PHF8
Chr XXLRPHD finger protein 8
Also known as: JHDM1F, KDM7B, MRXSSD, ZNF422
The protein functions as a histone lysine demethylase that removes methyl groups from histones to activate gene transcription, requiring Fe(2+), 2-oxoglutarate, and oxygen for catalytic activity. Loss-of-function mutations cause X-linked syndromic intellectual disability of the Siderius type, which is inherited in an X-linked recessive pattern. The pathogenic mechanism involves disrupted chromatin remodeling and transcriptional regulation due to impaired histone demethylase activity.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
PHF8 · 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