IFNA16

Summary

IFNA16 (interferon alpha 16, HGNC:5421) is a protein-coding gene on chromosome 9p21.3, encoding Interferon alpha-16 (P05015). 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; positive regulation of receptor signaling pathway via JAK-STAT; and type I interferon-mediated signaling pathway. Predicted to be located in extracellular region. Predicted to be active in extracellular space.

Source: NCBI Gene 3449 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 45 total
• Druggable target: yes
• MANE Select transcript: NM_002173

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5421
Approved symbol	IFNA16
Name	interferon alpha 16
Location	9p21.3
Locus type	gene with protein product
Status	Approved
Aliases	IFN-alphaO
Ensembl gene	ENSG00000147885
Ensembl biotype	protein_coding
OMIM	147580
Entrez	3449

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000380216

RefSeq mRNA: 1 — MANE Select: NM_002173 NM_002173

CCDS: CCDS34996

Canonical transcript exons

ENST00000380216 — 1 exons

Exon	Start	End
ENSE00001484124	21216373	21217311

Expression profiles

Bgee: expression breadth tissue_specific, 2 present calls, max score 59.82.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vastus lateralis	UBERON:0001379	59.82	gold quality
quadriceps femoris	UBERON:0001377	59.78	gold quality
thymus	UBERON:0002370	58.71	silver quality
epithelium of bronchus	UBERON:0002031	58.19	gold quality
cerebellar vermis	UBERON:0004720	57.59	gold 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
endometrium epithelium	UBERON:0004811	46.85	gold quality
lower esophagus mucosa	UBERON:0035834	39.57	gold quality
bone marrow cell	CL:0002092	39.28	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
ganglionic eminence	UBERON:0004023	35.49	gold quality
bone marrow	UBERON:0002371	34.65	gold quality
skeletal muscle tissue	UBERON:0001134	34.07	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	31.61	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
prefrontal cortex	UBERON:0000451	30.09	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
monocyte	CL:0000576	29.85	silver quality
leukocyte	CL:0000738	29.64	silver quality
liver	UBERON:0002107	29.00	gold quality
duodenum	UBERON:0002114	28.14	gold quality
primary visual cortex	UBERON:0002436	27.59	gold quality
lymph node	UBERON:0000029	27.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.82

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

24 targeting IFNA16, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-3171	99.49	69.06	776
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-6088	99.29	68.45	1284
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-5585-3P	98.25	67.41	941
HSA-MIR-924	97.78	66.21	681
HSA-MIR-4670-3P	97.37	68.35	1378
HSA-MIR-6894-3P	96.73	65.64	798

Literature-anchored findings (GeneRIF, showing 1)

• Cytokine pathway variants modulate platelet production: IFNA16 is a thrombocytosis susceptibility locus in humans. (PMID:35381074)

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), 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-16 — P05015 (reviewed: P05015)

Alternative names: Interferon alpha-WA

All UniProt accessions (2): P05015, A0A7R8C397

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_002164* (*=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 (4 total): disulfide bond 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05015-F1	84.42	0.51

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: 131 (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, KEGG_CYTOSOLIC_DNA_SENSING_PATHWAY, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, KEGG_AUTOIMMUNE_THYROID_DISEASE, GOBP_NATURAL_KILLER_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_HUMORAL_IMMUNE_RESPONSE

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), 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 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
cytokine receptor binding	1
protein-containing complex binding	1
signaling receptor binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1286 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFNA16	IL2	P01585	856
IFNA16	IFNG	P01579	762
IFNA16	IFNAR1	P17181	714
IFNA16	CR2	P20023	669
IFNA16	IFNL3	Q8IZI9	666
IFNA16	IL6	P05231	661
IFNA16	ISG15	P05161	641
IFNA16	TLR3	O15455	628
IFNA16	ABL1	P00519	624
IFNA16	GPT	P24298	624
IFNA16	CD4	P01730	620
IFNA16	MX1	P20591	611
IFNA16	TNF	P01375	608
IFNA16	CD8A	P01732	583
IFNA16	IL1B	P01584	581

IntAct

7 interactions, top by confidence:

A	B	Type	Score
HGS	IFNA16	psi-mi:“MI:0915”(physical association)	0.560
PARP2	IFNA16	psi-mi:“MI:0557”(adp ribosylation reaction)	0.440
IFNA16	IFNA13	psi-mi:“MI:0914”(association)	0.350
IFNA5	LGALS9	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): HGS (Two-hybrid), UBR3 (Affinity Capture-MS), IFNA7 (Affinity Capture-MS), IFNA13 (Affinity Capture-MS), IFNA16 (Affinity Capture-MS), APP (Reconstituted Complex)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

326 predictions. Top by Δscore:

Variant	Effect	Δscore
9:21216771:T:TC	acceptor_gain	0.7200
9:21217204:A:AC	donor_gain	0.7200
9:21217022:T:TA	donor_gain	0.7100
9:21216768:T:C	acceptor_gain	0.6600
9:21216521:A:AC	donor_gain	0.6400
9:21216556:T:C	donor_gain	0.6400
9:21216768:T:TC	acceptor_gain	0.6300
9:21216522:A:C	donor_gain	0.6200
9:21216602:CA:C	donor_gain	0.6200
9:21216873:T:A	donor_gain	0.6200
9:21217115:T:TA	donor_gain	0.6200
9:21216771:T:C	acceptor_gain	0.6100
9:21216605:T:A	donor_gain	0.6000
9:21216634:A:C	donor_gain	0.6000
9:21216929:T:TA	donor_gain	0.5800
9:21216569:AGTG:A	donor_gain	0.5600
9:21217004:T:C	donor_gain	0.5600
9:21216487:TAA:T	donor_gain	0.5500
9:21216488:AAA:A	donor_gain	0.5500
9:21216572:G:A	donor_gain	0.5500
9:21216893:T:TA	donor_gain	0.5500
9:21216718:T:A	donor_gain	0.5400
9:21216744:T:TA	donor_gain	0.5400
9:21216878:ACAGC:A	donor_gain	0.5400
9:21216879:CAGCC:C	donor_gain	0.5400
9:21216469:A:AC	donor_gain	0.5300
9:21217003:AT:A	donor_gain	0.5300
9:21216678:A:AC	donor_gain	0.5200
9:21216813:C:A	donor_gain	0.5200
9:21216879:C:CA	donor_gain	0.5200

AlphaMissense

1252 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:21216865:A:C	F147L	0.949
9:21216865:A:T	F147L	0.949
9:21216867:A:G	F147L	0.949
9:21217129:G:C	F59L	0.934
9:21217129:G:T	F59L	0.934
9:21217131:A:G	F59L	0.934
9:21216814:C:A	W164C	0.911
9:21216814:C:G	W164C	0.911
9:21217033:G:C	F91L	0.871
9:21217033:G:T	F91L	0.871
9:21217035:A:G	F91L	0.871
9:21217006:C:A	W100C	0.816
9:21217006:C:G	W100C	0.816
9:21216806:A:T	V167D	0.814
9:21216802:T:A	R168S	0.805
9:21216802:T:G	R168S	0.805
9:21216959:A:G	L116P	0.800
9:21216816:A:G	W164R	0.791
9:21216816:A:T	W164R	0.791
9:21216845:A:G	L154P	0.786
9:21216849:A:C	Y153D	0.786
9:21217037:A:G	L90P	0.786
9:21216870:A:G	Y146H	0.779
9:21216869:T:G	Y146S	0.778
9:21217130:A:C	F59C	0.766
9:21216821:C:G	C162S	0.758
9:21216822:A:T	C162S	0.758
9:21216869:T:C	Y146C	0.758
9:21217150:G:C	C52W	0.758
9:21216866:A:G	F147S	0.753

dbSNP variants (sampled 300 via entrez): RS1000022050 (9:21218532 T>C), RS1000302961 (9:21218352 G>C,T), RS1000638480 (9:21217642 T>G), RS1002218812 (9:21218627 G>A), RS1002640015 (9:21216185 G>A), RS1003698930 (9:21216286 A>G), RS1004051788 (9:21218055 T>G), RS1004105600 (9:21218180 G>A,T), RS1006397223 (9:21218891 C>T), RS1006449590 (9:21219070 G>C,T), RS1008240675 (9:21215900 T>A), RS1009193120 (9:21216590 G>A,C), RS1009780061 (9:21216177 G>A,C,T), RS1010287607 (9:21218601 A>G,T), RS1010649992 (9:21218357 A>G)

Disease associations

OMIM: gene MIM:147580 | 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
apocarotenal	increases expression	1
gardiquimod	decreases reaction, increases expression	1
Cadmium	decreases expression, increases abundance	1
beta Carotene	increases expression	1
Cadmium Chloride	increases abundance, decreases expression	1
Protein Kinase Inhibitors	decreases reaction, increases expression	1

Clinical trials (associated diseases)

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