KDM4A
Chr 1lysine demethylase 4A
Also known as: JHDM3A, JMJD2, JMJD2A, TDRD14A
This histone demethylase specifically removes trimethyl groups from lysine-9 and lysine-36 residues of histone H3, regulating gene expression through chromatin modification. Mutations cause autosomal dominant neurodevelopmental disorder with intellectual disability, seizures, and behavioral abnormalities. The gene is extremely intolerant to loss-of-function variants, indicating that proper dosage is critical for normal neurodevelopment.
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
159 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 | 7 | 0 | 7 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 105 | 4 | 0 | 109 |
Likely Benign | 0 | 3 | 0 | 3 | 6 |
Benign | 0 | 1 | 1 | 4 | 6 |
| Total | 0 | 109 | 13 | 7 | 129 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KDM4A · 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