Information on IRF3
Basic details
Alt. symbols: IIAE7
Approved name: interferon regulatory factor 3
Alt. names: interferon regulatory factor 3
Location: 19q13.33: 49659569 - 49665875 (-)
Gene type: protein_coding, 31 transcripts.
Scores: LoFtool: 0.228000 | pLI: 0.00321742 | LOEUF: 0.917
Normal function
IRF3 encodes a member of the interferon regulatory transcription factor (IRF) family that is a key transcriptional regulator of type I interferon (IFN)-dependent immune responses. Therefore, IRF3 plays a critical role in the innate immune response against DNA and RNA viruses. This protein is found in an inactive cytoplasmic form that upon serine/threonine phosphorylation forms a complex with CREBBP. This complex translocates to the nucleus and activates the transcription of interferons alpha (IFN-alpha) and beta (IFN-beta), as well as other interferon-induced (ISG) genes, by binding to an interferon-stimulated response element (ISRE) in their promoters. IRF3 can activate distinct gene expression programs and induce significant apoptosis in primary macrophages.
Dysfunction and disease
To date, 2 heterozygosity pathogenic missense IRF3 variants (R285Q, A277T) have been associated with susceptibility to herpes-specific infection-induced acute encephalopathy 7 (IIAE7) [MIM:616532] in 2 unrelated individuals (PMID: 26216125, 26513235). Infection-induced acute encephalopathy is a rare complication of human herpesvirus 1 (HHV-1) infection, occurring only in a small minority of HHV-1 infected individuals. It is characterized by hemorrhagic necrosis of parts of the temporal and front al lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. IIAE7 is inherited in an autosomal dominant mode, although with incomplete penetrance, since mutation carriers may not develop this condition (PMID: 26216125). The authors showed that the mutated (R285Q) IRF3 protein was unable to be phosphorylated at residue S386, therefore inhibiting self-dimerization and subsequent activation, ablating the IFN-mediated response upon HSV-1 infection. [Load More]
[Reviewed by Xiao P. Peng on 2021-06-07 09:42:32]
Associated conditions
| Acronym | Condition's_name | MOI | Mode_of_action |
OMIM_ID | No.cases |
|---|---|---|---|---|---|
IIAE7 |
Susceptibility to acute infection-induced encephalopathy type 7 | AD |
616532 |
0 (0 fams) |
Please mind that full curation (inclusion of all published patients) of this gene has not started yet. Please contact us if you want to volunteer.
Transcripts of IRF3
| Name | ENSEMBL_ID | LRG_ID | CCDS_ID | MANE | Transcript.type | Exons | Canonical | CDS_length | REFSEQ_ID |
|---|---|---|---|---|---|---|---|---|---|
| 223 | ENST00000599223.5 | CCDS56099 | protein_coding | 7 | No | 1055 | NM_001197124 | ||
| 201 | ENST00000309877.11 | CCDS12775 | protein_coding | 7 | No | 1691 | XM_047438783 | ||
| 202 | ENST00000377135.8 | CCDS59408 | protein_coding | 7 | No | 1442 | NM_001197125 | ||
| 222 | ENST00000599144.5 | CCDS59408 | protein_coding | 6 | No | 1117 | NM_001197126 | ||
| 203 | ENST00000377139.8 | CCDS12775 | Select | protein_coding | 8 | Yes | 1595 | NM_001197123,NM_001571 | |
| 221 | ENST00000598808.5 | CCDS59408 | protein_coding | 8 | No | 1468 | XM_024451494 | ||
| 225 | ENST00000600022.5 | CCDS59407 | protein_coding | 6 | No | 882 | NM_001197127 | ||
| 228 | ENST00000601291.5 | CCDS59409 | protein_coding | 8 | No | 1556 | NM_001197122 | ||
| 213 | ENST00000596765.5 | CCDS59407 | protein_coding | 5 | No | 710 | NM_001197128 |
Published variants
Found 1 variants
| Var.name | Exon/Intron | cDNA_pos. | CDS_change | Prot.change | Var.type | Var.class. | Patients |
|---|---|---|---|---|---|---|---|
| T75A |
EX3 | 403 | c.223A>G | p.Thr75Ala | missense_variant | Uncertain significance | 1 |
Please mind that full curation (inclusion of all published variants) of this gene has not started yet. Please contact us if you want to volunteer.
Diagnostic pitfalls & paradigms
Considerations to take into account when analyzing this gene
| Year | Paradigm ⓘ | PMID | Notes |
|---|---|---|---|
| - | Regions of Homology | - | |
| - | Cryptic splicing | - | Unreported or not recorded in our DB. |
| - | Uniparental disomy | - | Unreported or not recorded in our DB. |
| - | Mosaicism | - | Unreported or not recorded in our DB. |
| - | Incomplete penetrance | - | Unreported or not recorded in our DB. |
| - | Di-/oligo-genic inheritance | - | Unreported or not recorded in our DB. |
| - | Somatic reversion | - | Unreported or not recorded in our DB. |
References linked to variants in IRF3
| ID | Year | Title | Journal | PMID | Variants |
|---|---|---|---|---|---|
| 118 |
2021 | Establishing the Molecular Diagnoses in a Cohort of 291 Pati... | Front. Immunol. | 34975878 |
1 |