IRF9

interferon regulatory factor 9, the group of Interferon regulatory factors

Basic information

Region (hg38): 14:24161234-24168043

Previous symbols: [ "ISGF3G" ]

Links

ENSG00000213928 ∙ NCBI:10379 ∙ OMIM:147574 ∙ HGNC:6131 ∙ Uniprot:Q00978 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 65, susceptibility to viral infections (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 65	AR	Allergy/Immunology/Infectious	Individuals have been described with early-onset severe and recurrent viral infections, and antiinfectious prophylaxis (intravenous immunoglobulin has been described) and early and aggressive treatment of infections may be beneficial; live attenuated vaccines have been reported as resulting in poor outcomes in patients with impaired interferon responses	Allergy/Immunology/Infectious	30143481; 30826365

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IRF9 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IRF9 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				44	4	48
missense			84	2	1	87
nonsense			1			1
start loss						0
frameshift			4			4
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region			8	11	1	20
non coding			1	27	1	29
Total	0	0	92	73	6

Variants in IRF9

This is a list of pathogenic ClinVar variants found in the IRF9 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-24162152-C-T		not specified	Uncertain significance (Dec 21, 2023)
14-24162163-C-T			Uncertain significance (Jul 14, 2022)
14-24162172-C-A			Likely benign (Aug 14, 2024)
14-24162195-G-A			Benign (Feb 02, 2025)
14-24162198-G-A			Likely benign (Apr 03, 2022)
14-24162209-G-C			Uncertain significance (Oct 29, 2024)
14-24162211-G-A		not specified	Uncertain significance (Dec 10, 2024)
14-24162212-G-A			Uncertain significance (Jul 23, 2022)
14-24162222-C-T			Likely benign (Feb 10, 2022)
14-24162223-G-A			Uncertain significance (Oct 18, 2023)
14-24162228-G-A			Likely benign (Dec 18, 2024)
14-24162231-C-T		IRF9-related disorder	Benign/Likely benign (Jan 25, 2025)
14-24162243-A-T			Benign (Jan 09, 2025)
14-24162248-A-G			Uncertain significance (Feb 14, 2024)
14-24162249-G-A			Likely benign (Oct 14, 2024)
14-24162251-C-T			Uncertain significance (Aug 10, 2023)
14-24162252-C-T			Benign (Jan 29, 2025)
14-24162276-T-C			Likely benign (Feb 19, 2024)
14-24162291-C-T			Likely benign (Oct 28, 2022)
14-24162296-G-A		Immunodeficiency 65, susceptibility to viral infections	Uncertain significance (Jun 28, 2024)
14-24162311-C-G			Uncertain significance (May 23, 2024)
14-24162330-A-G			Uncertain significance (Jun 18, 2021)
14-24162333-G-A			Likely benign (Jul 20, 2021)
14-24162344-A-C			Likely benign (Jul 04, 2021)
14-24162947-C-T			Likely benign (Apr 17, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IRF9	protein_coding	protein_coding	ENST00000396864	8	5513

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.608	0.392	125738	0	6	125744	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.57	161	228	0.707	0.0000128	2551
Missense in Polyphen		48	93.605	0.51279		1036
Synonymous	1.26	73	88.0	0.830	0.00000483	778
Loss of Function	3.36	4	20.4	0.196	0.00000113	204

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000611	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000447	0.0000440
Middle Eastern	0.0000611	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor that mediates signaling by type I IFNs (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. IRF9/ISGF3G associates with the phosphorylated STAT1:STAT2 dimer to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state.
• Pathway: Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Influenza A - Homo sapiens (human);Necroptosis - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Measles - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Type III interferon signaling;The human immune response to tuberculosis;Interferon type I signaling pathways;Type II interferon signaling (IFNG);Cytokine Signaling in Immune system;Immune System;IFN alpha signaling;bone remodeling;Interferon gamma signaling;IFN-gamma pathway;Interferon alpha/beta signaling;Interferon Signaling (Consensus)

Intolerance Scores

• loftool: 0.147
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.91

Haploinsufficiency Scores

• pHI: 0.485
• hipred: Y
• hipred_score: 0.594
• ghis: 0.516

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.861

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Irf9
• Phenotype: skeleton phenotype; immune system phenotype; cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;cell surface receptor signaling pathway;defense response to virus;interferon-gamma-mediated signaling pathway;type I interferon signaling pathway
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding