RSAD2

Summary

RSAD2 (radical S-adenosyl methionine domain containing 2, HGNC:30908) is a protein-coding gene on chromosome 2p25.2, encoding S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 (Q8WXG1). Interferon-inducible antiviral protein which plays a major role in the cell antiviral state induced by type I and type II interferon.

The protein encoded by this gene is an interferon-inducible antiviral protein that belongs to the S-adenosyl-L-methionine (SAM) superfamily of enzymes. The protein plays a role in cellular antiviral response and innate immune signaling. Antiviral effects result from inhibition of viral RNA replication, interference in the secretory pathway, binding to viral proteins and dysregulation of cellular lipid metabolism. The protein has been found to inhibit both DNA and RNA viruses, including influenza virus, human immunodeficiency virus (HIV-1) and Zika virus.

Source: NCBI Gene 91543 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_080657

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30908
Approved symbol	RSAD2
Name	radical S-adenosyl methionine domain containing 2
Location	2p25.2
Locus type	gene with protein product
Status	Approved
Aliases	cig5, vig1, Viperin
Ensembl gene	ENSG00000134321
Ensembl biotype	protein_coding
OMIM	607810
Entrez	91543

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000382040, ENST00000442639, ENST00000474872, ENST00000477834, ENST00000489749, ENST00000679373, ENST00000679863, ENST00000680320, ENST00000680607

RefSeq mRNA: 2 — MANE Select: NM_080657 NM_001410702, NM_080657

CCDS: CCDS1656, CCDS92710

Canonical transcript exons

ENST00000382040 — 6 exons

Exon	Start	End
ENSE00000708884	6886935	6887164
ENSE00000708886	6890176	6890325
ENSE00000962065	6893671	6893703
ENSE00001490738	6895778	6898239
ENSE00001490740	6877777	6878146
ENSE00003603623	6883371	6883532

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 94.58.

FANTOM5 (CAGE): breadth broad, TPM avg 70.9411 / max 8312.7220, expressed in 648 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18683	69.8229	556
18681	0.9837	301
18684	0.0973	33
18682	0.0372	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	94.58	gold quality
decidua	UBERON:0002450	92.16	gold quality
monocyte	CL:0000576	86.85	gold quality
mononuclear cell	CL:0000842	86.68	gold quality
leukocyte	CL:0000738	86.52	gold quality
bronchial epithelial cell	CL:0002328	86.18	gold quality
palpebral conjunctiva	UBERON:0001812	85.81	gold quality
calcaneal tendon	UBERON:0003701	84.58	gold quality
pigmented layer of retina	UBERON:0001782	82.50	gold quality
trabecular bone tissue	UBERON:0002483	82.38	gold quality
amniotic fluid	UBERON:0000173	82.22	gold quality
right uterine tube	UBERON:0001302	82.19	gold quality
visceral pleura	UBERON:0002401	82.08	gold quality
epithelium of bronchus	UBERON:0002031	81.76	gold quality
bone marrow	UBERON:0002371	81.58	gold quality
bronchus	UBERON:0002185	81.20	gold quality
colonic epithelium	UBERON:0000397	80.64	gold quality
islet of Langerhans	UBERON:0000006	80.58	gold quality
colonic mucosa	UBERON:0000317	80.51	gold quality
mucosa of sigmoid colon	UBERON:0004993	80.20	gold quality
apex of heart	UBERON:0002098	80.13	gold quality
blood	UBERON:0000178	79.34	gold quality
granulocyte	CL:0000094	79.33	gold quality
lower lobe of lung	UBERON:0008949	79.08	gold quality
trigeminal ganglion	UBERON:0001675	78.48	gold quality
gall bladder	UBERON:0002110	78.45	gold quality
tendon	UBERON:0000043	78.34	gold quality
pleura	UBERON:0000977	78.28	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.04	gold quality
right lung	UBERON:0002167	77.91	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-53	yes	1199.05
E-ANND-3	yes	4.06
E-GEOD-75367	no	502.48

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF1, IRF6, PRDM1, ZBTB16

miRNA regulators (miRDB)

125 targeting RSAD2, 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-4673	100.00	66.64	1490
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 40)

• Viperin is expressed in atherosclerosis and induced in vascular cells by inflammatory stimuli and cytomegalovirus infection (PMID:15890971)
• ISG (interferon-stmiulated genese) viperin has anti-Hepatitis c virus activity in vitro; we postulate that viperin, and other ISGs, acts to limit HCV replication. (PMID:16108059)
• Results identify Viperin as a tightly regulated ISGF3 target gene, which is counter-regulated by PRDI-BF1. (PMID:16849320)
• poly(I:C) upregulated TLR3, thereby augmenting the primary (IFN-beta) and secondary (IDO and viperin) response genes (PMID:17626075)
• Overexpression of farnesyl diphosphate synthase reverses viperin-mediated inhibition of virus production and restores normal membrane fluidity. (PMID:18005724)
• This work, for the first time, provides strong evidence suggesting that viperin is a putative radical S-adenosyl-l-methionine (SAM) enzyme. (PMID:18077728)
• The results suggest that even though viperin gene expression is highly induced by Japanese encephalitis virus, it is negatively regulated at the protein level to counteract its antiviral effect. (PMID:18768981)
• The N-terminal amphipathic alpha-helix of viperin mediates localization to the cytosolic face of the endoplasmic reticulum and inhibits protein secretion (PMID:19074433)
• Viperin inhibits hepatitis C virus (HCV) by localizing to lipid droplets using a domain and mechanism similar to that used by HCV itself. (PMID:19920176)
• the first experimental evidence confirming that viperin is indeed a radical SAM enzyme provided. (PMID:20026307)
• Incubation of reduced viperin with SAM results in reductive cleavage of SAM to produce 5’-deoxyadenosine (5’-dAdo), a reaction characteristic of the radical SAM superfamily. (PMID:20176015)
• IFITM2 and IFITM3, disrupted early steps (entry and/or uncoating) of the viral infection, viperin, ISG20, and double-stranded-RNA-activated protein kinase, inhibited steps in west nile virus and dengue virus viral proteins and/or RNA biosynthesis. (PMID:20534863)
• Data idenified two cleavage sites for RNase MRP/RNase P in the coding sequence of viperin mRNA. (PMID:21053045)
• study shows human cytomegalovirus (HCMV)-induced viperin disrupts cellular metabolism to enhance infectious process; viperin interaction with vMIA resulted in viperin relocalization from endoplasmic reticulum to mitochondria (PMID:21527675)
• Viperin inhibits hepatitis C virus replication by interfering with binding of NS5A to host protein VAP-33. (PMID:21957124)
• We propose that viperin interacts with NS5A and the host factor, VAP-A, to limit hepatitis C virus replication at the replication complex. (PMID:22045669)
• Viperin is now known to act in different ways in the inhibition of the replication of different viruses that employ different mechanisms and organelles in their replication cycle. [Review] (PMID:22182524)
• Viperin is an alpha-beta protein containing iron-sulfur cluster at the center pocket. (PMID:22363738)
• Viperin restrict influenza H1N1 virus replication in vitro. (PMID:22377585)
• The restriction of Bunyamwera virus replication mediated by interferon is an accumulated effect of at least three interferon-stimulated genes viperin, MTAP44 and PKR. (PMID:22896602)
• inhibits replication of respiratory syncytial virus (PMID:23018837)
• viperin is a critical antiviral host protein that controls chikungunya virus infection. (PMID:23160199)
• Viperin is induced following dengue virus type-2 (DENV-2) infection and has anti-viral actions requiring the C-terminal end of viperin. (PMID:23638199)
• The data indicate that viperin is the major effector underlying the ability of HCMV to regulate cellular lipid metabolism. (PMID:23935494)
• These data suggest that viperin requires CIAO1 for [4Fe-4S] cluster assembly, and acts through an enzymatic, Fe-S cluster- and SAM-dependent mechanism to inhibit viral RNA synthesis. (PMID:24245804)
• data suggested that viperin impaired respiratory syncytial virus (RSV) transmission by inhibiting virus filament formation, providing a basis for its anti-virus activity in RSV-infected cells (PMID:25433308)
• Viperin was localized in trophoblast cells. HCMV IE1 mRNA expression was significantly inhibited by viperin RNA interference. (PMID:25814471)
• Viperin inhibits viral replication by interactiing with host cell proteins and viral proteins. [review] (PMID:25997337)
• Exposure to hepatitis B virus up-regulates viperin expression in vivo and in vitro in placental trophoblast, and lack of this up-regulation is associated with intrauterine transmission of hepatitis B virus. (PMID:27943419)
• Study demonstrated that viperin expression was significantly down-regulated in the epidermis of wart patient’s samples compared to normal samples. In cell culture viperin expression was reversed by E7-specific siRNA. HPV-2 E7 dampens viperin expression to evade antiviral activity in persistent infections. (PMID:28242342)
• Data suggest that CIA2B and MMS19 physically interact with C-terminus of viperin/RSAD2; CIAO1 appears to function as primary viperin-interacting protein; CIA2A binds to N-terminus of viperin in CIAO1-, CIA2B-, and MMS19-independent fashion. (CIA2B = metallochaperone CIA2B/FAM96B; MMS19 = transcription factor MMS19; CIAO1 = cytosolic iron-sulfur assembly component 1; CIA2A = metallochaperone CIA2A/Fam96a) (PMID:28615450)
• These results suggest that ZIKV can attenuate ISG expression to avoid the cellular antiviral innate response, thus allowing the virus to replicate unchecked. Moreover, we have identified that the ISG viperin has significant anti-ZIKV activity. (PMID:28667332)
• Data suggest that human viperin exerts “ancient radical” SAM-dependent activity in invading bacteria such as Escherichia coli; here, expression of recombinant viperin induces dramatically elongated morphology of “host”/pathogen cells. (SAM = S-adenosylmethionine) (PMID:28708394)
• Study shows that viperin induces capsid particle release by interacting and inhibiting the function of the cellular protein GBF1. (PMID:29046456)
• Viperin N-terminal is necessary for the interaction with Junin viral nucleoprotein. (PMID:29202415)
• Study reports the identification of geranyl pyrophosphate (GPP) and farnesyl pyrophosphate (FPP), two terpene intermediates in the mevalonate pathway, as substrates of human viperin. (PMID:29251770)
• RSAD2 and AIM2 Modulate Coxsackievirus A16 and Enterovirus A71 Replication in Neuronal Cells in Different Ways That May Be Associated with Their 5’ Nontranslated Regions. (PMID:29263272)
• viperin also reduced the stability of several other viral proteins in a NS3-dependent manner, suggesting a central role of NS3 in viperin’s antiflavivirus activity. (PMID:29321318)
• Viperin is antivirally active against many different viruses from different families and has been shown to inhibit several flaviviruses. Authors summarize the current knowledge about viperin and its role in antiflavivirus defense. [Review] (PMID:30059238)
• In this study, the authors report that Radical S-adenosyl methionine domain containing 2 (RSAD2) restricts measles virus infection at the stage of virus release in infected 293T cells. (PMID:30684519)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rsad2	ENSDARG00000004952
mus_musculus	Rsad2	ENSMUSG00000020641
rattus_norvegicus	Rsad2	ENSRNOG00000007539

Protein

Protein identifiers

S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 — Q8WXG1 (reviewed: Q8WXG1)

Alternative names: Cytomegalovirus-induced gene 5 protein, Radical S-adenosyl methionine domain-containing protein 2, Virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible

All UniProt accessions (5): A0A7P0T918, A0A7P0TA11, A0A7P0Z4E2, Q8WXG1, C9J674

UniProt curated annotations — full annotation on UniProt →

Function. Interferon-inducible antiviral protein which plays a major role in the cell antiviral state induced by type I and type II interferon. Catalyzes the conversion of cytidine triphosphate (CTP) to 3’-deoxy-3’,4’-didehydro-CTP (ddhCTP) via a SAM-dependent radical mechanism. In turn, ddhCTP acts as a chain terminator for the RNA-dependent RNA polymerases from multiple viruses and directly inhibits viral replication. Therefore, inhibits a wide range of DNA and RNA viruses, including human cytomegalovirus (HCMV), hepatitis C virus (HCV), west Nile virus (WNV), dengue virus, sindbis virus, influenza A virus, sendai virus, vesicular stomatitis virus (VSV), zika virus, and human immunodeficiency virus (HIV-1). Also promotes TLR7 and TLR9-dependent production of IFN-beta production in plasmacytoid dendritic cells (pDCs) by facilitating ‘Lys-63’-linked ubiquitination of IRAK1 by TRAF6. Plays a role in CD4+ T-cells activation and differentiation. Facilitates T-cell receptor (TCR)-mediated GATA3 activation and optimal T-helper 2 (Th2) cytokine production by modulating NFKB1 and JUNB activities. Can inhibit secretion of soluble proteins.

Subunit / interactions. Homodimer. Interacts with IRAK1 and TRAF6. Interacts with FPPS. Interacts with HADHB. Interacts (via C-terminus) with VAPA/VAP33 (via C-terminus). (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein vMIA/UL37; this interaction results in RSAD2/viperin relocalization from the endoplasmic reticulum to the mitochondria. (Microbial infection) Interacts (via N-terminus) with enterovirus A71 protein 2C; this interaction inhibits viral replication. (Microbial infection) Interacts with herpes simplex virus 1/HHV-1 glycoprotein D; this interaction inhibits HHV-1 replication by facilitating IRF7-mediated IFN-beta production.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus. Endoplasmic reticulum. Lipid droplet. Mitochondrion. Mitochondrion inner membrane. Mitochondrion outer membrane.

Post-translational modifications. Acetylated by HAT1. HAT1-mediated acetylation of Lys-197 in turn recruits UBE4A that stimulates RSAD2 polyubiquitination leading to proteasomal degradation. ‘Lys-6’-linked polyubiquitination at Lys-206 leads to RSAD2 protein degradation.

Activity regulation. IRAK1 and TRAF6 synergistically activate RSAD2 increasing its activity with CTP as substrate about 10-fold.

Cofactor. Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.

Domain organisation. The N-terminal region (1-42) is necessary for its localization to the endoplasmic reticulum membrane and lipid droplet.

Induction. By interferon type I, type II and bacterial lipopolysaccharides (LPS). Little or no induction by IFNG/IFN-gamma is observed in monocytic cell lines. Induced by infection with hepatitis C virus, yellow fever virus and Sendai virus, presumably through type I interferon pathway. Induction by infection with human cytomegalovirus (HCMV), stomatitis virus (VSV), chikungunya virus (CHIKV), Japanese encephalitis virus (JEV) occurs independent of the IFN pathway.

Miscellaneous. Up-regulated in atherosclerosis. Latent viruses like HCMV may be involved in atherogenesis by initiating local inflammation. This may induce up-regulation of antiviral gene RSAD2, which modulates lipids synthesis, and thus could play a role in abnormal lipid accumulation leading to atherosclerosis.

Similarity. Belongs to the radical SAM superfamily. RSAD2 family.

RefSeq proteins (2): NP_001397631, NP_542388* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006638	Elp3/MiaA/NifB-like_rSAM	Domain
IPR007197	rSAM	Domain
IPR013785	Aldolase_TIM	Homologous_superfamily
IPR026372	RSAD2	Family
IPR051196	RSAD2/Viperin_antiviral	Family
IPR058240	rSAM_sf	Homologous_superfamily

Pfam: PF04055

Catalyzed reactions (Rhea), 1 shown:

• CTP + AH2 + S-adenosyl-L-methionine = 3’-deoxy-3’,4’-didehydro-CTP + 5’-deoxyadenosine + L-methionine + A + H2O + H(+) (RHEA:65944)

UniProt features (17 total): mutagenesis site 6, binding site 3, sequence conflict 2, sequence variant 2, chain 1, domain 1, modified residue 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXG1-F1	87.32	0.76

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): 83; 87; 90

Post-translational modifications (2): 197, 206

Mutagenesis-validated functional residues (6):

Position	Phenotype
87	loss of ability to assemble an fe-s cluster and significant decrease in protein stability.
90	loss of ability to assemble an fe-s cluster and significant decrease in protein stability.
197	loss of acetylation.
206	loss of lys-6-linked ubiquitination.
358	complete loss of antiviral activity against zika virus.
83	loss of ability to assemble an fe-s cluster and significant decrease in protein stability.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-909733	Interferon alpha/beta signaling
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
R-HSA-913531	Interferon Signaling

MSigDB gene sets: 507 (showing top): LEE_SP4_THYMOCYTE, BROWNE_HCMV_INFECTION_4HR_UP, chr2p25, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_TOLL_LIKE_RECEPTOR_9_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION

GO Biological Process (12): response to virus (GO:0009615), positive regulation of toll-like receptor 7 signaling pathway (GO:0034157), positive regulation of toll-like receptor 9 signaling pathway (GO:0034165), CD4-positive, alpha-beta T cell activation (GO:0035710), CD4-positive, alpha-beta T cell differentiation (GO:0043367), negative regulation of viral genome replication (GO:0045071), innate immune response (GO:0045087), negative regulation of protein secretion (GO:0050709), positive regulation of immune response (GO:0050778), defense response to virus (GO:0051607), positive regulation of T-helper 2 cell cytokine production (GO:2000553), immune system process (GO:0002376)

GO Molecular Function (6): lyase activity (GO:0016829), metal ion binding (GO:0046872), 4 iron, 4 sulfur cluster binding (GO:0051539), catalytic activity (GO:0003824), protein binding (GO:0005515), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (9): fibrillar center (GO:0001650), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), mitochondrial inner membrane (GO:0005743), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), lipid droplet (GO:0005811), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Interferon Signaling	1
Immune System	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
intracellular membrane-bounded organelle	3
positive regulation of pattern recognition receptor signaling pathway	2
positive regulation of intracellular signal transduction	2
immune response	2
cellular anatomical structure	2
mitochondrial membrane	2
endomembrane system	2
response to other organism	1
toll-like receptor 7 signaling pathway	1
regulation of toll-like receptor 7 signaling pathway	1
toll-like receptor 9 signaling pathway	1
regulation of toll-like receptor 9 signaling pathway	1
alpha-beta T cell activation	1
CD4-positive, alpha-beta T cell activation	1
alpha-beta T cell differentiation	1
viral genome replication	1
regulation of viral genome replication	1
negative regulation of viral process	1
defense response to symbiont	1
protein secretion	1
regulation of protein secretion	1
negative regulation of protein transport	1
negative regulation of secretion by cell	1
positive regulation of immune system process	1
positive regulation of response to stimulus	1
regulation of immune response	1
defense response	1
response to virus	1
positive regulation of T cell cytokine production	1
positive regulation of type 2 immune response	1
T-helper 2 cell cytokine production	1
regulation of T-helper 2 cell cytokine production	1
biological_process	1
catalytic activity	1
cation binding	1
iron-sulfur cluster binding	1
molecular_function	1
binding	1
metal cluster binding	1

Protein interactions and networks

STRING

1658 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RSAD2	GGPS1	O95749	953
RSAD2	FDPS	P14324	952
RSAD2	IFI44L	Q53G44	909
RSAD2	OASL	Q15646	896
RSAD2	ISG15	P05161	890
RSAD2	MX1	P20591	888
RSAD2	TRAF6	Q9Y4K3	873
RSAD2	MX2	P20592	846
RSAD2	IFIT3	O14879	846
RSAD2	IFIT1	P09914	838
RSAD2	IFI27	P40305	826
RSAD2	IFI44	Q8TCB0	824
RSAD2	OAS1	P00973	821
RSAD2	IFNA13	P01562	814
RSAD2	IFNB1	P01574	812

IntAct

43 interactions, top by confidence:

A	B	Type	Score
RSAD2	VAPA	psi-mi:“MI:2364”(proximity)	0.660
RSAD2	VAPA	psi-mi:“MI:0403”(colocalization)	0.660
RSAD2	VAPA	psi-mi:“MI:0915”(physical association)	0.660
VAPA	RSAD2	psi-mi:“MI:0403”(colocalization)	0.660
VAPA	RSAD2	psi-mi:“MI:0914”(association)	0.660
RSAD2	APOC4	psi-mi:“MI:0915”(physical association)	0.560
APOC4	RSAD2	psi-mi:“MI:0915”(physical association)	0.560
RHBDD2	RSAD2	psi-mi:“MI:0915”(physical association)	0.560
APOC1	RSAD2	psi-mi:“MI:0915”(physical association)	0.560
RSAD2	UBAC1	psi-mi:“MI:0914”(association)	0.530
	RSAD2	psi-mi:“MI:0914”(association)	0.430
	RSAD2	psi-mi:“MI:0403”(colocalization)	0.430
RSAD2	CIAO1	psi-mi:“MI:0915”(physical association)	0.400
	RSAD2	psi-mi:“MI:0915”(physical association)	0.400
RSAD2		psi-mi:“MI:0915”(physical association)	0.400
RSAD2		psi-mi:“MI:0403”(colocalization)	0.380
	RSAD2	psi-mi:“MI:0403”(colocalization)	0.380
RSAD2		psi-mi:“MI:2364”(proximity)	0.380

BioGRID (41): UBAC1 (Affinity Capture-MS), SCNM1 (Affinity Capture-MS), CIAO1 (Affinity Capture-Western), SCNM1 (Affinity Capture-MS), UBAC1 (Affinity Capture-MS), CIAO1 (Affinity Capture-Western), FAM96A (Affinity Capture-Western), FAM96B (Affinity Capture-Western), MMS19 (Affinity Capture-Western), IRAK1 (Affinity Capture-Western), TRAF6 (Affinity Capture-Western), RSAD2 (Affinity Capture-Western), IRAK1 (Co-localization), TRAF6 (Co-localization), RSAD2 (Two-hybrid)

ESM2 similar proteins: A0A559KX76, A1L4V7, A2Y8B9, A3AZW5, A3BN26, B0F481, B9EYZ1, D9IL23, F4HYF3, F4I933, F4IY62, K7WIZ6, O50046, O64815, P32069, Q0JCU7, Q40424, Q43503, Q4IER0, Q5E9N5, Q5RCW8, Q5VS72, Q60649, Q67WQ7, Q67XX3, Q6DYE4, Q6ESZ9, Q6ZHE5, Q6ZKV8, Q7XJM2, Q84ZX8, Q8BZT9, Q8H1F7, Q8H4D4, Q8S2E5, Q8W4K1, Q8W5R1, Q8WXG1, Q93WU4, Q93YN4

Diamond homologs: A0A110A2W7, D5EID4, O70600, O93384, P0DW52, P0DW53, Q2HJF9, Q59026, Q5RCW8, Q5RH95, Q6EE23, Q8CBB9, Q8WXG1, Q9MZU4, A0A1S1YUU1, A0A244CMP0, P0DW49, A0A1H0NKS3, B0JNC2, B1X0G3, B9L851, P59038, Q50746, F8AME3, Q0W3L5, A0A1M7D0R2, A6UX30, A7MJ10, B7MGN9, B7NNL1, C5B7H2, P74557, Q46BK8, Q747W9, Q7MM75, Q7VLN1, Q87MY0, Q8D894, Q8ZGW5, Q9HKZ7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ZBTB16	“up-regulates quantity by expression”	RSAD2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

996 predictions. Top by Δscore:

Variant	Effect	Δscore
2:6878143:GCTG:G	donor_gain	1.0000
2:6883497:G:GT	donor_gain	1.0000
2:6883546:G:GT	donor_gain	1.0000
2:6883546:G:T	donor_gain	1.0000
2:6887161:GAAA:G	donor_gain	1.0000
2:6887165:G:GG	donor_gain	1.0000
2:6890290:G:GT	donor_gain	1.0000
2:6878145:TGG:T	donor_loss	0.9900
2:6878146:GGT:G	donor_loss	0.9900
2:6878147:G:GG	donor_gain	0.9900
2:6878147:G:T	donor_loss	0.9900
2:6878148:TGAG:T	donor_loss	0.9900
2:6878149:G:GT	donor_loss	0.9900
2:6878150:AGTA:A	donor_loss	0.9900
2:6883482:GCATC:G	donor_gain	0.9900
2:6883497:G:T	donor_gain	0.9900
2:6883510:G:GT	donor_gain	0.9900
2:6883512:A:T	donor_gain	0.9900
2:6886934:GGTGA:G	acceptor_gain	0.9900
2:6887160:GGAAA:G	donor_gain	0.9900
2:6887161:GAAAG:G	donor_gain	0.9900
2:6887162:A:T	donor_gain	0.9900
2:6887162:AAAG:A	donor_loss	0.9900
2:6887163:AAG:A	donor_loss	0.9900
2:6887164:AGT:A	donor_loss	0.9900
2:6887166:TA:T	donor_loss	0.9900
2:6887167:AAGTA:A	donor_loss	0.9900
2:6890322:GAAG:G	donor_gain	0.9900
2:6878110:G:GT	donor_gain	0.9800
2:6878140:G:GT	donor_gain	0.9800

AlphaMissense

2392 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:6878024:T:A	V75D	0.999
2:6878028:C:A	N76K	0.999
2:6878028:C:G	N76K	0.999
2:6878065:T:C	F89L	0.999
2:6878067:C:A	F89L	0.999
2:6878067:C:G	F89L	0.999
2:6878071:T:C	F91L	0.999
2:6878073:C:A	F91L	0.999
2:6878073:C:G	F91L	0.999
2:6883481:A:C	S153R	0.999
2:6883483:C:A	S153R	0.999
2:6883483:C:G	S153R	0.999
2:6883490:A:C	S156R	0.999
2:6883492:C:A	S156R	0.999
2:6883492:C:G	S156R	0.999
2:6883497:G:A	G158E	0.999
2:6887083:G:C	K219N	0.999
2:6887083:G:T	K219N	0.999
2:6887159:T:A	W245R	0.999
2:6887159:T:C	W245R	0.999
2:6893672:T:C	M297T	0.999
2:6895782:G:C	R309P	0.999
2:6895785:T:C	F310S	0.999
2:6878032:C:G	H78D	0.998
2:6878047:T:A	C83S	0.998
2:6878047:T:C	C83R	0.998
2:6878048:G:C	C83S	0.998
2:6878068:T:C	C90R	0.998
2:6878069:G:A	C90Y	0.998
2:6878070:T:G	C90W	0.998

dbSNP variants (sampled 300 via entrez): RS1000232648 (2:6895425 C>A), RS1000342741 (2:6892953 A>G), RS1000355839 (2:6889575 C>T), RS1000379159 (2:6893258 CA>C,CAA), RS1000464625 (2:6880281 A>G), RS1000472724 (2:6897629 T>A), RS1000619130 (2:6896893 G>A), RS1000745846 (2:6890701 T>A), RS1000810546 (2:6889328 T>C), RS1001046885 (2:6867325 C>T), RS1001081659 (2:6891553 G>A), RS1001096170 (2:6891003 T>G), RS1001154859 (2:6872776 T>G), RS1001189867 (2:6886096 C>A), RS1001380101 (2:6880755 G>A,T)

Disease associations

OMIM: gene MIM:607810 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90026412_7	Severe autoimmune type 2 diabetes	6.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects acetylation, affects methylation, decreases expression, increases expression	4
monomethylarsonous acid	affects acetylation, affects methylation, decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Formaldehyde	decreases expression, increases expression	2
Nickel	increases expression	2
Silicon Dioxide	increases expression	2
Tunicamycin	increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
PAM2-CSK4	increases expression	1
urushiol	decreases expression	1
testosterone enanthate	affects expression	1
alpha phellandrene	increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
nickel chloride	affects cotreatment, increases expression	1
chloroquine diphosphate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression, decreases reaction	1
avobenzone	increases expression	1
gadodiamide	increases expression	1
tofacitinib	decreases expression	1
abrine	increases 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
Resveratrol	increases expression	1
Temozolomide	increases expression	1
Acetaminophen	increases expression	1
Aflatoxins	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	increases abundance, increases expression	1
Azathioprine	decreases expression	1
Calcitriol	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2PU	Abcam A-549 RSAD2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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