IFNA14

Summary

IFNA14 (interferon alpha 14, HGNC:5420) is a protein-coding gene on chromosome 9p21.3, encoding Interferon alpha-14 (P01570). 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 3448 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 40 total
• Druggable target: yes
• MANE Select transcript: NM_002172

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5420
Approved symbol	IFNA14
Name	interferon alpha 14
Location	9p21.3
Locus type	gene with protein product
Status	Approved
Aliases	LEIF2H, IFN-alphaH
Ensembl gene	ENSG00000228083
Ensembl biotype	protein_coding
OMIM	147579
Entrez	3448

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000380222

RefSeq mRNA: 1 — MANE Select: NM_002172 NM_002172

CCDS: CCDS6501

Canonical transcript exons

ENST00000380222 — 1 exons

Exon	Start	End
ENSE00000927978	21239002	21240005

Expression profiles

Bgee: expression breadth tissue_specific, 3 present calls, max score 41.62.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0476 / max 23.7624, expressed in 8 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100206	0.0476	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	41.62	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
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
bone marrow	UBERON:0002371	33.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
cortex of kidney	UBERON:0001225	31.77	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.42	gold quality
liver	UBERON:0002107	28.88	gold quality
monocyte	CL:0000576	28.32	gold quality
leukocyte	CL:0000738	28.26	gold quality
duodenum	UBERON:0002114	28.14	gold quality
kidney	UBERON:0002113	27.98	gold quality
right coronary artery	UBERON:0001625	27.78	gold quality
primary visual cortex	UBERON:0002436	27.78	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
urinary bladder	UBERON:0001255	26.88	gold quality
blood	UBERON:0000178	26.60	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
right lobe of liver	UBERON:0001114	24.52	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): IRF1, IRF3, IRF5, IRF7

miRNA regulators (miRDB)

10 targeting IFNA14, 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-570-3P	99.96	72.41	4910
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-3171	99.49	69.06	776
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
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-924	97.78	66.21	681

Literature-anchored findings (GeneRIF, showing 3)

• Gene therapy with plasmids encoding IFN-beta and -alpha14, but not the commonly used -alpha2, confers long-term suppression of HIV-1 replication. (PMID:27729616)
• FISH analysis reveals CDKN2A and IFNA14 co-deletion is heterogeneous and is a prominent feature of glioblastoma. (PMID:38097874)
• 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), IFNA13 (ENSG00000233816), IFNA17 (ENSG00000234829), IFNA4 (ENSG00000236637)

Protein

Protein identifiers

Interferon alpha-14 — P01570 (reviewed: P01570)

Alternative names: Interferon alpha-H, Interferon lambda-2-H

All UniProt accessions (1): P01570

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_002163* (*=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): disulfide bond 2, signal peptide 1, chain 1, glycosylation site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01570-F1	85.41	0.55

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

Glycosylation sites (1): 95

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: 133 (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, 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, MORF_CTSB, KEGG_AUTOIMMUNE_THYROID_DISEASE

GO Biological Process (10): 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)

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
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

1368 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFNA14	IL2	P01585	855
IFNA14	IFNAR1	P17181	833
IFNA14	IFNG	P01579	762
IFNA14	CR2	P20023	670
IFNA14	IFNL3	Q8IZI9	667
IFNA14	IL6	P05231	661
IFNA14	ISG15	P05161	654
IFNA14	TLR3	O15455	628
IFNA14	ABL1	P00519	624
IFNA14	GPT	P24298	624
IFNA14	CD4	P01730	621
IFNA14	MX1	P20591	610
IFNA14	TNF	P01375	609
IFNA14	MX2	P20592	597
IFNA14	IFNAR2	P48551	587

IntAct

17 interactions, top by confidence:

A	B	Type	Score
IFNA14	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
IFNA21	IFIT3	psi-mi:“MI:0914”(association)	0.530
IFNA14	IFIT3	psi-mi:“MI:0914”(association)	0.530
IFNA5	IFNA13	psi-mi:“MI:0914”(association)	0.530
IFNA13	IFNA21	psi-mi:“MI:0914”(association)	0.530
IFNA14	IFIT1	psi-mi:“MI:0914”(association)	0.530
IFNA13	IFNA14	psi-mi:“MI:0914”(association)	0.530
M		psi-mi:“MI:0914”(association)	0.350
IFNA5	LGALS9	psi-mi:“MI:0914”(association)	0.350
IFNA14	AHCYL1	psi-mi:“MI:0914”(association)	0.350
IFNA14	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (29): STIM1 (Affinity Capture-MS), IFNA6 (Affinity Capture-MS), IFIT3 (Affinity Capture-MS), PLAT (Affinity Capture-MS), ISG15 (Affinity Capture-MS), IFIT1 (Affinity Capture-MS), IFNA14 (Affinity Capture-MS), IFNA14 (Affinity Capture-MS), IFIT3 (Affinity Capture-MS), IFNA14 (Affinity Capture-MS), ISG15 (Affinity Capture-MS), IFIT1 (Affinity Capture-MS), IFNA14 (Affinity Capture-MS), IFNA6 (Affinity Capture-MS), IFNA14 (Two-hybrid)

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	35
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

255 predictions. Top by Δscore:

Variant	Effect	Δscore
9:21239523:T:TA	donor_gain	0.7000
9:21239148:A:AC	donor_gain	0.6600
9:21239830:T:TA	donor_gain	0.6500
9:21239489:T:TA	donor_gain	0.6400
9:21239349:C:A	donor_gain	0.6200
9:21239633:AT:A	donor_gain	0.6100
9:21239183:T:C	donor_gain	0.6000
9:21239261:A:C	donor_gain	0.6000
9:21239149:A:C	donor_gain	0.5900
9:21239308:A:AC	donor_gain	0.5900
9:21239633:ATC:A	donor_gain	0.5900
9:21239559:T:TA	donor_gain	0.5800
9:21239577:T:TA	donor_gain	0.5700
9:21239634:T:C	donor_gain	0.5700
9:21239228:ACACT:A	donor_gain	0.5500
9:21239199:G:A	donor_gain	0.5400
9:21239348:T:TA	donor_gain	0.5400
9:21239368:AAT:A	donor_gain	0.5400
9:21239503:T:TA	donor_gain	0.5400
9:21239565:A:AC	donor_gain	0.5400
9:21239745:T:TA	donor_gain	0.5400
9:21239196:AGTG:A	donor_gain	0.5300
9:21239232:T:A	donor_gain	0.5300
9:21239262:C:CC	donor_gain	0.5300
9:21239374:T:TA	donor_gain	0.5100
9:21239547:TCC:T	donor_gain	0.5000
9:21239691:T:TG	acceptor_gain	0.5000
9:21239772:T:TA	donor_gain	0.5000
9:21239195:TAG:T	donor_gain	0.4900
9:21239258:TCA:T	donor_gain	0.4900

AlphaMissense

1274 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:21239495:G:C	F147L	0.942
9:21239495:G:T	F147L	0.942
9:21239497:A:G	F147L	0.942
9:21239759:A:C	F59L	0.889
9:21239759:A:T	F59L	0.889
9:21239761:A:G	F59L	0.889
9:21239444:C:A	W164C	0.888
9:21239444:C:G	W164C	0.888
9:21239636:C:A	W100C	0.819
9:21239636:C:G	W100C	0.819
9:21239663:G:C	F91L	0.798
9:21239663:G:T	F91L	0.798
9:21239665:A:G	F91L	0.798
9:21239446:A:G	W164R	0.797
9:21239446:A:T	W164R	0.797
9:21239638:A:G	W100R	0.787
9:21239638:A:T	W100R	0.787
9:21239436:A:T	V167D	0.784
9:21239667:A:G	L90P	0.770
9:21239780:G:C	C52W	0.768
9:21239432:T:A	R168S	0.762
9:21239432:T:G	R168S	0.762
9:21239442:T:A	E165V	0.761
9:21239450:A:C	C162W	0.747
9:21239475:A:G	L154P	0.743
9:21239431:C:G	A169P	0.738
9:21239451:C:G	C162S	0.733
9:21239452:A:T	C162S	0.733
9:21239782:A:G	C52R	0.732
9:21239781:C:G	C52S	0.724

dbSNP variants (sampled 300 via entrez): RS1000075166 (9:21240012 C>G,T), RS1000677259 (9:21241130 C>G), RS1001309584 (9:21238700 C>A,G,T), RS1002096217 (9:21238555 G>T), RS1002681216 (9:21239325 T>TG), RS1003538770 (9:21241215 A>G,T), RS1003655095 (9:21241424 A>G), RS1006434151 (9:21238713 C>G,T), RS1007782449 (9:21239262 C>A,G,T), RS1007788978 (9:21241754 C>T), RS1008504162 (9:21239794 A>T), RS1008667915 (9:21240474 C>T), RS1009566331 (9:21241667 A>C,G), RS1009937829 (9:21238519 A>T), RS1010581724 (9:21240282 T>A,C)

Disease associations

OMIM: gene MIM:147579 | 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
GCST005115_2	Response to mepolizumab in severe asthma	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008459	response to mepolizumab

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

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
apocarotenal	increases expression	1
hydroxyhydroquinone	decreases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	decreases methylation	1
Benzo(a)pyrene	increases methylation	1
Aflatoxin B1	decreases methylation	1
beta Carotene	increases expression	1

Clinical trials (associated diseases)

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