IFNA6

Summary

IFNA6 (interferon alpha 6, HGNC:5427) is a protein-coding gene on chromosome 9p21.3, encoding Interferon alpha-6 (P05013). 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. Biomarker of anogenital venereal wart.

Source: NCBI Gene 3443 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 37 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_021002

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5427
Approved symbol	IFNA6
Name	interferon alpha 6
Location	9p21.3
Locus type	gene with protein product
Status	Approved
Aliases	IFN-alphaK
Ensembl gene	ENSG00000120235
Ensembl biotype	protein_coding
OMIM	147566
Entrez	3443

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000259555, ENST00000380210

RefSeq mRNA: 1 — MANE Select: NM_021002 NM_021002

CCDS: CCDS6504

Canonical transcript exons

ENST00000380210 — 1 exons

Exon	Start	End
ENSE00004472046	21350318	21350887

Expression profiles

Bgee: expression breadth broad, 30 present calls, max score 65.56.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	65.56	silver quality
cervix squamous epithelium	UBERON:0006922	64.23	gold quality
triceps brachii	UBERON:0001509	63.89	gold quality
gluteal muscle	UBERON:0002000	63.76	gold quality
diaphragm	UBERON:0001103	63.23	gold quality
olfactory bulb	UBERON:0002264	62.88	gold quality
ileal mucosa	UBERON:0000331	60.22	silver quality
mucosa of urinary bladder	UBERON:0001259	59.58	gold quality
quadriceps femoris	UBERON:0001377	59.48	gold quality
vastus lateralis	UBERON:0001379	59.37	gold quality
nephron tubule	UBERON:0001231	59.10	gold quality
metanephric glomerulus	UBERON:0004736	56.73	gold quality
decidua	UBERON:0002450	56.55	gold quality
epithelium of nasopharynx	UBERON:0001951	55.84	gold quality
tibialis anterior	UBERON:0001385	54.62	silver quality
myocardium	UBERON:0002349	54.53	gold quality
lower lobe of lung	UBERON:0008949	53.43	silver quality
kidney epithelium	UBERON:0004819	53.14	gold quality
deltoid	UBERON:0001476	52.88	gold quality
cervix epithelium	UBERON:0004801	52.47	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
epithelial cell of pancreas	CL:0000083	52.16	gold quality
left ventricle myocardium	UBERON:0006566	51.78	gold quality
Brodmann (1909) area 46	UBERON:0006483	50.98	gold quality
oviduct epithelium	UBERON:0004804	50.38	gold quality
oocyte	CL:0000023	49.66	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
thymus	UBERON:0002370	48.62	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF1

Literature-anchored findings (GeneRIF, showing 1)

• 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): 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), IFNA4 (ENSG00000236637)

Protein

Protein identifiers

Interferon alpha-6 — P05013 (reviewed: P05013)

Alternative names: Interferon alpha-54, Interferon alpha-K

All UniProt accessions (3): A0A0A0MQU8, A0A7R8C308, P05013

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_066282* (*=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-P05013-F1	87.04	0.60

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: 111 (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, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, 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

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

1356 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFNA6	IL2	P01585	855
IFNA6	IFNG	P01579	762
IFNA6	IFNAR1	P17181	734
IFNA6	CR2	P20023	670
IFNA6	TLR3	O15455	669
IFNA6	IFNL3	Q8IZI9	667
IFNA6	IL6	P05231	661
IFNA6	ISG15	P05161	656
IFNA6	RIGI	O95786	633
IFNA6	ABL1	P00519	624
IFNA6	GPT	P24298	624
IFNA6	IFIH1	Q9BYX4	623
IFNA6	CD4	P01730	621
IFNA6	MX1	P20591	620
IFNA6	TNF	P01375	609

IntAct

15 interactions, top by confidence:

A	B	Type	Score
IFNA6	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
IFNA13	IFNA14	psi-mi:“MI:0914”(association)	0.530
IFNA6	TRAPPC5	psi-mi:“MI:0915”(physical association)	0.400
IFNA6	VGF	psi-mi:“MI:0915”(physical association)	0.400
IFNA6	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): IFNA6 (Affinity Capture-MS), IFNA6 (Affinity Capture-MS), IFNA6 (Affinity Capture-MS), IFNA6 (Affinity Capture-MS), IFNA6 (Affinity Capture-MS), IFNA6 (Affinity Capture-MS), IFNA6 (Two-hybrid), IFNA6 (Affinity Capture-MS), IFNA6 (Affinity Capture-MS), IFNA6 (Affinity Capture-MS), TRAPPC5 (Affinity Capture-MS), IFNA6 (Affinity Capture-MS), VGF (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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	29
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
442489	GRCh37/hg19 9p24.3-q21.33(chr9:203861-88189913)x3	Pathogenic

SpliceAI

57 predictions. Top by Δscore:

Variant	Effect	Δscore
9:21350865:A:T	acceptor_gain	0.6200
9:21350729:C:CT	acceptor_gain	0.5800
9:21350643:TC:T	acceptor_gain	0.5000
9:21350511:T:TA	donor_gain	0.4600
9:21350727:TTCAG:T	acceptor_gain	0.4600
9:21350733:C:CT	acceptor_gain	0.4300
9:21350861:C:CT	acceptor_gain	0.4300
9:21350529:T:TA	donor_gain	0.4100
9:21350864:C:CT	acceptor_gain	0.4100
9:21350730:A:T	acceptor_gain	0.3900
9:21350734:A:T	acceptor_gain	0.3800
9:21350728:T:G	acceptor_gain	0.3700
9:21350725:CCTT:C	acceptor_loss	0.3600
9:21350726:C:A	acceptor_loss	0.3600
9:21350727:T:C	acceptor_loss	0.3600
9:21350644:C:A	acceptor_gain	0.3400
9:21350726:C:CC	acceptor_gain	0.3400
9:21350721:CTGTC:C	acceptor_gain	0.3300
9:21350855:C:CT	acceptor_gain	0.3300
9:21350426:C:A	acceptor_gain	0.3100
9:21350866:G:GC	acceptor_gain	0.2900
9:21350353:T:C	acceptor_gain	0.2800
9:21350420:CT:C	acceptor_gain	0.2800
9:21350642:CTCA:C	acceptor_gain	0.2800
9:21350707:ATCTG:A	acceptor_gain	0.2800
9:21350866:G:C	acceptor_gain	0.2800
9:21350861:C:T	acceptor_gain	0.2700
9:21350722:TGTC:T	acceptor_gain	0.2500
9:21350856:A:T	acceptor_gain	0.2400
9:21350862:A:T	acceptor_gain	0.2400

AlphaMissense

1250 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:21350447:G:C	F147L	0.936
9:21350447:G:T	F147L	0.936
9:21350449:A:G	F147L	0.936
9:21350711:G:C	F59L	0.908
9:21350711:G:T	F59L	0.908
9:21350713:A:G	F59L	0.908
9:21350396:C:A	W164C	0.884
9:21350396:C:G	W164C	0.884
9:21350588:C:A	W100C	0.787
9:21350588:C:G	W100C	0.787
9:21350712:A:C	F59C	0.778
9:21350398:A:G	W164R	0.772
9:21350398:A:T	W164R	0.772
9:21350388:A:T	V167D	0.758
9:21350615:G:C	F91L	0.754
9:21350615:G:T	F91L	0.754
9:21350617:A:G	F91L	0.754
9:21350452:A:G	Y146H	0.753
9:21350624:G:C	F88L	0.745
9:21350624:G:T	F88L	0.745
9:21350626:A:G	F88L	0.745
9:21350451:T:C	Y146C	0.742
9:21350394:T:A	E165V	0.739
9:21350732:A:C	C52W	0.739
9:21350451:T:G	Y146S	0.738
9:21350448:A:G	F147S	0.733
9:21350384:T:A	R168S	0.731
9:21350384:T:G	R168S	0.731
9:21350427:A:G	L154P	0.729
9:21350734:A:G	C52R	0.725

dbSNP variants (sampled 300 via entrez): RS1000037362 (9:21351796 G>A), RS1000108674 (9:21352314 C>T), RS1001117880 (9:21351826 C>T), RS1003577261 (9:21350739 A>C,G), RS1004587659 (9:21352067 C>T), RS1005408564 (9:21352873 C>T), RS1006000583 (9:21351777 G>A), RS1006379011 (9:21351562 A>G,T), RS1007807951 (9:21351130 A>C,G), RS1008814051 (9:21349876 T>C), RS1010166605 (9:21352047 C>A,T), RS1010568222 (9:21351855 T>C), RS1011759455 (9:21349970 T>C), RS10123853 (9:21350911 G>A,C), RS10124601 (9:21351482 G>A)

Disease associations

OMIM: gene MIM:147566 | 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
GCST002949_9	Epilepsy and lamotrigine-induced maculopapular eruptions	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:1001253	maculopapular eruption

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

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
quercitrin	affects expression	1
Cadmium	decreases expression, increases abundance	1
Cadmium Chloride	decreases expression, increases abundance	1
Permethrin	decreases expression	1

Clinical trials (associated diseases)

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