IRF2

Chr 4

interferon regulatory factor 2

Also known as: IRF-2

Interferon regulatory factor 2 functions as a transcriptional regulator that primarily represses interferon and interferon-inducible genes while also activating histone H4 and IL7 expression. Mutations cause neurodevelopmental disorder with epilepsy, spasticity, and brain abnormalities, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants, indicating strong selective pressure for its normal function.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
34
Pubs (1 yr)
105
P/LP submissions
0%
P/LP missense
0.42
LOEUF
LOF
Mechanism· predicted
Clinical SummaryIRF2
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.80) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
105 unique Pathogenic / Likely Pathogenic· 46 VUS of 172 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.42LOEUF
pLI 0.798
Z-score 3.33
OE 0.16 (0.070.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.31Z-score
OE missense 0.56 (0.480.65)
122 obs / 217.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.16 (0.070.42)
00.351.4
Missense OE0.56 (0.480.65)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 3 / 18.5Missense obs/exp: 122 / 217.9Syn Z: 0.68
DN
0.3594th %ile
GOF
0.2198th %ile
LOF
0.75top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.42

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

ClinVar Variant Classifications

172 submitted variants in ClinVar

Classification Summary

Pathogenic96
Likely Pathogenic9
VUS46
Likely Benign3
Benign2
96
Pathogenic
9
Likely Pathogenic
46
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
96
0
96
Likely Pathogenic
0
0
9
0
9
VUS
1
34
11
0
46
Likely Benign
0
0
1
2
3
Benign
0
0
0
2
2
Total1341174156

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

View in ClinVar →

Protein Context — Lollipop Plot

IRF2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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