IFNA4 interferon alpha 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: IFNA4provided by HGNC
Official Full Name: interferon alpha 4provided by HGNC
Primary source: HGNC:HGNC:5425
See related: Ensembl:ENSG00000236637 MIM:147564; AllianceGenome:HGNC:5425
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: INFA4; IFN-alpha4a
Summary: Predicted to enable cytokine activity and type I interferon receptor binding activity. Predicted to be involved in several processes, including B cell activation; lymphocyte activation involved in immune response; and response to exogenous dsRNA. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Dec 2024]
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Genomic context

Location:: 9p21.3

Exon count:: 1

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (21186618..21187587, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (21200472..21201441, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (21186617..21187586, complement)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The mechanism of action of Spi-B in the transcriptional activation of the interferon-alpha4 gene.
Title: The mechanism of action of Spi-B in the transcriptional activation of the interferon-α4 gene.
Heterozygous IFNA4 variants is a cause of impaired function and CD-susceptibility genes in Chinese individuals from multiple center based study.
Title: Exome sequencing identifies novel compound heterozygous IFNA4 and IFNA10 mutations as a cause of impaired function in Crohn's disease patients.
Observational study of gene-disease association. (HuGE Navigator)
Title: Dengue hemorrhagic fever is associated with polymorphisms in JAK1.
suppression of IFN signaling and IFN production by SOC3 occurs during HSV-1 infection
Title: Induction of suppressor of cytokine signaling-3 by herpes simplex virus type 1 contributes to inhibition of the interferon signaling pathway.
Alpha interferon suppresses the cyclin D3 and cdc25A genes, leading to a reversible G0-like arrest.
Title: Alpha interferon suppresses the cyclin D3 and cdc25A genes, leading to a reversible G0-like arrest.

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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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Cytokines induced in vitro by HIV-1 gp120 in normal peripheral blood mononuclear cells (PBMC) include interferon-alpha (IFN-alpha) and IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-10, IL-1 alpha and IL-1 beta	PubMed
	env	HIV-1 gp120-mediated inhibition of IFN-alpha production involves CD4 and BDCA2 in plasmacytoid dendritic cells	PubMed
	env	HIV-1 gp120 inhibits CpG-A-induced secretion of IFN-alpha and IFN-beta proteins in PBMCs	PubMed
	env	TLR-9-induced IFN-alpha production is inhibited by both monomeric and trimeric HIV-1 gp120 in plasmacytoid dendritic cells (pDC)	PubMed
	env	HIV-1 gp120-specific cell mediated cytotoxicity (CMC) is enhanced by IL-2 or the combination of IL-2 and IFN-alpha	PubMed
	env	Interferon-alpha- and interferon-gamma-induced sialoadhesin-expressing monocytes adsorb HIV-1 through interaction with the sialic acid residues on the viral envelope glycoprotein gp120	PubMed
	env	Treatment of cells with IFN reduces HIV-1 gp120 incorporation, as well as HIV-1 envelope-mediated incorporation of ICAM-1, into virions resulting in viruses that exhibit a significantly decreased ability to become bound to CD4+ target cells	PubMed
	env	Sulfate containing galactolipids such as sulfatides on responder cells may be part of the HIV-1 gp120-membrane complex that initiates the induction of interferon (IFN)	PubMed
	env	Interaction of HIV-1 gp120 with cell-associated CD4 leads to the induction of IFN alpha; preincubation of cells with anti-CD4 or the presence of soluble CD4 during incubation inhibits IFN alpha induction	PubMed
	env	HIV-1 gp41 or gp120 synthetic peptides induce the production of interleukin (IL)-1 and tumor necrosis factor (TNF); in contrast, gp41 or gp120 synthetic peptides are able to depress the production of interferon (IFN)-alpha, IFN-gamma, and IL-2	PubMed
Envelope surface glycoprotein gp160, precursor	env	IFN alpha treated effector clones (gp120+CD8+ HPB-ALL/HIV) simultaneously downregulate CD8 expression and upregulate expression of both major histocompatibility antigen complex class I (MHC-I) and HIV-1 gp120/gp160	PubMed
Envelope transmembrane glycoprotein gp41	env	HIV-1 gp41 selectively enhances MHC class I, ICAM-1, IFN-alpha, IFN-beta, and IFN-omega expression in H9 cells	PubMed
Nef	nef	HIV-1 isolate R3A Nef mutants G2, WL58, RR106, LL165, E160NNSLL165, and DD175 fail to induce release of IFN-alpha in pDCs, suggesting that the Nef function responsible for CD4 downregulation is crucial for pDCs stimulation by R3A	PubMed
	nef	A highly pathogenic HIV-1 isolate R3A induces release of IFN-alpha in a Nef-dependent manner in plasmacytoid dendritic cells (pDCs)	PubMed
Pr55(Gag)	gag	HIV-1 Gag virus-like particles induce production of IFN-alpha in human monocyte-derived dendritic cells, which upregulates expression of APOBEC3G/F and increases incorporation of APOBEC3G/F into nascent virions	PubMed
	gag	Interferon alpha inhibits the release of HIV-1 Gag/capsid proteins from infected cells by inducing changes in posttranslational modifications of Gag proteins	PubMed
Tat	tat	HIV-1 Tat inhibits CpG-A-induced secretion of IFN-alpha and IFN-beta proteins in PBMCs	PubMed
	tat	HIV-1 Tat upregulates IFN-alpha secretion by macrophages, an effect that augments MIP-1alpha and MIP-1beta secretion and induces immunosuppression of uninfected T cells	PubMed
	tat	IFN treatment significantly reduces HIV-1 mRNA levels from a Tat defective provirus, suggesting Tat can overcome the inhibitory effects of IFN on HIV-1 replication	PubMed
	tat	HIV-1 Tat enhances translation of the interferon-inducible enzymes 2-5A synthetase and dsRNA-dependent protein kinase, suggesting interaction of Tat with interferons during HIV-1 replication	PubMed
Vif	vif	IFN-alpha enhances APOBEC3G expression and inhibits suppression of APOBEC3G by HIV-1 Vif	PubMed
Vpr	vpr	Synthetic HIV-1 Vpr substantially inhibits type I IFN-alpha production by pDCs without inducing apoptosis in pDCs	PubMed
Vpu	vpu	IFNalpha/ribavirin treatment in vivo induces APOBEC3G, APOBEC3F, and BST-2 expression and results in hyper-mutations in viral genome and A11G/S61A mutations in HIV-1 Vpu. These two mutations in Vpu enhances the interaction between BST-2 and Vpu	PubMed
	vpu	IFNalpha induces retention of viral particles on the surface of fibroblasts, T cells, or primary lymphocytes infected with HIV-1 lacking the Vpu protein. HIV-1 Vpu counteracts the IFNalpha-induced retention of virus particles	PubMed
reverse transcriptase	gag-pol	Infection of IFN-alpha-treated primary macrophages, dendritic cells, and activated PBLs by HIV-2 and SIVmac is inhibited more potently than HIV-1 and the differential inhibition by IFN-alpha is caused by defects of vDNA accumulation by RT activity	PubMed
	gag-pol	IFN-alpha interferes with the initiation of HIV-1 reverse transcription resulting in a significant reduction in the relative levels of HIV-1 proviral DNA	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:482091

SGC35314 (e-PCR)
- UniSTS:74318

IFNA10_134 (e-PCR)
- UniSTS:277346

IFNA4_1232 (e-PCR)
- UniSTS:277351

NoName (e-PCR)
- UniSTS:484035

IFNA17_1865 (e-PCR)
- UniSTS:280773

RH47035 (e-PCR)
- UniSTS:6113

RH69109 (e-PCR)
- UniSTS:19700

NoName (e-PCR)
- UniSTS:486143

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cytokine activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables type I interferon receptor binding	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in B cell activation involved in immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in T cell activation involved in immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in adaptive immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to virus	NAS Non-traceable Author Statement more info	PubMed
involved_in defense response to virus	IEA Inferred from Electronic Annotation more info
involved_in humoral immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in natural killer cell activation involved in immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to exogenous dsRNA	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to virus	TAS Traceable Author Statement more info	PubMed
involved_in type I interferon-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in type I interferon-mediated signaling pathway	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: interferon alpha-4

Names: IFN-alpha-4; interferon alpha-4B; interferon alpha-76; interferon alpha-M1

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.