IRF2BP2

Chr 1AD

interferon regulatory factor 2 binding protein 2

NCBI Gene: 359948ENSG00000168264UniProt: Q7Z5L9

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)

Primary Disease Associations & Inheritance

?Immunodeficiency, common variable, 14MIM #617765
AD
696
ClinVar variants
17
Pathogenic / LP
0.85
pLI score
0
Active trials
Clinical Summary— IRF2BP2
🧬
Gene-Disease Validity (ClinGen)
immunodeficiency, common variable, 14 · ADLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 414 VUS of 696 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.45LOEUF
pLI 0.846
Z-score 2.72
OE 0.10 (0.03–0.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.62Z-score
OE missense 0.89 (0.79–0.99)
213 obs / 240.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.10 (0.03–0.45)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.79–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.78
0≤1.21.6
LoF obs/exp: 1 / 10.5Missense obs/exp: 213 / 240.1Syn Z: -6.28

ClinVar Variant Classifications

696 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic4
VUS414
Likely Benign251
Benign11
Conflicting3
13
Pathogenic
4
Likely Pathogenic
414
VUS
251
Likely Benign
11
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
2
0
2
0
4
VUS
20
350
44
0
414
Likely Benign
1
2
18
230
251
Benign
0
0
2
9
11
Conflicting
—3
Total2335279239696

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

IRF2BP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Immunodeficiency, common variable, 14

MIM #617765

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genotypic and Phenotypic Characteristics of Acute Promyelocytic Leukemia Translocation Variants.
Mannan A et al.·Hematol Oncol Stem Cell Ther
2020Review
Super-enhancer-driven IRF2BP2 enhances ALK activity and promotes neuroblastoma cell proliferation.
Chen Y et al.·Neuro Oncol
2024
IRF2BP2 deficiency: An important form of common variable immunodeficiency with inflammation.
Udemgba C et al.·J Allergy Clin Immunol
2025
NTRK1-rearranged histiocytosis: clinicopathologic and molecular features.
Fragneau R et al.·Blood Adv
2025
Novel mutation and expanding phenotype in IRF2BP2 deficiency.
Körholz J et al.·Rheumatology (Oxford)
2023Case report
An IRF2BP2 Variant in a Pediatric Patient with Common Variable Immunodeficiency.
Tekcan D et al.·Pediatr Allergy Immunol Pulmonol
2025Case report
Agmatine-IRF2BP2 interaction induces M2 phenotype of microglia by increasing IRF2-KLF4 signaling.
Kim J et al.·Inflamm Res
2023
[Variant acute promyelocytic leukemia with IRF2BP2-RARA fusion gene: a case report and literature review].
Wu CY et al.·Zhonghua Xue Ye Xue Za Zhi
2023Review
Novel hypermorphic variants in IRF2BP2 identified in patients with common variable immunodeficiency and autoimmunity.
Anim M et al.·Clin Immunol
2024Cohort
IRF2BP2 Reduces Macrophage Inflammation and Susceptibility to Atherosclerosis.
Chen HH et al.·Circ Res
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools