IRF2BPL

Chr 14AD

interferon regulatory factor 2 binding protein like

Also known as: C14orf4, EAP1, NEDAMSS

NCBI Gene: 64207 ENSG00000119669 UniProt: Q9H1B7 OMIM: 611720

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a transcription factor that may play a role in regulating female reproductive function. [provided by RefSeq, Jun 2012]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.411 OMIM phenotype

Clinical Summary— IRF2BPL

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Gene-Disease Validity (ClinGen)

neurodegenerative disease · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.41LOEUF

pLI 0.836

Z-score 3.42

OE 0.16 (0.07–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.73Z-score

OE missense 0.90 (0.83–0.98)

377 obs / 419.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.16 (0.07–0.41)

0≤0.351.4

Missense OE?0.90 (0.83–0.98)

0≤0.61.4

Synonymous OE?1.88

0≤1.21.6

LoF obs/exp: 3 / 19.1Missense obs/exp: 377 / 419.3Syn Z: -9.69

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongIRF2BPL-related neurodevelopmental disorderLOFAD

This gene — mechanism propensity

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.1

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

References