IRF7
protein-codinginterferon regulatory factor 7, the group of Interferon regulatory factors
Gene summary
This gene encodes interferon regulatory factor 7, a member of the interferon regulatory transcription factor (IRF) family. It has been shown to play a role in the transcriptional activation of virus-inducible cellular genes, including interferon beta chain genes. Inducible expression of IRF7 is largely restricted to lymphoid tissue. The encoded protein plays an important role in the innate immune response against DNA and RNA viruses. [provided by RefSeq, Jul 2021]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014597
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0014597
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious
Intervention: Allergy/Immunology/Infectious
Rationale: An individual has been described as developing severe respiratory distress following influenza infection, and awareness may allow preventive measures and rapid management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IRF7 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001572.5. 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 | 7 | 169 | 2 | 178 | ||
| missense | 1 | 354 | 12 | 367 | ||
| nonsense | 12 | 12 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 29 | 30 | |||
| splice donor/acceptor (+/-2bp) | 18 | 1 | 19 | |||
| Total | 0 | 2 | 420 | 182 | 2 | 606 |
Highest pathogenic variant AF is 0.000004177592
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001563.2 | 10 | MANE Select | |
| Ensembl | ENSP00000434009.2 | 10 | MANE Select | |
| RefSeq | NP_001427369.1 | 9 | Standard | |
| RefSeq | NP_001427371.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
- Influenza A - Homo sapiens (human)
- Cytosolic DNA-sensing pathway - Homo sapiens (human)
- Toll-like receptor signaling pathway - Homo sapiens (human)
- NOD-like receptor signaling pathway - Homo sapiens (human)
Biological Process
- negative regulation of transcription by RNA polymerase II
- regulation of adaptive immune response
- transcription by RNA polymerase II
- cellular response to DNA damage stimulus
- response to virus
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
- endosome membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000397566
- Coding exons
- 9
- Length
- 3447
- Individuals with no LoFs
- 125370
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 40
- Defined
- 125410
- p
- 0.000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.851 | 368 | 325 | 1.13 | 0.0000219 | 3196 |
| Missense (PolyPhen) | 111 | 124.87 | 0.8889 | 1311 | ||
| Synonymous | -2.84 | 193 | 149 | 1.30 | 0.0000108 | 1113 |
| Loss of Function | -0.374 | 21 | 19.2 | 1.09 | 8.25e-7 | 222 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00033 | 0.00031 | rare |
| Latino/Admixed American | 0.00019 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00028 | 0.00025 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88- independent pathway and the TLR-activated, MyD88-dependent pathway. Required during both the early and late phases of the IFN gene induction but is more critical for the late than for the early phase. Exists in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization where along with other coactivators it can activate transcription of the type I IFN and ISG genes. Can also play a role in regulating adaptive immune responses by inducing PSMB9/LMP2 expression, either directly or through induction of IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) and may play a role in the regulation of EBV latency. Can activate distinct gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages. {ECO:0000269|PubMed:11073981, ECO:0000269|PubMed:12374802, ECO:0000269|PubMed:15361868, ECO:0000269|PubMed:17404045}.;
- Disease
- DISEASE: Immunodeficiency 39 (IMD39) [MIM:616345]: A primary immunodeficiency causing severe, life-threatening acute respiratory distress upon infection with H1N1 influenza A. {ECO:0000269|PubMed:25814066}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.369
Intolerance Scores
- LoFtool
- 0.0953
- RVIS EVS
- -0.27
- RVIS percentile EVS
- 34.82
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.888
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |