IFIT1

Summary

IFIT1 (interferon induced protein with tetratricopeptide repeats 1, HGNC:5407) is a protein-coding gene on chromosome 10q23.31, encoding Antiviral innate immune response effector IFIT1 (P09914). Plays a key role in the innate immune response as part of an interferon-dependent multiprotein complex, recognizing and sequestering viral RNAs that lack host-specific 2’-O-methylation at their 5’ cap.

This gene encodes a protein containing tetratricopeptide repeats that was originally identified as induced upon treatment with interferon. The encoded protein may inhibit viral replication and translational initiation. This gene is located in a cluster on chromosome 10 with five other closely related genes. There is a pseudogene for this gene on chromosome 13. Alternatively spliced transcript variants encoding multiple isoforms have been observed.

Source: NCBI Gene 3434 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 65 total — 1 pathogenic
• MANE Select transcript: NM_001548

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5407
Approved symbol	IFIT1
Name	interferon induced protein with tetratricopeptide repeats 1
Location	10q23.31
Locus type	gene with protein product
Status	Approved
Aliases	GARG-16, ISG56
Ensembl gene	ENSG00000185745
Ensembl biotype	protein_coding
OMIM	147690
Entrez	3434

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000371804, ENST00000546318

RefSeq mRNA: 5 — MANE Select: NM_001548 NM_001270927, NM_001270928, NM_001270929, NM_001270930, NM_001548

CCDS: CCDS31243, CCDS59220

Canonical transcript exons

ENST00000371804 — 2 exons

Exon	Start	End
ENSE00001456127	89402281	89406487
ENSE00001456129	89392623	89392717

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 93.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.4144 / max 1862.9706, expressed in 1445 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106143	32.4144	1445

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	93.73	gold quality
trigeminal ganglion	UBERON:0001675	93.33	gold quality
biceps brachii	UBERON:0001507	93.30	gold quality
renal glomerulus	UBERON:0000074	93.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.18	gold quality
decidua	UBERON:0002450	93.16	gold quality
metanephric glomerulus	UBERON:0004736	92.74	gold quality
palpebral conjunctiva	UBERON:0001812	92.67	gold quality
kidney epithelium	UBERON:0004819	91.65	gold quality
subthalamic nucleus	UBERON:0001906	90.83	gold quality
germinal epithelium of ovary	UBERON:0001304	90.54	gold quality
amniotic fluid	UBERON:0000173	90.48	gold quality
parietal pleura	UBERON:0002400	90.36	gold quality
nephron tubule	UBERON:0001231	90.02	gold quality
superior vestibular nucleus	UBERON:0007227	89.95	gold quality
middle temporal gyrus	UBERON:0002771	89.60	gold quality
cerebellar vermis	UBERON:0004720	89.54	gold quality
pleura	UBERON:0000977	89.26	gold quality
frontal pole	UBERON:0002795	89.26	gold quality
dorsal root ganglion	UBERON:0000044	89.23	gold quality
penis	UBERON:0000989	89.17	gold quality
paraflocculus	UBERON:0005351	89.14	gold quality
orbitofrontal cortex	UBERON:0004167	89.04	gold quality
vastus lateralis	UBERON:0001379	88.99	gold quality
synovial joint	UBERON:0002217	88.80	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.70	gold quality
tendon of biceps brachii	UBERON:0008188	88.64	gold quality
Brodmann (1909) area 10	UBERON:0013541	88.59	gold quality
inferior vagus X ganglion	UBERON:0005363	88.34	gold quality
lateral nuclear group of thalamus	UBERON:0002736	88.27	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-7037	yes	3407.95
E-MTAB-10662	yes	1481.56
E-HCAD-13	yes	12.10
E-MTAB-9388	yes	10.40
E-ANND-3	yes	6.32
E-MTAB-5061	yes	6.16
E-MTAB-7052	no	6592.65
E-GEOD-99795	no	1705.61
E-MTAB-6058	no	49.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF3, IRF9, PTPN22, STAT1, ZNF395

miRNA regulators (miRDB)

104 targeting IFIT1, 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-3646	100.00	73.56	5283
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6785-5P	99.82	68.68	4428

Literature-anchored findings (GeneRIF, showing 40)

• The expression of interferon-induced genes IFI-54K and IFI-56K in the infected cells was found to increase 50-100-fold (PMID:12708317)
• We observed that, although double-stranded RNA or Sendai virus infection induced the two genes with similar kinetics, their induction kinetics in response to interferon-beta were quite different. (PMID:16973618)
• The authors present evidence that P56 (ISG56 protein), the expression of which is strongly induced by IFN, double-stranded RNA and viruses, mediates the anti-HPV effect of IFN. (PMID:19008854)
• ISG56 is a mediator of negative-feedback regulation of virus-triggered induction of type I IFNs and cellular antiviral responses (PMID:19416887)
• Expression of ifi56 is enhanced significantly when the differentiation of APL cells was induced by all-trans retinoic acid. (PMID:21129252)
• ISG56 interacts with ribosomal protein L15 in gastric cancer cells. (PMID:21612406)
• IFIT1 bound PPP-RNA antagonizes viruses by sequestering specific viral nucleic acids. (PMID:21642987)
• Hepatitis C virus infection suppresses the upregulation of a subset of effector molecules, including ISG56 and IFITM1. (PMID:21976647)
• Data suggested that PIV5 mRNAs are methylated at the 2’-hydroxyl group and that ISG56/IFIT1 inhibits the translation of PIV5 mRNA by some unrecognized mechanism. Also ISG56/IFIT1 is primarily responsible for the IFN-induced inhibition of PIV5. (PMID:23052390)
• crystal structures of human IFIT5, its complex with PPP-RNAs, and an amino-terminal fragment of IFIT1 (PMID:23334420)
• ISG56 may play a role in immune and inflammatory reactions induced by toll-like receptor 3 signaling in human mesangial cells. (PMID:23363937)
• protein expression is inhibited by hepatitis C virus (PMID:23529855)
• TLR4 signaling, induced by LPS, increases the expression of melanoma differentiation-associated gene 5 (MDA5) and interferon (PMID:23684765)
• Results indicate that miR-203 is an interferon-inducible miRNA that can negatively regulate a number of cellular mRNAs, including an interferon-stimulated gene target, IFIT1/ISG56, by destabilizing its mRNA transcript. (PMID:23785202)
• Data show that interferon-induced proteins with tetratricopeptide repeats 1 and 2 (IFIT1 and IFIT2) contribute to the regulation of hepatitis B virus (HBV) replication, likely at both transcriptional and posttranscriptional steps. (PMID:23867918)
• The specificity of IFIT1 for 2’O-unmethylated RNA serves as potent antiviral mechanism against viruses lacking 2’O-methyltransferase activity and at the same time allows unperturbed progression of the antiviral program in infected cells. (PMID:24098121)
• Reovirus T3D infection induced STAT-1, ISG-15, IFIT-1, Mx1, and IFIT-3 expression. (PMID:25905045)
• IFIT1 is not a dominant restriction factor against three different families of negative-sense RNA viruses. (PMID:26157117)
• there is a positive feedback loop between phosphorylated STAT1 and ISG56, ISG54 or ISG60. (PMID:26423178)
• Glioblastoma patients with high IFIT1 and low MGMT expression have an improved prognosis. (PMID:26980050)
• Human IFIT1 and mouse IFIT1B have divergent antiviral specificities: only IFIT1 proteins inhibit a virus encoding a cap 2’O-methyltransferase. (PMID:27240734)
• All the rubulaviruses tested were sensitive to the antiviral action of ISG56/IFIT1. (PMID:27512068)
• Taken together, this study revealed that IFIT1 played an important antiviral role in human cytomegalovirus infected fetal astrocytes. (PMID:27589693)
• IFIT1 significantly inhibited human parainfluenza virus type 3, whereas IFIT2, IFIT3, and IFIT5 were less effective or not at all. (PMID:27707917)
• IFIT1 is involved in the regulation of IFNalpha treatment for chronic hepatitis B and its polymorphism rs303218 can predict the end point virological response. (PMID:27956805)
• 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)
• Induction of IFIT1 in response to H9N2 virus infection or viral particle inoculation was more sensitive in HUVECs than in BEAS-2Bs. Data offers new insight into the innate immune response of endothelial cells to H9N2 virus infection. (PMID:29629559)
• Beyond the well-studied role of cytosolic IFIT1 in restricting viral replication, data demonstrate a function for nuclear IFIT1 in differential transcriptional regulation of separate branches of the LPS-induced gene program. (PMID:30282041)
• A statistically positive correlation of p-EGFR(Y1068) expression with IFIT1 and IFIT3 in OSCC tumors. (PMID:30626937)
• HEV RNA-dependent RNA polymerase (RdRp) binds to IFIT1, thereby protecting the viral RNA from IFIT1-mediated translation inhibition. (PMID:30702423)
• Intrahepatic immune changes after hepatitis c virus eradication by direct-acting antiviral therapy. (PMID:31444947)
• The results uncovered a large ensemble of RNA secondary structures of diverse size and shape in the different viruses, which showed little correspondence to the phylogeny of the viruses. Unexpectedly, the 50UTR of several viral genomes in this family did not fold into any structure, suggesting either their extreme sensitivity to IFIT1 or the existence of alternative viral mechanisms of subverting IFIT1 function. (PMID:31502557)
• IFIT1 and IFITM3 were overexpressed in head and neck squamous cell carcinoma and indicated poor prognoses for patients with head and neck squamous cell carcinoma. (PMID:31977029)
• ISG56 is involved in CXCL10 expression induced by TLR3 signaling in BEAS-2B bronchial epithelial cells. (PMID:32363951)
• Development of bis-ANS-based modified fluorescence titration assay for IFIT/RNA studies. (PMID:32962861)
• Comprehensive analysis of the prognosis and biological significance for IFIT family in skin cutaneous melanoma. (PMID:34763233)
• Lysyl oxidase-like 2 promotes stemness and enhances antitumor effects of gefitinib in head and neck cancer via IFIT1 and IFIT3. (PMID:37496288)
• Kruppel-like factor 13 acts as a tumor suppressor in thyroid carcinoma by downregulating IFIT1. (PMID:37817224)
• IFIT1 modulates the proliferation, migration and invasion of pancreatic cancer cells via Wnt/beta-catenin signaling. (PMID:38536650)
• TLR3 signaling-induced interferon-stimulated gene 56 plays a role in the pathogenesis of rheumatoid arthritis. (PMID:38881847)

Cross-species orthologs

8 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

Paralogs (4): IFIT3 (ENSG00000119917), IFIT2 (ENSG00000119922), IFIT5 (ENSG00000152778), IFIT1B (ENSG00000204010)

Protein

Protein identifiers

Antiviral innate immune response effector IFIT1 — P09914 (reviewed: P09914)

Alternative names: Interferon-induced 56 kDa protein, Interferon-induced protein with tetratricopeptide repeats 1

All UniProt accessions (1): P09914

UniProt curated annotations — full annotation on UniProt →

Function. Plays a key role in the innate immune response as part of an interferon-dependent multiprotein complex, recognizing and sequestering viral RNAs that lack host-specific 2’-O-methylation at their 5’ cap. By distinguishing these RNAs from host mRNAs, inhibits their translation by competing with the translation initiation factor eIF4E. Could also prevent viral replication through its interaction with DNA replication origin-binding protein E1 of several viruses. Causes the translocation of E1 from the nucleus to the cytoplasm and can also inhibit its helicase activity in vitro. Exhibits antiviral activity against many viruses from the Flaviviridae (West Nile virus, Dengue virus, hepatitis C virus), Coronaviridae (human 229E coronavirus, SARS-CoV-2 and SARS-CoV), Poxviridae (vaccinia virus) and Togaviridae (Sindbis virus) families.

Subunit / interactions. Component of an interferon-dependent multiprotein complex, at least composed of IFIT1, IFIT2 and IFIT3. Interacts (via TPR repeats 1-4) with RPL15. Interacts with STING1/MITA; could disrupt STING1 interaction with MAVS or TBK1, acting as a negative-feedback regulator of virus-triggered signaling. Interacts with EIF3E; this could be an alternative way to inhibit translation.

Subcellular location. Cytoplasm.

Post-translational modifications. Phosphorylated. ISGylated.

Induction. By type I interferons, dsRNAs and viruses.

Similarity. Belongs to the IFIT family.

Isoforms (2)

UniProt ID	Names	Canonical?
P09914-1	1	yes
P09914-2	2

RefSeq proteins (5): NP_001257856, NP_001257857, NP_001257858, NP_001257859, NP_001539* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR013105	TPR_2	Repeat
IPR019734	TPR_rpt	Repeat

Pfam: PF07719, PF13181, PF13424

UniProt features (73 total): helix 27, mutagenesis site 20, repeat 10, binding site 6, sequence conflict 3, turn 3, chain 1, splice variant 1, sequence variant 1, strand 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
5UDI	X-RAY DIFFRACTION	1.58
5UDK	X-RAY DIFFRACTION	1.65
5UDL	X-RAY DIFFRACTION	1.65
5UDJ	X-RAY DIFFRACTION	1.69
4HOU	X-RAY DIFFRACTION	1.95
6C6K	X-RAY DIFFRACTION	2.54
5W5I	X-RAY DIFFRACTION	2.65
5W5H	X-RAY DIFFRACTION	2.79

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09914-F1	94.29	0.87

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 (6): 147; 190; 259; 289; 290; 336

Mutagenesis-validated functional residues (20):

Position	Phenotype
34	abolishes ppp-rna-binding.
38	loss of capped rna-binding.
38	abolishes ppp-rna-binding.
42	decreased capped rna-binding. decreased translation inhibition of viral rnas lacking 2’-o-methylation of the 5’ cap.
42	reduced ppp-rna-binding. decreased capped rna-binding. decreased translation inhibition of viral rnas lacking 2’-o-methy
46	decreased capped rna-binding. decreased translation inhibition of viral rnas lacking 2’-o-methylation of the 5’ cap.
48	no effect on capped rna-binding.
147	decreased capped rna-binding. decreased translation inhibition of viral rnas lacking 2’-o-methylation of the 5’ cap.
147	loss of capped rna-binding. loss of translation inhibition of viral rnas lacking 2’-o-methylation of the 5’ cap.
151	loss of capped rna-binding. loss of translation inhibition of viral rnas lacking 2’-o-methylation of the 5’ cap.
157	reduced ppp-rna-binding. reduced capped rna-binding. loss of capped rna-binding and decreased translation inhibition of
176	decreased capped rna-binding. decreased translation inhibition of viral rnas lacking 2’-o-methylation of the 5’ cap.
187	loss of capped rna-binding. loss of translation inhibition of viral rnas lacking 2’-o-methylation of the 5’ cap.
187	abolishes ppp-rna-binding. loss of capped rna-binding. loss of translation inhibition of viral rnas lacking 2’-o-methyla
216	no effect on capped rna-binding.
218	decreased capped rna-binding. decreased translation inhibition of viral rnas lacking 2’-o-methylation of the 5’ cap.
255	abolishes ppp-rna-binding.
289	decreased capped rna-binding. loss of capped rna-binding and decreased translation inhibition of viral rnas lacking 2’-o
290	decreased capped rna-binding. loss of capped rna-binding and decreased translation inhibition of viral rnas lacking 2’-o

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-909733	Interferon alpha/beta signaling

MSigDB gene sets: 451 (showing top): AGGAAGC_MIR5163P, BROWNE_HCMV_INFECTION_4HR_UP, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, MODULE_52, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, DORN_ADENOVIRUS_INFECTION_12HR_UP, BECKER_TAMOXIFEN_RESISTANCE_UP, MODULE_45, GOBP_REGULATION_BY_VIRUS_OF_VIRAL_PROTEIN_LEVELS_IN_HOST_CELL, GOZGIT_ESR1_TARGETS_DN, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GOBP_RESPONSE_TO_TYPE_I_INTERFERON

GO Biological Process (12): response to virus (GO:0009615), intracellular transport of viral protein in host cell (GO:0019060), positive regulation of viral genome replication (GO:0045070), negative regulation of viral genome replication (GO:0045071), defense response to virus (GO:0051607), cellular response to type I interferon (GO:0071357), cellular response to exogenous dsRNA (GO:0071360), antiviral innate immune response (GO:0140374), negative regulation of viral translation (GO:1904972), immune system process (GO:0002376), innate immune response (GO:0045087), response to other organism (GO:0051707)

GO Molecular Function (4): RNA binding (GO:0003723), enzyme inhibitor activity (GO:0004857), RNA sequestering activity (GO:0140610), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), host cell (GO:0043657)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Antimicrobial mechanism of IFN-stimulated genes	1
Interferon Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
viral genome replication	2
regulation of viral genome replication	2
negative regulation of viral process	2
cellular anatomical structure	2
response to other organism	1
symbiont intracellular protein transport in host	1
regulation by virus of viral protein levels in host cell	1
positive regulation of viral process	1
defense response	1
response to virus	1
response to type I interferon	1
cellular response to cytokine stimulus	1
response to exogenous dsRNA	1
cellular response to dsRNA	1
innate immune response	1
defense response to virus	1
viral translation	1
regulation of viral translation	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
nucleic acid binding	1
catalytic activity	1
enzyme regulator activity	1
molecular function inhibitor activity	1
RNA binding	1
molecular sequestering activity	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
host cellular component	1

Protein interactions and networks

STRING

2981 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFIT1	RIGI	O95786	966
IFIT1	ISG15	P05161	934
IFIT1	MX1	P20591	918
IFIT1	IFIH1	Q9BYX4	914
IFIT1	IRF3	Q14653	903
IFIT1	IFIT3	O14879	895
IFIT1	IFNB1	P01574	890
IFIT1	TBK1	Q9UHD2	883
IFIT1	IRF7	Q92985	882
IFIT1	IFI44	Q8TCB0	865
IFIT1	CXCL10	P02778	861
IFIT1	IFNA13	P01562	857
IFIT1	IFI44L	Q53G44	852
IFIT1	OASL	Q15646	851
IFIT1	OAS2	P29728	838

IntAct

57 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
IFIT2	IFIT3	psi-mi:“MI:0914”(association)	0.780
IFIT2	IFIT1	psi-mi:“MI:0915”(physical association)	0.750
E1	IFIT1	psi-mi:“MI:0915”(physical association)	0.640
IFIT1	E1	psi-mi:“MI:0915”(physical association)	0.640
IFIT1	E1	psi-mi:“MI:0403”(colocalization)	0.640
IFIT1	E1	psi-mi:“MI:0407”(direct interaction)	0.640
STING1	IFIT2	psi-mi:“MI:0914”(association)	0.560
STING1	IFIT1	psi-mi:“MI:0915”(physical association)	0.560
IFNA21	IFIT3	psi-mi:“MI:0914”(association)	0.530
IFNA14	IFIT3	psi-mi:“MI:0914”(association)	0.530

BioGRID (106): IFIT3 (Two-hybrid), IFIT1 (Affinity Capture-MS), IFIT1 (Affinity Capture-MS), IFIT1 (Affinity Capture-MS), IFIT3 (Two-hybrid), IFIT3 (Two-hybrid), IFIT1 (Affinity Capture-MS), IFIT1 (Affinity Capture-MS), IFIT1 (Affinity Capture-MS), IFIT1 (Affinity Capture-MS), IFIT1 (Affinity Capture-MS), IFIT1 (Affinity Capture-MS), IFIT1 (Affinity Capture-MS), IFIT1 (Affinity Capture-MS), IFIT1 (Affinity Capture-MS)

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 34 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
Regulation of IFNA/IFNB signaling	7	133.7×	6e-13
TRAF6 mediated IRF7 activation	8	132.4×	2e-14
Evasion by RSV of host interferon responses	8	113.5×	5e-14
Interferon alpha/beta signaling	10	66.2×	8e-15
SARS-CoV-2 activates/modulates innate and adaptive immune responses	10	38.8×	5e-13
Factors involved in megakaryocyte development and platelet production	7	20.2×	5e-07

GO biological processes:

GO term	Partners	Fold	FDR
B cell activation involved in immune response	6	234.1×	9e-12
natural killer cell activation involved in immune response	6	220.3×	9e-12
T cell activation involved in immune response	6	156.0×	6e-11
response to exogenous dsRNA	6	117.0×	3e-10
type I interferon-mediated signaling pathway	7	89.2×	6e-11
humoral immune response	7	72.8×	2e-10
cellular response to virus	7	52.0×	2e-09
defense response to virus	12	30.8×	2e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	59
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
831108	NC_000010.11:g.(?89338661)(89612048_?)del	Pathogenic

SpliceAI

284 predictions. Top by Δscore:

Variant	Effect	Δscore
10:89402276:TACA:T	acceptor_loss	1.0000
10:89402278:CA:C	acceptor_loss	1.0000
10:89402279:A:AG	acceptor_gain	1.0000
10:89402280:G:GA	acceptor_gain	1.0000
10:89402280:GT:G	acceptor_gain	1.0000
10:89402280:GTACA:G	acceptor_gain	1.0000
10:89392715:GAG:G	donor_gain	0.9900
10:89392718:G:GA	donor_loss	0.9900
10:89392719:T:G	donor_loss	0.9900
10:89399886:T:A	acceptor_gain	0.9900
10:89402278:C:G	acceptor_gain	0.9900
10:89402280:GTA:G	acceptor_gain	0.9900
10:89402280:GTAC:G	acceptor_gain	0.9900
10:89392718:G:GG	donor_gain	0.9800
10:89402270:T:TA	acceptor_gain	0.9800
10:89402277:A:AG	acceptor_gain	0.9800
10:89399880:T:TA	acceptor_gain	0.9700
10:89400004:G:GG	donor_gain	0.9700
10:89392714:TGAG:T	donor_gain	0.9600
10:89392715:GAGG:G	donor_gain	0.9600
10:89399878:T:TA	acceptor_gain	0.9500
10:89399884:ACT:A	acceptor_gain	0.9500
10:89399999:GAACT:G	donor_gain	0.9500
10:89393188:A:AG	donor_gain	0.9400
10:89399884:A:AG	acceptor_gain	0.9400
10:89392713:ATGAG:A	donor_gain	0.9200
10:89392716:AG:A	donor_gain	0.9200
10:89392717:GG:G	donor_gain	0.9200
10:89400495:T:G	donor_gain	0.9000
10:89399885:C:G	acceptor_gain	0.8600

AlphaMissense

3169 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:89403150:G:A	G292E	0.976
10:89403429:G:A	G385D	0.973
10:89403149:G:T	G292W	0.972
10:89403434:T:C	F387L	0.971
10:89403436:T:A	F387L	0.971
10:89403436:T:G	F387L	0.971
10:89403527:A:C	S418R	0.971
10:89403529:T:A	S418R	0.971
10:89403529:T:G	S418R	0.971
10:89403248:G:C	A325P	0.970
10:89402336:T:C	F21L	0.968
10:89402338:T:A	F21L	0.968
10:89402338:T:G	F21L	0.968
10:89402765:T:C	F164L	0.968
10:89402767:T:A	F164L	0.968
10:89402767:T:G	F164L	0.968
10:89403060:G:C	R262P	0.966
10:89403312:T:C	L346P	0.966
10:89403467:G:C	A398P	0.963
10:89403149:G:A	G292R	0.960
10:89403149:G:C	G292R	0.960
10:89403605:G:T	G444W	0.958
10:89402900:G:C	A209P	0.956
10:89403605:G:A	G444R	0.955
10:89403605:G:C	G444R	0.955
10:89402344:G:C	W23C	0.954
10:89402344:G:T	W23C	0.954
10:89403468:C:A	A398E	0.952
10:89402342:T:A	W23R	0.950
10:89402342:T:C	W23R	0.950

dbSNP variants (sampled 300 via entrez): RS1000120552 (10:89405637 T>C), RS1000322054 (10:89403984 C>T), RS1000494037 (10:89405927 C>T), RS1000638985 (10:89391323 C>G), RS1000752167 (10:89398458 C>T), RS1000896582 (10:89391864 T>C), RS1001098524 (10:89404385 C>T), RS1001348079 (10:89404762 C>T), RS1001377803 (10:89404528 T>C), RS1001597773 (10:89400843 G>A), RS1001654591 (10:89397118 G>A), RS1001764980 (10:89406976 A>T), RS1001949169 (10:89392662 G>A), RS1002160516 (10:89391777 C>T), RS1002165916 (10:89392978 G>A)

Disease associations

OMIM: gene MIM:147690 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs304478	IFIT1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression, decreases expression	6
Estradiol	affects cotreatment, increases expression, decreases expression	6
Benzo(a)pyrene	increases expression, increases methylation, decreases reaction, decreases expression	4
Lipopolysaccharides	affects cotreatment, decreases reaction, affects expression, increases expression, affects reaction	4
Tretinoin	decreases expression, increases expression	4
Valproic Acid	affects expression, increases expression	4
Cyclosporine	decreases expression	4
Air Pollutants	decreases expression, increases abundance	3
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment	3
bisphenol A	decreases expression, increases expression	2
trichostatin A	affects expression, increases expression	2
nickel sulfate	decreases expression, increases expression	2
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects cotreatment, increases expression, decreases reaction	2
epigallocatechin gallate	decreases expression, affects cotreatment	2
monomethylarsonous acid	decreases expression	2
dimethylarsinous acid	decreases expression, increases expression	2
tofacitinib	decreases reaction, increases expression, decreases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression, increases expression	2
Temozolomide	affects response to substance, increases expression	2
Acetaminophen	decreases expression	2
Azathioprine	decreases expression	2
Benzene	increases expression	2
Calcitriol	decreases expression	2
Doxorubicin	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Plant Extracts	affects expression, affects reaction, increases expression	2
Prednisolone	decreases expression, decreases reaction, increases expression, increases response to substance	2
Silicon Dioxide	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8MR	Ubigene HCT 116 IFIT1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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