IRF2BP2

interferon regulatory factor 2 binding protein 2

Basic information

Region (hg38): 1:234604268-234610178

Links

ENSG00000168264 ∙ NCBI:359948 ∙ OMIM:615332 ∙ HGNC:21729 ∙ Uniprot:Q7Z5L9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency, common variable, 14 (Limited), mode of inheritance: Unknown
• immunodeficiency, common variable, 14 (Limited), mode of inheritance: AD
• immunodeficiency, common variable, 14 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency, common variable, 14	AD	Allergy/Immunology/Infectious	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious	27016798

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IRF2BP2 gene.

• not provided (417 variants)
• Inborn genetic diseases (27 variants)
• Immunodeficiency, common variable, 14 (18 variants)
• IRF2BP2-related condition (5 variants)
• not specified (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IRF2BP2 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			1	159	16	176
missense			210	3	4	217
nonsense			8			8
start loss						0
frameshift			8			8
inframe indel		1	16	1	1	19
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding			1	6	1	8
Total	0	1	244	169	22

Variants in IRF2BP2

This is a list of pathogenic ClinVar variants found in the IRF2BP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-234607137-T-C			Uncertain significance (Jul 28, 2022)
1-234607140-C-G			Likely benign (Feb 20, 2022)
1-234607140-C-T			Likely benign (Jan 03, 2022)
1-234607140-CGA-C			Uncertain significance (Mar 26, 2021)
1-234607143-GTCTC-G		Varicella, severe recurrent	Uncertain significance (-)
1-234607145-C-T			Uncertain significance (Oct 16, 2022)
1-234607174-G-A		Immunodeficiency, common variable, 14	Uncertain significance (Oct 24, 2022)
1-234607191-T-C			Likely benign (Feb 19, 2021)
1-234607203-A-G			Likely benign (Feb 06, 2022)
1-234607206-G-A			Likely benign (Nov 07, 2021)
1-234607213-G-A			Uncertain significance (Oct 04, 2022)
1-234607214-G-T			Uncertain significance (Feb 01, 2023)
1-234607215-G-A			Likely benign (Mar 16, 2023)
1-234607215-G-T			Likely benign (Apr 22, 2023)
1-234607219-T-A			Uncertain significance (Dec 11, 2023)
1-234607219-T-C		not specified	Uncertain significance (Dec 14, 2023)
1-234607220-T-C			Uncertain significance (Jan 29, 2024)
1-234607224-G-A			Likely benign (May 16, 2022)
1-234607228-A-T			Uncertain significance (Jul 12, 2022)
1-234607229-C-A		not specified	Uncertain significance (Jan 06, 2024)
1-234607229-C-G			Uncertain significance (Jun 25, 2022)
1-234607229-C-T			Uncertain significance (Nov 28, 2021)
1-234607245-C-T			Likely benign (Sep 04, 2021)
1-234607249-C-T		Immunodeficiency, common variable, 14	Pathogenic (Nov 13, 2017)
1-234607256-A-G			Uncertain significance (Jul 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IRF2BP2	protein_coding	protein_coding	ENST00000366609	2	5257

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.846	0.154	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.622	213	240	0.887	0.0000113	3624
Missense in Polyphen		84	107.36	0.78239		1304
Synonymous	-6.28	188	106	1.78	0.00000540	1263
Loss of Function	2.72	1	10.5	0.0951	4.53e-7	157

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a transcriptional corepressor in a IRF2- dependent manner; this repression is not mediated by histone deacetylase activities (PubMed:12799427). Represses the NFAT1- dependent transactivation of NFAT-responsive promoters (PubMed:21576369). Acts as a coactivator of VEGFA expression in cardiac and skeletal muscles (PubMed:20702774). Plays a role in immature B-cell differentiation (PubMed:27016798). {ECO:0000269|PubMed:12799427, ECO:0000269|PubMed:20702774, ECO:0000269|PubMed:21576369, ECO:0000269|PubMed:27016798}.
• Disease: DISEASE: Immunodeficiency, common variable, 14 (CVID14) [MIM:617765]: A primary immunodeficiency resulting in recurrent sinopulmonary infections since early childhood, and characterized by hypogammaglobulinemia with undetectable IgG and IgA, poor response to vaccination, and decreased levels of switched memory B cells. CVID14 inheritance is autosomal dominant. {ECO:0000269|PubMed:27016798}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.110

Haploinsufficiency Scores

• pHI: 0.863
• hipred: N
• hipred_score: 0.378
• ghis: 0.626

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.992

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Irf2bp2
• Phenotype: embryo phenotype; liver/biliary system phenotype; hematopoietic 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); growth/size/body region phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;immature B cell differentiation;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus;nucleoplasm;cytoplasm
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription activator activity, RNA polymerase II-specific;metal ion binding