KDM8
Chr 16lysine demethylase 8
Also known as: JMJD5
KDM8 encodes a bifunctional enzyme that acts as both an endopeptidase cleaving histone N-terminal tails and a 2-oxoglutarate-dependent monooxygenase, playing critical roles in transcriptional regulation, mitosis, cell cycle progression, and circadian gene expression. The gene shows very low constraint to loss-of-function variants (pLI = 0.00003, LOEUF = 0.836), suggesting tolerance to haploinsufficiency. No established Mendelian diseases have been associated with KDM8 mutations in pediatric populations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
KDM8 · 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