IFNA8

Summary

IFNA8 (interferon alpha 8, HGNC:5429) is a protein-coding gene on chromosome 9p21.3, encoding Interferon alpha-8 (P32881). 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 act upstream of or within defense response to virus. Predicted to be located in extracellular region. Predicted to be active in extracellular space.

Source: NCBI Gene 3445 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 29 total
• Druggable target: yes
• MANE Select transcript: NM_002170

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5429
Approved symbol	IFNA8
Name	interferon alpha 8
Location	9p21.3
Locus type	gene with protein product
Status	Approved
Aliases	IFN-alphaB
Ensembl gene	ENSG00000120242
Ensembl biotype	protein_coding
OMIM	147568
Entrez	3445

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000380205

RefSeq mRNA: 1 — MANE Select: NM_002170 NM_002170

CCDS: CCDS6507

Canonical transcript exons

ENST00000380205 — 1 exons

Exon	Start	End
ENSE00001484098	21409117	21410185

Expression profiles

Bgee: expression breadth tissue_specific, 7 present calls, max score 41.06.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1275 / max 123.0952, expressed in 10 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96282	0.1275	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar cortex	UBERON:0002129	41.06	silver quality
cerebellum	UBERON:0002037	40.99	silver quality
cerebellar hemisphere	UBERON:0002245	40.79	silver quality
right hemisphere of cerebellum	UBERON:0014890	39.82	silver quality
granulocyte	CL:0000094	37.29	gold 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
primary visual cortex	UBERON:0002436	36.46	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	35.32	gold quality
prefrontal cortex	UBERON:0000451	34.85	silver quality
muscle tissue	UBERON:0002385	32.48	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
frontal cortex	UBERON:0001870	31.46	silver quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
duodenum	UBERON:0002114	28.14	gold quality
leukocyte	CL:0000738	28.08	gold quality
liver	UBERON:0002107	28.04	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	27.61	gold quality
lymph node	UBERON:0000029	27.57	gold quality
monocyte	CL:0000576	27.49	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.94	gold quality
urinary bladder	UBERON:0001255	26.85	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.47

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

29 targeting IFNA8, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-1468-3P	99.96	72.74	3797
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-4503	99.85	71.45	1869
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-4796-5P	99.34	70.06	810
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-3129-3P	97.85	67.63	1246
HSA-MIR-5583-5P	97.85	67.61	1243
HSA-MIR-4475	97.36	66.95	761
HSA-MIR-1182	96.41	64.89	336
HSA-MIR-6823-5P	96.26	65.69	919
HSA-MIR-371B-3P	94.48	66.59	345
HSA-MIR-3655	86.11	61.77	117

Literature-anchored findings (GeneRIF, showing 5)

• Data describe the species specificity of IFN-alphas, the residues in murine IFN-alpha4 that preclude strong affinity interactions with human IFNAR1 and 2, and residues in human IFN-alpha8 that resemble a receptor interactive domain in murine IFN-alpha4. (PMID:17517919)
• variation at IFNA2 -173 and IFNA8 -884 conditions reduced IFN-alpha production, and increased susceptibility to SMA and mortality (PMID:22570109)
• IFN-alpha8 and -alpha10 most potently enhanced expression of IFN-gamma, IL-2, and IL-4. (PMID:24030809)
• These data suggest that increased IFN-alpha8 activity may promote the loss of T cells by accelerating cell turnover and activation-induced cell death while decreasing the renewal of T cells by inhibiting the proliferative effect of IL-7. (PMID:25063872)
• 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), 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), IFNA4 (ENSG00000236637)

Protein

Protein identifiers

Interferon alpha-8 — P32881 (reviewed: P32881)

Alternative names: Interferon alpha-B, Interferon alpha-B2

All UniProt accessions (2): A0A7R8C381, P32881

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.

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

RefSeq proteins (1): NP_002161* (*=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 (18 total): helix 9, disulfide bond 2, sequence conflict 2, signal peptide 1, chain 1, turn 1, sequence variant 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6JHD	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32881-F1	85.18	0.52

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: 128 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, MORF_ITGA2, 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, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, MORF_RAD51L3, KEGG_CYTOSOLIC_DNA_SENSING_PATHWAY, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM

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 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 (4): cytokine activity (GO:0005125), cytokine receptor binding (GO:0005126), type I interferon receptor binding (GO:0005132), 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 dsRNA	1
defense response	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
signaling receptor binding	1
cytokine receptor binding	1
protein-containing complex binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

10 interactions, top by confidence:

A	B	Type	Score
IFNA8	GPR152	psi-mi:“MI:0915”(physical association)	0.560
IFNA8	IFIT3	psi-mi:“MI:0914”(association)	0.530
IFNA4	IFNA13	psi-mi:“MI:0914”(association)	0.530
IFNA8	UBR3	psi-mi:“MI:0914”(association)	0.530
IFNA8	IFNA21	psi-mi:“MI:0914”(association)	0.350
IFNA8	GPR152	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (26): UBR3 (Affinity Capture-MS), IFNA13 (Affinity Capture-MS), IFIT3 (Affinity Capture-MS), ADAMTS1 (Affinity Capture-MS), OMA1 (Affinity Capture-MS), ISG15 (Affinity Capture-MS), IFIT1 (Affinity Capture-MS), IFNA8 (Affinity Capture-MS), UBR3 (Affinity Capture-MS), ISG15 (Affinity Capture-MS), OMA1 (Affinity Capture-MS), IFIT1 (Affinity Capture-MS), IFIT3 (Affinity Capture-MS), APOE (Affinity Capture-MS), IFNA13 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

230 predictions. Top by Δscore:

Variant	Effect	Δscore
9:21409552:G:GT	donor_gain	0.7800
9:21409522:C:G	donor_gain	0.6200
9:21409888:T:G	donor_gain	0.6000
9:21409764:A:T	donor_gain	0.5600
9:21409948:G:GT	donor_gain	0.5600
9:21410137:A:G	acceptor_gain	0.5600
9:21409553:A:T	donor_gain	0.5500
9:21409868:GTCA:G	donor_gain	0.5500
9:21410136:A:AG	acceptor_gain	0.5500
9:21409763:G:GT	donor_gain	0.5300
9:21409983:T:G	donor_gain	0.5300
9:21409420:G:GC	acceptor_gain	0.5200
9:21409867:TGTC:T	donor_gain	0.5200
9:21409459:G:GT	donor_gain	0.5100
9:21409552:G:T	donor_gain	0.5100
9:21410141:T:TA	acceptor_gain	0.5100
9:21409276:AAC:A	donor_gain	0.5000
9:21409277:ACA:A	donor_gain	0.5000
9:21410138:A:AG	acceptor_gain	0.5000
9:21409588:G:GT	donor_gain	0.4900
9:21409933:A:G	donor_gain	0.4900
9:21409967:T:G	donor_gain	0.4900
9:21409967:T:TG	donor_gain	0.4800
9:21410138:AATT:A	acceptor_gain	0.4800
9:21409808:T:G	donor_gain	0.4700
9:21409479:TGAGA:T	acceptor_gain	0.4600
9:21409546:A:AG	donor_gain	0.4600
9:21409673:T:TA	donor_gain	0.4600
9:21409674:T:TA	donor_gain	0.4600
9:21409884:A:T	donor_gain	0.4600

AlphaMissense

1248 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:21409615:T:C	F147L	0.936
9:21409617:C:A	F147L	0.936
9:21409617:C:G	F147L	0.936
9:21409351:T:C	F59L	0.916
9:21409353:T:A	F59L	0.916
9:21409353:T:G	F59L	0.916
9:21409668:G:C	W164C	0.840
9:21409668:G:T	W164C	0.840
9:21409447:T:C	F91L	0.814
9:21409449:C:A	F91L	0.814
9:21409449:C:G	F91L	0.814
9:21409523:T:C	L116P	0.770
9:21409352:T:G	F59C	0.769
9:21409330:T:C	C52R	0.742
9:21409637:T:C	L154P	0.731
9:21409612:T:C	Y146H	0.726
9:21409445:T:C	L90P	0.717
9:21409438:T:C	F88L	0.712
9:21409440:C:A	F88L	0.712
9:21409440:C:G	F88L	0.712
9:21409685:A:T	E170V	0.708
9:21409332:C:G	C52W	0.707
9:21409633:T:G	Y153D	0.705
9:21409330:T:A	C52S	0.704
9:21409331:G:C	C52S	0.704
9:21409616:T:C	F147S	0.703
9:21409616:T:G	F147C	0.697
9:21409676:T:A	V167D	0.690
9:21409662:T:G	C162W	0.687
9:21409660:T:A	C162S	0.684

dbSNP variants (sampled 300 via entrez): RS1000853564 (9:21407191 C>G,T), RS1003444118 (9:21410524 A>G,T), RS1004162725 (9:21407264 T>A), RS1004432517 (9:21407438 C>G), RS1004989880 (9:21407587 G>A,T), RS1005192257 (9:21410300 C>T), RS1006578729 (9:21409626 C>A), RS1007476772 (9:21408777 T>C), RS1008000221 (9:21408557 G>A), RS1008606989 (9:21409807 G>C,T), RS1009664898 (9:21409127 G>A,C), RS1009985587 (9:21407818 CTTTT>C,CTTT,CTTTTT), RS1010430959 (9:21408029 A>G), RS1011080860 (9:21410462 G>T), RS1012509181 (9:21410627 A>C)

Disease associations

OMIM: gene MIM:147568 | 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

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Sorafenib	affects cotreatment, affects phosphorylation	1
Cadmium	decreases expression, increases abundance	1
Mercury	increases expression	1
Tretinoin	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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