IFNL4 interferon lambda 4 (gene/pseudogene) [Homo sapiens (human)] - Gene

Summary

Official Symbol: IFNL4provided by HGNC
Official Full Name: interferon lambda 4 (gene/pseudogene)provided by HGNC
Primary source: HGNC:HGNC:44480
See related: Ensembl:ENSG00000272395 MIM:615090; AllianceGenome:HGNC:44480
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: IFNAN
Summary: This gene is a polymorphic pseudogene which, in some humans, encodes the interferon (IFN) lambda 4 protein. Humans are polymorphic for the dinucleotide TT/deltaG allele. Compared to the ancestral state in non-human primates, the TT allele produces a frameshift in the coding region of this gene which is predicted to induce nonsense-mediated mRNA decay. This allele, and an allele in the first intron of this gene, have experienced a rapid increase in frequency and show indications of positive selection. The ancestral states of these alleles are associated with an impaired ability to clear hepatitis C virus. This gene, like other type III interferons (IFNs), interacts with the IFN lambda receptor complex (IFNLR) whose signaling is generally restricted to epithelial cells. This gene resides in a cluster of four type III IFN genes and at least two pseudogenes on chromosome 19q13.2. In general, interferons are produced in response to viral infection and block viral replication and propagation to uninfected cells by activating the JAK-STAT pathway and up-regulating antiviral genes. Multiple alternatively spliced transcripts have been described for this gene but their biological validity and protein coding status is still being ascertained. [provided by RefSeq, May 2017]
Annotation information: Annotation category: suggests misassembly; Note: Genetic polymorphisms result in both protein coding and non-coding alleles of this gene.
Expression: Low expression observed in reference dataset See more
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Genomic context

Location:: 19q13.2

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (39246314..39248856, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (42050583..42053125, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (39736954..39739496, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Variants of IFNL4 Gene in Amazonian and Northern Brazilian Populations.
Title: Variants of IFNL4 Gene in Amazonian and Northern Brazilian Populations.
IFNL4 Genotypes and Risk of Childhood Burkitt Lymphoma in East Africa.
Title: IFNL4 Genotypes and Risk of Childhood Burkitt Lymphoma in East Africa.
A Novel Inactive Isoform with a Restored Reading Frame Is Expressed from the Human Interferon Lambda 4 TT Allele at rs368234815.
Title: A Novel Inactive Isoform with a Restored Reading Frame Is Expressed from the Human Interferon Lambda 4 TT Allele at rs368234815.
Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV.
Title: Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV.
IFNL3/4 polymorphisms as a two-edged sword: An association with COVID-19 outcome.
Title: IFNL3/4 polymorphisms as a two-edged sword: An association with COVID-19 outcome.
No Association of IFNL4 Genotype With Opportunistic Infections and Cancers Among Men With Human Immunodeficiency Virus 1 Infection.
Title: No Association of IFNL4 Genotype With Opportunistic Infections and Cancers Among Men With Human Immunodeficiency Virus 1 Infection.
Relevance of HLA-DP/DQ and INF-lambda4 Polymorphisms to COVID-19 Outcomes.
Title: Relevance of HLA-DP/DQ and INF-λ4 Polymorphisms to COVID-19 Outcomes.
Polymorphisms of the MxA and MxB genes are associated with biochemical indices and viral subtypes in Yunnan HCV patients.
Title: Polymorphisms of the MxA and MxB genes are associated with biochemical indices and viral subtypes in Yunnan HCV patients.
Genetic polymorphisms in the IFNL4, MxA, and MxB genes were associated with biochemical index of chronic HBV patients from Yunnan, China.
Title: Genetic polymorphisms in the IFNL4, MxA, and MxB genes were associated with biochemical index of chronic HBV patients from Yunnan, China.
Genetic polymorphisms of Endoplasmic reticulum amino peptidase 1 (ERAP1) and Interferon lambda 4 (IFN-lambda4) in Egyptian patients with type 1 diabetes mellitus.
Title: Genetic polymorphisms of Endoplasmic reticulum amino peptidase 1 (ERAP1) and Interferon lambda 4 (IFN-λ4) in Egyptian patients with type 1 diabetes mellitus.

Submit: New GeneRIF Correction See all GeneRIFs (124)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Sofosbuvir response MedGen: CN238522 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of spontaneous resolution of hepatitis C virus infection: data from multiple cohorts. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cytokine activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables signaling receptor binding	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in cellular response to virus	NAS Non-traceable Author Statement more info	PubMed
involved_in defense response to virus	IBA Inferred from Biological aspect of Ancestor more info
involved_in defense response to virus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in innate immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of immune response	IEA Inferred from Electronic Annotation more info
involved_in type III interferon-mediated signaling pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in tyrosine phosphorylation of STAT protein	IDA Inferred from Direct Assay more info	PubMed
involved_in tyrosine phosphorylation of STAT protein	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: interferon lambda-4

Names: IFN-lambda-4; interferon, lambda 4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_055295.1 RefSeqGene

Range

5001..7543

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001276254.2 → NP_001263183.2 interferon lambda-4 precursor

See identical proteins and their annotated locations for NP_001263183.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents a protein coding transcript of this gene. Human populations are polymorphic for a frameshifting single nucleotide insertion in this transcript and thus transcripts with the alternate allele are non-coding.

Source sequence(s)

JN806234

UniProtKB/Swiss-Prot

K9M1A5, K9M1U5, K9M269, K9M2P7

UniProtKB/TrEMBL

A0A7R8C3A5

Conserved Domains (1) summary

pfam15177
Location:24 → 175

IL28A; Interleukin-28A

RNA

NR_074079.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2, non-coding) has a single frameshifting nucleotide insertion, compared to variant 1, which renders this transcript subject to nonsense-mediated mRNA decay (NMD). Human populations are polymorphic for a frameshifting single nucleotide insertion in this transcript and thus transcripts with the alternate allele are protein coding. The non-coding allele is represented in GRCh38.

Source sequence(s)

JN806227

Related

ENST00000606380.2