IRF1
interferon regulatory factor 1, the group of Interferon regulatory factors
Basic information
Region (hg38): 5:132440440-132508719
Links
Phenotypes
GenCC
Source:
No genCC data.
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Immunodeficiency 117, mycobacteriosis, autosomal recessive | AR | Allergy/Immunology/Infectious | Individuals have been described as being of increased risk of mycobacterial infections, including disseminated disease after BCG vaccination, and awareness may allow preventative measures as well as early and aggressive management of infection | Allergy/Immunology/Infectious | 36736301 |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the IRF1 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 | 2 | |||||
| missense | 5 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 11 | 12 | ||||
| Total | 0 | 0 | 5 | 1 | 13 |
Variants in IRF1
This is a list of pathogenic ClinVar variants found in the IRF1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-132484052-G-A | not specified | Uncertain significance (Jun 29, 2022) | ||
| 5-132484106-T-C | not specified | Benign (Jan 24, 2024) | ||
| 5-132484108-G-A | not specified | Benign (Jan 24, 2024) | ||
| 5-132484229-C-A | not specified | Benign (Jan 24, 2024) | ||
| 5-132484278-T-C | not specified | Benign (Jan 24, 2024) | ||
| 5-132484285-C-T | not specified | Benign (Jan 24, 2024) | ||
| 5-132484497-G-T | not specified | Uncertain significance (May 06, 2024) | ||
| 5-132484499-T-C | not provided (-) | |||
| 5-132484583-C-A | not specified | Benign (Jan 24, 2024) | ||
| 5-132485554-G-A | not specified | Benign (Jan 24, 2024) | ||
| 5-132486174-T-G | not specified | Benign (Jan 24, 2024) | ||
| 5-132486338-C-T | not specified | Uncertain significance (May 01, 2024) | ||
| 5-132486363-T-C | not specified | Benign (Jan 24, 2024) | ||
| 5-132486380-A-G | not specified | Benign (Jan 24, 2024) | ||
| 5-132486441-T-C | not specified | Benign (Jan 24, 2024) | ||
| 5-132486532-T-C | not specified | Benign (Jan 24, 2024) | ||
| 5-132486577-A-G | not specified | Uncertain significance (Aug 02, 2021) | ||
| 5-132486667-G-A | not specified | Uncertain significance (Jul 28, 2021) | ||
| 5-132486696-G-A | IRF1-related disorder | Likely benign (Jun 10, 2019) | ||
| 5-132486824-G-A | Immunodeficiency 117 | Pathogenic (Jan 10, 2024) | ||
| 5-132486835-G-A | not specified | Uncertain significance (Jun 13, 2024) | ||
| 5-132486961-C-G | not specified | Uncertain significance (May 26, 2022) | ||
| 5-132486973-G-C | Benign (Jun 20, 2018) | |||
| 5-132487031-T-C | not specified | Uncertain significance (Dec 19, 2023) | ||
| 5-132487827-A-G | not specified | Benign (Jan 24, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| IRF1 | protein_coding | protein_coding | ENST00000245414 | 9 | 9190 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.991 | 0.00910 | 125715 | 0 | 3 | 125718 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.35 | 92 | 181 | 0.508 | 0.00000960 | 2149 |
| Missense in Polyphen | 23 | 69.727 | 0.32986 | 803 | ||
| Synonymous | 0.608 | 63 | 69.4 | 0.907 | 0.00000389 | 593 |
| Loss of Function | 3.77 | 1 | 18.5 | 0.0541 | 9.77e-7 | 208 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000123 | 0.000123 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000884 | 0.00000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses. These include the regulation of IFN and IFN-inducible genes, host response to viral and bacterial infections, regulation of many genes expressed during hematopoiesis, inflammation, immune responses and cell proliferation and differentiation, regulation of the cell cycle and induction of growth arrest and programmed cell death following DNA damage. Stimulates both innate and acquired immune responses through the activation of specific target genes and can act as a transcriptional activator and repressor regulating target genes by binding to an interferon- stimulated response element (ISRE) in their promoters. Its target genes for transcriptional activation activity include: genes involved in anti-viral response, such as IFN-alpha/beta, DDX58/RIG-I, TNFSF10/TRAIL, OAS1/2, PIAS1/GBP, EIF2AK2/PKR and RSAD2/viperin; antibacterial response, such as NOS2/INOS; anti- proliferative response, such as p53/TP53, LOX and CDKN1A; apoptosis, such as BBC3/PUMA, CASP1, CASP7 and CASP8; immune response, such as IL7, IL12A/B and IL15, PTGS2/COX2 and CYBB; DNA damage responses and DNA repair, such as POLQ/POLH; MHC class I expression, such as TAP1, PSMB9/LMP2, PSME1/PA28A, PSME2/PA28B and B2M and MHC class II expression, such as CIITA. Represses genes involved in anti-proliferative response, such as BIRC5/survivin, CCNB1, CCNE1, CDK1, CDK2 and CDK4 and in immune response, such as FOXP3, IL4, ANXA2 and TLR4. Stimulates p53/TP53-dependent transcription through enhanced recruitment of EP300 leading to increased acetylation of p53/TP53. Plays an important role in immune response directly affecting NK maturation and activity, macrophage production of IL12, Th1 development and maturation of CD8+ T-cells. Also implicated in the differentiation and maturation of dendritic cells and in the suppression of regulatory T (Treg) cells development. Acts as a tumor suppressor and plays a role not only in antagonism of tumor cell growth but also in stimulating an immune response against tumor cells. {ECO:0000269|PubMed:15226432, ECO:0000269|PubMed:15509808, ECO:0000269|PubMed:17516545, ECO:0000269|PubMed:17942705, ECO:0000269|PubMed:18084608, ECO:0000269|PubMed:18497060, ECO:0000269|PubMed:18641303, ECO:0000269|PubMed:19404407, ECO:0000269|PubMed:19851330, ECO:0000269|PubMed:21389130, ECO:0000269|PubMed:22200613, ECO:0000269|PubMed:22367195}.;
- Disease
- DISEASE: Gastric cancer (GASC) [MIM:613659]: A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. {ECO:0000269|PubMed:10395927, ECO:0000269|PubMed:9679752}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
- Pathway
- Pertussis - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Prolactin Signaling Pathway;Apoptosis;JAK-STAT;Apoptotic Signaling Pathway;IL-6 signaling pathway;The human immune response to tuberculosis;Senescence and Autophagy in Cancer;Type II interferon signaling (IFNG);the information processing pathway at the ifn beta enhancer;Cytokine Signaling in Immune system;IL12 signaling mediated by STAT4;Factors involved in megakaryocyte development and platelet production;Immune System;Glucocorticoid receptor regulatory network;Hemostasis;Interferon gamma signaling;IFN-gamma pathway;Interferon alpha/beta signaling;Interferon Signaling;Regulation of Telomerase;IL6-mediated signaling events
(Consensus)
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- loftool
- 0.268
- rvis_EVS
- -0.01
- rvis_percentile_EVS
- 53.19
Haploinsufficiency Scores
- pHI
- 0.723
- hipred
- Y
- hipred_score
- 0.794
- ghis
- 0.510
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Irf1
- Phenotype
- neoplasm; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; endocrine/exocrine gland 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); cellular phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- regulation of adaptive immune response;transcription by RNA polymerase II;apoptotic process;cell cycle arrest;blood coagulation;negative regulation of cell population proliferation;positive regulation of type I interferon production;positive regulation of interferon-beta production;regulation of MyD88-dependent toll-like receptor signaling pathway;cellular response to interferon-beta;CD8-positive, alpha-beta T cell differentiation;positive regulation of interleukin-12 biosynthetic process;regulation of innate immune response;negative regulation of regulatory T cell differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;defense response to virus;regulation of cell cycle;interferon-gamma-mediated signaling pathway;type I interferon signaling pathway;cellular response to mechanical stimulus;regulation of CD8-positive, alpha-beta T cell proliferation
- Cellular component
- nuclear chromatin;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 activator activity, RNA polymerase II-specific;DNA binding;protein binding