IRF2BPL

Chr 14AD

interferon regulatory factor 2 binding protein like

Also known as: C14orf4, EAP1, NEDAMSS

This gene encodes a transcription factor that regulates female reproductive function. Mutations cause a neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures through an autosomal dominant inheritance pattern. The pathogenic mechanism involves loss of function, consistent with the protein's high intolerance to loss-of-function variants.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.411 OMIM phenotype
Clinical SummaryIRF2BPL
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Gene-Disease Validity (ClinGen)
neurodegenerative disease · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.84) — some intolerance to loss-of-function variants.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — IRF2BPL
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.41LOEUF
pLI 0.836
Z-score 3.42
OE 0.16 (0.070.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.73Z-score
OE missense 0.90 (0.830.98)
377 obs / 419.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.16 (0.070.41)
00.351.4
Missense OE0.90 (0.830.98)
00.61.4
Synonymous OE1.88
01.21.6
LoF obs/exp: 3 / 19.1Missense obs/exp: 377 / 419.3Syn Z: -9.69
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongIRF2BPL-related neurodevelopmental disorderLOFAD
DN
0.2997th %ile
GOF
0.2895th %ile
LOF
0.85top 5%

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

LOFprediction above median · 1 literature citation · LOEUF 0.41

Literature Evidence

LOFHeterozygous loss of function variants in the IRF2BPL are a newly described cause of neurodevelopmental disabilities and epilepsy.PMID:31432588

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

IRF2BPL · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
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