IFNE

Summary

IFNE (interferon epsilon, HGNC:18163) is a protein-coding gene on chromosome 9p21.3, encoding Interferon epsilon (Q86WN2). Type I interferon required for maintaining basal levels of IFN-regulated genes, including 2’-5’-oligoadenylate synthetase, IRF7 and ISG15, in the female reproductive tract.

Predicted to enable cytokine activity and type I interferon receptor binding activity. Predicted to be involved in several processes, including defense response to other organism; lymphocyte activation involved in immune response; and positive regulation of receptor signaling pathway via JAK-STAT. Predicted to be located in extracellular region. Predicted to be active in extracellular space.

Source: NCBI Gene 338376 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_176891

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18163
Approved symbol	IFNE
Name	interferon epsilon
Location	9p21.3
Locus type	gene with protein product
Status	Approved
Aliases	IFNE1
Ensembl gene	ENSG00000184995
Ensembl biotype	protein_coding
OMIM	615223
Entrez	338376

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000448696

RefSeq mRNA: 1 — MANE Select: NM_176891 NM_176891

CCDS: CCDS34997

Canonical transcript exons

ENST00000448696 — 1 exons

Exon	Start	End
ENSE00001940219	21480839	21482313

Expression profiles

Bgee: expression breadth broad, 86 present calls, max score 64.70.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1881 / max 85.6525, expressed in 12 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100214	0.1881	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	64.70	gold quality
cartilage tissue	UBERON:0002418	63.68	silver quality
right uterine tube	UBERON:0001302	60.98	gold quality
esophagus mucosa	UBERON:0002469	59.24	gold quality
lower esophagus mucosa	UBERON:0035834	58.27	gold quality
cerebellar hemisphere	UBERON:0002245	54.78	gold quality
cerebellar cortex	UBERON:0002129	54.76	gold quality
right hemisphere of cerebellum	UBERON:0014890	54.27	gold quality
jejunal mucosa	UBERON:0000399	54.13	silver quality
cerebellum	UBERON:0002037	53.49	gold quality
skin of hip	UBERON:0001554	53.12	gold quality
duodenum	UBERON:0002114	52.55	gold quality
vagina	UBERON:0000996	51.54	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	50.19	gold quality
endometrium	UBERON:0001295	50.07	gold quality
small intestine Peyer’s patch	UBERON:0003454	50.06	gold quality
urinary bladder	UBERON:0001255	49.90	gold quality
adenohypophysis	UBERON:0002196	49.80	gold quality
small intestine	UBERON:0002108	49.70	gold quality
body of stomach	UBERON:0001161	49.32	gold quality
pituitary gland	UBERON:0000007	48.77	gold quality
metanephros cortex	UBERON:0010533	47.91	gold quality
upper leg skin	UBERON:0004262	47.78	silver quality
stomach	UBERON:0000945	47.45	gold quality
right lobe of thyroid gland	UBERON:0001119	46.32	gold quality
metanephros	UBERON:0000081	45.60	gold quality
left lobe of thyroid gland	UBERON:0001120	45.43	gold quality
fundus of stomach	UBERON:0001160	45.40	gold quality
nasal cavity mucosa	UBERON:0001826	45.24	gold quality
lower lobe of lung	UBERON:0008949	45.17	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CDX2, ETS2, JUN

miRNA regulators (miRDB)

15 targeting IFNE, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-508-3P	98.66	69.62	887
HSA-MIR-6777-3P	95.35	64.30	699
HSA-MIR-5191	95.22	64.69	354
HSA-MIR-1231	95.10	65.63	663

Literature-anchored findings (GeneRIF, showing 15)

• The structue and mRNA expression pattern of IFN-epsilon1 suggest that it may have a function distinct from those other members of type I INF. (PMID:15233997)
• TNF-alpha leads to stabilization of IFN-epsilon mRNA, increased IFN-epsilon synthesis, engagement of type I IFNRs, increased STAT1 expression and phosphorylation, and up-regulation of retinoic acid-inducible gene-I expression (PMID:17878351)
• A meta-analysis and a single-nucleotide polymorphism (SNP) rs1333049 representing the 9p21.3 locus provide unprecedented evidence for association between genetic variants at chromosome 9p21.3 and risk of coronary artery disease. (PMID:18362232)
• In macrophages IFN-tau increased the synthesis of 2’,5’-oligoadenylate synthetase/RNase L, MxA protein, IL-10 & IL-6, but not of IL-1ss or TNF-alpha. (PMID:18842358)
• genetic polymorphism is related to onset time of vitiligo in Korean patients (PMID:23802172)
• Full-length IFN-epsilon 5’UTR markedly suppressed mRNA expression under basal conditions. It contains 2 stable stem-loop structures which associate with importin 9. Loop 1 is essential for regulation of mRNA expression. (PMID:23851686)
• T Allele of nonsense polymorphism (rs2039381, Gln71Stop) of interferon-epsilon is a risk factor for the development of intracerebral hemorrhage. (PMID:24055696)
• female sex workers decreased susceptibility to HIV-1 infection also have increased levels of IFNE gene and protein expression in the cervical epithelium (PMID:26555708)
• IFN epsilon protects macrophages against HIV infection through a type I IFN independent mechanism. (PMID:27942584)
• human IFNvarepsilon suppresses HIV replication at multiple stages of infection. (PMID:28045025)
• average vaginal IFNe across pregnancy was lower in women with genital herpes simplex virus compared to healthy women (PMID:29905034)
• Spatiotemporal regulation of human IFN-epsilon and innate immunity in the female reproductive tract. (PMID:35862222)
• Constitutive expression and distinct properties of IFN-epsilon protect the female reproductive tract from Zika virus infection. (PMID:36897927)
• Interferon-epsilon is a tumour suppressor and restricts ovarian cancer. (PMID:37587335)
• Upregulation of IFNE in cervical biopsies of patients with high-risk human papillomavirus infections. (PMID:38156399)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ifnphi2	ENSDARG00000069012
danio_rerio	ifnphi3	ENSDARG00000070676
mus_musculus	Ifne	ENSMUSG00000045364
rattus_norvegicus	Ifne	ENSRNOG00000024204

Paralogs (16): IFNA6 (ENSG00000120235), IFNA8 (ENSG00000120242), IFNA21 (ENSG00000137080), IFNA5 (ENSG00000147873), IFNA16 (ENSG00000147885), IFNK (ENSG00000147896), IFNB1 (ENSG00000171855), IFNW1 (ENSG00000177047), IFNA10 (ENSG00000186803), IFNA2 (ENSG00000188379), IFNA1 (ENSG00000197919), IFNA7 (ENSG00000214042), IFNA14 (ENSG00000228083), IFNA13 (ENSG00000233816), IFNA17 (ENSG00000234829), IFNA4 (ENSG00000236637)

Protein

Protein identifiers

Interferon epsilon — Q86WN2 (reviewed: Q86WN2)

Alternative names: Interferon epsilon-1

All UniProt accessions (2): Q86WN2, A0A7R8GUQ9

UniProt curated annotations — full annotation on UniProt →

Function. Type I interferon required for maintaining basal levels of IFN-regulated genes, including 2’-5’-oligoadenylate synthetase, IRF7 and ISG15, in the female reproductive tract. Directly mediates protection against viral and bacterial genital infections.

Subcellular location. Secreted.

Tissue specificity. Endometrium-specific.

Induction. By estrogens.

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

RefSeq proteins (1): NP_795372* (*=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 (6 total): glycosylation site 2, signal peptide 1, chain 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86WN2-F1	81.94	0.41

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 (1): 53–163

Glycosylation sites (2): 95, 104

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 60 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_VIRUS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_NATURAL_KILLER_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_HUMORAL_IMMUNE_RESPONSE, GOBP_ADAPTIVE_IMMUNE_RESPONSE, GOBP_NATURAL_KILLER_CELL_ACTIVATION, GOBP_DEFENSE_RESPONSE_TO_VIRUS, GOMF_CYTOKINE_ACTIVITY, GOBP_IMMUNE_EFFECTOR_PROCESS

GO Biological Process (12): 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), humoral immune response (GO:0006959), defense response to bacterium (GO:0042742), response to exogenous dsRNA (GO:0043330), defense response to virus (GO:0051607), type I interferon-mediated signaling pathway (GO:0060337), cellular response to virus (GO:0098586), defense response (GO:0006952), signal transduction (GO:0007165)

GO Molecular Function (3): cytokine activity (GO:0005125), type I interferon receptor binding (GO:0005132), cytokine receptor binding (GO:0005126)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune response	4
lymphocyte activation involved in immune response	3
defense response	2
response to virus	2
T cell activation	1
B cell activation	1
natural killer cell activation	1
innate immune response	1
response to bacterium	1
response to dsRNA	1
cellular response to type I interferon	1
interferon-mediated signaling pathway	1
response to stress	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
receptor ligand activity	1
cytokine receptor binding	1
protein-containing complex binding	1
signaling receptor binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

564 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFNE	IFNAR1	P17181	977
IFNE	IFNAR2	P48551	955
IFNE	IFNA13	P01562	887
IFNE	IFNL1	Q8IU54	718
IFNE	IFNL2	Q8IZJ0	717
IFNE	IFNL3	Q8IZI9	697
IFNE	IFNK	Q9P0W0	696
IFNE	IFNLR1	Q8IU57	621
IFNE	IRF9	Q00978	580
IFNE	STAT2	P52630	579
IFNE	IFNB1	P01574	575
IFNE	KLHL9	Q9P2J3	560
IFNE	TYK2	P29597	548
IFNE	IRF7	Q92985	533
IFNE	RIGI	O95786	527

IntAct

4 interactions, top by confidence:

A	B	Type	Score
IFNE	FAT1	psi-mi:“MI:0914”(association)	0.530
IFNE	NAGLU	psi-mi:“MI:0914”(association)	0.350
IFNE	ACACB	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): FAM198A (Affinity Capture-MS), GPR98 (Affinity Capture-MS), FAT4 (Affinity Capture-MS), BACE2 (Affinity Capture-MS), CD109 (Affinity Capture-MS), NAGLU (Affinity Capture-MS), FAT1 (Affinity Capture-MS), FRAS1 (Affinity Capture-MS), GYLTL1B (Affinity Capture-MS), GPR98 (Affinity Capture-MS), FAT1 (Affinity Capture-MS), BACE2 (Affinity Capture-MS), LRIG1 (Affinity Capture-MS), FAT4 (Affinity Capture-MS), FAM198A (Affinity Capture-MS)

ESM2 similar proteins: A2T6Z6, A7UHZ5, O35256, O46673, O77812, O97798, P01574, P01575, P01576, P01577, P01578, P03180, P05012, P07351, P0C6Z6, P0CAP9, P0DMS7, P18893, P22301, P29456, P42165, P43480, P46651, P47965, P48411, P51496, P51497, P55029, P68677, P68678, P70499, P79338, Q0Z972, Q13007, Q28374, Q29055, Q5Q0V6, Q6XZW6, Q80ZF2, Q86WN2

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

117 predictions. Top by Δscore:

Variant	Effect	Δscore
9:21481152:ACT:A	acceptor_gain	0.7200
9:21481304:G:C	donor_gain	0.6900
9:21481153:C:CC	acceptor_gain	0.6300
9:21481297:C:CT	donor_gain	0.6300
9:21481315:T:TA	donor_gain	0.6200
9:21481652:C:T	acceptor_gain	0.6200
9:21481500:CTT:C	acceptor_gain	0.6100
9:21481285:C:CT	donor_gain	0.6000
9:21481286:T:TT	donor_gain	0.6000
9:21481153:CTG:C	acceptor_gain	0.5600
9:21481150:AGACT:A	acceptor_gain	0.5300
9:21481151:GACTG:G	acceptor_gain	0.5300
9:21481154:T:A	acceptor_gain	0.5300
9:21481655:G:GT	acceptor_gain	0.5200
9:21481297:CCA:C	donor_gain	0.5100
9:21481303:A:AC	donor_gain	0.5100
9:21481303:AG:A	donor_gain	0.4900
9:21481537:CACTG:C	acceptor_gain	0.4900
9:21481645:G:GT	acceptor_gain	0.4600
9:21481646:T:TT	acceptor_gain	0.4600
9:21481149:GAGAC:G	acceptor_gain	0.4400
9:21481298:C:CT	donor_gain	0.4400
9:21481303:AGCTT:A	donor_gain	0.4400
9:21481528:TGTGG:T	acceptor_gain	0.4400
9:21481284:A:AC	donor_gain	0.4300
9:21481503:C:CC	acceptor_gain	0.4300
9:21481539:CTG:C	acceptor_gain	0.4300
9:21481346:G:C	donor_gain	0.4100
9:21481547:T:A	acceptor_gain	0.4100
9:21481150:AGAC:A	acceptor_loss	0.4000

AlphaMissense

1385 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:21481251:G:C	F148L	0.970
9:21481251:G:T	F148L	0.970
9:21481253:A:G	F148L	0.970
9:21481515:A:C	F60L	0.946
9:21481515:A:T	F60L	0.946
9:21481517:A:G	F60L	0.946
9:21481516:A:C	F60C	0.892
9:21481252:A:G	F148S	0.881
9:21481192:A:T	V168D	0.867
9:21481260:T:A	K145N	0.864
9:21481260:T:G	K145N	0.864
9:21481516:A:G	F60S	0.859
9:21481537:C:G	C53S	0.858
9:21481538:A:T	C53S	0.858
9:21481183:T:A	E171V	0.856
9:21481428:G:C	F89L	0.847
9:21481428:G:T	F89L	0.847
9:21481430:A:G	F89L	0.847
9:21481538:A:G	C53R	0.846
9:21481252:A:C	F148C	0.839
9:21481255:T:G	Y147S	0.836
9:21481174:C:G	R174P	0.833
9:21481255:T:C	Y147C	0.833
9:21481256:A:C	Y147D	0.833
9:21481182:T:A	E171D	0.831
9:21481182:T:G	E171D	0.831
9:21481419:G:C	F92L	0.831
9:21481419:G:T	F92L	0.831
9:21481421:A:G	F92L	0.831
9:21481183:T:C	E171G	0.822

dbSNP variants (sampled 300 via entrez): RS1000775958 (9:21483807 G>C,T), RS1001436179 (9:21481980 A>G), RS1002521449 (9:21483167 C>T), RS1003898717 (9:21483454 T>C), RS1004098337 (9:21483682 G>C), RS1004896940 (9:21483186 T>C), RS1005909675 (9:21481884 C>G,T), RS1007862203 (9:21484181 A>G), RS1008252831 (9:21482253 A>C), RS1008586877 (9:21480623 T>C), RS1010039652 (9:21482013 T>C), RS1010476120 (9:21484053 T>C), RS1010681660 (9:21480976 T>A), RS10125074 (9:21482090 G>A,T), RS1013392894 (9:21483094 T>C)

Disease associations

OMIM: gene MIM:615223 | 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
GCST002173_2	Lipid traits	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	increases expression, decreases expression	2
aristolochic acid I	increases expression	1
urushiol	increases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
vanadyl sulfate	increases expression	1
pentanal	decreases expression	1
jinfukang	decreases expression	1
(+)-JQ1 compound	increases expression	1
Acetaminophen	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Vanadates	increases expression	1
Sodium Selenite	decreases expression	1
Cadmium Chloride	increases expression	1
S-Nitrosoglutathione	increases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1U9	Abcam HeLa IFNE KO	Cancer cell line	Female
CVCL_D7RQ	Ubigene A-549 IFNE KO	Cancer cell line	Male
CVCL_D8MT	Ubigene HCT 116 IFNE KO	Cancer cell line	Male
CVCL_E0EM	Ubigene HeLa IFNE KO	Cancer cell line	Female

Clinical trials (associated diseases)

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