ERF
Chr 19ADETS2 repressor factor
Also known as: CHYTS, CRS4, PE-2, PE2
ERF encodes a transcriptional repressor that binds to the ETS2 promoter and regulates genes involved in cellular proliferation and trophoblast differentiation. Mutations cause Chitayat syndrome and craniosynostosis 4, both inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI 0.99), indicating that haploinsufficiency is likely not tolerated in the general population.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
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
ERF · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Clinical Study of Fianlimab in Combination With Cemiplimab Versus Pembrolizumab in Adolescent and Adult Patients With Previously Untreated Unresectable Locally Advanced or Metastatic Melanoma
ACTIVE NOT RECRUITINGTepotinib Phase II in NSCLC Harboring MET Alterations (VISION)
ACTIVE NOT RECRUITINGEvaluation of Efficacy and Safety of Cemiplimab as First Line Treatment for Advanced Basal Cell Carcinoma (BCC) Patients
RECRUITINGA Trial to See if the Combination of Fianlimab With Cemiplimab Works Better Than Pembrolizumab for Preventing or Delaying Melanoma From Coming Back After it Has Been Removed With Surgery
ACTIVE NOT RECRUITINGA Clinical Trial of Three Study Medicines (Encorafenib, Binimetinib, and Pembrolizumab) in Patients With Advanced or Metastatic Melanoma
ACTIVE NOT RECRUITINGAdjuvant Nivolumab Treatment in Stage II (IIA, IIB, IIC) High-risk Melanoma
ACTIVE NOT RECRUITINGA Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung Cancer
RECRUITINGHuman Milk Oligosaccharides (HMOs) and Gut Microbiota, Immune System in Antarctica
ENROLLING BY INVITATIONExternal Resources
Links to major genomics databases and tools