IFNL3

Summary

IFNL3 (interferon lambda 3, HGNC:18365) is a protein-coding gene on chromosome 19q13.2, encoding Interferon lambda-3 (Q8IZI9). Cytokine with antiviral, antitumour and immunomodulatory activities.

This gene encodes a cytokine distantly related to type I interferons and the IL-10 family. This gene, interleukin 28A (IL28A), and interleukin 29 (IL29) are three closely related cytokine genes that form a cytokine gene cluster on a chromosomal region mapped to 19q13. Expression of the cytokines encoded by the three genes can be induced by viral infection. All three cytokines have been shown to interact with a heterodimeric class II cytokine receptor that consists of interleukin 10 receptor, beta (IL10RB) and interleukin 28 receptor, alpha (IL28RA).

Source: NCBI Gene 282617 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 51 total
• MANE Select transcript: NM_172139

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18365
Approved symbol	IFNL3
Name	interferon lambda 3
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	IL-28B, IL28C
Ensembl gene	ENSG00000197110
Ensembl biotype	protein_coding
OMIM	607402
Entrez	282617

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000413851, ENST00000613087

RefSeq mRNA: 2 — MANE Select: NM_172139 NM_001346937, NM_172139

CCDS: CCDS12530, CCDS86765

Canonical transcript exons

ENST00000413851 — 5 exons

Exon	Start	End
ENSE00002236960	39244788	39245006
ENSE00002465012	39244008	39244157
ENSE00002483176	39243824	39243907
ENSE00002523980	39244417	39244494
ENSE00003714809	39243553	39243730

Expression profiles

Bgee: expression breadth broad, 15 present calls, max score 97.89.

Top tissues by expression

110 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	97.89	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	52.25	silver quality
granulocyte	CL:0000094	42.71	silver quality
bone marrow cell	CL:0002092	38.94	gold quality
superior frontal gyrus	UBERON:0002661	38.16	silver 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
sural nerve	UBERON:0015488	35.99	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
prefrontal cortex	UBERON:0000451	35.17	silver quality
bone marrow	UBERON:0002371	34.51	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
frontal cortex	UBERON:0001870	32.75	silver quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
primary visual cortex	UBERON:0002436	31.69	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
blood	UBERON:0000178	30.73	silver quality
skin of abdomen	UBERON:0001416	30.43	silver quality
cerebral cortex	UBERON:0000956	30.27	silver quality
placenta	UBERON:0001987	30.15	silver quality
temporal lobe	UBERON:0001871	29.97	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
amygdala	UBERON:0001876	29.54	silver quality
zone of skin	UBERON:0000014	29.48	silver quality
urinary bladder	UBERON:0001255	29.40	silver quality
leukocyte	CL:0000738	28.94	gold quality
tonsil	UBERON:0002372	28.75	gold quality
skin of leg	UBERON:0001511	28.53	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	28.44	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.48

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELF4, IFI16, IRF1, IRF2, IRF3, IRF7, IRF8, IRF9, NFKB1, NFKB2, NFKB, RELA, RELB, STAT1, TXK

Literature-anchored findings (GeneRIF, showing 40)

• identified from the human genomic sequence a family of three cytokines, designated interleukin 28A (IL-28A), IL-28B and IL-29, that are distantly related to type I interferons (IFNs) and the IL-10 family (PMID:12469119)
• closely positioned genes on human chromosome 19 encode distinct but paralogous proteins, which we designate interferon-lambda1 (IFN-lambda1), IFN-lambda2 and IFN-lambda3 (PMID:12483210)
• IFN-lambdas are thus able to generate tolerogenic DCs, an activity that could thwart IFN-beta functions (PMID:16478884)
• Human interferon-lambda3 is a potent member of the type III interferon family. (PMID:18987645)
• recent findings about the biology of IFN-lambdas and their pathophysiological roles in viral infection, cancer, and immune responses of the innate and adaptive arms.[review] (PMID:19304895)
• The crystal structure of human IFN-lambda3 was determined and the interaction with its receptor complex through structure-based site-directed mutagenesis, was characterized. (PMID:19457860)
• primary role for IL28B in resolution of HCV infection (PMID:19759533)
• The association of the IL28B locus with natural and treatment-associated control of HCV indicates the importance of innate immunity and interferon lambda in the pathogenesis of HCV infection. (PMID:20060832)
• Chronic hepatitis C patients with the rs12979860 CC responder genotype may have a lower endogenous IFN response to the virus. (PMID:20235331)
• Interferon-alpha treatment in patients with hepatitis C affect gene expression regulation in interferon lambda3 expression. (PMID:20346265)
• Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. (PMID:20399780)
• The expression of hepatic interferon-stimulated genes is strongly associated with treatment response and genetic variation of IL28B in chronic hepatitis C. (PMID:20434452)
• a close association of IL-28B SNPs with treatment response of hepatitis C. (PMID:20455677)
• the proportion of HCV wild type core amino acids 70 and 91 was significantly greater (p=1.21 x 10(-4) and 0.034) and levels of gamma-GTP significantly lower (p=0.001) in patients homozygous for the IL28 major allele (PMID:20576307)
• different rates of viral genotype infection depending on the IL28B variant as well as an association of this locus with natural and treatment-mediated response were found. (PMID:20578254)
• An IL-28B polymorphism was associated with an sustained viral response in patients infected with genotype 2/3 HCV who did not achieve a rapid viral response. (PMID:20621700)
• The SNP rs12979860 upstream of IL28B is associated with spontaneous clearance of HCV. Women with the C/T or T/T genotype who did not develop jaundice had a lower chance of spontaneous clearance of HCV infection. (PMID:20637200)
• In patients with recurrent HCV infection after orthotopic liver transplantation, combination analyses of single nucleotide polymorphisms of IL28B in recipient and donor tissues and mutations in HCV RNA allow prediction of SVR to PEG-IFN/RBV therapy. (PMID:20708617)
• During recent hepatitis C virus infection, genetic variations in IL28B region were associated with spontaneous but not treatment-induced clearance. Early therapeutic intervention could be recommended for individuals with unfavorable IL28B genotypes. (PMID:20803561)
• IL28B gene variations independently predict sustained virologic response in human immunodeficiency virus/hepatitis C virus-coinfected patients with hepatitis C virus genotype 1 and non-genotype 1 hepatitis C virus infection. (PMID:20804372)
• good response IL28B variant was strongly associated with lower level interferon-stimulated gene (ISG) expression. results suggest that IL28B genotype may explain the relationship between hepatic ISG expression and HCV treatment outcome. (PMID:20931559)
• association between IL28B and hepatitis C virus clearance (PMID:20950615)
• The C/C genotype of rs12979860 was not associated with HBV recovery, resistance to HIV infection, or HIV disease progression. This IL28B single-nucleotide polymorphism affects the immune response to HCV but not to HBV or HIV (PMID:20977343)
• 28B genotype is more frequent in individuals who have cleared an acute hepatitis C infection. (PMID:21038423)
• IL28B polymorphisms and HCV core amino acid 70 substitutions contribute independently to an SVR to peg-interferon plus ribavirin combination therapy. (PMID:21068134)
• These findings suggest that IL28B may account for some differences in hepatitis C outcome but that other factors including the viral genotype, host genetics and the host-virus interaction are likely to influence the outcome of infection. (PMID:21070502)
• IL-28 polymorphisms are associated with sustained virologic response and with natural viral clearance in hepatitis C (PMID:21080244)
• IL28B genotype and hepatic expression of interferon stimulated genes are independent predictors of response to treatment with pegIFN-alpha and ribavirin in patients with chronic hepatitis C. (PMID:21111740)
• The IL28B SNP rs12979860 CC genotype, lower age, and HCV genotype 2 were significantly associated with sustained virological response in HCV genotype 2/3-infected patients. (PMID:21112657)
• The favorable IL28B SNP rs8099917 genotype is associated with a steep decline in viral load by the second week of chronic hepatitis C treatment. (PMID:21112660)
• The IL28B polymorphism and mutations in the IFN sensitivity determining region of HCV were significant pre-treatment predictors of response to PEG-IFN/RBV. (PMID:21129805)
• IL28B polymorphism is associated with both side effects and clearance of hepatitis C during interferon-alpha therapy. (PMID:21133812)
• Among chronic HCV patients treated with peg-interferon plus ribavirin therapy, liver mRNA levels of IL28B, MxA, PKR, OAS1, and ISG15 were significantly or marginally lower in responders who became negative for HCV RNA. (PMID:21145800)
• In general IL-29 serum levels exceeded IL-28A/B at least twofold, with IL-29 and IL-28A/B levels being significantly higher in carriers of the rs12979860 C allele than in TT homozygous individuals in hepatitis C (PMID:21145813)
• IL-28B rs12979860 C/T polymorphism T allele is more prevalent in patients with viral cirrhosis due to HCV in comparison to other aetiologies and to patients with mild chronic hepatitis C. (PMID:21146242)
• evidence for a dominant, but not exclusive impact of the donor rather than the recipient IL28B genetic background on the natural course and treatment outcome of HCV liver graft reinfection (PMID:21147186)
• The rs8099917 TT genotype is significantly independently predictive of rapid virological response, which is the single best predictor of sustained virological response, in Asian HCV-2 patients. (PMID:21254157)
• When IL28B genotype is combined with pretreatment serum IP-10 measurement, the predictive value for discrimination between sustained virological response and nonresponse is significantly improved, especially in non-CC genotypes. (PMID:21254158)
• Recipient IL28B TT genotype is associated with more severe histological recurrence of HCV. Recipient and donor liver IL28B genotype are strongly and independently associated with IFN-based treatment response in patients after liver transplantation. (PMID:21254179)
• both the IL-28B variants and viral genotypes predicting a sustained virological response and the factors predicting an unsustained virological response were found together more often than expected. (PMID:21254188)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ifnl2	ENSMUSG00000059128
mus_musculus	Ifnl3	ENSMUSG00000060747
rattus_norvegicus		ENSRNOG00000077856
rattus_norvegicus		ENSRNOG00000082401

Paralogs (2): IFNL1 (ENSG00000182393), IFNL2 (ENSG00000183709)

Protein

Protein identifiers

Interferon lambda-3 — Q8IZI9 (reviewed: Q8IZI9)

Alternative names: Cytokine Zcyto22, Interleukin-28B, Interleukin-28C

All UniProt accessions (3): A0A0C4DGW8, A0A7R8C2Z6, Q8IZI9

UniProt curated annotations — full annotation on UniProt →

Function. Cytokine with antiviral, antitumour and immunomodulatory activities. Plays a critical role in the antiviral host defense, predominantly in the epithelial tissues. Acts as a ligand for the heterodimeric class II cytokine receptor composed of IL10RB and IFNLR1, and receptor engagement leads to the activation of the JAK/STAT signaling pathway resulting in the expression of IFN-stimulated genes (ISG), which mediate the antiviral state. Has a restricted receptor distribution and therefore restricted targets: is primarily active in epithelial cells and this cell type-selective action is because of the epithelial cell-specific expression of its receptor IFNLR1. Seems not to be essential for early virus-activated host defense in vaginal infection, but plays an important role in Toll-like receptor (TLR)-induced antiviral defense. Plays a significant role in the antiviral immune defense in the intestinal epithelium. Exerts an immunomodulatory effect by up-regulating MHC class I antigen expression.

Subcellular location. Secreted.

Induction. By viral infections or double-stranded RNA.

Similarity. Belongs to the type-III (or lambda) interferon family.

RefSeq proteins (2): NP_001333866, NP_742151* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029177	INF_lambda	Family
IPR038326	IFN-lambda_sf	Homologous_superfamily

Pfam: PF15177

UniProt features (30 total): helix 12, mutagenesis site 6, sequence conflict 4, disulfide bond 3, sequence variant 2, signal peptide 1, chain 1, strand 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3HHC	X-RAY DIFFRACTION	2.8
5T5W	X-RAY DIFFRACTION	2.85
9BPV	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZI9-F1	85.82	0.74

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 (3): 37–136, 71–169, 188–195

Mutagenesis-validated functional residues (6):

Position	Phenotype
121	46 fold decrease in antiviral activity.
176	40 fold decrease in antiviral activity.
179	650 fold decrease in antiviral activity.
57	51 fold decrease in antiviral activity.
58	43 fold decrease in antiviral activity.
118	68 fold decrease in antiviral activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8854691	Interleukin-20 family signaling

MSigDB gene sets: 51 (showing top): GOBP_CELLULAR_RESPONSE_TO_VIRUS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, CAGCTG_AP4_Q5, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, IRF1_Q6, GOBP_VIRAL_GENOME_REPLICATION, GOBP_VIRAL_LIFE_CYCLE, IRF_Q6, GOBP_DEFENSE_RESPONSE_TO_VIRUS, GOMF_CYTOKINE_ACTIVITY, GOMF_SIGNALING_RECEPTOR_BINDING

GO Biological Process (7): cell surface receptor signaling pathway via JAK-STAT (GO:0007259), type III interferon-mediated signaling pathway (GO:0038196), negative regulation of viral genome replication (GO:0045071), innate immune response (GO:0045087), positive regulation of immune response (GO:0050778), defense response to virus (GO:0051607), cellular response to virus (GO:0098586)

GO Molecular Function (2): signaling receptor binding (GO:0005102), cytokine activity (GO:0005125)

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

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by Interleukins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune response	2
response to virus	2
cell surface receptor signaling pathway via STAT	1
cellular response to type III interferon	1
interferon-mediated signaling pathway	1
viral genome replication	1
regulation of viral genome replication	1
negative regulation of viral process	1
defense response to symbiont	1
positive regulation of immune system process	1
positive regulation of response to stimulus	1
regulation of immune response	1
defense response	1
protein binding	1
receptor ligand activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

796 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFNL3	IFNLR1	Q8IU57	999
IFNL3	IL10RB	Q08334	994
IFNL3	IFNL1	Q8IU54	971
IFNL3	IFNL2	Q8IZJ0	961
IFNL3	IFNA13	P01562	875
IFNL3	IFNA2	P01563	868
IFNL3	IFNAR1	P17181	836
IFNL3	ITPA	Q9BY32	835
IFNL3	IL10	P22301	813
IFNL3	IL10RA	Q13651	812
IFNL3	STAT1	P42224	745
IFNL3	IL22	Q9GZX6	739
IFNL3	IL22RA2	Q969J5	733
IFNL3	IL20RA	Q9UHF4	733
IFNL3	IL26	Q9NPH9	724

IntAct

5 interactions, top by confidence:

A	B	Type	Score
SDCBP	IFNL3	psi-mi:“MI:0407”(direct interaction)	0.440
IFNL3	ISG15	psi-mi:“MI:0915”(physical association)	0.400
IFNL3	STAT1	psi-mi:“MI:0915”(physical association)	0.400
IFNL3	HIKESHI	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): ISG15 (Affinity Capture-MS), IFNL3 (Positive Genetic), IL12RB1 (Positive Genetic), MYC (Positive Genetic), NOD2 (Positive Genetic), TNFRSF1A (Positive Genetic), C11orf73 (Affinity Capture-MS), B3GALNT2 (Affinity Capture-MS), STAT1 (Affinity Capture-MS)

ESM2 similar proteins: A5PJ93, A6NH21, A6QQ85, A8MVS5, B0FP48, E5RIL1, E9PY61, O75631, P0C6B2, P38574, P42701, P57785, Q08351, Q15904, Q561R0, Q5T7M4, Q63148, Q64280, Q6AZ51, Q6IEE6, Q6PRD1, Q6ZVW7, Q75VT8, Q7TN60, Q80YF6, Q864V4, Q867C0, Q8BH06, Q8BX43, Q8CHT6, Q8CJ26, Q8IZI9, Q8IZJ0, Q8K4C2, Q8K5A9, Q8N3T6, Q8N9H8, Q8NAC3, Q8NFR9, Q8R2Z0

Diamond homologs: B4ER10, Q4VK74, Q8CGK6, Q8IU54, Q8IZI9, Q8IZJ0, K9M1U5

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
IFNL3	up-regulates	IFNLR1	binding
IFNL3	up-regulates	IL10RB	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	4
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

435 predictions. Top by Δscore:

Variant	Effect	Δscore
19:39243728:CTC:C	acceptor_gain	1.0000
19:39243820:TCAC:T	donor_loss	1.0000
19:39243821:CACCT:C	donor_loss	1.0000
19:39243822:A:AC	donor_gain	1.0000
19:39243822:AC:A	donor_gain	1.0000
19:39243823:C:CA	donor_gain	1.0000
19:39243823:CC:C	donor_gain	1.0000
19:39243823:CCT:C	donor_gain	1.0000
19:39243823:CCTT:C	donor_gain	1.0000
19:39243823:CCTTT:C	donor_gain	1.0000
19:39243903:TGGAT:T	acceptor_gain	1.0000
19:39243907:TCT:T	acceptor_loss	1.0000
19:39243908:C:A	acceptor_loss	1.0000
19:39243908:C:CC	acceptor_gain	1.0000
19:39244006:A:AC	donor_gain	1.0000
19:39244007:C:CC	donor_gain	1.0000
19:39244007:CA:C	donor_gain	1.0000
19:39244413:TCACC:T	donor_loss	1.0000
19:39244414:CA:C	donor_loss	1.0000
19:39244415:A:C	donor_loss	1.0000
19:39244491:CTTC:C	acceptor_gain	1.0000
19:39244786:A:AC	donor_gain	1.0000
19:39244787:C:CC	donor_gain	1.0000
19:39244809:AAAGG:A	donor_gain	1.0000
19:39243729:TC:T	acceptor_gain	0.9900
19:39243729:TCC:T	acceptor_loss	0.9900
19:39243730:CC:C	acceptor_gain	0.9900
19:39243730:CCTG:C	acceptor_loss	0.9900
19:39243731:C:CC	acceptor_gain	0.9900
19:39243904:GGAT:G	acceptor_gain	0.9900

AlphaMissense

1250 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:39244809:A:C	F53L	0.959
19:39244809:A:T	F53L	0.959
19:39244811:A:G	F53L	0.959
19:39244797:T:A	K57N	0.925
19:39244797:T:G	K57N	0.925
19:39244806:C:A	K54N	0.925
19:39244806:C:G	K54N	0.925
19:39243854:C:A	W154C	0.922
19:39243854:C:G	W154C	0.922
19:39244798:T:A	K57I	0.902
19:39244842:G:C	F42L	0.902
19:39244842:G:T	F42L	0.902
19:39244844:A:G	F42L	0.902
19:39243669:T:G	D185A	0.896
19:39243692:G:C	N177K	0.896
19:39243692:G:T	N177K	0.896
19:39244448:A:C	F76C	0.887
19:39243702:A:T	V174D	0.886
19:39244810:A:G	F53S	0.885
19:39243668:G:C	D185E	0.884
19:39243668:G:T	D185E	0.884
19:39244135:A:G	L94S	0.881
19:39244802:C:G	A56P	0.876
19:39243669:T:A	D185V	0.874
19:39243670:C:G	D185H	0.861
19:39243657:A:T	V189D	0.857
19:39244123:A:G	L98P	0.857
19:39244130:C:G	A96P	0.849
19:39243678:A:T	L182H	0.847
19:39244125:C:A	E97D	0.847

dbSNP variants (sampled 300 via entrez): RS1000017325 (19:39243558 G>A,C,T), RS1000068148 (19:39243281 G>A), RS1001017756 (19:39244548 C>T), RS1003426909 (19:39246228 C>T), RS1003888415 (19:39245982 A>G), RS1003985706 (19:39245038 G>C), RS1004337871 (19:39245368 G>A), RS1004936794 (19:39246689 T>C,G), RS1005397451 (19:39246328 G>A), RS1007689912 (19:39243206 G>C), RS1008283278 (19:39244318 G>A,T), RS1009775316 (19:39244818 C>A,T), RS1009791502 (19:39244582 T>C), RS1010785004 (19:39245948 G>A), RS1010795005 (19:39245671 ATT>A,AT,ATTTT)

Disease associations

OMIM: gene MIM:607402 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000465_3	Response to hepatitis C treatment	1.000000e-28
GCST000485_1	Response to hepatitis C treatment	9.000000e-09
GCST000486_1	Response to hepatitis C treatment	3.000000e-32
GCST000557_1	Chronic hepatitis C infection	6.000000e-09
GCST000944_1	Response to hepatitis C treatment	1.000000e-20
GCST001418_1	Lipid levels in hepatitis C treatment	5.000000e-17
GCST001867_1	Chronic hepatitis C infection	2.000000e-30
GCST002967_3	Mucinous ovarian carcinoma	7.000000e-13
GCST002967_6	Mucinous ovarian carcinoma	1.000000e-08
GCST007631_2	Hepatitis C (spontaneous viral clearance)	6.000000e-50
GCST007632_1	Hepatitis C (spontaneous viral clearance)	1.000000e-15
GCST007633_1	Hepatitis C (spontaneous viral clearance)	7.000000e-24
GCST007634_1	Hepatitis C (spontaneous viral clearance)	3.000000e-12
GCST011999_13	Hepatitis C (spontaneous viral clearance)	5.000000e-21
GCST011999_5	Hepatitis C (spontaneous viral clearance)	4.000000e-25

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0009785	remission

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=true)

PharmGKB clinical annotations

28 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs117648444	Efficacy	3	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Chronic hepatitis C virus infection
rs11881222	Efficacy	2A	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Hepatitis C virus infection;HIV infectious disease
rs12979860	Efficacy	1A	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin;telaprevir	Chronic hepatitis C virus infection
rs12979860	Efficacy	3	interferons	Hepatitis C virus infection
rs12979860	Efficacy	3	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin;simeprevir	Chronic hepatitis C virus infection
rs12979860	Efficacy	3	daclatasvir;peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Chronic hepatitis C virus infection
rs12979860	Efficacy	3	ledipasvir;sofosbuvir	Chronic hepatitis C virus infection
rs12979860	Metabolism/PK	3	tenofovir	HIV infectious disease
rs12979860	Efficacy	1A	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Hepatitis C virus infection
rs12979860	Efficacy	1A	boceprevir;peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Chronic hepatitis C virus infection
rs12979860	Efficacy	3	deleobuvir;faldaprevir	Chronic hepatitis C virus infection
rs12979860	Efficacy	3	ledipasvir;sofosbuvir	Chronic hepatitis C virus infection;Recurrence
rs12979860	Efficacy	3	sofosbuvir;velpatasvir;voxilaprevir	Chronic hepatitis C virus infection
rs12979860	Efficacy	3	peginterferon alfa-2a;peginterferon alfa-2b	Myeloproliferative Disorder
rs12979860	Efficacy	3	peginterferon alfa-2a	Hepatitis B;Chronic
rs12979860	Efficacy	3	sofosbuvir	Chronic hepatitis C virus infection
rs12980275	Efficacy	3	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Chronic hepatitis C virus infection
rs28416813	Efficacy	3	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Chronic hepatitis C virus infection;HIV infectious disease
rs4803217	Efficacy	3	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Hepatitis C virus infection;HIV infectious disease
rs4803219	Efficacy	3	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Chronic hepatitis C virus infection
rs7248668	Efficacy	3	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Chronic hepatitis C virus infection
rs8099917	Efficacy	1B	interferons;peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Chronic hepatitis C virus infection
rs8099917	Efficacy	2A	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin;telaprevir	Chronic hepatitis C virus infection
rs8099917	Efficacy	3	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin;simeprevir	Hepatitis C virus infection
rs8099917	Efficacy	3	ledipasvir;sofosbuvir	Chronic hepatitis C virus infection
rs8103142	Efficacy	3	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Hepatitis C virus infection
rs8105790	Efficacy	3	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Chronic hepatitis C virus infection

PharmGKB variants

11 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4803217	IFNL3	3	5.00	1	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin
rs4803219	IFNL3	3	5.50	1	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin
rs7248668	IFNL3	3	5.50	1	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin
rs8099917	IFNL3, IFNL4	1B	93.25	4	interferons;peginterferon alfa-2a;peginterferon alfa-2b;ribavirin;peginterferon alfa-2a;peginterferon alfa-2b;ribavirin;telaprevir;peginterferon alfa-2a;peginterferon alfa-2b;ribavirin;simeprevir;ledipasvir;sofosbuvir
rs8103142	IFNL3	3	3.50	1	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin
rs8105790	IFNL3	3	5.50	1	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin
rs11881222	IFNL3	2A	11.50	1	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin
rs12979860	IFNL3, IFNL4	1A	350.50	15	boceprevir;peginterferon alfa-2a;peginterferon alfa-2b;ribavirin;peginterferon alfa-2a;peginterferon alfa-2b;ribavirin;peginterferon alfa-2a;peginterferon alfa-2b;ribavirin;telaprevir;peginterferon alfa-2a;peginterferon alfa-2b;ribavirin;simeprevir;ledipasvir;sofosbuvir;daclatasvir;peginterferon alfa-2a;peginterferon alfa-2b;ribavirin;sofosbuvir;velpatasvir;voxilaprevir;peginterferon alfa-2a;peginterferon alfa-2b;peginterferon alfa-2a;sofosbuvir
rs12980275	IFNL3	3	6.50	1	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin
rs28416813	IFNL3	3	5.00	1	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin
rs117648444	IFNL3, IFNL4	3	3.50	1	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin

PharmGKB dosing guidelines

1 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
CPIC	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Annotation of CPIC Guideline for peginterferon alfa-2a, peginterferon alfa-2b, ribavirin and IFNL3		yes

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Ribavirin	affects cotreatment, affects response to substance, increases response to substance	3
peginterferon alfa-2a	affects cotreatment, affects response to substance	2
fluorene-9-bisphenol	increases expression	1
alpha phellandrene	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
perfluorooctanoic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
perfluorohexanesulfonic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2NG	Abcam A-549 IFNL3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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