IRF7

interferon regulatory factor 7, the group of Interferon regulatory factors

Basic information

Region (hg38): 11:612553-615983

Links

ENSG00000185507 ∙ NCBI:3665 ∙ OMIM:605047 ∙ HGNC:6122 ∙ Uniprot:Q92985 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 39 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 39	AR	Allergy/Immunology/Infectious	An individual has been described as developing severe respiratory distress following influenza infection, and awareness may allow preventive measures and rapid management	Allergy/Immunology/Infectious	25814066

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IRF7 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IRF7 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			7	139	7	153
missense			279	5	2	286
nonsense			9			9
start loss						0
frameshift			19			19
inframe indel			3			3
splice donor/acceptor (+/-2bp)			8			8
splice region			20	14	4	38
non coding			6	69	13	88
Total	0	0	331	213	22

Variants in IRF7

This is a list of pathogenic ClinVar variants found in the IRF7 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-612604-TGGGCTGCTCCAGCTTTCTGGAGTTCTCATTAGACTGGGTTCTAGGC-T		Immunodeficiency 39	Uncertain significance (Aug 27, 2022)
11-612649-G-A		Immunodeficiency 39	Uncertain significance (Oct 26, 2022)
11-612651-G-A		Immunodeficiency 39	Likely benign (Jul 26, 2023)
11-612667-A-G		Immunodeficiency 39	Uncertain significance (Jul 17, 2023)
11-612678-C-G		Immunodeficiency 39	Uncertain significance (May 19, 2023)
11-612680-C-G		Immunodeficiency 39	Uncertain significance (Apr 10, 2021)
11-612680-C-T		Immunodeficiency 39	Uncertain significance (Jan 25, 2024)
11-612681-G-A		Immunodeficiency 39	Likely benign (Nov 04, 2020)
11-612681-G-T		Immunodeficiency 39	Likely benign (Oct 03, 2023)
11-612686-C-T		Immunodeficiency 39	Uncertain significance (Oct 03, 2019)
11-612687-G-A		Immunodeficiency 39	Likely benign (Jan 20, 2024)
11-612689-C-T		Immunodeficiency 39	Uncertain significance (Sep 26, 2022)
11-612696-G-T		Immunodeficiency 39	Uncertain significance (May 22, 2023)
11-612704-C-T		Immunodeficiency 39 • not specified	Conflicting classifications of pathogenicity (Dec 26, 2023)
11-612705-G-A		Immunodeficiency 39 • IRF7-related disorder	Likely benign (Feb 06, 2022)
11-612705-G-T		Immunodeficiency 39	Uncertain significance (Aug 26, 2021)
11-612713-G-A		Immunodeficiency 39	Likely benign (Apr 23, 2022)
11-612723-G-A		Immunodeficiency 39	Likely benign (Mar 18, 2022)
11-612734-T-C		Immunodeficiency 39	Uncertain significance (Sep 17, 2023)
11-612738-C-T		Immunodeficiency 39	Uncertain significance (Feb 06, 2023)
11-612742-G-C		Immunodeficiency 39	Uncertain significance (Sep 16, 2022)
11-612747-C-T		Immunodeficiency 39	Likely benign (Nov 08, 2023)
11-612751-C-T		Immunodeficiency 39	Uncertain significance (Apr 23, 2023)
11-612757-C-A		Immunodeficiency 39	Uncertain significance (Dec 27, 2023)
11-612761-G-C		not specified	Uncertain significance (May 30, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IRF7	protein_coding	protein_coding	ENST00000397566	9	3447

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.45e-15	0.00656	125370	0	40	125410	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.851	368	325	1.13	0.0000219	3196
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000518	0.000495
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000278	0.000247
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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.
• Pathway: 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);Viral carcinogenesis - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;Apoptosis;Structural Pathway of Interleukin 1 (IL-1);Apoptotic Signaling Pathway;TLR4 Signaling and Tolerance;Toll-like Receptor Signaling;RIG-I-like Receptor Signaling;Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;Senescence and Autophagy in Cancer;Toll-like Receptor Signaling Pathway;Toll Like Receptor 7/8 (TLR7/8) Cascade;TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling;the information processing pathway at the ifn beta enhancer;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;TICAM1-dependent activation of IRF3/IRF7;Toll Like Receptor 3 (TLR3) Cascade;Toll-Like Receptors Cascades;TRAF6 mediated IRF7 activation;DDX58/IFIH1-mediated induction of interferon-alpha/beta;DEx/H-box helicases activate type I IFN and inflammatory cytokines production ;Innate Immune System;Immune System;TRAF3-dependent IRF activation pathway;MyD88 dependent cascade initiated on endosome;Interferon gamma signaling;Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon;Cytosolic sensors of pathogen-associated DNA ;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;Interferon alpha/beta signaling;Interferon Signaling;Regulation of nuclear SMAD2/3 signaling (Consensus)

Recessive Scores

• pRec: 0.369

Intolerance Scores

• loftool: 0.0953
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.82

Haploinsufficiency Scores

• pHI: 0.135
• hipred: Y
• hipred_score: 0.566
• ghis: 0.539

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.888

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Irf7
• Phenotype: immune system 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); hematopoietic system phenotype; homeostasis/metabolism phenotype

Gene ontology

• 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;immunoglobulin mediated immune response;establishment of viral latency;regulation of type I interferon production;positive regulation of type I interferon production;interferon-alpha production;interferon-beta production;positive regulation of interferon-alpha production;positive regulation of interferon-beta production;regulation of MyD88-dependent toll-like receptor signaling pathway;regulation of MyD88-independent toll-like receptor signaling pathway;TRIF-dependent toll-like receptor signaling pathway;MDA-5 signaling pathway;innate immune response;type I interferon biosynthetic process;regulation of monocyte differentiation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;regulation of immune response;defense response to virus;interferon-gamma-mediated signaling pathway;type I interferon signaling pathway;positive regulation of type I interferon-mediated signaling pathway;negative regulation of macrophage apoptotic process
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;endosome membrane
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;protein binding