IRF2BPL

Chr 14AD

interferon regulatory factor 2 binding protein like

Also known as: C14orf4, EAP1, NEDAMSS

NCBI Gene: 64207ENSG00000119669UniProt: Q9H1B7

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

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizuresMIM #618088
AD
580
ClinVar variants
111
Pathogenic / LP
0.84
pLI score
1
Active trials
Clinical Summary— IRF2BPL
🧬
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.
📋
ClinVar Variants
111 Pathogenic / Likely Pathogenic· 320 VUS of 580 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.73Z-score
OE missense 0.90 (0.83–0.98)
377 obs / 419.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.16 (0.07–0.41)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.83–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.88
0≤1.21.6
LoF obs/exp: 3 / 19.1Missense obs/exp: 377 / 419.3Syn Z: -9.69

ClinVar Variant Classifications

580 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic55
Likely Pathogenic56
VUS320
Likely Benign118
Benign20
Conflicting11
55
Pathogenic
56
Likely Pathogenic
320
VUS
118
Likely Benign
20
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
28
3
24
0
55
Likely Pathogenic
28
8
20
0
56
VUS
9
283
28
0
320
Likely Benign
1
21
23
73
118
Benign
1
0
10
9
20
Conflicting
—11
Total6731510582580

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

View 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.

Gene2Phenotype Curations

IRF2BPL-related neurodevelopmental disorder

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures

MIM #618088

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — IRF2BPL
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and genetic spectrum of patients with IRF2BPL syndrome.
Iwama K et al.·J Hum Genet
2025Cohort
Clinical characterization of IRF2BPL mutation: Case series and review of the literature.
Lou X et al.·Medicine (Baltimore)
2025Review
IRF2BPL gene mutation: Expanding on neurologic phenotypes.
Shelkowitz E et al.·Am J Med Genet A
2019Review
Recent genetic advances in early-onset dystonia.
Steel D et al.·Curr Opin Neurol
2020Review
Neurological phenomenology of the IRF2BPL mutation syndrome: Analysis of a new case and systematic review of the literature.
Pisano S et al.·Seizure
2022Case report
IRF2BPL: A new genotype for progressive myoclonus epilepsies.
Costa C et al.·Epilepsia
2023
Genetic analysis of IRF2BPL in a Taiwanese dystonia cohort: The genotype and phenotype correlation.
Chen PS et al.·Ann Clin Transl Neurol
2024Cohort
IRF2BPL as a novel causative gene for progressive myoclonus epilepsy.
Gardella E et al.·Epilepsia
2023
De novo variants of IRF2BPL result in developmental epileptic disorder.
Wang Y et al.·Orphanet J Rare Dis
2024
IRF2BPL-Related Disorder, Causing Neurodevelopmental Disorder with Regression, Abnormal Movements, Loss of Speech and Seizures (NEDAMSS) Is Characterized by Pathology Consistent with DRPLA.
Venkateswaran S et al.·Mov Disord
2024Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools