IFNA4

Summary

IFNA4 (interferon alpha 4, HGNC:5425) is a protein-coding gene on chromosome 9p21.3, encoding Interferon alpha-4 (P05014). Produced by macrophages, IFN-alpha have antiviral activities.

Predicted to enable cytokine activity and type I interferon receptor binding activity. Predicted to be involved in several processes, including lymphocyte activation involved in immune response; response to exogenous dsRNA; and type I interferon-mediated signaling pathway. Predicted to be located in extracellular region. Predicted to be active in extracellular space.

Source: NCBI Gene 3441 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 40 total
• Druggable target: yes
• MANE Select transcript: NM_021068

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5425
Approved symbol	IFNA4
Name	interferon alpha 4
Location	9p21.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC142200, IFN-alpha4a
Ensembl gene	ENSG00000236637
Ensembl biotype	protein_coding
OMIM	147564
Entrez	3441

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000421715

RefSeq mRNA: 1 — MANE Select: NM_021068 NM_021068

CCDS: CCDS6498

Canonical transcript exons

ENST00000421715 — 1 exons

Exon	Start	End
ENSE00003978309	21186618	21187587

Expression profiles

Bgee: expression breadth tissue_specific, 2 present calls, max score 37.62.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	37.62	gold quality
apex of heart	UBERON:0002098	37.58	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
prefrontal cortex	UBERON:0000451	31.36	gold quality
cerebellar hemisphere	UBERON:0002245	31.12	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
cerebellar cortex	UBERON:0002129	30.91	gold quality
right uterine tube	UBERON:0001302	30.88	gold quality
cerebellum	UBERON:0002037	30.81	gold quality
tonsil	UBERON:0002372	30.78	gold quality
primary visual cortex	UBERON:0002436	30.71	gold quality
right hemisphere of cerebellum	UBERON:0014890	30.60	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
leukocyte	CL:0000738	28.36	gold quality
liver	UBERON:0002107	28.33	gold quality
duodenum	UBERON:0002114	28.14	gold quality
monocyte	CL:0000576	27.79	gold quality
lymph node	UBERON:0000029	27.57	gold quality
superior frontal gyrus	UBERON:0002661	27.34	gold quality
urinary bladder	UBERON:0001255	26.80	gold quality
blood	UBERON:0000178	26.53	gold quality
caudate nucleus	UBERON:0001873	26.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, IRF1, IRF2, IRF3, IRF5, IRF7, IRF8, NFKB, PITX1, RELA

miRNA regulators (miRDB)

21 targeting IFNA4, 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-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-323A-5P	98.59	65.13	651
HSA-MIR-595	98.25	67.44	699
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-197-3P	98.09	69.23	1004
HSA-MIR-924	97.78	66.21	681
HSA-MIR-144-5P	97.66	69.90	531
HSA-MIR-6894-3P	96.73	65.64	798
HSA-MIR-4636	91.87	64.93	40

Literature-anchored findings (GeneRIF, showing 4)

• suppression of IFN signaling and IFN production by SOC3 occurs during HSV-1 infection (PMID:15163721)
• Heterozygous IFNA4 variants is a cause of impaired function and CD-susceptibility genes in Chinese individuals from multiple center based study. (PMID:26000985)
• The mechanism of action of Spi-B in the transcriptional activation of the interferon-alpha4 gene. (PMID:32111355)
• Alpha interferon suppresses the cyclin D3 and cdc25A genes, leading to a reversible G0-like arrest. (PMID:8668211)

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), IFNA2 (ENSG00000188379), IFNA1 (ENSG00000197919), IFNA7 (ENSG00000214042), IFNA14 (ENSG00000228083), IFNA13 (ENSG00000233816), IFNA17 (ENSG00000234829)

Protein

Protein identifiers

Interferon alpha-4 — P05014 (reviewed: P05014)

Alternative names: Interferon alpha-4B, Interferon alpha-76, Interferon alpha-M1

All UniProt accessions (1): P05014

UniProt curated annotations — full annotation on UniProt →

Function. Produced by macrophages, IFN-alpha have antiviral activities. Interferon stimulates the production of two enzymes: a protein kinase and an oligoadenylate synthetase.

Subcellular location. Secreted.

Polymorphism. Two forms exist; alpha-4a (shown here) and alpha-4b. They seem to be equally abundant.

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

RefSeq proteins (1): NP_066546* (*=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 (7 total): sequence variant 3, disulfide bond 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05014-F1	85.46	0.54

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): 24–122, 52–162

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: 119 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_VIRUS, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, HOFMANN_CELL_LYMPHOMA_UP, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, KEGG_CYTOSOLIC_DNA_SENSING_PATHWAY, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, MORF_ZNF10, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, KEGG_AUTOIMMUNE_THYROID_DISEASE

GO Biological Process (11): 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), response to virus (GO:0009615), 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)

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

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
response to virus	2
T cell activation	1
B cell activation	1
natural killer cell activation	1
innate immune response	1
response to other organism	1
response to dsRNA	1
defense response	1
cellular response to type I interferon	1
interferon-mediated signaling pathway	1
response to stress	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

1362 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFNA4	IFNAR1	P17181	891
IFNA4	IL2	P01585	834
IFNA4	IRF7	Q92985	816
IFNA4	IFNG	P01579	773
IFNA4	TLR3	O15455	728
IFNA4	ISG15	P05161	726
IFNA4	IRF3	Q14653	722
IFNA4	RIGI	O95786	698
IFNA4	IFIH1	Q9BYX4	695
IFNA4	IFNL3	Q8IZI9	690
IFNA4	CR2	P20023	672
IFNA4	MX1	P20591	672
IFNA4	IL6	P05231	667
IFNA4	MAVS	Q7Z434	650
IFNA4	IFNAR2	P48551	637

IntAct

18 interactions, top by confidence:

A	B	Type	Score
TNNI3	IFNA4	psi-mi:“MI:0915”(physical association)	0.590
IFNA4	ALDOA	psi-mi:“MI:0915”(physical association)	0.560
ALDOA	IFNA4	psi-mi:“MI:0915”(physical association)	0.560
IFNA21	IFIT3	psi-mi:“MI:0914”(association)	0.530
IFNA5	IFNA13	psi-mi:“MI:0914”(association)	0.530
IFNA4	IFNA13	psi-mi:“MI:0914”(association)	0.530
RECK	IFNA4	psi-mi:“MI:0914”(association)	0.530
IFNA13	IFNA21	psi-mi:“MI:0914”(association)	0.530
IFNA13	IFNA14	psi-mi:“MI:0914”(association)	0.530
M		psi-mi:“MI:0914”(association)	0.350
IFNA4	CTSV	psi-mi:“MI:0914”(association)	0.350

BioGRID (50): IFNA4 (Two-hybrid), IFNA4 (Affinity Capture-MS), IFNA4 (Affinity Capture-MS), IFNA7 (Affinity Capture-MS), IFNA4 (Affinity Capture-MS), IFNA8 (Affinity Capture-MS), IFNA13 (Affinity Capture-MS), IFNA4 (Affinity Capture-MS), IFNA2 (Affinity Capture-MS), ISG15 (Affinity Capture-MS), IFNA4 (Affinity Capture-MS), IFNA4 (Affinity Capture-MS), IFNA4 (Affinity Capture-MS), IFNA8 (Affinity Capture-MS), IFNA7 (Affinity Capture-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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

259 predictions. Top by Δscore:

Variant	Effect	Δscore
9:21186944:T:A	donor_gain	0.7100
9:21186860:A:C	donor_gain	0.6800
9:21186904:A:AC	donor_gain	0.6700
9:21186924:A:AC	donor_gain	0.6400
9:21187155:T:TA	donor_gain	0.6100
9:21186945:C:A	donor_gain	0.6000
9:21187119:T:TA	donor_gain	0.5800
9:21186904:A:C	acceptor_gain	0.5700
9:21186966:T:TA	donor_gain	0.5700
9:21186970:T:A	donor_gain	0.5700
9:21187168:A:C	donor_gain	0.5700
9:21187287:T:TG	acceptor_gain	0.5700
9:21186819:G:C	donor_gain	0.5500
9:21186919:A:AC	donor_gain	0.5500
9:21187064:CT:C	acceptor_gain	0.5300
9:21187430:A:AC	donor_gain	0.5300
9:21186748:A:C	donor_gain	0.5200
9:21186927:A:AC	donor_gain	0.5200
9:21186973:T:TA	donor_gain	0.5200
9:21187039:C:A	donor_gain	0.5200
9:21187104:A:AC	donor_gain	0.5100
9:21187105:C:CC	donor_gain	0.5100
9:21187167:CATG:C	donor_gain	0.5100
9:21187248:T:TA	donor_gain	0.5100
9:21186782:T:C	donor_gain	0.5000
9:21186994:T:TC	acceptor_gain	0.4900
9:21187161:A:AC	donor_gain	0.4900
9:21186905:T:C	donor_gain	0.4800
9:21187173:T:TA	donor_gain	0.4800
9:21186828:CACTG:C	acceptor_gain	0.4700

AlphaMissense

1247 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:21187091:G:C	F147L	0.927
9:21187091:G:T	F147L	0.927
9:21187093:A:G	F147L	0.927
9:21187355:G:C	F59L	0.925
9:21187355:G:T	F59L	0.925
9:21187357:A:G	F59L	0.925
9:21187040:C:A	W164C	0.899
9:21187040:C:G	W164C	0.899
9:21187259:G:C	F91L	0.834
9:21187259:G:T	F91L	0.834
9:21187261:A:G	F91L	0.834
9:21187232:C:A	W100C	0.804
9:21187232:C:G	W100C	0.804
9:21187042:A:G	W164R	0.788
9:21187042:A:T	W164R	0.788
9:21187032:A:T	V167D	0.784
9:21187185:A:G	L116P	0.776
9:21187263:A:G	L90P	0.765
9:21187071:A:G	L154P	0.764
9:21187028:T:A	R168S	0.755
9:21187028:T:G	R168S	0.755
9:21187356:A:C	F59C	0.726
9:21187075:A:C	Y153D	0.725
9:21187376:G:C	C52W	0.724
9:21187092:A:G	F147S	0.716
9:21187378:A:G	C52R	0.712
9:21187095:T:G	Y146S	0.708
9:21187047:C:G	C162S	0.707
9:21187048:A:T	C162S	0.707
9:21187377:C:G	C52S	0.702

dbSNP variants (sampled 300 via entrez): RS1000338497 (9:21188418 C>T), RS1001411417 (9:21188453 A>T), RS1003734990 (9:21189134 T>C), RS1003808795 (9:21189278 G>A,C), RS1005424956 (9:21187947 T>A), RS1005566571 (9:21186299 G>C), RS1006017042 (9:21188593 A>G,T), RS1006504773 (9:21188732 CAT>C), RS1007631207 (9:21189081 C>A), RS1008510966 (9:21187391 G>A), RS1009837101 (9:21188951 T>A,C), RS1009867442 (9:21188440 A>G), RS1010169494 (9:21188321 T>G), RS1011676503 (9:21186705 C>G,T), RS1011897088 (9:21186997 T>C)

Disease associations

OMIM: gene MIM:147564 | 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: yes

ChEMBL targets (1): CHEMBL3856161 (PROTEIN FAMILY)

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
cobaltous chloride	decreases expression, increases expression	1
Glyphosate	increases expression	1
Benzo(a)pyrene	increases methylation	1
Hydrogen Peroxide	increases expression	1
Lipopolysaccharides	decreases reaction, increases expression	1
Triclosan	decreases reaction, increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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