PHF23
Chr 17PHD finger protein 23
Also known as: hJUNE-1b
PHF23 encodes a zinc-binding protein that negatively regulates autophagy by promoting ubiquitination and degradation of LRSAM1, an E3 ubiquitin ligase essential for autophagy responses. Mutations cause autosomal dominant developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and developmental regression. The gene is highly constrained against loss-of-function variants, indicating that PHF23 haploinsufficiency is likely not tolerated in the general population.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
105 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 26 | 0 | 26 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 56 | 10 | 0 | 66 |
Likely Benign | 0 | 1 | 0 | 0 | 1 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 57 | 39 | 0 | 96 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PHF23 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools