IRF9
interferon regulatory factor 9, the group of Interferon regulatory factors
Basic information
Region (hg38): 14:24161234-24168043
Previous symbols: [ "ISGF3G" ]
Links
Phenotypes
GenCC
Source:
- immunodeficiency 65, susceptibility to viral infections (Limited), mode of inheritance: Unknown
Clinical Genomic Database
Source:
| 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
- not_provided (207 variants)
- not_specified (35 variants)
- Immunodeficiency_65,_susceptibility_to_viral_infections (5 variants)
- IRF9-related_disorder (3 variants)
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. These statistics are base on transcript: NM_000006084.5. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 50 | 54 | ||||
| missense | 104 | 112 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 4 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 0 | 0 | 110 | 57 | 5 |
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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