IFNL3

interferon lambda 3, the group of Interferons

Basic information

Region (hg38): 19:39243454-39245250

Previous symbols: [ "IL28B" ]

Links

ENSG00000197110 ∙ NCBI:282617 ∙ OMIM:607402 ∙ HGNC:18365 ∙ Uniprot:Q8IZI9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Drug metabolism, IL28B-related	AD	Pharmacogenomic	Variants may have pharmacogenomic importance, as selection and dosing of medications (including peg-interferon and ribavirin) may be affected by the presence of variants	General	19684573; 19749758; 19749757; 19759533; 21254158; 21993426; 21443535; 21951981

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IFNL3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IFNL3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			18	1	6	25
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	18	1	6

Variants in IFNL3

This is a list of pathogenic ClinVar variants found in the IFNL3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-39243660-C-T		not specified	Uncertain significance (Feb 27, 2024)
19-39243672-C-T		not specified	Uncertain significance (Dec 07, 2021)
19-39243681-A-C		not specified	Uncertain significance (Aug 17, 2021)
19-39243682-G-A		not specified	Uncertain significance (Apr 28, 2023)
19-39243712-C-T			Benign (Aug 08, 2018)
19-39243825-T-G		not specified	Uncertain significance (Mar 27, 2023)
19-39243829-T-C		not specified	Uncertain significance (Jul 05, 2023)
19-39243839-C-G		not specified	Uncertain significance (Jan 04, 2024)
19-39243843-A-G		not specified	Uncertain significance (Nov 13, 2023)
19-39243850-G-A			Benign (Jul 16, 2018)
19-39243861-T-C		not specified	Uncertain significance (May 09, 2024)
19-39243865-G-A		not specified	Uncertain significance (Mar 27, 2023)
19-39243867-C-T		not specified	Uncertain significance (Oct 03, 2022)
19-39243873-C-T		not specified	Uncertain significance (Mar 11, 2022)
19-39244094-T-C			Benign (Aug 16, 2018)
19-39244133-C-G			Benign (Aug 16, 2018)
19-39244143-G-A		not specified	Likely benign (Mar 26, 2024)
19-39244148-G-A		not specified	Uncertain significance (Nov 01, 2022)
19-39244283-A-G		peginterferon alfa-2b response - Efficacy • ribavirin response - Efficacy • peginterferon alfa-2a response - Efficacy	drug response (Mar 24, 2021)
19-39244423-C-G		not specified	Uncertain significance (Nov 22, 2023)
19-39244460-C-T			Benign (Aug 16, 2018)
19-39244466-T-C		not specified	Likely benign (Mar 09, 2018)
19-39244835-G-C		not specified	Uncertain significance (Feb 27, 2023)
19-39244871-C-G		not specified	Uncertain significance (Dec 18, 2023)
19-39244888-A-T		not specified	Uncertain significance (May 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IFNL3	protein_coding	protein_coding	ENST00000413851	5	1401

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.42e-8	0.0443	125716	0	15	125731	0.0000597

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.16	158	122	1.30	0.00000758	1230
Missense in Polyphen		23	24.97	0.92111		328
Synonymous	-0.453	60	55.7	1.08	0.00000347	436
Loss of Function	-1.01	10	7.09	1.41	3.01e-7	83

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000145	0.000145
Ashkenazi Jewish	0.00	0.00
East Asian	0.000327	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.000327	0.000326
South Asian	0.0000665	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:12469119, ECO:0000269|PubMed:12483210}.
• Pathway: Jak-STAT signaling pathway - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);JAK-STAT-Core;Type III interferon signaling (Consensus)

Recessive Scores

• pRec: 0.101

Intolerance Scores

• rvis_EVS: 1.28
• rvis_percentile_EVS: 93.77

Haploinsufficiency Scores

• pHI: 0.0398
• hipred: N
• hipred_score: 0.112

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ifnl3
• Phenotype: hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: JAK-STAT cascade;regulation of signaling receptor activity;cytokine-mediated signaling pathway;negative regulation of viral genome replication;innate immune response;positive regulation of immune response;defense response to virus
• Cellular component: extracellular region;extracellular space
• Molecular function: signaling receptor binding;cytokine activity