IRF4

Chr 6

interferon regulatory factor 4

Also known as: IMD131, LSIRF, MUM1, NF-EM5, SHEP8

NCBI Gene: 3662ENSG00000137265UniProt: Q15306

The protein encoded by this gene belongs to the IRF (interferon regulatory factor) family of transcription factors, characterized by an unique tryptophan pentad repeat DNA-binding domain. The IRFs are important in the regulation of interferons in response to infection by virus, and in the regulation of interferon-inducible genes. This family member is lymphocyte specific and negatively regulates Toll-like-receptor (TLR) signaling that is central to the activation of innate and adaptive immune systems. A chromosomal translocation involving this gene and the IgH locus, t(6;14)(p25;q32), may be a cause of multiple myeloma. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2010]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMultiple myeloma
UniProtImmunodeficiency 131

Clinical highlights

Gene-disease validity (ClinGen)
combined immunodeficiency · ADDefinitivesufficient evidence for diagnostic panels
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.
3
Active trials
286
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.38
LOEUF
LOF
Mechanism· predicted
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.38LOEUF
pLI 0.857
Z-score 3.78
OE 0.17 (0.08–0.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
2.85Z-score
OE missense 0.52 (0.45–0.59)
144 obs / 277.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.17 (0.08–0.38)
0≤0.351.4
Missense OE?0.52 (0.45–0.59)
0≤0.61.4
Synonymous OE?0.96
0≤1.21.6
LoF obs/exp: 4 / 24.0Missense obs/exp: 144 / 277.9Syn Z: 0.31

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

IRF4 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients