IRF2

Chr 4

interferon regulatory factor 2

Also known as: IRF-2

NCBI Gene: 3660 ENSG00000168310 UniProt: P14316 OMIM: 147576

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.

OMIM ResearchSummary from RefSeq, UniProt

IRF2 encodes interferon regulatory factor 2, a member of the interferon regulatory transcription factor (IRF) family. IRF2 competitively inhibits the IRF1-mediated transcriptional activation of interferons alpha and beta, and presumably other genes that employ IRF1 for transcription activation. However, IRF2 also functions as a transcriptional activator of histone H4. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.42

Clinical Summary— IRF2

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.80) — some intolerance to loss-of-function variants.

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ClinVar Variants

35 VUS of 55 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.42LOEUF

pLI 0.798

Z-score 3.33

OE 0.16 (0.07–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.31Z-score

OE missense 0.56 (0.48–0.65)

122 obs / 217.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.16 (0.07–0.42)

0≤0.351.4

Missense OE?0.56 (0.48–0.65)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 3 / 18.5Missense obs/exp: 122 / 217.9Syn Z: 0.68

This gene — mechanism propensity

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

55 submitted variants in ClinVar

ClinVar

Classification Summary

VUS35

Likely Benign2

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	34	0	35
Likely Benign	0	0	2	2
Benign	0	0	2	2
Total	1	34	4	39

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

View in ClinVar →

108 pathogenic / likely-pathogenic (of 120) ClinVar copy-number / structural variants overlap IRF2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →