IFNA4

protein-coding

interferon alpha 4, the group of Interferons

Gene summary

Predicted to enable cytokine activity and type I interferon receptor binding activity. Predicted to be involved in several processes, including lymphocyte activation involved in immune response; response to exogenous dsRNA; and type I interferon-mediated signaling pathway. Predicted to be located in extracellular region. Predicted to be active in obsolete extracellular space. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_021068.4

Inheritance

—

ClinVar variants

U:33B:5

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e —

Max pathogenic AF

—

Genomic locus

chr9:21,186,618-21,187,587

External References & Databases

Ensembl (ENSG00000236637)

Transcript & Mutation Effects

hg38 • Region Span ~1.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IFNA4 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 34

not providedTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Multisystem inflammatory syndrome in childrenTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021068.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense			32 clinvar	2 clinvar	1 clinvar	35
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	33	4	1	38

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021068.4	RefSeq	NP_066546.1	1	MANE Select
ENST00000421715.3	Ensembl	ENSP00000412897.1	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

PI3K-Akt signaling pathway - Homo sapiens (human)
Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
Jak-STAT signaling pathway - Homo sapiens (human)
Influenza A - Homo sapiens (human)
Autoimmune thyroid disease - Homo sapiens (human)

Biological Process

adaptive immune response
T cell activation involved in immune response
natural killer cell activation involved in immune response
humoral immune response
blood coagulation

Molecular Function

cytokine activity
type I interferon receptor binding
protein binding

Cellular Component

extracellular region
extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000421715
Coding exons: 1
Length: 982

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.65	140	94.8	1.48	0.00000434	1240
Missense (PolyPhen)		32	19.667	1.6271		294
Synonymous	-1.49	52	40.0	1.30	0.00000207	364
Loss of Function

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Produced by macrophages, IFN-alpha have antiviral activities. Interferon stimulates the production of two enzymes: a protein kinase and an oligoadenylate synthetase.;

Intolerance Scores

LoFtool: 0.857
RVIS EVS: 1.06
RVIS percentile EVS: 91.47

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0139

Gene Damage Prediction

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