IFIT3

Summary

IFIT3 (interferon induced protein with tetratricopeptide repeats 3, HGNC:5411) is a protein-coding gene on chromosome 10q23.31, encoding Interferon-induced protein with tetratricopeptide repeats 3 (O14879). IFN-induced antiviral protein which acts as an inhibitor of cellular as well as viral processes, cell migration, proliferation, signaling, and viral replication.

Enables identical protein binding activity. Involved in antiviral innate immune response; negative regulation of apoptotic process; and negative regulation of cell population proliferation. Located in cytosol and mitochondrion.

Source: NCBI Gene 3437 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 65 total
• MANE Select transcript: NM_001549

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5411
Approved symbol	IFIT3
Name	interferon induced protein with tetratricopeptide repeats 3
Location	10q23.31
Locus type	gene with protein product
Status	Approved
Aliases	ISG60, RIG-G, CIG-49, IFI60, GARG-49, IRG2
Ensembl gene	ENSG00000119917
Ensembl biotype	protein_coding
OMIM	604650
Entrez	3437

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 15 protein_coding

ENST00000371811, ENST00000371818, ENST00000679438, ENST00000679536, ENST00000679583, ENST00000679781, ENST00000679897, ENST00000679923, ENST00000680037, ENST00000680085, ENST00000680779, ENST00000681178, ENST00000681207, ENST00000681277, ENST00000681376

RefSeq mRNA: 4 — MANE Select: NM_001549 NM_001031683, NM_001289758, NM_001289759, NM_001549

CCDS: CCDS31241, CCDS7402, CCDS91298

Canonical transcript exons

ENST00000371818 — 2 exons

Exon	Start	End
ENSE00001603488	89327997	89328078
ENSE00003844588	89338661	89340968

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 96.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.3000 / max 4319.4835, expressed in 1429 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106125	47.6179	1258
106131	16.6225	979
106126	1.9435	257
106124	0.7972	342
106138	0.2509	87
106139	0.0679	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trigeminal ganglion	UBERON:0001675	96.75	gold quality
jejunal mucosa	UBERON:0000399	95.86	gold quality
pericardium	UBERON:0002407	94.96	gold quality
lower lobe of lung	UBERON:0008949	93.02	gold quality
dorsal root ganglion	UBERON:0000044	92.79	gold quality
penis	UBERON:0000989	92.71	gold quality
palpebral conjunctiva	UBERON:0001812	92.70	gold quality
monocyte	CL:0000576	92.64	gold quality
endothelial cell	CL:0000115	92.56	gold quality
leukocyte	CL:0000738	92.46	gold quality
mononuclear cell	CL:0000842	92.35	gold quality
synovial joint	UBERON:0002217	91.96	gold quality
blood	UBERON:0000178	91.22	gold quality
calcaneal tendon	UBERON:0003701	90.75	gold quality
germinal epithelium of ovary	UBERON:0001304	90.56	gold quality
amniotic fluid	UBERON:0000173	90.08	gold quality
skin of hip	UBERON:0001554	89.91	gold quality
decidua	UBERON:0002450	89.82	gold quality
duodenum	UBERON:0002114	89.36	gold quality
granulocyte	CL:0000094	88.84	gold quality
visceral pleura	UBERON:0002401	88.60	gold quality
jejunum	UBERON:0002115	88.59	gold quality
gall bladder	UBERON:0002110	88.38	gold quality
parietal pleura	UBERON:0002400	88.38	gold quality
pleura	UBERON:0000977	88.30	gold quality
urethra	UBERON:0000057	87.91	gold quality
right lung	UBERON:0002167	87.73	gold quality
layer of synovial tissue	UBERON:0007616	87.65	gold quality
nasal cavity mucosa	UBERON:0001826	87.38	gold quality
right adrenal gland	UBERON:0001233	87.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7052	yes	12100.81
E-CURD-53	yes	3532.44
E-MTAB-10662	yes	968.73
E-MTAB-8884	yes	697.44
E-HCAD-8	yes	602.66
E-HCAD-4	yes	54.60
E-HCAD-13	yes	13.28
E-ANND-3	yes	7.88
E-MTAB-9689	no	198.14

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, IRF1, IRF4, IRF9, REL, SPI1, STAT1, STAT2

miRNA regulators (miRDB)

27 targeting IFIT3, 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-548AT-5P	99.96	70.83	2666
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-487A-5P	98.85	69.37	993
HSA-MIR-487B-5P	98.85	69.48	987
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-876-5P	97.99	68.49	1345
HSA-MIR-127-5P	97.78	67.64	869
HSA-MIR-873-3P	96.84	66.09	786
HSA-MIR-3167	96.81	67.09	1236
HSA-MIR-34A-3P	96.80	67.70	805
HSA-MIR-2861	95.24	65.47	1056
HSA-MIR-5681B	94.82	69.30	514

Literature-anchored findings (GeneRIF, showing 40)

• The induction of IFIT4 transcription by IFN-alpha depends upon sequential activation of PKCdelta, JNK and STAT1, and the influence of PKCdelta or JNK on IFN-alpha-mediated induction of IFIT4 is dependent upon the phosphorylation of STAT1 at Ser-727. (PMID:17933493)
• IFIT4 may play roles in promoting monocyte differentiation into dendritic cell-like cells (DCLCs) and in directing DCLCs to modulate T-helper-1 cell differentiation, thus contributing to the autoimmunity and pathogenesis of systemic lupus erythematosus. (PMID:18706081)
• Induction of RIG-G by retinoic acid in NB4 cells resulted, to some extent, from an IFNalpha autocrine pathway, a finding that suggests a novel mechanism for the signal cross-talk between IFNalpha and retinoic acid. (PMID:19351818)
• All-trans retinoic acid upregulated RIG-G in NB4 cells by upregulating IRF1, IRF9 and STAT2. (PMID:20137113)
• The complex STAT2/IRF-9 is the key factor mediating the expression of RIG-G gene regulated by IFN-alpha. (PMID:20403236)
• transcription factors for the reporter gene. CONCLUSION: Both ISRE I and ISRE II on the RIG-G promoter are the binding sites for the complex of transcription factors. They are required for RIG-G expression, and ISRE I has a preferential role over ISRE II. (PMID:20533260)
• Identification of alpha interferon-induced genes associated with antiviral activity in Daudi cells and characterization of IFIT3 as a novel antiviral gene. (PMID:20686046)
• concluded that the expression of RIG-G was independent on the classical JAK-STAT pathway, but could be greatly increased by it. (PMID:21056555)
• our study characterizes IFIT3 as an important modulator in innate immunity (PMID:21813773)
• RIG-G gene expression is closely correlated with the cross-talk between all-trans retinoic acid and IFN-alpha-induced signaling pathways in NB4 tumor cells. (PMID:22490698)
• these findings reveal for the first time the negative regulation of Rig-G on SCF-E3 ligase activities through disrupting CSN complex, not only contributing to further investigation on biological functions of Rig-G, but also leading to better understanding of the CSN complex as a potential target in tumor diagnosis and treatment. (PMID:23415865)
• protective roles of IFIT3 following IFN-alpha production in DV infection of human lung epithelial cells (PMID:24223959)
• In cell models of dengue virus 2 infection, authors found that IFITM3 contributed to both the baseline and interferon-induced inhibition of virus entry. (PMID:25131332)
• The transcription factor SOX9, which is linked to regulation of hypoxia-related genes, was identified as a key mediator of upregulation of the oncogene IFIT3 and thereby sustaining a “pseudoinflammatory” cellular condition in pancreatic tumors. (PMID:25650658)
• Reovirus T3D infection induced STAT-1, ISG-15, IFIT-1, Mx1 and IFIT-3 expression. (PMID:25905045)
• there is a positive feedback loop between phosphorylated STAT1 and ISG56, ISG54 or ISG60. (PMID:26423178)
• results indicated that RIG-G level was high in maturated cells and low in blast cells, and suggested that RIG-G might play a role in the differentiation of bone marrow hemocytes in vivo (PMID:26686474)
• Among the associated variants were two in regions previously unreported for COPD; a low frequency non-synonymous SNP in MOCS3 (rs7269297, pdiscovery=3.08x10(-6), preplication=0.019) and a rare SNP in IFIT3, which emerged in the meta-analysis (rs140549288, pmeta=8.56x10(-6)). (PMID:26917578)
• These findings indicated that hepatitis B virus-induced miR146a attenuates cell-intrinsic anti-viral innate immunity through targeting RIG-I and RIG-G. (PMID:27210312)
• IFNL3 and HLA-DPB1 independently affected viral control at 3- and 6-mo postpartum. Together, these findings support a model where spontaneous control of HCV such as sometimes follows pregnancy is governed by genetic polymorphisms that affect type III IFN signaling and virus-specific cellular immune responses. (PMID:27601657)
• these data suggest that postpartum, the normalization of the physiological rheostat controlling IFN signaling depends on IFNL3 genotype. (PMID:27601663)
• Low RIG-G expression is associated with lung cancer. (PMID:27602766)
• HSV-1 was shown for the first time to evade the antiviral function of IFIT3 via UL41. (PMID:27681138)
• Higher expression of IFIT3 enhances anti-apoptotic activity and chemotherapy resistance of pancreatic ductal adenocarcinoma cells. High expression of IFIT3 was independently correlated to shorter patients’ survival and may serve as a prognostic marker. (PMID:28210844)
• Biomarker expression in pancreatic ductal adenocarcinoma (PDAC) of CXCR4, SMAD4, SOX9 and IFIT3 will be prospectively assessed by immunohistochemistry and verified by rt.-PCR from tumor and adjacent healthy pancreatic tissue of surgical specimen. (PMID:28356064)
• IFIT1 and IFIT3 interact through a C-terminal motif. IFIT3 stabilizes IFIT1 protein expression, promotes IFIT1 binding to a cap0 Zika virus reporter mRNA and enhances IFIT1 translation inhibition. (PMID:29554348)
• We provided the evidence that IFIT3 was up-regulated during hepatic ischemia-reperfusion injury (IRI) and knockdown of IFIT3 exerted potent protective effects against hepatic IRI in vitro and in vivo. Our findings not only revealed the mechanism for IFIT3-regulated hepatic IRI, but also proposed potential clinical significance of treatment targeting IFIT3 for patients undergoing liver resection and liver transplantation. (PMID:29734133)
• Levels of IFIT3 were significantly elevated in human systemic lupus erythematosus monocytes, and this was positively correlated with the activity of the cGAS/STING signaling pathway. In vitro, the expression of VACV70-induced IFNbeta was reduced by knockdown of IFIT3, whereas overexpression of IFIT3 produced an opposite effect. Finally, IFIT3 was found to interact with both STING and TANK-binding kinase 1. (PMID:29806091)
• ISG60 constitutes a negative feedback loop in the downstream of TLR3 signaling in brain capillary endothelial cells. (PMID:30195920)
• A statistically positive correlation of p-EGFR(Y1068) expression with IFIT1 and IFIT3 in OSCC tumors. (PMID:30626937)
• Inflammatory IFIT3 renders chemotherapy resistance by regulating post-translational modification of VDAC2 in pancreatic cancer. (PMID:32641986)
• Novel evidence for retinoic acid-induced G (Rig-G) as a tumor suppressor by activating p53 signaling pathway in lung cancer. (PMID:32741018)
• Interferon-Induced Protein With Multiple Tetratricopeptide Repeats 3 Is Associated With Response to Chemotherapy and Recurrence but Not With Survival. (PMID:33122518)
• Interferon-induced protein with tetratricopeptide repeats 3 may be a key factor in primary biliary cholangitis. (PMID:34075171)
• Retinoic Acid-Induced Gene G(RIG-G) as a Novel Monitoring Biomarker in Leukemia and Its Clinical Applications. (PMID:34356051)
• IFIT3 (interferon induced protein with tetratricopeptide repeats 3) modulates STAT1 expression in small extracellular vesicles. (PMID:34622927)
• Human IFIT3 Protein Induces Interferon Signaling and Inhibits Adenovirus Immediate Early Gene Expression. (PMID:34724821)
• Comprehensive analysis of the prognosis and biological significance for IFIT family in skin cutaneous melanoma. (PMID:34763233)
• Identified Three Interferon Induced Proteins as Novel Biomarkers of Human Ischemic Cardiomyopathy. (PMID:34884921)
• IFIT3 Is Increased in Serum from Patients with Chronic Hepatitis B Virus (HBV) Infection and Promotes the Anti-HBV Effect of Interferon Alpha via JAK-STAT2 In Vitro. (PMID:36314949)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	ifit10	ENSDARG00000007467
danio_rerio	ifit15	ENSDARG00000043584
danio_rerio	ifit16	ENSDARG00000056976
danio_rerio	ifit8	ENSDARG00000057173
danio_rerio	ifit14	ENSDARG00000071012
danio_rerio		ENSDARG00000088069
danio_rerio	ifit11	ENSDARG00000090537
danio_rerio	ifit12	ENSDARG00000090977
mus_musculus	Ifit3b	ENSMUSG00000062488
mus_musculus	Ifit3	ENSMUSG00000074896
rattus_norvegicus	Ifit3	ENSRNOG00000022839

Paralogs (4): IFIT2 (ENSG00000119922), IFIT5 (ENSG00000152778), IFIT1 (ENSG00000185745), IFIT1B (ENSG00000204010)

Protein

Protein identifiers

Interferon-induced protein with tetratricopeptide repeats 3 — O14879 (reviewed: O14879)

Alternative names: CIG49, ISG-60, Interferon-induced 60 kDa protein, Interferon-induced protein with tetratricopeptide repeats 4, Retinoic acid-induced gene G protein

All UniProt accessions (6): O14879, A0A7P0T7D6, A0A7P0T855, A0A7P0TA20, A0A7P0Z4G0, Q5T765

UniProt curated annotations — full annotation on UniProt →

Function. IFN-induced antiviral protein which acts as an inhibitor of cellular as well as viral processes, cell migration, proliferation, signaling, and viral replication. Enhances MAVS-mediated host antiviral responses by serving as an adapter bridging TBK1 to MAVS which leads to the activation of TBK1 and phosphorylation of IRF3 and phosphorylated IRF3 translocates into nucleus to promote antiviral gene transcription. Exhibits an antiproliferative activity via the up-regulation of cell cycle negative regulators CDKN1A/p21 and CDKN1B/p27. Normally, CDKN1B/p27 turnover is regulated by COPS5, which binds CDKN1B/p27 in the nucleus and exports it to the cytoplasm for ubiquitin-dependent degradation. IFIT3 sequesters COPS5 in the cytoplasm, thereby increasing nuclear CDKN1B/p27 protein levels. Up-regulates CDKN1A/p21 by down-regulating MYC, a repressor of CDKN1A/p21. Can negatively regulate the apoptotic effects of IFIT2.

Subunit / interactions. Component of an interferon-dependent multiprotein complex, at least composed of IFIT1, IFIT2 and IFIT3. Interacts with IFIT1 and IFIT2. Interacts (via N-terminus) with MAVS, TBK1, TRAF6 and RIGI. Interacts with COPS5.

Subcellular location. Cytoplasm. Mitochondrion.

Tissue specificity. Expression significantly higher in peripheral blood mononuclear cells (PBMCs) and monocytes from systemic lupus erythematosus (SLE) patients than in those from healthy individuals (at protein level). Spleen, lung, leukocytes, lymph nodes, placenta, bone marrow and fetal liver.

Induction. By type I interferons, dsRNAs and viruses.

Similarity. Belongs to the IFIT family.

RefSeq proteins (4): NP_001026853, NP_001276687, NP_001276688, NP_001540* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat

Pfam: PF13176, PF13181, PF13424

UniProt features (21 total): repeat 8, modified residue 3, sequence conflict 3, helix 3, chain 1, compositionally biased region 1, turn 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6C6K	X-RAY DIFFRACTION	2.54

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14879-F1	75.04	0.32

Functional residue map

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

Post-translational modifications (3): 203, 237, 478

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-909733	Interferon alpha/beta signaling

MSigDB gene sets: 425 (showing top): BROWNE_HCMV_INFECTION_4HR_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, PEREZ_TP63_TARGETS, MODULE_45, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN, BENNETT_SYSTEMIC_LUPUS_ERYTHEMATOSUS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_6

GO Biological Process (8): negative regulation of cell population proliferation (GO:0008285), response to virus (GO:0009615), negative regulation of apoptotic process (GO:0043066), defense response to virus (GO:0051607), antiviral innate immune response (GO:0140374), immune system process (GO:0002376), innate immune response (GO:0045087), response to other organism (GO:0051707)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interferon Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	2
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
response to other organism	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
defense response	1
response to virus	1
innate immune response	1
defense response to virus	1
biological_process	1
immune response	1
defense response to symbiont	1
response to external biotic stimulus	1
biological process involved in interspecies interaction between organisms	1
protein binding	1
binding	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2812 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFIT3	IFIT2	P09913	929
IFIT3	IFI44	Q8TCB0	914
IFIT3	IFIT1	P09914	895
IFIT3	IFI44L	Q53G44	888
IFIT3	STAT1	P42224	887
IFIT3	ISG15	P05161	879
IFIT3	IFITM3	Q01628	876
IFIT3	MX1	P20591	870
IFIT3	IFIH1	Q9BYX4	860
IFIT3	RSAD2	Q8WXG1	846
IFIT3	OASL	Q15646	827
IFIT3	IFI6	P09912	812
IFIT3	IFITM1	P13164	801
IFIT3	IFI27	P40305	800
IFIT3	STAT2	P52630	764
IFIT3	RIGI	O95786	764

IntAct

98 interactions, top by confidence:

A	B	Type	Score
IFIT3	IFIT1	psi-mi:“MI:0915”(physical association)	0.920
IFIT1	IFIT3	psi-mi:“MI:0915”(physical association)	0.920
IFIT1	IFIT3	psi-mi:“MI:0914”(association)	0.920
IFIT3	IFIT1	psi-mi:“MI:0914”(association)	0.920
IFIT3	TMEM183A	psi-mi:“MI:0915”(physical association)	0.780
TMEM183A	IFIT3	psi-mi:“MI:0915”(physical association)	0.780
IFIT2	IFIT3	psi-mi:“MI:0914”(association)	0.780
IFIT3	IFIT2	psi-mi:“MI:0915”(physical association)	0.780
TPM3	IFIT3	psi-mi:“MI:0915”(physical association)	0.700
IFIT3	TPM3	psi-mi:“MI:0915”(physical association)	0.700
IFIT3	IFIT3	psi-mi:“MI:0915”(physical association)	0.680
IFIT3	DEUP1	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (123): IFIT3 (Two-hybrid), TPM3 (Two-hybrid), TMEM183A (Two-hybrid), HAUS1 (Two-hybrid), CCDC67 (Two-hybrid), AQPEP (Two-hybrid), IFIT3 (Affinity Capture-MS), IFIT3 (Affinity Capture-MS), IFIT3 (Affinity Capture-MS), IFIT3 (Affinity Capture-MS), IFIT3 (Two-hybrid), IFIT3 (Two-hybrid), CCDC67 (Two-hybrid), IFIT3 (Two-hybrid), IFIT3 (Affinity Capture-Western)

ESM2 similar proteins: A1L1K3, A5A6J9, A6H6E9, B0BF33, D3ZSP7, O14879, O88196, P09913, P09914, P97357, Q14AT2, Q14D04, Q15573, Q32NR4, Q3B7U2, Q4R6I5, Q4R6M4, Q4R7V1, Q4V7F0, Q5H9U9, Q5PQQ9, Q5PQS3, Q5U2X2, Q5XIR8, Q5ZKK3, Q5ZLS8, Q60462, Q64112, Q64282, Q64345, Q6AYP3, Q6IQY5, Q7Z3E5, Q80VM3, Q86VD1, Q8C6S9, Q8CHY7, Q8IYW2, Q8K2A7, Q8NA56

Diamond homologs: A5A6J9, O14879, P09913, P09914, Q13325, Q4R5F5, Q5T764, Q60462, Q64112, Q64282, Q64345

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 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
TRAF6 mediated IRF7 activation	6	87.8×	4e-09
Regulation of IFNA/IFNB signaling	5	84.5×	1e-07
Evasion by RSV of host interferon responses	6	75.3×	8e-09
Interferon alpha/beta signaling	8	46.9×	7e-10
SARS-CoV-2 activates/modulates innate and adaptive immune responses	6	20.6×	1e-05
Factors involved in megakaryocyte development and platelet production	5	12.8×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
B cell activation involved in immune response	5	175.5×	1e-08
natural killer cell activation involved in immune response	5	165.2×	1e-08
T cell activation involved in immune response	5	117.0×	4e-08
response to exogenous dsRNA	5	87.8×	2e-07
type I interferon-mediated signaling pathway	6	68.8×	3e-08
humoral immune response	5	46.8×	3e-06
cellular response to virus	6	40.1×	4e-07
defense response to virus	10	23.1×	3e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

287 predictions. Top by Δscore:

Variant	Effect	Δscore
10:89338660:GTGA:G	acceptor_gain	1.0000
10:89328074:ATGAG:A	donor_loss	0.9900
10:89328075:TGAGG:T	donor_loss	0.9900
10:89328076:GAGG:G	donor_loss	0.9900
10:89328077:AG:A	donor_loss	0.9900
10:89328078:GG:G	donor_loss	0.9900
10:89328079:GTC:G	donor_loss	0.9900
10:89328080:T:G	donor_loss	0.9900
10:89338659:A:AG	acceptor_gain	0.9900
10:89338660:G:GA	acceptor_gain	0.9900
10:89338660:GT:G	acceptor_gain	0.9900
10:89338658:CAGTG:C	acceptor_gain	0.9800
10:89338659:AGT:A	acceptor_gain	0.9800
10:89338659:AGTGA:A	acceptor_gain	0.9800
10:89338660:GTG:G	acceptor_gain	0.9800
10:89338660:GTGAG:G	acceptor_gain	0.9800
10:89328068:G:T	donor_gain	0.9700
10:89328076:GAG:G	donor_gain	0.9600
10:89328079:G:GG	donor_gain	0.9500
10:89338657:ACAGT:A	acceptor_gain	0.9300
10:89328634:G:T	donor_gain	0.9100
10:89328631:TGGG:T	donor_gain	0.9000
10:89328077:AGGTC:A	donor_gain	0.8900
10:89328078:G:C	donor_gain	0.8900
10:89328632:GGGA:G	donor_gain	0.8900
10:89338116:G:A	acceptor_gain	0.8900
10:89328076:GAGGT:G	donor_gain	0.8800
10:89328080:T:A	donor_gain	0.8800
10:89328081:CAGT:C	donor_gain	0.8800
10:89328434:T:TA	donor_gain	0.8500

AlphaMissense

3245 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:89338713:T:C	F20L	0.975
10:89338715:C:A	F20L	0.975
10:89338715:C:G	F20L	0.975
10:89339130:T:C	F159L	0.964
10:89339132:T:A	F159L	0.964
10:89339132:T:G	F159L	0.964
10:89338952:C:A	N99K	0.963
10:89338952:C:G	N99K	0.963
10:89338707:T:C	C18R	0.943
10:89338957:C:A	A101D	0.940
10:89339085:T:A	W144R	0.931
10:89339085:T:C	W144R	0.931
10:89338884:G:C	A77P	0.930
10:89339087:G:C	W144C	0.930
10:89339087:G:T	W144C	0.930
10:89339397:G:C	A248P	0.929
10:89338719:T:A	W22R	0.926
10:89338719:T:C	W22R	0.926
10:89338721:G:C	W22C	0.926
10:89338721:G:T	W22C	0.926
10:89338956:G:C	A101P	0.926
10:89339082:G:T	G143W	0.925
10:89338959:T:A	W102R	0.915
10:89338959:T:C	W102R	0.915
10:89339433:G:C	A260P	0.915
10:89339403:T:C	F250L	0.914
10:89339405:T:A	F250L	0.914
10:89339405:T:G	F250L	0.914
10:89339394:G:C	A247P	0.912
10:89339919:G:A	G422R	0.910

dbSNP variants (sampled 300 via entrez): RS1000239689 (10:89329439 A>G), RS1000447597 (10:89335407 T>C), RS1000800502 (10:89335673 T>C), RS1000915879 (10:89330156 A>T), RS1001266239 (10:89329833 C>T), RS1001734315 (10:89329531 G>C), RS1002387073 (10:89337845 G>C), RS1002737167 (10:89331143 A>T), RS1002845108 (10:89337848 A>G), RS1003203994 (10:89338059 T>C), RS1003349064 (10:89337547 G>C), RS1003586836 (10:89326587 T>A), RS1003696718 (10:89332822 G>C), RS1004154148 (10:89328329 A>C), RS1004297966 (10:89334828 C>T)

Disease associations

OMIM: gene MIM:604650 | 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
GCST008957_4	Hormone measurements	2.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	increases expression, increases reaction, affects expression, affects cotreatment	7
Valproic Acid	affects expression, decreases expression, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
(+)-JQ1 compound	decreases expression	3
Air Pollutants	decreases expression, increases abundance	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
Lipopolysaccharides	affects expression, increases expression, affects reaction, affects cotreatment, decreases reaction	3
Particulate Matter	increases expression, decreases expression, increases abundance	3
sodium arsenite	affects cotreatment, increases expression	2
bisphenol S	decreases methylation, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Benzene	increases expression	2
Benzo(a)pyrene	decreases expression, increases expression, decreases reaction	2
Copper	affects binding, increases expression	2
Formaldehyde	decreases expression, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Plant Extracts	increases expression, affects expression, affects reaction	2
Smoke	decreases expression, increases abundance, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Triclosan	increases expression, affects cotreatment	2
Cyclosporine	decreases expression, increases expression	2
Asbestos, Serpentine	decreases expression, increases expression	2
afuresertib	increases expression	1
FR900359	increases phosphorylation	1
testosterone enanthate	affects expression	1
ethylbenzene	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1FW	Abcam A-549 IFIT3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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