IRF2

Summary

IRF2 (interferon regulatory factor 2, HGNC:6117) is a protein-coding gene on chromosome 4q35.1, encoding Interferon regulatory factor 2 (P14316). DNA-binding transcription factor that specifically binds to the upstream regulatory region of type I interferon (IFN) and IFN-inducible genes and regulates their expression.

IRF2 encodes interferon regulatory factor 2, a member of the interferon regulatory transcription factor (IRF) family. IRF2 competitively inhibits the IRF1-mediated transcriptional activation of interferons alpha and beta, and presumably other genes that employ IRF1 for transcription activation. However, IRF2 also functions as a transcriptional activator of histone H4.

Source: NCBI Gene 3660 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 54 total
• Transcription factor: yes — 68 downstream targets (CollecTRI)
• MANE Select transcript: NM_002199

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6117
Approved symbol	IRF2
Name	interferon regulatory factor 2
Location	4q35.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000168310
Ensembl biotype	protein_coding
OMIM	147576
Entrez	3660

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 23 protein_coding, 5 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000393593, ENST00000502750, ENST00000504340, ENST00000505067, ENST00000506230, ENST00000507523, ENST00000509274, ENST00000510814, ENST00000512020, ENST00000696840, ENST00000696841, ENST00000696842, ENST00000696843, ENST00000696844, ENST00000696845, ENST00000696846, ENST00000696847, ENST00000696848, ENST00000696849, ENST00000696850, ENST00000696851, ENST00000696852, ENST00000696853, ENST00000883917, ENST00000883918, ENST00000883919, ENST00000883920, ENST00000956294, ENST00000956295, ENST00000956296

RefSeq mRNA: 1 — MANE Select: NM_002199 NM_002199

CCDS: CCDS3835

Canonical transcript exons

ENST00000393593 — 9 exons

Exon	Start	End
ENSE00001124936	184390703	184390749
ENSE00001124942	184398915	184399079
ENSE00003611539	184419469	184419568
ENSE00003629533	184418532	184418708
ENSE00003690438	184428978	184429070
ENSE00003785156	184418167	184418213
ENSE00003787642	184408158	184408275
ENSE00003968614	184474379	184474550
ENSE00003968639	184387729	184389066

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 96.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.9530 / max 513.7185, expressed in 1808 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55146	23.1436	1805
55145	2.6571	603
55144	1.7920	409
55142	1.2540	481
55143	0.1063	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	96.00	gold quality
leukocyte	CL:0000738	95.72	gold quality
mononuclear cell	CL:0000842	95.72	gold quality
blood	UBERON:0000178	95.59	gold quality
calcaneal tendon	UBERON:0003701	95.05	gold quality
granulocyte	CL:0000094	92.87	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.64	gold quality
vermiform appendix	UBERON:0001154	92.61	gold quality
spleen	UBERON:0002106	92.43	gold quality
lymph node	UBERON:0000029	92.35	gold quality
rectum	UBERON:0001052	91.73	gold quality
right adrenal gland	UBERON:0001233	91.61	gold quality
right adrenal gland cortex	UBERON:0035827	91.61	gold quality
left adrenal gland	UBERON:0001234	91.54	gold quality
bone marrow cell	CL:0002092	91.47	gold quality
left adrenal gland cortex	UBERON:0035825	91.26	gold quality
colonic epithelium	UBERON:0000397	91.19	gold quality
gall bladder	UBERON:0002110	91.08	gold quality
adrenal gland	UBERON:0002369	91.00	gold quality
right lung	UBERON:0002167	90.53	gold quality
popliteal artery	UBERON:0002250	90.34	gold quality
tibial artery	UBERON:0007610	90.34	gold quality
adrenal cortex	UBERON:0001235	90.11	gold quality
palpebral conjunctiva	UBERON:0001812	89.96	gold quality
body of pancreas	UBERON:0001150	89.93	gold quality
right coronary artery	UBERON:0001625	89.85	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.57	gold quality
right lobe of liver	UBERON:0001114	89.41	gold quality
aorta	UBERON:0000947	89.38	gold quality
muscle of leg	UBERON:0001383	89.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7037	yes	158.19
E-ANND-3	yes	7.64

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

68 targets.

Target	Regulation
ABCC8
AGTR2	Repression
BCL2L1
BLMH
CAMK4
CASP1
CASP8
CAT
CCL5	Activation
CD74
CDK2
CDKN1A	Activation
CEACAM1
CIITA	Activation
CREBBP
CTSS	Activation
CXCL10	Activation
CXCL11	Activation
CXCR4	Repression
CYBB	Activation
DST	Repression
ERAP2	Unknown
FASLG	Activation
FGFR1
H4C14	Unknown
HLA-E
IFI27	Activation
IFI35	Repression
IFN1@
IFNA1

JASPAR motifs

Motif	Name	Family
MA0051.1	IRF2	Interferon-regulatory factors
MA0051.2	IRF2	Interferon-regulatory factors

JASPAR matrix evidence (PMIDs): PMID:7687740

Upstream regulators (CollecTRI, top): CIITA, IRF1, IRF2, MYC, PITX1, STAT1

miRNA regulators (miRDB)

153 targeting IRF2, 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-3163	100.00	77.23	8605
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4731-5P	99.89	67.23	2537

Literature-anchored findings (GeneRIF, showing 40)

• IRF-1 and IRF-2 induced by IFN-gamma bind to three distinct IL-4 promoter sites and function as transcriptional repressors (PMID:12479817)
• IRF2 is a potential susceptibility gene for psoriasis. (PMID:14962090)
• Results suggest that the functional interplay between interferon regulatory factors 1 and 2 serves as an elaborate and cooperative mechanism for regulation of interleukin-7 production essential for local immune regulation within human intestinal mucosa. (PMID:15226432)
• IRF-2 is involved in up-regulation of nonmuscle myosin heavy chain II-A gene expression in cell differentiation (PMID:15496418)
• IFN-gamma-IRF system is involved in BPAG1 gene regulation in type-1 helper T-cell inflammatory skin conditions, such as psoriasis vulgaris (PMID:15560761)
• In cells transfected with both IRF-2 and p300/CBP-associated factor , IRF-2 associated with endogenous nucleolin. (PMID:16582966)
• IRF8 cooperates with PU.1 and IRF-2 to activate a composite ets/IRF-cis element in the NF1 promoter. The conserved IRF domain tyrosine in ICSBP/IRF8 is required for interaction with the DNA-bound PU.1-IRF2 heterodimer. (PMID:17200120)
• IRF-2 regulates NF-kappaB activity via the modulation of NF-kappaB subcellular localization. (PMID:18395009)
• IRF2 interacts with the SUMO-E3 ligase PIASy and is sumoylated in vivo (PMID:18514056)
• PTB binding to multiple sites within IRF2 5’UTR leads to a conformational change in the RNA that facilitate binding of other trans-acting factors to mediate internal initiation of translation (PMID:19756143)
• IRF-2 activates RIG-I promoter through ISRE-like site as well as IRF-1 and IFN-alpha stimulation. (PMID:20034464)
• IRF-2 activates the HPV-16 P97 promoter in vivo. (PMID:20129639)
• IFN regulatory factor 2 (Irf2) has a regulatory role in trypsinogen5 gene transcription, which is resistant to a major endogenous trypsin inhibitor, Spink3 (PMID:22042864)
• The results suggested that distinct markers in IRF2 may be associated with atopic dermatitis and eczema herpeticum (which may depend upon ethnic ancestry) and genetic variants in IRF2 may contribute to an abnormal immune response to herpes simplex virus. (PMID:22113474)
• these results suggest that IRF-2 plays an important role in the tumorigenesis of pancreatic cancer and down-regulation of IRF-2 would be a new treatment target for pancreatic cancer. (PMID:22119988)
• IRF2 overexpression protects against I/R injury by decreasing IRF1-dependent injury and may represent a novel therapeutic strategy. (PMID:22744333)
• miR-221 directly inhibits the expression of SOCS3 and IRF2. (PMID:24607843)
• Data suggest that interferon regulatory factors 1 and 2 (IRF1 and IRF2) may serve as potential targets of therapy. (PMID:24632547)
• IRF2genes were not associated with pancreatitis. 4 variants were found: c.123G>A (novel), c.651C>T, c.744G>A, and c.638C>T, p.P213L. (PMID:25207663)
• the association of IRF2 with susceptibility to systemic lupus erythematosus (PMID:25285625)
• It might play as a tumor suppressor by regulating P53 signaling in gastric cancer. (PMID:26173586)
• miR-450 targets IRF2 and thus supresses lung cancer cell proliferation and invasion. (PMID:27246609)
• In a genome wide are study to identify acute kidney injury risk in critically ill patients, the locus on chromosome 4, located 150 kb upstream of IRF2 was identified to regulate immunity pathways related to kidney disease risk gene APOL1. Disruption of IRF-2 has been found to up-regulate the inflammatory response to infection. (PMID:27576016)
• Our study primarily suggests IRF-2 as a potential prognostic biomarker in colorectal cancer (PMID:28465494)
• These finding suggests that miR-302b inhibits key transcription factors and cytokines by targeting ERBB4, IRF2 and CXCR4, implicating its role in the inhibition of CRI in EC. (PMID:28467773)
• The effects of IRF2 suppresses non-small cell lung cancer by promoting cell apoptosis, inhibiting cell proliferation and migration ability. (PMID:28471447)
• Study shows that IRF2 knockdown inhibits growth, colony formation of OCI/AML-2, OCI/AML-3, and THP-1 cells. In addition, IRF2 knockdown induces apoptosis of acute myeloid leukemia (AML) cells by regulating apoptotic effectors. Further mechanism analysis shows that INPP4B contributes to the effects of IRF2 on apoptosis and growth of AML cells. Thus, IRF2 serves as an important regulator in AML by targeting INPP4B. (PMID:28579269)
• Data suggest that MIR1290 expression is remarkably upregulated in non-small-cell lung carcinoma tissues compared to adjacent normal lung tissues; IRF2 appears to be a direct target of MIR1290. (MIR1290 = microRNA-1290; IRF2 = interferon regulatory factor-2) (PMID:29275213)
• This review focusses on current knowledge of the roles of IRF-1 and IRF-2 in human cancer, with particular attention paid to the impact of IRF-1 inactivation. (PMID:29599126)
• Results identified IRF2 as a target of miR-18a. Furthermore, H19 regulated IRF2 expression level through miR-18a. (PMID:30536700)
• miR-664 was remarkably high in cutaneous squamous cell carcinomas (cSCC) patient specimens and cSCC cell lines. Study identified IRF2 as a direct downstream target of miR-664. Knockdown of IRF2 reverses pro-tumorigenesis phenotype of miR-664; whereas IRF2 over-expression inhibits miR-664 tumorigenesis in cSCC. Together, it revealed miR-664 functions as an oncogene in cSCC via suppression of IRF2. (PMID:31138473)
• Knockdown of IRF-1 reduces the stimulation of TRIM14 transcription by IFN-alpha, suggesting that IRF-1 is involved in the activation of TRIM14 by IFN-I. IRF-2 has little effect on IFN-alpha-induced TRIM14 transcription but is essential for the basal transcription of TRIM14. (PMID:31150153)
• IRF-2 was involved in regulating the invasion and migration of gastric cancer cells and negatively regulates the expression of MMP-1. (PMID:31350707)
• IRF2 is a repressor of PD-L1. Thus, by downregulating a single nonessential gene, tumors become harder to see (reduced Ag presentation), more inhibitory (increased checkpoint inhibitor), and less susceptible to being killed by CD8(+) T cells. (PMID:31471524)
• Exosomes derived from human bone marrow mesenchymal stem cells transfer miR-222-3p to suppress acute myeloid leukemia cell proliferation by targeting IRF2/INPP4B. (PMID:31968218)
• IRF2-INPP4B axis inhibits apoptosis of acute myeloid leukaemia cells via regulating T helper 1/2 cell differentiation. (PMID:32115737)
• ELF1 activated long non-coding RNA CASC2 inhibits cisplatin resistance of non-small cell lung cancer via the miR-18a/IRF-2 signaling pathway. (PMID:32271431)
• Interferon regulatory factor 1 (IRF-1) and IRF-2 regulate PD-L1 expression in hepatocellular carcinoma (HCC) cells. (PMID:32377817)
• Apolipoprotein L1 is transcriptionally regulated by SP1, IRF1 and IRF2 in hepatoma cells. (PMID:32671843)
• IRF2-mediated upregulation of lncRNA HHAS1 facilitates the osteogenic differentiation of bone marrow-derived mesenchymal stem cells by acting as a competing endogenous RNA. (PMID:34185419)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	irf2a	ENSDARG00000007387
danio_rerio	irf2b	ENSDARG00000040465
mus_musculus	Irf2	ENSMUSG00000031627
rattus_norvegicus	Irf2	ENSRNOG00000009824

Paralogs (8): IRF6 (ENSG00000117595), IRF1 (ENSG00000125347), IRF3 (ENSG00000126456), IRF5 (ENSG00000128604), IRF4 (ENSG00000137265), IRF8 (ENSG00000140968), IRF7 (ENSG00000185507), IRF9 (ENSG00000213928)

Protein

Protein identifiers

Interferon regulatory factor 2 — P14316 (reviewed: P14316)

All UniProt accessions (11): A0A8Q3SIV4, A0A8Q3SIZ2, A0A8Q3SIZ8, A0A8Q3SJ30, D6R9N5, D6RB08, P14316, D6RED1, H0Y956, K4DIA4, K4DIA5

UniProt curated annotations — full annotation on UniProt →

Function. DNA-binding transcription factor that specifically binds to the upstream regulatory region of type I interferon (IFN) and IFN-inducible genes and regulates their expression. Mainly acts as a transcription repressor, repressing expression. Also acts as an activator for several genes including H4 and IL7. Constitutively binds to the ISRE promoter to activate IL7. Involved in cell cycle regulation through binding the site II (HiNF-M) promoter region of H4 and activating transcription during cell growth. Antagonizes IRF1 transcriptional activation. Unable to bind to IRF2BP1 and IRF2BP2 corepressors and cannot mediate repression.

Subunit / interactions. Interacts with BRD7, IRF2BP1 and IRF2BP2. Interacts with CREBBP in growing cells; the interaction acetylates IRF2 and regulates IRF2-dependent H4 promoter activity. Interacts with TASOR2; promoting recruitment of the HUSH2 complex to interferon-stimulated genes and transcription silencing.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Expressed throughout the epithelium of the colon. Also expressed in lamina propria.

Post-translational modifications. Acetylated by CBP/ p300 during cell-growth. Acetylation on Lys-75 is required for stimulation of H4 promoter activity. The major sites of sumoylation are Lys-137 and Lys-293. Sumoylation with SUMO1 increases its transcriptional repressor activity on IRF1 and diminishes its ability to activate ISRE and H4 promoter.

Induction. By viruses and IFN.

Similarity. Belongs to the IRF family.

Isoforms (2)

UniProt ID	Names	Canonical?
P14316-1	1	yes
P14316-2	2, IRF-2s, IRF-2[S]

RefSeq proteins (1): NP_002190* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001346	Interferon_reg_fact_DNA-bd_dom	Domain
IPR017431	IRF1/IRF2	Family
IPR019817	Interferon_reg_fac_CS	Conserved_site
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily

Pfam: PF00605

UniProt features (23 total): cross-link 5, mutagenesis site 5, modified residue 3, region of interest 3, compositionally biased region 3, chain 1, DNA-binding region 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8YTG	X-RAY DIFFRACTION	1.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14316-F1	64.75	0.31

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 (8): 225, 137, 137, 166, 260, 293, 75, 78

Mutagenesis-validated functional residues (5):

Position	Phenotype
75	diminished acetylation by both crebbp/p300 and pcaf. greatly reduced enhancement of h4 promoter activity.
78	greatly diminished acetylation by pcaf. lesser loss of acetylation by crebbp/p300. loss of dna binding and no enhancemen
137	some loss of sumoylation. increases irf2-mediation activation of isre and h4 promoters. increased inhibition of irf1-med
166	little loss of sumoylation. increases irf2-mediation activation of isre and h4 promoters. increased inhibition of irf1-m
293	some loss of sumoylation. increases irf2-mediation activation of isre and h4 promoters. increased inhibition of irf1-med

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-5620971	Pyroptosis
R-HSA-877300	Interferon gamma signaling
R-HSA-909733	Interferon alpha/beta signaling
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-109582	Hemostasis
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
R-HSA-5218859	Regulated Necrosis
R-HSA-5357801	Programmed Cell Death
R-HSA-913531	Interferon Signaling

MSigDB gene sets: 333 (showing top): GCACCTT_MIR18A_MIR18B, MORF_MSH3, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, BECKER_TAMOXIFEN_RESISTANCE_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, MORF_ATRX, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, KYNG_DNA_DAMAGE_DN, GOBP_NEGATIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, MORF_ESR1, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, IRF7_01, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM

GO Biological Process (9): negative regulation of transcription by RNA polymerase II (GO:0000122), immune system process (GO:0002376), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), cell population proliferation (GO:0008283), negative regulation of type I interferon production (GO:0032480), toll-like receptor 3 signaling pathway (GO:0034138), positive regulation of transcription by RNA polymerase II (GO:0045944), defense response to virus (GO:0051607)

GO Molecular Function (10): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), transcription cis-regulatory region binding (GO:0000976), protein binding (GO:0005515)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), focal adhesion (GO:0005925)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Interferon Signaling	2
Regulated Necrosis	1
Hemostasis	1
Immune System	1
Programmed Cell Death	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
transcription cis-regulatory region binding	2
negative regulation of DNA-templated transcription	1
biological_process	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular process	1
negative regulation of cytokine production	1
regulation of type I interferon production	1
type I interferon production	1
endolysosomal toll-like receptor signaling pathway	1
positive regulation of DNA-templated transcription	1
defense response	1
response to virus	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transcription regulator activity	1
DNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
cell-substrate junction	1

Protein interactions and networks

STRING

2062 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IRF2	IRF2BP2	Q7Z5L9	920
IRF2	IRF1	P10914	831
IRF2	MDM2	Q00987	782
IRF2	IRF2BP1	Q8IU81	754
IRF2	IFNA13	P01562	752
IRF2	SPI1	P17947	745
IRF2	STAT2	P52630	735
IRF2	IFNB1	P01574	720
IRF2	IFNG	P01579	687
IRF2	IRF2BPL	Q9H1B7	630
IRF2	STAT1	P42224	628
IRF2	RELA	Q04206	623
IRF2	IFNA2	P01563	615
IRF2	IFNA17	P01571	582
IRF2	IFIT2	P09913	581

IntAct

48 interactions, top by confidence:

A	B	Type	Score
FOXK2	IRF2	psi-mi:“MI:0915”(physical association)	0.770
IRF2	FOXK1	psi-mi:“MI:0915”(physical association)	0.710
IRF2	TASOR2	psi-mi:“MI:0915”(physical association)	0.620
IRF2	CTSS	psi-mi:“MI:0914”(association)	0.530
ATG7	IRF2	psi-mi:“MI:0915”(physical association)	0.500
IRF2	PPP3CB	psi-mi:“MI:0915”(physical association)	0.500
IRF2	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
WLS	IRF2	psi-mi:“MI:0915”(physical association)	0.370
NFE2L2	IRF2	psi-mi:“MI:0915”(physical association)	0.370
IFNA10	IRF2	psi-mi:“MI:0915”(physical association)	0.370
IFNA21	IRF2	psi-mi:“MI:0915”(physical association)	0.370
IFNA7	IRF2	psi-mi:“MI:0915”(physical association)	0.370
	IRF2	psi-mi:“MI:0915”(physical association)	0.370
IRF2	TNFSF10	psi-mi:“MI:0915”(physical association)	0.370
TNFSF13B	IRF2	psi-mi:“MI:0915”(physical association)	0.370
TNFSF10	IRF2	psi-mi:“MI:0915”(physical association)	0.370
FKBP7	IRF2	psi-mi:“MI:0915”(physical association)	0.370
FOXK2	PHF20L1	psi-mi:“MI:0914”(association)	0.350
IRF2	VWA8	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
IRF2	AP5Z1	psi-mi:“MI:0914”(association)	0.350
AKT1	IRF2	psi-mi:“MI:2364”(proximity)	0.270
FBXW7	IRF2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (148): NCL (Affinity Capture-MS), NCL (Affinity Capture-Western), IRF2 (Protein-peptide), IRF2 (Affinity Capture-MS), IRF2BPL (Affinity Capture-MS), FAM208B (Affinity Capture-MS), CTSS (Affinity Capture-MS), IRF2BP2 (Affinity Capture-MS), IRF2BP1 (Affinity Capture-MS), FOXK2 (Affinity Capture-MS), FOXK1 (Affinity Capture-MS), HCFC2 (Affinity Capture-MS), PRDM1 (Phenotypic Suppression), IRF2 (Reconstituted Complex), IRF2 (Biochemical Activity)

ESM2 similar proteins: A0FIN4, A2VD01, A9ZLX4, D2HNW6, D4A7U2, O88974, O94988, P10914, P14316, P15314, P16236, P17433, P17947, P23570, P23906, P49140, Q00IB7, Q13506, Q13905, Q15047, Q1LY51, Q3B7M3, Q3SZP0, Q3TTA7, Q3UWM4, Q4V7W5, Q5HYC2, Q5RJA1, Q5XJV7, Q61122, Q62722, Q6A098, Q6AI12, Q6BDS1, Q6DFR2, Q6GQL0, Q6PKU1, Q6ZMT4, Q6ZNC4, Q80TJ7

Diamond homologs: A0FIN4, O14896, P10914, P14316, P15314, P23570, P23611, P23906, P56477, P70671, P97431, Q00978, Q02556, Q08DD6, Q13568, Q14653, Q15306, Q3SZP0, Q4JF28, Q58DJ0, Q61179, Q64287, Q764M6, Q8R4E0, Q90643, Q90871, Q90876, Q98925, Q92985, P70434, F5HF68

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
IRF2BP1	“up-regulates activity”	IRF2	binding
IRF2BP2	“up-regulates activity”	IRF2	binding
IRF2	“down-regulates quantity by repression”	DST	“transcriptional regulation”
IRF2	“up-regulates quantity by expression”	TAP1	“transcriptional regulation”
STAT1	“up-regulates activity”	IRF2	binding
IRF2	“up-regulates quantity by expression”	CIITA	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 31 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
SARS-CoV-2 activates/modulates innate and adaptive immune responses	5	18.6×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
defense response to virus	5	12.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2679 predictions. Top by Δscore:

Variant	Effect	Δscore
4:184390755:C:CT	acceptor_gain	1.0000
4:184398909:GCTTA:G	donor_loss	1.0000
4:184398910:CTTA:C	donor_loss	1.0000
4:184398911:TTACC:T	donor_loss	1.0000
4:184398912:TAC:T	donor_loss	1.0000
4:184398913:ACC:A	donor_loss	1.0000
4:184398914:CCTG:C	donor_gain	1.0000
4:184399079:AC:A	acceptor_loss	1.0000
4:184399080:C:CC	acceptor_gain	1.0000
4:184399080:CTT:C	acceptor_loss	1.0000
4:184408272:CTTG:C	acceptor_gain	1.0000
4:184408276:C:CC	acceptor_gain	1.0000
4:184418530:A:AC	donor_loss	1.0000
4:184418531:CCTTT:C	donor_gain	1.0000
4:184418704:CTTTC:C	acceptor_gain	1.0000
4:184418705:TTTC:T	acceptor_gain	1.0000
4:184418706:TTCCT:T	acceptor_loss	1.0000
4:184418707:TC:T	acceptor_gain	1.0000
4:184418708:CC:C	acceptor_gain	1.0000
4:184418709:C:CC	acceptor_gain	1.0000
4:184418709:CT:C	acceptor_loss	1.0000
4:184418714:A:T	acceptor_gain	1.0000
4:184428974:TCA:T	donor_loss	1.0000
4:184428975:CACCT:C	donor_loss	1.0000
4:184428977:C:CA	donor_loss	1.0000
4:184429066:GTGCC:G	acceptor_gain	1.0000
4:184429067:TGCC:T	acceptor_gain	1.0000
4:184429068:GCC:G	acceptor_gain	1.0000
4:184429068:GCCC:G	acceptor_loss	1.0000
4:184429069:CC:C	acceptor_gain	1.0000

AlphaMissense

2328 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:184418564:A:G	M111T	1.000
4:184418567:C:G	R110P	1.000
4:184418570:T:G	Y109S	1.000
4:184418571:A:C	Y109D	1.000
4:184418571:A:G	Y109H	1.000
4:184418571:A:T	Y109N	1.000
4:184418573:A:T	V108D	1.000
4:184418575:C:A	R107S	1.000
4:184418575:C:G	R107S	1.000
4:184418576:C:A	R107M	1.000
4:184418576:C:G	R107T	1.000
4:184418577:T:C	R107G	1.000
4:184418582:G:T	A105D	1.000
4:184418591:C:A	G102V	1.000
4:184418591:C:T	G102E	1.000
4:184418592:C:G	G102R	1.000
4:184418592:C:T	G102R	1.000
4:184418602:G:C	S98R	1.000
4:184418602:G:T	S98R	1.000
4:184418604:T:G	S98R	1.000
4:184418624:A:T	I91N	1.000
4:184418628:C:G	D90H	1.000
4:184418633:A:C	L88W	1.000
4:184418633:A:G	L88S	1.000
4:184418636:G:A	S87F	1.000
4:184418637:A:G	S87P	1.000
4:184418638:A:C	N86K	1.000
4:184418638:A:T	N86K	1.000
4:184418639:T:A	N86I	1.000
4:184418639:T:G	N86T	1.000

dbSNP variants (sampled 300 via entrez): RS1000022595 (4:184458224 A>G), RS1000061676 (4:184395852 G>A), RS10000856 (4:184425049 T>A,C), RS1000091324 (4:184403416 G>A), RS1000194315 (4:184425189 T>A), RS1000280715 (4:184455740 A>C), RS1000290779 (4:184467778 G>C), RS1000332788 (4:184445168 T>G), RS1000340896 (4:184462006 A>G), RS1000377571 (4:184462008 C>G), RS1000411290 (4:184400335 CTTTT>C,CTTT,CTTTTT), RS10004280 (4:184422405 A>G), RS1000434244 (4:184461802 A>C), RS1000449458 (4:184417181 A>T), RS1000531192 (4:184433637 T>C)

Disease associations

OMIM: gene MIM:147576 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002591_19	Lewy body disease	1.000000e-06
GCST002591_32	Lewy body disease	9.000000e-07
GCST003542_88	Night sleep phenotypes	8.000000e-06
GCST003656_3	Acute kidney injury in critical illness	2.000000e-07
GCST004146_31	Chronic lymphocytic leukemia	4.000000e-08
GCST006993_6	Hippocampal volume in Alzheimer’s disease dementia	2.000000e-07
GCST009028_28	Adverse response to drug	2.000000e-07
GCST009357_14	Nonsyndromic cleft lip	4.000000e-08
GCST90014023_19	Type 1 diabetes	2.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006799	Lewy body dementia measurement
EFO:0005035	hippocampal volume
EFO:0009658	adverse effect
EFO:0003959	cleft lip

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	3
Valproic Acid	affects expression, decreases expression, decreases methylation	3
Air Pollutants	affects expression, increases abundance, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	increases methylation	2
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
afimoxifene	decreases expression, decreases reaction	1
sodium arsenite	decreases expression	1
nickel chloride	increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
Zoledronic Acid	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Estrogens	decreases expression, decreases reaction	1
Flavonoids	increases expression	1
Melphalan	decreases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	decreases expression	1

Cellosaurus cell lines

9 cell lines: 6 cancer cell line, 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A3F0	SEES3-1V human IRF2, clone1	Embryonic stem cell	Male
CVCL_A3F1	SEES3-1V human IRF2, clone2	Embryonic stem cell	Male
CVCL_A3F2	SEES3-1V human IRF2, clone3	Embryonic stem cell	Male
CVCL_B1G1	Abcam A-549 IRF2 KO 2	Cancer cell line	Male
CVCL_B2NJ	Abcam A-549 IRF2 KO 1	Cancer cell line	Male
CVCL_SS90	HAP1 IRF2 (-) 1	Cancer cell line	Male
CVCL_SS91	HAP1 IRF2 (-) 2	Cancer cell line	Male
CVCL_SS92	HAP1 IRF2 (-) 3	Cancer cell line	Male
CVCL_SS93	HAP1 IRF2 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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