IRF2BP2

Chr 1AD

interferon regulatory factor 2 binding protein 2

Also known as: CVID14, LRIR2

NCBI Gene: 359948 ENSG00000168264 UniProt: Q7Z5L9 OMIM: 615332

The protein acts as a transcriptional corepressor that interacts with interferon regulatory factor-2 and plays a role in immature B-cell differentiation. Mutations cause common variable immunodeficiency with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.85, LOEUF 0.45), indicating intolerance to protein disruption.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an interferon regulatory factor-2 (IRF2) binding protein that interacts with the C-terminal transcriptional repression domain of IRF2. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismADLOEUF 0.451 OMIM phenotype

Clinical Summary— IRF2BP2

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Gene-Disease Validity (ClinGen)

immunodeficiency, common variable, 14 · ADLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

0.62Z-score

OE missense 0.89 (0.79–0.99)

213 obs / 240.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.10 (0.03–0.45)

0≤0.351.4

Missense OE?0.89 (0.79–0.99)

0≤0.61.4

Synonymous OE?1.78

0≤1.21.6

LoF obs/exp: 1 / 10.5Missense obs/exp: 213 / 240.1Syn Z: -6.28

This gene — mechanism propensity

0.2299th %ile

GOF

0.2398th %ile

LOF

0.87top 5%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · LOEUF 0.45

GOF1 literature citation

Literature Evidence

GOFExtensive gastrointestinal workup was unrevealing, but whole-exome sequencing identified two autosomal dominant gene variants: NLRP12 (loss of function) and IRF2BP2 (gain of function).1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References