IFNA2

Summary

IFNA2 (interferon alpha 2, HGNC:5423) is a protein-coding gene on chromosome 9p21.3, encoding Interferon alpha-2 (P01563). Produced by macrophages, IFN-alpha have antiviral activities.

This gene is a member of the alpha interferon gene cluster on chromosome 9. The encoded cytokine is a member of the type I interferon family that is produced in response to viral infection as a key part of the innate immune response with potent antiviral, antiproliferative and immunomodulatory properties. This cytokine, like other type I interferons, binds a plasma membrane receptor made of IFNAR1 and IFNAR2 that is ubiquitously expressed, and thus is able to act on virtually all body cells. The encoded protein is effective in reducing the symptoms and duration of the common cold and in treating many types of cancer, including some hematological malignancies and solid tumors. A deficiency of type I interferon in the blood is thought to be a hallmark of severe COVID-19 and may provide a rationale for a combined therapeutic approach.

Source: NCBI Gene 3440 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 37 total
• Druggable target: yes
• MANE Select transcript: NM_000605

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5423
Approved symbol	IFNA2
Name	interferon alpha 2
Location	9p21.3
Locus type	gene with protein product
Status	Approved
Aliases	IFNA, IFN-alphaA
Ensembl gene	ENSG00000188379
Ensembl biotype	protein_coding
OMIM	147562
Entrez	3440

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000380206

RefSeq mRNA: 1 — MANE Select: NM_000605 NM_000605

CCDS: CCDS6506

Canonical transcript exons

ENST00000380206 — 1 exons

Exon	Start	End
ENSE00001484102	21384255	21385398

Expression profiles

Bgee: expression breadth broad, 33 present calls, max score 95.58.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0948 / max 80.7921, expressed in 9 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100210	0.0948	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.58	silver quality
metanephric glomerulus	UBERON:0004736	55.97	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
corpus callosum	UBERON:0002336	48.78	silver quality
endometrium epithelium	UBERON:0004811	46.85	gold quality
quadriceps femoris	UBERON:0001377	44.83	gold quality
vastus lateralis	UBERON:0001379	43.87	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
thymus	UBERON:0002370	43.24	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
skin of hip	UBERON:0001554	41.85	silver quality
putamen	UBERON:0001874	41.54	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
oviduct epithelium	UBERON:0004804	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
lower lobe of lung	UBERON:0008949	40.29	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.31

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
HLA-B	Activation

Upstream regulators (CollecTRI, top): ELF4, IRF1, IRF3, IRF5, IRF7

miRNA regulators (miRDB)

46 targeting IFNA2, 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-3134	100.00	66.43	777
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-18A-5P	99.29	71.05	806
HSA-MIR-18B-5P	99.29	71.05	806
HSA-MIR-4735-3P	99.14	69.85	777

Literature-anchored findings (GeneRIF, showing 40)

• Angiogenic activity of rat mast cells in the chick embryo chorioallantoic membrane is down-regulated by treatment with recombinant human alpha-2a interferon and partly mediated by fibroblast growth factor-2. (alpha-2a interferon) (PMID:12010658)
• Possession of the IFNA17 polymorphism (551T–>G), with higher levels of IFN-alpha significantly increases the risk of sarcoidosis. (PMID:15004750)
• Data describe the mapping of the complete binding region of IFNAR1 on IFNalpha2 using a panel of 21 single alanine mutant proteins. (PMID:16171819)
• In vivo induction of ITGA-11 is detected in spleen and lungs of human recombinant IFN-alpha 2-treated BALB/c mice. (PMID:16697656)
• Findings indicate that the deletion in the promoter of the IFN-alpha-2 gene reduces the transcription of this gene in vitro and this could also be one cause of susceptibility to hepatitis B. (PMID:16920161)
• Plasmacytoid dendritic cells in atherosclerotic plaque sense microbial motifs and amplify cytolytic T-cell functions. IFN-alpha emerged as a potent regulator of T-cell function. (PMID:17116765)
• Differential transcription occurring early in atopic dermatitis skin was indicated for CCL18, CCL13, IFNalpha2, PPARalpha and PPARgamma. (PMID:17181634)
• study reports that, in addition to promoting T cell chemotaxis, IFN-alpha2 enhances T cell adhesion to integrin ligands, which is associated with integrin clustering on the T cell surface and enhanced conjugate formation with dendritic cells (PMID:17477817)
• IFNalpha is able to interfere with IL-6 signaling by inhibiting STAT3 activity and the abrogation of STAT3 activity accounts for the ability of IFNalpha to induce apoptosis in myeloma cells. (PMID:17880940)
• we propose that HIV-1 expresses Vpu to counteract an IFNalpha-induced, general host defense that inhibits dissemination of enveloped virions from the surface of infected cells. (PMID:18005734)
• Results demonstrated that two individual IFN-alphas interact differentially with IFNAR2-EC and influence each other during this interaction. (PMID:18027911)
• Recombinant human IFN-alpha 2b causes programmed cell death in nondiseased renal epithelial cells. IFN-alpha-induced apoptosis is directed by an extrinsic death receptor signaling pathway, amplified by an intrinsic mitochondrial pathway. (PMID:18032529)
• Recombinant INFA2 may have antitumor activity against Merkel cell carcinoma. (PMID:18584346)
• IFN-alpha2b possibly controls chemotaxis by regulating the interaction between CXCL10 and CXCR3A (PMID:18729739)
• Mutation of the IFNAR-1 receptor binding site of human IFN-alpha2 generates type I IFN competitive antagonists. (PMID:18937499)
• This is the first report of positive association of IFNA gene in SLE, especially the role of specific subtypes IFNA1 and IFNA5. (PMID:19000144)
• The worldwide distribution of indel polymorphism in the gene coding for IFNA2 was analyzed. (PMID:19055755)
• analysis of the complex between a human anti-interferon antibody fragment and human interferon alpha-2A (PMID:19153447)
• IFNalpha-mediated downregulation of Hepatitis C virus gene expression is abolished by acrolein, a major component of cigarette smoke (PMID:19345260)
• Results suggest that the differential activities of the interferon subtypes alpha2 and beta are dictated not only by the intrinsic ligand/receptor binding kinetics but also by the density of cell surface receptor components. (PMID:19564411)
• Pharmacological inhibition of Mnk kinases or siRNA-mediated knockdown of Mnk1 and Mnk2 results in partial reversal of the suppressive effects of IFNalpha on normal and leukemic hematopoietic progenitors. (PMID:19574459)
• Data show that serum concentrations of pegylated interferon alpha-2b increased in a dose-related manner. (PMID:19621225)
• C1q inhibits immune complex-induced interferon-alpha production in plasmacytoid dendritic cells. (PMID:19790049)
• Strategies are described to maximize expression of rightly processed human INF alpha2b protein in Pichia. (PMID:20159042)
• These findings indicate that the expression of MxA, 2’,5’-OAS and PKR are up-regulate by PI3K-AKT signal pathway, and Raf-MEK-ERK signal pathway has a negative regulatory effect on the expression of MxA and no significant effect on 2’,5’-OAS and PKR. (PMID:20309637)
• The result suggests that hyper-induction of TNF-alpha in human macrophages is not always associated with a highly pathogenic phenotype of avian and human influenza viruses. (PMID:20532927)
• Studies indicate that it remains unclear whether interruption of IFNalphaA and IL-10 signaling in the absence of CD73 activity results from a deficiency of its product adenosine or an accumulation of its substrate nucleotides. (PMID:21057730)
• Data show that pDCs and type I IFNs promote inflammatory responses and wound healing in injured skin. (PMID:21115688)
• we have demonstrated that IFNalpha2, a type I interferon, increases the expression of TLR3 on human dermal fibroblasts (PMID:21223583)
• Degos disease is a distinct vascular injury syndrome whereby a dysregulated interferon-alpha response in concert with membranolytic attack complex deposition may contribute to the unique vascular changes. (PMID:21411783)
• Interferon alpha 2 regulates MAPK and STAT1 pathways in human hepatoma cells. (PMID:21466707)
• Structural AA changes in the C-helix interacting with IFNAlphaR1 may change the signaling dynamics leading to elevated APOBEC3 & lower IDO by an engineered mutant derived from the amino-terminal region of IFNalpha21b and the COOH-terminus from IFNalpha2c. (PMID:21757613)
• The crystal structures of two human type I IFN ternary signaling complexes containing IFNalpha2 and IFNomega reveal recognition modes and heterotrimeric architectures that are unique among the cytokine receptor superfamily but conserved between type I IFNs. (PMID:21854986)
• IFNalpha rapidly down-regulates BCL-6 mRNA in purified mouse normal germinal center B cells. (PMID:22204827)
• protein kinase, DNA-activated catalytic polypeptide (PRKDC), was confirmed to play a role in MyD88-induced IFNA2 activation and IL-8 secretion (PMID:22332739)
• Data indicate that the production of IFN-alpha in supernatant of transfected cells was about 3.15 ng/mL. (PMID:22482409)
• variation at IFNA2 -173 and IFNA8 -884 conditions reduced IFN-alpha production, and increased susceptibility to SMA and mortality (PMID:22570109)
• Pre-treatment waking hypothalamic-pituitary-adrenal (HPA) axis response is greater in subjects switching to major depressive disorder during INFalpha2a treatment and may constitute a vulnerability factor in patients with hepatitis C virus infection. (PMID:22571879)
• monocytes manage the impact of TNF-alpha and type I/II interferons in rheumatoid arthritis and systemic lupus erythematosus (PMID:22610275)
• Results showed that missense mutations in transmembrane protein 2 p.Ser1254Asn, interferon alpha 2 p.Ala120Thr, its regulator NLR family member X1 p.Arg707Cys, and complement component 2 p.Glu318Asp were associated with chronic hepatitis B. (PMID:22610944)

Cross-species orthologs

34 orthologs

Organism	Symbol	Gene ID
danio_rerio	ifnphi2	ENSDARG00000069012
danio_rerio	ifnphi3	ENSDARG00000070676
mus_musculus	Ifna13	ENSMUSG00000063376
mus_musculus	Ifna4	ENSMUSG00000070904
mus_musculus	Ifna12	ENSMUSG00000073811
mus_musculus	Ifna2	ENSMUSG00000078354
mus_musculus	Ifna16	ENSMUSG00000078355
mus_musculus	Ifna9	ENSMUSG00000095270
mus_musculus	Ifna1	ENSMUSG00000095498
mus_musculus	Ifna14	ENSMUSG00000095896
mus_musculus	Ifna15	ENSMUSG00000096011
mus_musculus	Ifna5	ENSMUSG00000096682
mus_musculus	Ifnab	ENSMUSG00000100079
mus_musculus	Ifna11	ENSMUSG00000100549
mus_musculus	Ifna7	ENSMUSG00000100713
mus_musculus	Ifna6	ENSMUSG00000101252
rattus_norvegicus		ENSRNOG00000071845
rattus_norvegicus	Ifna12l	ENSRNOG00000072681
rattus_norvegicus	Ifna16l1	ENSRNOG00000074841
rattus_norvegicus		ENSRNOG00000075722
rattus_norvegicus		ENSRNOG00000076372
rattus_norvegicus	Ifna4	ENSRNOG00000077072
rattus_norvegicus	Ifna2	ENSRNOG00000078310
rattus_norvegicus	Ifna5	ENSRNOG00000079725
rattus_norvegicus	Ifna1l1	ENSRNOG00000079800
rattus_norvegicus		ENSRNOG00000079804
rattus_norvegicus		ENSRNOG00000081823
rattus_norvegicus		ENSRNOG00000082441
rattus_norvegicus		ENSRNOG00000082845
rattus_norvegicus		ENSRNOG00000083047
rattus_norvegicus	Ifna1	ENSRNOG00000084770
rattus_norvegicus		ENSRNOG00000085373
rattus_norvegicus		ENSRNOG00000085882
rattus_norvegicus		ENSRNOG00000086565

Paralogs (16): IFNA6 (ENSG00000120235), IFNA8 (ENSG00000120242), IFNA21 (ENSG00000137080), IFNA5 (ENSG00000147873), IFNA16 (ENSG00000147885), IFNK (ENSG00000147896), IFNB1 (ENSG00000171855), IFNW1 (ENSG00000177047), IFNE (ENSG00000184995), IFNA10 (ENSG00000186803), IFNA1 (ENSG00000197919), IFNA7 (ENSG00000214042), IFNA14 (ENSG00000228083), IFNA13 (ENSG00000233816), IFNA17 (ENSG00000234829), IFNA4 (ENSG00000236637)

Protein

Protein identifiers

Interferon alpha-2 — P01563 (reviewed: P01563)

Alternative names: Interferon alpha-A

All UniProt accessions (2): P01563, A0A7R8GUN5

UniProt curated annotations — full annotation on UniProt →

Function. Produced by macrophages, IFN-alpha have antiviral activities.

Subunit / interactions. Interacts with IFNAR2.

Subcellular location. Secreted.

Polymorphism. Three alleles exist; alpha-2A, alpha-2B (shown here) and alpha-2C. Allele alpha-2B is the predominant allele while allele alpha-2A is less predominant and alpha-2C only a minor allelic variant.

Similarity. Belongs to the type-I (or alpha/beta) interferon family.

RefSeq proteins (1): NP_000596* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000471	Interferon_alpha/beta/delta	Family
IPR009079	4_helix_cytokine-like_core	Homologous_superfamily

Pfam: PF00143

UniProt features (26 total): helix 9, sequence variant 4, strand 3, turn 3, sequence conflict 2, disulfide bond 2, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
9GVO	X-RAY DIFFRACTION	1.81
3S9D	X-RAY DIFFRACTION	2
9GVL	X-RAY DIFFRACTION	2.01
1RH2	X-RAY DIFFRACTION	2.9
4YPG	X-RAY DIFFRACTION	3
4Z5R	X-RAY DIFFRACTION	3
9GW5	X-RAY DIFFRACTION	4
3SE3	X-RAY DIFFRACTION	4
1ITF	SOLUTION NMR
2HYM	SOLUTION NMR
2KZ1	SOLUTION NMR
2LAG	SOLUTION NMR
2LMS	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01563-F1	85.92	0.59

Antibody-complex structures (SAbDab): 5 — 4YPG, 4Z5R, 9GVL, 9GVO, 9GW5

Functional residue map

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

Disulfide bonds (2): 24–121, 52–161

Glycosylation sites (1): 129

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-909733	Interferon alpha/beta signaling
R-HSA-912694	Regulation of IFNA/IFNB signaling
R-HSA-933541	TRAF6 mediated IRF7 activation
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-9833109	Evasion by RSV of host interferon responses

MSigDB gene sets: 216 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, MORF_ITGA2, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_CELLULAR_RESPONSE_TO_VIRUS, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_PRODUCTION_OF_MOLECULAR_MEDIATOR_OF_IMMUNE_RESPONSE

GO Biological Process (23): adaptive immune response (GO:0002250), T cell activation involved in immune response (GO:0002286), B cell activation involved in immune response (GO:0002312), natural killer cell activation involved in immune response (GO:0002323), apoptotic process (GO:0006915), inflammatory response (GO:0006954), humoral immune response (GO:0006959), cell surface receptor signaling pathway (GO:0007166), cell-cell signaling (GO:0007267), negative regulation of gene expression (GO:0010629), negative regulation of interleukin-13 production (GO:0032696), negative regulation of interleukin-5 production (GO:0032714), response to exogenous dsRNA (GO:0043330), negative regulation of T cell differentiation (GO:0045581), negative regulation of DNA-templated transcription (GO:0045892), host-mediated suppression of symbiont invasion (GO:0046597), defense response to virus (GO:0051607), type I interferon-mediated signaling pathway (GO:0060337), cell surface receptor signaling pathway via STAT (GO:0097696), cellular response to virus (GO:0098586), negative regulation of T-helper 2 cell cytokine production (GO:2000552), defense response (GO:0006952), signal transduction (GO:0007165)

GO Molecular Function (4): cytokine activity (GO:0005125), type I interferon receptor binding (GO:0005132), cytokine receptor binding (GO:0005126), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Interferon Signaling	1
Interferon alpha/beta signaling	1
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1
SARS-CoV-2-host interactions	1
Hemostasis	1
RSV-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune response	4
lymphocyte activation involved in immune response	3
innate immune response	2
defense response	2
negative regulation of cytokine production	2
response to virus	2
T cell activation	1
B cell activation	1
natural killer cell activation	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
signal transduction	1
cell communication	1
signaling	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
interleukin-13 production	1
regulation of interleukin-13 production	1
interleukin-5 production	1
regulation of interleukin-5 production	1
response to dsRNA	1
T cell differentiation	1
regulation of T cell differentiation	1
negative regulation of lymphocyte differentiation	1
negative regulation of T cell activation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
host-mediated perturbation of symbiont process	1
cellular response to type I interferon	1
interferon-mediated signaling pathway	1
cell surface receptor signaling pathway	1
receptor ligand activity	1
cytokine receptor binding	1
protein-containing complex binding	1
signaling receptor binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1772 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFNA2	IFNAR1	P17181	997
IFNA2	IFNAR2	P48551	991
IFNA2	IFNG	P01579	965
IFNA2	IL1B	P01584	912
IFNA2	IFNL1	Q8IU54	903
IFNA2	IL6	P05231	900
IFNA2	IL1A	P01583	896
IFNA2	IL2	P01585	889
IFNA2	IRF7	Q92985	888
IFNA2	IL10	P22301	884
IFNA2	CSF2	P04141	868
IFNA2	IFNL3	Q8IZI9	868
IFNA2	TLR7	Q9NYK1	868
IFNA2	FGF2	P09038	863
IFNA2	IL3	P08700	852

IntAct

15 interactions, top by confidence:

A	B	Type	Score
IFNA2	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
IFNAR2	IFNA2	psi-mi:“MI:0407”(direct interaction)	0.540
IFNA2	IFIT3	psi-mi:“MI:0914”(association)	0.530
IFNA4	IFNA13	psi-mi:“MI:0914”(association)	0.530
PGLYRP1	IFNA2	psi-mi:“MI:0914”(association)	0.530
IFNA2	PLEC	psi-mi:“MI:0915”(physical association)	0.400
IFNA2	IFNAR1	psi-mi:“MI:0915”(physical association)	0.400
M		psi-mi:“MI:0914”(association)	0.350
EIF4A1	IFNA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): IFNA5 (Affinity Capture-MS), IFIT3 (Affinity Capture-MS), ZER1 (Affinity Capture-MS), ISG15 (Affinity Capture-MS), IFNA2 (Affinity Capture-MS), ISG15 (Affinity Capture-MS), IFNA2 (Affinity Capture-MS), IFNA5 (Affinity Capture-MS), IFNA2 (Affinity Capture-MS), IFIT3 (Affinity Capture-MS), UBR3 (Affinity Capture-MS), IFNA2 (Two-hybrid), IFNA2 (Reconstituted Complex), IFNA2 (Co-purification), PLEC (Proximity Label-MS)

ESM2 similar proteins: O46633, P01562, P01563, P01566, P01567, P01568, P01569, P01570, P01571, P01572, P05000, P05002, P05003, P05004, P05005, P05006, P05007, P05008, P05009, P05010, P05013, P05014, P05015, P07348, P07349, P07352, P09235, P15696, P28169, P28171, P28172, P32881, P49876, P49877, P49878, P49879, P56828, P56829, P56830, P56831

Diamond homologs: A7UHZ5, O46633, O77812, O97945, P01562, P01563, P01566, P01567, P01568, P01569, P01570, P01571, P01572, P01573, P01574, P01575, P01576, P01577, P01578, P05000, P05001, P05002, P05003, P05004, P05005, P05006, P05007, P05008, P05009, P05010, P05011, P05012, P05013, P05014, P05015, P06799, P07348, P07349, P07350, P07351

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
IFNA2	“up-regulates quantity by stabilization”	“ISGF3 complex”
IFNA2	“up-regulates quantity by expression”	HLA-B	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	4
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

186 predictions. Top by Δscore:

Variant	Effect	Δscore
9:21385200:T:C	donor_gain	0.5900
9:21385224:T:TA	donor_gain	0.5700
9:21384552:A:AC	donor_gain	0.5000
9:21385229:C:CT	donor_gain	0.4700
9:21385230:T:TT	donor_gain	0.4700
9:21385276:TG:T	donor_gain	0.4600
9:21385227:TGC:T	donor_gain	0.4500
9:21384632:C:CA	donor_gain	0.4400
9:21384773:C:CG	donor_gain	0.4300
9:21385282:G:A	donor_gain	0.4300
9:21384455:A:AC	donor_gain	0.4200
9:21384566:T:TA	donor_gain	0.4100
9:21385139:T:TA	donor_gain	0.4100
9:21384987:G:C	donor_gain	0.4000
9:21385088:T:TG	acceptor_gain	0.4000
9:21384553:A:C	donor_gain	0.3900
9:21384905:A:AC	donor_gain	0.3900
9:21384906:C:CC	donor_gain	0.3900
9:21384962:A:AC	donor_gain	0.3900
9:21384730:T:C	donor_gain	0.3800
9:21384795:T:TC	acceptor_gain	0.3800
9:21384968:CAGG:C	donor_gain	0.3800
9:21384974:T:TA	donor_gain	0.3800
9:21385049:T:TA	donor_gain	0.3800
9:21384768:CCTTA:C	donor_loss	0.3700
9:21384769:CTT:C	donor_loss	0.3700
9:21384770:TTACT:T	donor_loss	0.3700
9:21384771:TA:T	donor_loss	0.3700
9:21384772:AC:A	donor_loss	0.3700
9:21385194:T:A	donor_gain	0.3700

AlphaMissense

1242 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:21384892:G:C	F146L	0.943
9:21384892:G:T	F146L	0.943
9:21384894:A:G	F146L	0.943
9:21385153:A:C	F59L	0.929
9:21385153:A:T	F59L	0.929
9:21385155:A:G	F59L	0.929
9:21384841:C:A	W163C	0.893
9:21384841:C:G	W163C	0.893
9:21385060:G:C	F90L	0.800
9:21385060:G:T	F90L	0.800
9:21385062:A:G	F90L	0.800
9:21384833:A:T	V166D	0.790
9:21385033:C:A	W99C	0.790
9:21385033:C:G	W99C	0.790
9:21385174:G:C	C52W	0.784
9:21384843:A:G	W163R	0.778
9:21384843:A:T	W163R	0.778
9:21384829:T:A	R167S	0.770
9:21384829:T:G	R167S	0.770
9:21384872:A:G	L153P	0.769
9:21384896:T:G	Y145S	0.766
9:21384986:A:G	L115P	0.766
9:21384848:C:G	C161S	0.762
9:21384849:A:T	C161S	0.762
9:21384893:A:G	F146S	0.753
9:21384847:A:C	C161W	0.746
9:21385176:A:G	C52R	0.745
9:21384897:A:G	Y145H	0.744
9:21385154:A:C	F59C	0.737
9:21384896:T:C	Y145C	0.734

dbSNP variants (sampled 300 via entrez): RS1000122363 (9:21386078 C>T), RS1001075147 (9:21384604 A>C,T), RS1002164350 (9:21384013 G>A,C,T), RS1002427114 (9:21385584 T>A,G), RS1002672656 (9:21387184 T>G), RS1003437033 (9:21386855 G>C,T), RS1003802934 (9:21383760 T>A,C), RS1003845481 (9:21383979 T>A,C), RS1004245977 (9:21385803 T>A), RS1004848594 (9:21386039 C>A), RS1005212228 (9:21386909 C>A), RS1008482794 (9:21386200 T>C,G), RS1008534955 (9:21386545 A>C,G,T), RS1009635006 (9:21387221 G>C,T), RS1011054681 (9:21385887 A>G)

Disease associations

OMIM: gene MIM:147562 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST90002389_347	Lymphocyte percentage of white cells	2.000000e-10
GCST90002398_252	Neutrophil count	3.000000e-09
GCST90002399_73	Neutrophil percentage of white cells	4.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3713000 (SINGLE PROTEIN), CHEMBL3856161 (PROTEIN FAMILY)

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
Arsenic Trioxide	affects cotreatment, decreases expression	2
Dacarbazine	increases expression, affects cotreatment, affects reaction	2
Lipopolysaccharides	affects reaction, affects binding, decreases reaction, increases secretion, increases reaction (+1 more)	2
Ribavirin	affects reaction, increases secretion, affects binding, increases reaction, increases activity (+3 more)	2
fluorene-9-bisphenol	increases expression	1
bisphenol A	increases expression	1
mono-(2-ethylhexyl)phthalate	increases methylation, increases abundance	1
zinc chloride	decreases expression	1
ferrous sulfate	decreases expression	1
1-nitropyrene	decreases expression	1
nitazoxanide	increases activity, increases phosphorylation, increases reaction	1
rottlerin	decreases reaction, increases expression, increases activity, increases phosphorylation	1
bisphenol B	increases expression	1
BIX 01294	increases response to substance, increases activity, increases cleavage, increases expression, increases reaction	1
2’-hydroxyflavanone	decreases reaction, increases secretion	1
CpG ODN 2216	increases expression, decreases reaction	1
PF 3758309	increases expression	1
UNC 0638	increases response to substance, increases expression, increases reaction	1
theaflavin-3,3’-digallate	affects expression	1
Bortezomib	increases activity, affects cotreatment	1
Sorafenib	affects cotreatment, affects phosphorylation	1
Decitabine	increases activity, increases cleavage, increases reaction	1
Acetaminophen	increases expression	1
Gemcitabine	affects cotreatment, increases expression	1
Amiloride	decreases reaction, increases expression	1
Asbestos	increases expression	1
Butyrates	decreases reaction, increases expression	1
Calcitriol	increases expression	1
Cannabidiol	increases expression	1
Cycloheximide	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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