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…

Primary Disease Associations & Inheritance

?Immunodeficiency, common variable, 14MIM #617765

Clinical highlights

Gene–disease validity (ClinGen)

Limited · immunodeficiency, common variable, 14 · AD · ClinGen 2021

not for standalone diagnostic reporting

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.45

LOEUF

Multiple*

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in IRF2BP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 75

1,057 rare PASS variants

Rare truncating (LoF)

1 in 2,700

49 rare PASS variants

Rare synonymous (reference)

1 in 69

586 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IRF2BP2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 92	1 in 3,300
South Asian	~43k	1 in 67	1 in 2,100
Remaining (unassigned)	~30k	1 in 69	≈ 1 in 7,500
European (Finnish)	~27k	1 in 240	1 in 470
Admixed American	~22k	1 in 62	≈ 1 in 6,400
African / African American	~21k	1 in 71	1 in 4,000
East Asian	~20k	1 in 110	≈ 1 in 4,700
Ashkenazi Jewish	~13k	1 in 240	≈ 1 in 12,000
Middle Eastern	~2,884	1 in 77	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 1 of 2 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 2.? see exons ↓