028691)
• The activation of RIG-I/MDA-5 leads to the C-terminal transmembrane-dependent dimerization of the MAVS N-terminal caspase recruitment domain, thereby providing an interface for direct binding to and activation of the downstream effector TRAF3. (PMID:19193783)
• Data show that DeltaIPS-1 could decrease the secretory volume of IFN-beta in HEK293T cell and could not completely suppress the CPE of the cell infected by HSV-1. (PMID:19351494)
• recruitment of IKKepsilon to the mitochondria upon MAVS K500 ubiquitination plays a modulatory role in the cascade leading to NF-kappaB activation and expression of inflammatory and antiviral genes (PMID:19380491)
• Polo-like kinase 1 (PLK1) regulates interferon (IFN) induction by MAVS (PMID:19546225)
• Report shows that Rig-I, but not MAVS, is cleaved during cytomegalovirus infection. (PMID:19591957)
• show that interferon-beta promoter stimulator 1 (IPS-1) binds DAP3 and induces anoikis by caspase activation. (PMID:19644511)
• Data revealed that Mfn2 interacted with the carboxyl-terminal region of MAVS through a heptad repeat region, providing a structural perspective on the regulation of the mitochondrial antiviral response. (PMID:19690333)
• recognition of a viral ssRNA genome, Nod2 used the adaptor protein MAVS to activate IRF3. (PMID:19701189)
• PCBP2-AIP4 axis defines a new signaling cascade for MAVS degradation and ‘fine tuning’ of antiviral innate immunity. (PMID:19881509)
• c-Abl modulates innate immune response through MAVS. (PMID:19914245)
• study reports MAVS protein level is reduced in Dengue virus-infected cells & that caspases 1 & 3 cleave MAVS at residue D429; MAVS is also a proapoptotic molecule that triggers disruption of the mitochondrial membrane potential & activation of caspases (PMID:20032188)
• the pre-activation status of the endogenous IFN system in the liver of patients with CHC is in part regulated by cleavage of MAVS. (PMID:20044805)
• DDX3 can bind viral RNA to join it in the IPS-1 complex. The 622-662 a.a DDX3 C-terminal region directly bound to the IPS-1 CARD-like domain. (PMID:20127681)
• Chlamydia pneumoniae infection of vascular endothelial cells activates mitochondrial antiviral signaling protein (MAVS) which stimulates IRF3- and IRF7-dependent signals controlling bacterial growth and modulating development of vascular lesions. (PMID:20154210)
• Influenza virus A PB2 protein interacts with MAVS and inhibits MAVS-mediated beta interferon expression. (PMID:20538852)
• Study suggests that HBV can target the RIG-I signaling by HBX-mediated MAVS downregulation, thereby attenuating the antiviral response of the innate immune system. (PMID:20554965)
• viral infection as well as transfection with 5’ppp-RNA resulted in the redistribution of IPS-1 to form speckle-like aggregates in cells. (PMID:20661427)
• These findings demonstrate that the viral polymerase plays an important role for regulating host anti-viral response through the binding to IPS-1 and inhibition of IFNbeta production. (PMID:20699220)
• indicate that Hepatitis B virus X protein inhibits signaling by components upstream but not downstream of VISA (PMID:20711230)
• Chikungunya virus induces via IPS-1 accumulation of IRF-3 dependent antiviral gene mRNA. (PMID:20962078)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mavs	ENSDARG00000069733
mus_musculus	Mavs	ENSMUSG00000037523
rattus_norvegicus	Mavs	ENSRNOG00000025295

Protein

Protein identifiers

Mitochondrial antiviral-signaling protein — Q7Z434 (reviewed: Q7Z434)

Alternative names: CARD adapter inducing interferon beta, Interferon beta promoter stimulator protein 1, Putative NF-kappa-B-activating protein 031N, Virus-induced-signaling adapter

All UniProt accessions (1): Q7Z434

UniProt curated annotations — full annotation on UniProt →

Function. Adapter required for innate immune defense against viruses. Acts downstream of DHX33, RIGI and IFIH1/MDA5, which detect intracellular dsRNA produced during viral replication, to coordinate pathways leading to the activation of NF-kappa-B, IRF3 and IRF7, and to the subsequent induction of antiviral cytokines such as IFNB and RANTES (CCL5). Peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state. Upon viral infection, peroxisomal MAVS induces the rapid interferon-independent expression of defense factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon-dependent signaling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response. May activate the same pathways following detection of extracellular dsRNA by TLR3. May protect cells from apoptosis. Involved in NLRP3 inflammasome activation by mediating NLRP3 recruitment to mitochondria.

Subunit / interactions. Self-associates and polymerizes (via CARD domains) to form 400 nM long three-stranded helical filaments on mitochondria, filament nucleation requires interaction with RIGI whose CARD domains act as a template for filament assembly. Interacts with RIGI, IFIH1/MDA5, TRAF2, TRAF6 and C1QBP. May interact with FADD, RIPK1, CHUK and IKBKB. Interacts (when phosphorylated) with IRF3; following activation and phosphorylation on the pLxIS motif by TBK1, recruits IRF3. Interacts with NLRX1. Interaction with NLRX1 requires the CARD domain. Interacts with PSMA7. Interacts with TRAFD1. Interacts (via C-terminus) with PCBP2 in a complex containing MAVS/IPS1, PCBP2 and ITCH. Interacts with CYLD. Interacts with SRC. Interacts with DHX58/LGP2 and IKBKE. Interacts with STING1. Interacts with IFIT3 (via N-terminus). Interacts with TBK1 only in the presence of IFIT3. Interacts with TTLL12; the interaction prevents MAVS binding to TBK1 and IKBKE. Interacts with MUL1. Interacts with ANKRD17. Interacts with NDFIP1. Interacts with SMURF1; the interaction is mediated by NDFIP1 and leads to MAVS ubiquitination and degradation. Interacts with UBXN1; this interaction inhibits MAVS-mediated antiviral pathway. Interacts (via C-terminus) with GPATCH3; the interaction is markedly increased upon viral infection. Directly interacts (via CARD domain) with ATG5 and ATG12, either as ATG5 and ATG12 monomers or as ATG12-ATG5 conjugates. Interacts with DHX33 (via the helicase C-terminal domain). Interacts with DDX3X (via C-terminus); this interaction occurs rapidly, but transiently after Sendai virus infection. The interaction with DDX3X potentiates MAVS-mediated IFNB induction. Conversely inhibition of this interaction, for instance by HCV core protein, prevents MAVS-mediated IFNB induction. Transiently interacts with TRAF3 early during Sendai virus infection. Interacts with CLPB; the interaction is enhanced by Sendai virus infection. Interacts with TRAF3IP3. Interacts with TOMM70; the interaction is enhanced by Sendai virus infection. Interacts with ZNFX1. Interacts with N4BP3; this interaction promotes the polyubiquitination of MAVS. Interacts with TAX1BP1; this interaction induces MAVS polyubiquitination. Interacts with NLRP3; promoting NLRP3 recruitment to mitochondria and activation of the NLRP3 inflammasome. Interacts with ECSIT; this interaction bridges RIGI to the MAVS complex at the mitochondrion. Interacts with UBL7; this interaction promotes MAVS ‘Lys-27’-linked ubiquitination leading to type I interferon production. Interacts (via transmembrane domain) with SMIM30/MAVI1 (via transmembrane domain); the interaction disrupts MAVS interaction with RIGI and inhibits MAVS aggregation, resulting in the repression of type I interferon signaling and innate immune responses. (Microbial infection) Interacts with hepatitis C virus (HCV) NS3/4A protease; this interaction leads to MAVS cleavage, thereby preventing the establishment of an antiviral state. (Microbial infection) Interacts with hepatitis GB virus B NS3/4A protease; this interaction leads to MAVS cleavage. (Microbial infection) Interacts with human respiratory syncytial virus/HRSV protein NS1; this interaction disrupts MAVS binding to RIGI. (Microbial infection) Interacts with Andes virus Nnon-structural protein NS-S; this interaction may reduce MAVS ubiquitination and leads to inhibition of MAVS-induced type-I IFN signaling pathway. (Microbial infection) Interacts with Seneca Valley virus protease 3C; this interaction allows the cleavage of MAVS and subsequent suppression of host innate immunity. (Microbial infection) Interacts with SARS-CoV virus protein ORF9b; this interaction mediates MAVS proteasomal degradation. (Microbial infection) Interacts with SARS-CoV-2 virus protein M; this interaction impairs MAVS self-association and its recruitment of downstream components. (Microbial infection) Interacts with foot-and-mouth disease virus protein VP1; this interaction competes with TRAF3 interaction to MAVS leading to suppression of host innate immunity. (Microbial infection) Interacts with Epstein-Barr virus protein BILF1; this interaction mediates MAVS routing from mitochondria to lysosomes. (Microbial infection) Interacts with human enterovirus D68 protein VP3; this interaction inhibits MAVS leading to suppression of host innate immunity.

Subcellular location. Mitochondrion outer membrane. Mitochondrion. Peroxisome.

Tissue specificity. Present in T-cells, monocytes, epithelial cells and hepatocytes (at protein level). Ubiquitously expressed, with highest levels in heart, skeletal muscle, liver, placenta and peripheral blood leukocytes.

Post-translational modifications. Following activation, phosphorylated by TBK1 at Ser-442 in the pLxIS motif. The phosphorylated pLxIS motif constitutes an IRF3-binding motif, leading to recruitment of the transcription factor IRF3 to induce type-I interferons and other cytokines. Ubiquitinated. Undergoes ‘Lys-48’-linked polyubiquitination catalyzed by ITCH; ITCH-dependent polyubiquitination is mediated by the interaction with PCBP2 and leads to MAVS/IPS1 proteasomal degradation. Ubiquitinated by RNF125, leading to its degradation by the proteasome. Undergoes ‘Lys-48’-linked ubiquitination catalyzed by SMURF1. Undergoes ‘Lys-48’-linked ubiquitination catalyzed by MARCHF5 at Lys-7 and Lys-500, leading to proteasomal degradation. Ubiquitinated via ‘Lys-63’-linked ubiquitination at Lys-10, Lys-311 and Lys-461 by UBE2N and TRIM31, promoting MAVS polymerization and formation of three-stranded helical filaments on mitochondria. Undergoes ‘Lys-63’-linked ubiquitination leading to enhanced interaction between MAVS and TRAF2. Undergoes ‘Lys-27’-linked ubiquitination by TRIM21 leading to enhanced interaction between MAVS and TBK1. Deubiquitinated by USP10 leading to attenuation of RIGI-mediated MAVS aggregation and production of type I interferon. Undergoes ‘Lys-48’-linked polyubiquitination catalyzed by RNF115 leading to its degradation. Deubiquitinated by USP4 at Lys-461, leading to maintain MAVS protein stability, resulting in increased production of type I interferons (IFN-I) and enhanced antiviral innate immune responses against viral infections. Palmitoylated by ZHDDC4. Palmitoylation promotes MAVS stabilization and activation by inhibiting ‘Lys-48’- but facilitating ‘Lys-63’-linked ubiquitination. Proteolytically cleaved by apoptotic caspases during apoptosis, leading to its inactivation. Cleavage by CASP3 during virus-induced apoptosis inactivates it, preventing cytokine overproduction. (Microbial infection) Cleaved and degraded by hepatitis A virus (HAV) protein 3ABC allowing the virus to disrupt the activation of host IRF3 through the MDA5 pathway. (Microbial infection) Cleaved by the protease 2A of coxsackievirus B3, poliovirus and enterovirus 71 allowing the virus to disrupt the host type I interferon production. (Microbial infection) Cleaved by Seneca Valley virus protease 3C allowing the virus to suppress interferon type-I production. (Microbial infection) Cleaved by HCV protease NS3/4A, thereby preventing the establishment of an antiviral state. (Microbial infection) UFMylated by ULF1 in association with Epstein-Barr virus BILF1; leading to MAVS routing to the lysosome.

Domain organisation. The pLxIS motif constitutes an IRF3-binding motif: following phosphorylation by TBK1, the phosphorylated pLxIS motif of MAVS recruits IRF3. IRF3 is then phosphorylated and activated by TBK1 to induce type-I interferons and other cytokines. Both CARD and transmembrane domains are essential for antiviral function. The CARD domain is responsible for interaction with RIGI and IFIH1/MDA5. The transmembrane domain and residues 300-444 are essential for its interaction with DHX58/LGP2.

Miscellaneous. Selectively activates an IFNbeta but not an IL8 promoter. Interacts with RIP1 and FADD and exhibits anti-viral activity against VSV infection.

Isoforms (6)

UniProt ID	Names	Canonical?
Q7Z434-1	1	yes
Q7Z434-2	2
Q7Z434-3	3
Q7Z434-4	4
Q7Z434-5	5, MAVS1b, exon 3 deletion
Q7Z434-6	6, MAVS1a, exon 2 deletion

RefSeq proteins (3): NP_001193420, NP_001372592, NP_065797* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR031964	CARD_dom	Domain
IPR042144	CARD_IPS1	Domain
IPR052787	MAVS	Family

Pfam: PF16739

UniProt features (116 total): mutagenesis site 30, modified residue 16, compositionally biased region 9, site 9, region of interest 8, helix 8, splice variant 8, cross-link 7, sequence variant 5, sequence conflict 4, strand 3, initiator methionine 2, topological domain 2, chain 1, short sequence motif 1, transmembrane region 1, lipid moiety-binding region 1, domain 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
3RC5	X-RAY DIFFRACTION	1.6
2VGQ	X-RAY DIFFRACTION	2.1
5JEK	X-RAY DIFFRACTION	2.4
4Z8M	X-RAY DIFFRACTION	2.95
7DNI	ELECTRON MICROSCOPY	3.2
8WKW	ELECTRON MICROSCOPY	3.21
4P4H	X-RAY DIFFRACTION	3.4
3J6J	ELECTRON MICROSCOPY	3.64
3J6C	ELECTRON MICROSCOPY	9.6
2MS7	SOLID-STATE NMR
2MS8	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z434-F1	56.31	0.19

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 (9): 148–149 ((microbial infection) cleavage; by viral seneca valley virus protease 3c); 148 ((microbial infection) cleavage by cv3b); 208–209 ((microbial infection) cleavage by protease 2a of enterovirus 71); 250–251 ((microbial infection) cleavage by protease 2a of enterovirus 71); 264–265 ((microbial infection) cleavage by protease 2a of enterovirus 71); 427–428 ((microbial infection) cleavage; by hav protein 3abc); 429–430 (cleavage; by casp3); 490–491 (cleavage; by casp3); 508–509 ((microbial infection) cleavage; by hcv and hepatitis gb virus b ns3/4a protease complex)

Post-translational modifications (24): 2, 2, 152, 157, 165, 180, 188, 215, 222, 233, 234, 236, 253, 258, 408, 442, 79, 7, 10, 311 …

Mutagenesis-validated functional residues (30):

Position	Phenotype
7	abolished ubiquitination by marchf5; when associated with r-500.
10	abolished ubiquitination by trim31; when associated with r-311 and r-461.
26	impairs filament formation and abolishes antiviral signaling activity.
54	impairs ability to induce ifn-beta. loss of interaction with the atg5-atg12 conjugate.
56	impairs filament formation and abolishes antiviral signaling activity.
67–69	impairs ability to induce ifn-beta.
145	no interaction with traf2.
148	complete loss of cleavage by seneca valley virus protease 3c.
155	no interaction with traf6; when associated with d-457.
159	no effect on cleavage by seneca valley virus protease 3c.
162	no effect on cleavage by seneca valley virus protease 3c.
196	no effect on cleavage by seneca valley virus protease 3c.
198	no effect on cleavage by seneca valley virus protease 3c.
209	complete loss of cleavage by protease 2a of enterovirus 71.
251	complete loss of cleavage by protease 2a of enterovirus 71.
265	complete loss of cleavage by enterovirus 71.
311	abolished ubiquitination by trim31; when associated with r-10 and r-461.
325	abolished ubiquitination by trim21.
427	no cleavage by hhav 3abc.
429	decreased cleavage by casp3. abolished cleavage by casp3; when associated with a-490.
435	no effect on cleavage by ns3/4a protease complex.
442	abolished ability to bind and activate irf3.
452	no effect on cleavage by ns3/4a protease complex.
457	no interaction with traf6; when associated with d-155.
461	abolished ubiquitination by trim31; when associated with r-10 and r-311.

Function

Pathways and Gene Ontology

Reactome pathways

30 pathways

ID	Pathway
R-HSA-168928	DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-5689896	Ovarian tumor domain proteases
R-HSA-918233	TRAF3-dependent IRF activation pathway
R-HSA-933541	TRAF6 mediated IRF7 activation
R-HSA-933542	TRAF6 mediated NF-kB activation
R-HSA-933543	NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10
R-HSA-936440	Negative regulators of DDX58/IFIH1 signaling
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-9833109	Evasion by RSV of host interferon responses
R-HSA-9833482	PKR-mediated signaling
R-HSA-9920588	Dengue virus activates/modulates innate and adaptive immune responses
R-HSA-1169410	Antimicrobial mechanism of IFN-stimulated genes
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-392499	Metabolism of proteins
R-HSA-5663205	Infectious disease
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification
R-HSA-913531	Interferon Signaling
R-HSA-9678108	SARS-CoV-1 Infection
R-HSA-9679506	SARS-CoV Infections
R-HSA-9692914	SARS-CoV-1-host interactions
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9705683	SARS-CoV-2-host interactions
R-HSA-9820952	Respiratory Syncytial Virus Infection Pathway
R-HSA-9824446	Viral Infection Pathways
R-HSA-9833110	RSV-host interactions

MSigDB gene sets: 336 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, HORIUCHI_WTAP_TARGETS_DN, WANG_CLIM2_TARGETS_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT

GO Biological Process (34): activation of innate immune response (GO:0002218), positive regulation of defense response to virus by host (GO:0002230), positive regulation of myeloid dendritic cell cytokine production (GO:0002735), cytoplasmic pattern recognition receptor signaling pathway (GO:0002753), signal transduction (GO:0007165), positive regulation of type I interferon production (GO:0032481), positive regulation of interferon-alpha production (GO:0032727), positive regulation of interferon-beta production (GO:0032728), positive regulation of interleukin-6 production (GO:0032755), positive regulation of interleukin-8 production (GO:0032757), positive regulation of tumor necrosis factor production (GO:0032760), cellular response to interferon-beta (GO:0035458), intracellular signal transduction (GO:0035556), positive regulation of protein import into nucleus (GO:0042307), defense response to bacterium (GO:0042742), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), negative regulation of viral genome replication (GO:0045071), innate immune response (GO:0045087), positive regulation of transcription by RNA polymerase II (GO:0045944), protein tetramerization (GO:0051262), defense response to virus (GO:0051607), type I interferon-mediated signaling pathway (GO:0060337), positive regulation of type I interferon-mediated signaling pathway (GO:0060340), positive regulation of response to cytokine stimulus (GO:0060760), protein localization to mitochondrion (GO:0070585), cellular response to exogenous dsRNA (GO:0071360), positive regulation of chemokine (C-C motif) ligand 5 production (GO:0071651), positive regulation of IP-10 production (GO:0071660), antiviral innate immune response (GO:0140374), regulation of peroxisome organization (GO:1900063), positive regulation of NLRP3 inflammasome complex assembly (GO:1900227), immune system process (GO:0002376), mRNA transcription (GO:0009299), NLRP3 inflammasome complex assembly (GO:0044546)

GO Molecular Function (10): protein kinase binding (GO:0019901), protein-macromolecule adaptor activity (GO:0030674), signaling adaptor activity (GO:0035591), identical protein binding (GO:0042802), CARD domain binding (GO:0050700), molecular adaptor activity (GO:0060090), protein serine/threonine kinase binding (GO:0120283), DNA-binding transcription factor binding (GO:0140297), molecular condensate scaffold activity (GO:0140693), protein binding (GO:0005515)

GO Cellular Component (7): ubiquitin ligase complex (GO:0000151), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), peroxisomal membrane (GO:0005778), mitochondrial membrane (GO:0031966), peroxisome (GO:0005777), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
DDX58/IFIH1-mediated induction of interferon-alpha/beta	5
Immune System	2
Innate Immune System	1
Deubiquitination	1
SARS-CoV-1-host interactions	1
SARS-CoV-2-host interactions	1
RSV-host interactions	1
Antimicrobial mechanism of IFN-stimulated genes	1
Dengue Virus-Host Interactions	1
Interferon Signaling	1
Disease	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of cytokine production	4
positive regulation of type I interferon production	2
protein binding	2
protein-macromolecule adaptor activity	2
binding	2
activation of immune response	1
positive regulation of innate immune response	1
regulation of defense response to virus by host	1
myeloid dendritic cell cytokine production	1
positive regulation of dendritic cell cytokine production	1
regulation of myeloid dendritic cell cytokine production	1
positive regulation of myeloid leukocyte mediated immunity	1
positive regulation of myeloid leukocyte cytokine production involved in immune response	1
pattern recognition receptor signaling pathway	1
intracellular receptor signaling pathway	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of type I interferon production	1
type I interferon production	1
interferon-alpha production	1
regulation of interferon-alpha production	1
interferon-beta production	1
regulation of interferon-beta production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
response to interferon-beta	1
cellular response to cytokine stimulus	1
intracellular anatomical structure	1
signal transduction	1
protein import into nucleus	1
regulation of protein import into nucleus	1
positive regulation of nucleocytoplasmic transport	1

Protein interactions and networks

STRING

2750 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAVS	TBK1	Q9UHD2	999
MAVS	RIGI	O95786	999
MAVS	IFIH1	Q9BYX4	999
MAVS	DHX58	Q96C10	998
MAVS	IKBKE	Q14164	998
MAVS	NLRX1	Q86UT6	997
MAVS	TRAF3	Q13114	996
MAVS	TRAF6	Q9Y4K3	994
MAVS	IRF3	Q14653	987
MAVS	ATG12	O94817	986
MAVS	NLRP3	Q96P20	983
MAVS	ATG5	Q9H1Y0	982
MAVS	STING1	Q86WV6	968
MAVS	TRADD	Q15628	963
MAVS	NOD2	Q9HC29	952

IntAct

289 interactions, top by confidence:

A	B	Type	Score
MAVS	RIGI	psi-mi:“MI:0914”(association)	0.960
MAVS	RIGI	psi-mi:“MI:0915”(physical association)	0.960
RIGI	MAVS	psi-mi:“MI:0915”(physical association)	0.960
RIGI	MAVS	psi-mi:“MI:0914”(association)	0.960
TBK1	TBKBP1	psi-mi:“MI:0914”(association)	0.860
STING1	MAVS	psi-mi:“MI:0915”(physical association)	0.840
SOD1	CCS	psi-mi:“MI:0914”(association)	0.830
PLK1	SPAG9	psi-mi:“MI:0914”(association)	0.790
MAVS	IFIH1	psi-mi:“MI:0915”(physical association)	0.770
IKBKE	CDC37	psi-mi:“MI:0914”(association)	0.770
HSPA8	GAK	psi-mi:“MI:0914”(association)	0.760
TRAF2	MAVS	psi-mi:“MI:0915”(physical association)	0.740
	MAVS	psi-mi:“MI:0915”(physical association)	0.730
	MAVS	psi-mi:“MI:0407”(direct interaction)	0.730
	MAVS	psi-mi:“MI:0403”(colocalization)	0.730
MAVS		psi-mi:“MI:0914”(association)	0.730

BioGRID (730): MIB2 (Affinity Capture-MS), MAVS (Affinity Capture-Western), MAVS (Two-hybrid), ABL1 (Affinity Capture-Western), MAVS (Affinity Capture-Western), MAVS (Far Western), MAVS (Affinity Capture-MS), MAVS (Affinity Capture-MS), MAVS (Affinity Capture-MS), MAVS (Affinity Capture-MS), IFIT3 (Affinity Capture-Western), TBK1 (Affinity Capture-Western), MAVS (Affinity Capture-Western), MAVS (Affinity Capture-Western), MAVS (Affinity Capture-Western)

ESM2 similar proteins: A0A096MK47, A0A1D5RMD1, A2AQH4, A6NCI8, A8MUA0, A8MX80, B2RRE4, B7ZNG4, E9Q3S4, O15027, O94854, P70670, Q0GGX2, Q12802, Q12815, Q3URK3, Q3V0A6, Q5DTT3, Q5F2C3, Q5FW52, Q5H9F3, Q5SW25, Q5SWP3, Q5VV67, Q5VWP3, Q5VYM1, Q66HG9, Q69ZZ9, Q6NXZ1, Q6NZN1, Q6P1W5, Q711Q0, Q7TSG5, Q7Z434, Q86TB3, Q8K4E0, Q8N5Q1, Q8N9G6, Q8NFU7, Q8VCF0

Diamond homologs: Q66HG9, Q7Z434, Q8VCF0

SIGNOR signaling

22 interactions.

A	Effect	B	Mechanism
MAVS	up-regulates	CASP8	relocalization
DDX58	“up-regulates activity”	MAVS	binding
IFIH1	“up-regulates activity”	MAVS	binding
MAVS	“up-regulates activity”	IRF3	binding
MAVS	“up-regulates activity”	IKBKE	binding
MAVS	“up-regulates activity”	TBK1	binding
MAVS	“up-regulates activity”	STING1	binding
9b	“down-regulates quantity by destabilization”	MAVS
NLRX1	“down-regulates activity”	MAVS	binding
PCBP2	“down-regulates quantity by destabilization”	MAVS	binding
ITCH	“down-regulates quantity by destabilization”	MAVS	ubiquitination
ECSIT	“up-regulates activity”	MAVS	binding
MAVS	“up-regulates quantity by expression”	IFNB1	“transcriptional regulation”
M	“down-regulates activity”	MAVS	binding
RNF5	“down-regulates quantity by destabilization”	MAVS	ubiquitination
TRIM25	“down-regulates quantity by destabilization”	MAVS	polyubiquitination
FAF1	“down-regulates activity”	MAVS	binding
PRKACA	“down-regulates activity”	MAVS	phosphorylation
ABL1	“up-regulates activity”	MAVS	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 161 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
TRAF3-dependent IRF activation pathway	6	41.5×	7e-07
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	5	27.3×	6e-05
TRAF6 mediated NF-kB activation	6	24.9×	1e-05
TRAF6 mediated IRF7 activation	7	24.2×	2e-06
SARS-CoV-1 activates/modulates innate immune responses	9	22.2×	6e-08
Negative regulators of DDX58/IFIH1 signaling	7	20.8×	4e-06
PINK1-PRKN Mediated Mitophagy	5	16.2×	4e-04
DDX58/IFIH1-mediated induction of interferon-alpha/beta	7	16.1×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic pattern recognition receptor signaling pathway	7	43.7×	7e-08
cellular response to exogenous dsRNA	5	37.1×	3e-05
positive regulation of interferon-alpha production	7	31.9×	3e-07
positive regulation of interferon-beta production	9	24.8×	7e-08
positive regulation of type I interferon production	8	23.7×	3e-07
type I interferon-mediated signaling pathway	9	21.8×	1e-07
toll-like receptor 4 signaling pathway	5	18.5×	6e-04
canonical NF-kappaB signal transduction	6	15.5×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	58
Likely benign	7
Benign	5

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
973562	NC_000020.11:g.3863511_3918336del	Pathogenic

SpliceAI

1470 predictions. Top by Δscore:

Variant	Effect	Δscore
20:3854556:A:AG	acceptor_gain	1.0000
20:3854557:G:GT	acceptor_gain	1.0000
20:3854557:GT:G	acceptor_gain	1.0000
20:3854557:GTCT:G	acceptor_gain	1.0000
20:3854557:GTCTC:G	acceptor_gain	1.0000
20:3854738:CCAGG:C	donor_loss	1.0000
20:3854742:G:GC	donor_loss	1.0000
20:3854743:T:G	donor_loss	1.0000
20:3854752:G:T	donor_gain	1.0000
20:3857805:GCCTC:G	donor_gain	1.0000
20:3857810:G:GG	donor_gain	1.0000
20:3861501:A:T	donor_gain	1.0000
20:3862250:GCAG:G	acceptor_loss	1.0000
20:3862252:A:AG	acceptor_gain	1.0000
20:3862253:G:GG	acceptor_gain	1.0000
20:3862253:GA:G	acceptor_gain	1.0000
20:3862409:AGCAG:A	donor_loss	1.0000
20:3862410:GCAG:G	donor_gain	1.0000
20:3862410:GCAGG:G	donor_loss	1.0000
20:3862411:CAGG:C	donor_loss	1.0000
20:3862412:AG:A	donor_loss	1.0000
20:3862413:GGT:G	donor_loss	1.0000
20:3862414:GTAT:G	donor_loss	1.0000
20:3862415:T:A	donor_loss	1.0000
20:3866021:G:GT	donor_gain	1.0000
20:3847391:GGCT:G	donor_gain	0.9900
20:3847392:GCTG:G	donor_gain	0.9900
20:3854552:TTCCA:T	acceptor_gain	0.9900
20:3854553:TCCA:T	acceptor_gain	0.9900
20:3854554:CCAGT:C	acceptor_gain	0.9900

AlphaMissense

3460 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:3857719:T:A	W68R	0.998
20:3857719:T:C	W68R	0.998
20:3857721:G:C	W68C	0.997
20:3857721:G:T	W68C	0.997
20:3857702:T:A	L62H	0.994
20:3854679:T:C	F19L	0.993
20:3854680:T:C	F19S	0.993
20:3854681:T:A	F19L	0.993
20:3854681:T:G	F19L	0.993
20:3857690:T:C	L58P	0.993
20:3857702:T:C	L62P	0.993
20:3854659:T:A	I12N	0.992
20:3854725:T:C	L34P	0.992
20:3857744:T:C	L76P	0.992
20:3854716:T:C	L31P	0.991
20:3857693:T:C	F59S	0.991
20:3854659:T:C	I12T	0.990
20:3854725:T:A	L34H	0.990
20:3857642:T:C	L42P	0.990
20:3854659:T:G	I12S	0.989
20:3857647:G:C	A44P	0.988
20:3857711:G:C	R65P	0.988
20:3857741:C:A	A75E	0.988
20:3857720:G:C	W68S	0.987
20:3854721:T:C	C33R	0.986
20:3854737:A:T	D38V	0.985
20:3854740:A:C	Q39P	0.985
20:3857645:G:C	R43P	0.985
20:3857666:G:A	G50E	0.985
20:3857744:T:A	L76Q	0.985

dbSNP variants (sampled 300 via entrez): RS1000067003 (20:3850074 C>A,G,T), RS1000074642 (20:3864888 G>C), RS1000193857 (20:3875809 C>T), RS1000341650 (20:3859316 G>A,C), RS1000416889 (20:3870271 C>T), RS1000443815 (20:3849229 G>A,T), RS1000480251 (20:3847713 C>G,T), RS1000580658 (20:3847944 G>A), RS1000761648 (20:3874617 G>T), RS1000937406 (20:3858446 G>A,C), RS1000972331 (20:3869235 C>T), RS1001069544 (20:3863281 C>G), RS1001209969 (20:3871042 G>A), RS1001336928 (20:3853520 A>G), RS1001339662 (20:3845320 A>C)

Disease associations

OMIM: gene MIM:609676 | disease phenotypes: MIM:234200

GenCC curated gene-disease

Mondo (1): pantothenate kinase-associated neurodegeneration (MONDO:0009319)

Orphanet (1): Pantothenate kinase-associated neurodegeneration (Orphanet:157850)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000576_3	Asthma	8.000000e-06
GCST90002401_308	Platelet distribution width	2.000000e-14
GCST90002401_309	Platelet distribution width	8.000000e-10
GCST90002401_310	Platelet distribution width	5.000000e-16

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006211	Pantothenate Kinase-Associated Neurodegeneration	C10.228.140.079.800; C10.228.140.744.320; C10.228.662.575; C10.574.500.700; C16.320.400.650

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523363 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.41	Kd	392.7	nM	CHEMBL5653589
6.41	ED50	393.9	nM	CHEMBL5653589
5.28	Kd	5243	nM	CHEMBL3752910
5.28	ED50	5259	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 6 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148725: Binding affinity to human MAVS incubated for 45 mins by Kinobead based pull down assay	kd	0.3927	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148725: Binding affinity to human MAVS incubated for 45 mins by Kinobead based pull down assay	kd	5.2434	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases methylation	5
sodium arsenite	increases expression, increases abundance	2
bisphenol S	affects expression, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
GSK-J4	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
ginger extract	affects cotreatment, affects expression, increases abundance	1
dicrotophos	increases expression	1
beauvericin	increases expression	1
bisphenol A	increases abundance, affects cotreatment, affects expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
ochratoxin A	decreases expression	1
phenyl-N-tert-butylnitrone	decreases reaction, increases expression	1
coumarin	decreases phosphorylation	1
chromium hexavalent ion	decreases expression, increases abundance	1
lipopolysaccharide, Escherichia coli O111 B4	increases expression, affects reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4341445	Binding	Binding affinity to MAVS in human A549 cells lysates grown on SILAC media at 10 uM incubated for 1 hr by LC-MS/MS analysis relative to untreated control	Profiling withanolide A for therapeutic targets in neurodegenerative diseases. — Bioorg Med Chem

Cellosaurus cell lines

10 cell lines: 8 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A7ZM	A549-Dual KO-MAVS	Cancer cell line	Male
CVCL_A8BA	THP1-Dual KO-MAVS	Cancer cell line	Male
CVCL_B9MF	Abcam A-549 MAVS KO	Cancer cell line	Male
CVCL_D7GX	Ubigene HEK293T MAVS KO	Transformed cell line	Female
CVCL_D7UU	Ubigene A-549 MAVS KO	Cancer cell line	Male
CVCL_D9JX	Ubigene HEK293 MAVS KO	Transformed cell line	Female
CVCL_F1M6	HyCyte A-549 KO-hMAVS	Cancer cell line	Male
CVCL_JA65	NtG20.i7	Cancer cell line	Male
CVCL_SX36	HAP1 MAVS (-) 1	Cancer cell line	Male
CVCL_SX37	HAP1 MAVS (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01741532	PHASE3	COMPLETED	Efficacy and Safety Study of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN)
NCT02174848	PHASE3	COMPLETED	Long-term Deferiprone Treatment in Patients With Pantothenate Kinase-Associated Neurodegeneration
NCT03041116	PHASE3	TERMINATED	Efficacy and Safety Study of Fosmetpantotenate (RE-024) in PKAN Participants
NCT01838018	Not specified	COMPLETED	Brain Perfusion in Pantothenate Kinase-associated Neurodegeneration (PKAN)
NCT02635841	Not specified	NO_LONGER_AVAILABLE	Compassionate Use of Deferiprone in Patients With PKAN
NCT03333200	Not specified	RECRUITING	Longitudinal Study of Neurodegenerative Disorders
NCT04182763	Not specified	COMPLETED	CoA-Z in Pantothenate Kinase-associated Neurodegeneration (PKAN)
NCT05522374	Not specified	RECRUITING	TIRCON International NBIA Registry