IRF8
interferon regulatory factor 8, the group of Interferon regulatory factors |MicroRNA protein coding host genes
Basic information
Region (hg38): 16:85899116-85922606
Previous symbols: [ "ICSBP1" ]
Links
Phenotypes
GenCC
Source:
- immunodeficiency 32B (Moderate), mode of inheritance: AR
- Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency (Supportive), mode of inheritance: AD
- Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency (Strong), mode of inheritance: AD
- Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency (Strong), mode of inheritance: AD
- immunodeficiency 32B (Strong), mode of inheritance: AR
- immunodeficiency 32B (Moderate), mode of inheritance: AR
- immunodeficiency 32B (Moderate), mode of inheritance: AR
- Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Immunodeficiency 32A; Immunodeficiency 32B | AD | Allergy/Immunology/Infectious | Individuals with Immunodeficiency 32A (CD11C-positive/CD1C-positive dendritic cell deficiency) have been described as demonstrating disseminated BCG disease that was amenable to treatment, and preventive measures, as well as prompt treatment of infection, may be beneficial; Individuals with Immunodeficiency 32B (monocyte and dendritic cell deficiency) demonstrate immunodeficiency, with severe opportunistic infections, and prophylactic measures and prompt and aggressive treatment of infections may be beneficial; HSCT has been described | Allergy/Immunology/Infectious | 21524210 |
ClinVar
This is a list of variants' phenotypes submitted to
- Immunodeficiency_32B (371 variants)
- Mendelian_susceptibility_to_mycobacterial_diseases_due_to_partial_IRF8_deficiency (369 variants)
- not_provided (29 variants)
- Inborn_genetic_diseases (29 variants)
- IRF8-related_disorder (13 variants)
- not_specified (8 variants)
- Inherited_Immunodeficiency_Diseases (1 variants)
- Esophageal_atresia/tracheoesophageal_fistula (1 variants)
- See_cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the IRF8 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002163.4. 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 | 114 | 127 | ||||
| missense | 176 | 188 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 7 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 1 | 3 | 189 | 123 | 8 |
Highest pathogenic variant AF is 0.0000065674544
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| IRF8 | protein_coding | protein_coding | ENST00000268638 | 8 | 23807 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.948 | 0.0519 | 125740 | 0 | 5 | 125745 | 0.0000199 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.19 | 220 | 275 | 0.799 | 0.0000199 | 2775 |
| Missense in Polyphen | 70 | 133.74 | 0.5234 | 1352 | ||
| Synonymous | -1.67 | 135 | 112 | 1.20 | 0.00000823 | 814 |
| Loss of Function | 3.81 | 3 | 22.5 | 0.133 | 0.00000121 | 230 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000564 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000264 | 0.0000264 |
| Middle Eastern | 0.0000564 | 0.0000544 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Plays a role as a transcriptional activator or repressor (PubMed:25122610). Specifically binds to the upstream regulatory region of type I IFN and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)). Plays a negative regulatory role in cells of the immune system. Involved in CD8(+) dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF8 and activation of genes (By similarity). Positively regulates macroautophagy in dendritic cells (PubMed:29434592). {ECO:0000250|UniProtKB:P23611, ECO:0000269|PubMed:25122610, ECO:0000269|PubMed:29434592}.;
- Disease
- DISEASE: Immunodeficiency 32A (IMD32A) [MIM:614893]: An immunologic disorder characterized by abnormal peripheral blood myeloid phenotype with a marked loss of CD11C-positive/CD1C dendritic cells, resulting in selective susceptibility to mycobacterial infections. {ECO:0000269|PubMed:21524210}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Immunodeficiency 32B (IMD32B) [MIM:226990]: An autosomal recessive primary immunodeficiency characterized by monocyte and dendritic cell deficiency, myeloproliferation, and susceptibility to severe opportunistic infections, including disseminated BCG infection and oral candidiasis. {ECO:0000269|PubMed:21524210, ECO:0000269|PubMed:25122610}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Pertussis - Homo sapiens (human);Vitamin D Receptor Pathway;Development of pulmonary dendritic cells and macrophage subsets;Type II interferon signaling (IFNG);Cytokine Signaling in Immune system;Immune System;Interferon gamma signaling;Interferon alpha/beta signaling;GMCSF-mediated signaling events;Validated targets of C-MYC transcriptional repression;Interferon Signaling
(Consensus)
Recessive Scores
- pRec
- 0.449
Intolerance Scores
- loftool
- 0.174
- rvis_EVS
- -0.18
- rvis_percentile_EVS
- 40.45
Haploinsufficiency Scores
- pHI
- 0.111
- hipred
- Y
- hipred_score
- 0.851
- ghis
- 0.542
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.991
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Irf8
- Phenotype
- homeostasis/metabolism phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; 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); neoplasm; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype;
Zebrafish Information Network
- Gene name
- irf8
- Affected structure
- neutrophil
- Phenotype tag
- abnormal
- Phenotype quality
- increased amount
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;phagocytosis;autophagy;immune response;myeloid cell differentiation;positive regulation of interferon-gamma production;positive regulation of interleukin-12 production;defense response to bacterium;defense response to protozoan;negative regulation of growth of symbiont in host;positive regulation of transcription by RNA polymerase II;interferon-gamma-mediated signaling pathway;type I interferon signaling pathway;cellular response to lipopolysaccharide;cellular response to interferon-gamma
- 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 repressor activity, RNA polymerase II-specific;protein binding