IFNK

Summary

IFNK (interferon kappa, HGNC:21714) is a protein-coding gene on chromosome 9p21.2, encoding Interferon kappa (Q9P0W0). May play a role in the regulation of immune cell function.

This gene encodes a member of the type I interferon family. Type I interferons are a group of related glycoproteins that play an important role in host defenses against viral infections. This protein is expressed in keratinocytes and the gene is found on chromosome 9, adjacent to the type I interferon cluster.

Source: NCBI Gene 56832 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 24 total
• MANE Select transcript: NM_020124

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21714
Approved symbol	IFNK
Name	interferon kappa
Location	9p21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000147896
Ensembl biotype	protein_coding
OMIM	615326
Entrez	56832

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000276943

RefSeq mRNA: 1 — MANE Select: NM_020124 NM_020124

CCDS: CCDS6521

Canonical transcript exons

ENST00000276943 — 2 exons

Exon	Start	End
ENSE00000982282	27524290	27524961
ENSE00000982283	27526007	27526498

Expression profiles

Bgee: expression breadth broad, 43 present calls, max score 99.63.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1924 / max 107.5891, expressed in 13 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96372	0.0882	11
96371	0.0495	8
96369	0.0366	7
96370	0.0122	4
96373	0.0058	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	99.63	gold quality
cartilage tissue	UBERON:0002418	63.09	silver quality
calcaneal tendon	UBERON:0003701	62.45	gold quality
adrenal tissue	UBERON:0018303	61.89	gold quality
corpus callosum	UBERON:0002336	61.57	gold quality
tendon	UBERON:0000043	54.48	gold quality
colonic epithelium	UBERON:0000397	52.52	silver quality
monocyte	CL:0000576	48.50	gold quality
lower lobe of lung	UBERON:0008949	47.65	silver quality
leukocyte	CL:0000738	47.37	gold quality
bone marrow cell	CL:0002092	46.84	gold quality
buccal mucosa cell	CL:0002336	45.04	gold quality
skeletal muscle tissue	UBERON:0001134	44.37	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
blood	UBERON:0000178	43.27	gold quality
muscle tissue	UBERON:0002385	42.71	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
tonsil	UBERON:0002372	42.38	gold quality
granulocyte	CL:0000094	42.27	silver quality
hindlimb stylopod muscle	UBERON:0004252	41.43	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
oviduct epithelium	UBERON:0004804	41.34	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
skin of hip	UBERON:0001554	40.82	silver quality
amniotic fluid	UBERON:0000173	40.69	gold quality
bone marrow	UBERON:0002371	40.68	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting IFNK, 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-8087	99.90	69.55	1351
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-4635	98.74	67.63	1339
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-3151-3P	97.80	66.16	479
HSA-MIR-596	97.48	63.13	469
HSA-MIR-6773-5P	97.04	64.30	595
HSA-MIR-3152-5P	96.98	66.88	819
HSA-MIR-6724-5P	96.41	63.11	507

Literature-anchored findings (GeneRIF, showing 15)

• IFN-kappa is able to directly modulate cytokine release from monocytes and dendritic cells, inhibit inducible IL-12 release from monocytes, and bind strongly to heparin. (PMID:12391192)
• This is the first report showing an epigenetic silencing of type I IFN after HPV16 oncogene expression (PMID:19887612)
• IFN-kappa is down-regulated in cervical keratinocytes harboring HPV, which may be a contributing factor in the progression of a cervical lesion (PMID:20479716)
• Studied IFNK single nucleotide polymorphisms in 3982 Systemic lupus erythematosus cases and 4275 controls. (PMID:20706608)
• The viral E6 and E7 oncogenes are sufficient for interferon-kappa repression, with E6 being mainly responsible. (PMID:21849431)
• This study demonstrates that E2 proteins of high risk human papillomavirus reduce STING and IFN-kappa transcription. (PMID:24614210)
• These results suggest that high-risk human papillomavirus 31 target interferon kappa to prevent Sp100 expression and identify Sp100 as an interferon-stimulated gene with anti-human papillomavirus activity. (PMID:26491169)
• investigation of common variable immunodeficiency (CVID) from 2 German families; report on the occurrence of a common and one novel truncating IFNK mutation in cases with CVID; the frequency distribution of c.30_31insTGTT in cases and controls as well as the observed segregation patterns in CVID families exclude IFNK mutations as major risk factor in CVID (PMID:28324805)
• The loss of E5 in keratinocytes maintaining the complete HPV16 genome results in the derepression of IFNK transcription and subsequent JAK/STAT-dependent upregulation of several IFN-stimulated genes (ISGs) at both the mRNA and protein levels. (PMID:31666385)
• MDA5(+) Dermatomyositis Is Associated with Stronger Skin Type I Interferon Transcriptomic Signature with Upregulation of IFN-kappa Transcript. (PMID:31955963)
• Interferon Kappa Is Important for Keratinocyte Host Defense against Herpes Simplex Virus-1. (PMID:32352019)
• IFN-kappa Is a Rheostat for Development of Psoriasiform Inflammation. (PMID:34364883)
• IFN-kappa is critical for normal wound repair and is decreased in diabetic wounds. (PMID:35358091)
• Identification of the prognostic value of Th1/Th2 ratio and a novel prognostic signature in basal-like breast cancer. (PMID:36694223)
• Keratinocytes sense and eliminate CRISPR DNA through STING/IFN-kappa activation and APOBEC3G induction. (PMID:36928117)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ifnphi2	ENSDARG00000069012
danio_rerio	ifnphi3	ENSDARG00000070676
mus_musculus	Ifnk	ENSMUSG00000042993
rattus_norvegicus	Ifnk	ENSRNOG00000022990

Paralogs (16): IFNA6 (ENSG00000120235), IFNA8 (ENSG00000120242), IFNA21 (ENSG00000137080), IFNA5 (ENSG00000147873), IFNA16 (ENSG00000147885), 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 kappa — Q9P0W0 (reviewed: Q9P0W0)

All UniProt accessions (1): Q9P0W0

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in the regulation of immune cell function. Cytokine that imparts cellular protection against viral infection in a species-specific manner. Activates the interferon-stimulated response element signaling pathway. It is able to directly modulate cytokine release from monocytes and dendritic cells. Binds heparin.

Subcellular location. Secreted.

Tissue specificity. Expressed in keratinocytes, monocytes and in resting dendritic cells.

Induction. By viral infection, upon exposure to double-stranded RNA, or upon treatment with either interferon-gamma or interferon-beta.

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

RefSeq proteins (1): NP_064509* (*=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): disulfide bond 2, sequence variant 2, signal peptide 1, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P0W0-F1	82.77	0.47

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): 30–128, 59–181

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 75 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, YAATNRNNNYNATT_UNKNOWN, GOBP_CELLULAR_RESPONSE_TO_VIRUS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, AREB6_01, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_NATURAL_KILLER_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_HUMORAL_IMMUNE_RESPONSE

GO Biological Process (16): 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), regulation of DNA-templated transcription (GO:0006355), humoral immune response (GO:0006959), negative regulation of cell population proliferation (GO:0008285), response to virus (GO:0009615), cytokine-mediated signaling pathway (GO:0019221), natural killer cell activation (GO:0030101), response to exogenous dsRNA (GO:0043330), positive regulation of innate immune response (GO:0045089), 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 (3): cytokine activity (GO:0005125), type I interferon receptor binding (GO:0005132), cytokine receptor binding (GO:0005126)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune response	4
lymphocyte activation involved in immune response	3
innate immune response	2
response to virus	2
T cell activation	1
B cell activation	1
natural killer cell activation	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
response to other organism	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
lymphocyte activation	1
response to dsRNA	1
positive regulation of response to biotic stimulus	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of innate immune response	1
positive regulation of immune response	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
cellular anatomical structure	1

Protein interactions and networks

STRING

566 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFNK	IFNAR1	P17181	970
IFNK	IFNAR2	P48551	920
IFNK	IFNA13	P01562	851
IFNK	IFNL1	Q8IU54	713
IFNK	IFNL2	Q8IZJ0	697
IFNK	IFNE	Q86WN2	696
IFNK	IFNL3	Q8IZI9	692
IFNK	MOB3B	Q86TA1	647
IFNK	IFNB1	P01574	625
IFNK	IFNLR1	Q8IU57	610
IFNK	IRF9	Q00978	584
IFNK	TYK2	P29597	581
IFNK	STAT2	P52630	580
IFNK	MX1	P20591	534
IFNK	IRF3	Q14653	531
IFNK	IRF7	Q92985	531

IntAct

0 interactions, top by confidence:

BioGRID (1): IFNK (Affinity Capture-MS)

ESM2 similar proteins: A2T6Z6, O46673, O70615, O97798, P01244, P01576, P01577, P03180, P05012, P06880, P0C6Z6, P0CAP9, P0DMS7, P14059, P18893, P22301, P29456, P37886, P43480, P46651, P47965, P48411, P51496, P51497, P51746, P55029, P68677, P68678, P79338, Q0Z972, Q25BC1, Q28374, Q29055, Q29408, Q2PE73, Q5Q0V6, Q6A2H4, Q6XZW6, Q865X4, Q8CJ70

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

182 predictions. Top by Δscore:

Variant	Effect	Δscore
9:27524911:GAT:G	donor_gain	0.8300
9:27525986:C:G	acceptor_gain	0.8300
9:27524913:T:G	donor_gain	0.7000
9:27524954:GAAA:G	donor_gain	0.6800
9:27524786:AGAAG:A	donor_gain	0.6300
9:27525985:A:AG	acceptor_gain	0.6300
9:27524951:G:GT	donor_gain	0.6000
9:27524957:ATAAG:A	donor_loss	0.5700
9:27524958:TAAG:T	donor_loss	0.5700
9:27524959:AAG:A	donor_loss	0.5700
9:27524960:AG:A	donor_loss	0.5700
9:27524961:GGT:G	donor_loss	0.5700
9:27524962:GTAT:G	donor_loss	0.5700
9:27524963:T:G	donor_loss	0.5700
9:27525992:T:G	acceptor_gain	0.5500
9:27524964:A:T	donor_loss	0.5200
9:27525982:C:A	acceptor_gain	0.5100
9:27524704:A:AC	donor_gain	0.5000
9:27525185:GAA:G	donor_gain	0.4800
9:27525982:CGCA:C	acceptor_gain	0.4700
9:27524916:T:A	donor_gain	0.4600
9:27525900:T:TA	acceptor_gain	0.4500
9:27525901:A:AA	acceptor_gain	0.4500
9:27525116:A:T	donor_gain	0.4400
9:27525981:TCGCA:T	acceptor_gain	0.4100
9:27525994:TACC:T	acceptor_gain	0.4100
9:27526006:GA:G	acceptor_gain	0.3700
9:27525123:A:AG	donor_gain	0.3600
9:27525983:GCA:G	acceptor_gain	0.3600
9:27525984:CAC:C	acceptor_gain	0.3600

AlphaMissense

1403 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:27524832:T:C	F166L	0.953
9:27524834:C:A	F166L	0.953
9:27524834:C:G	F166L	0.953
9:27524532:T:C	F66L	0.951
9:27524534:T:A	F66L	0.951
9:27524534:T:G	F66L	0.951
9:27524850:T:C	F172L	0.926
9:27524852:C:A	F172L	0.926
9:27524852:C:G	F172L	0.926
9:27524511:T:A	C59S	0.895
9:27524512:G:C	C59S	0.895
9:27524511:T:C	C59R	0.892
9:27524885:G:C	W183C	0.871
9:27524885:G:T	W183C	0.871
9:27524628:T:C	F98L	0.865
9:27524630:C:A	F98L	0.865
9:27524630:C:G	F98L	0.865
9:27524533:T:G	F66C	0.849
9:27524854:T:C	L173P	0.849
9:27524499:T:C	F55L	0.848
9:27524501:T:A	F55L	0.848
9:27524501:T:G	F55L	0.848
9:27524513:T:G	C59W	0.844
9:27524595:T:C	F87L	0.842
9:27524597:C:A	F87L	0.842
9:27524597:C:G	F87L	0.842
9:27524896:G:C	R187P	0.837
9:27524902:A:T	E189V	0.832
9:27524470:T:C	L45P	0.830
9:27524893:T:A	V186D	0.824

dbSNP variants (sampled 300 via entrez): RS1000550340 (9:27522338 A>G), RS1000811544 (9:27522453 G>A), RS1001666969 (9:27526782 A>C,G), RS1001762320 (9:27526465 C>G), RS1002327305 (9:27525444 C>G), RS1002340447 (9:27525166 C>A,G), RS1002812591 (9:27522902 C>G), RS1003653745 (9:27524127 A>G), RS1003800113 (9:27523938 T>G), RS1004384241 (9:27525453 G>C), RS1005347740 (9:27524000 T>G), RS1005357596 (9:27523727 A>G), RS1005389367 (9:27524151 A>G,T), RS1006362879 (9:27523121 CT>C,CTT), RS1007256446 (9:27524478 C>A,G,T)

Disease associations

OMIM: gene MIM:615326 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000211_1	Response to TNF antagonist treatment	5.000000e-07
GCST000481_2	Amyotrophic lateral sclerosis	1.000000e-08
GCST000481_7	Amyotrophic lateral sclerosis	7.000000e-09
GCST000763_10	Immunoglobulin A	9.000000e-06
GCST000781_1	Amyotrophic lateral sclerosis	9.000000e-11
GCST001847_1	Urinary symptoms in response to radiotherapy in prostate cancer	7.000000e-07
GCST005851_12	Delirium	9.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004653	response to TNF antagonist
EFO:0004747	protein measurement
EFO:0008008	lower urinary tract symptom

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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
sodium arsenite	decreases expression	1
monomethylarsonous acid	decreases expression	1
Curcumin	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Valproic Acid	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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