KDM5A
Chr 12ARlysine demethylase 5A
Also known as: NEDEHC, RBBP-2, RBBP2, RBP2
The KDM5A protein is a histone demethylase that specifically removes methyl groups from lysine 4 of histone H3, playing a central role in gene regulation and transcriptional control of developmental genes including Hox proteins and circadian rhythm genes. Mutations cause El Hayek-Chahrour neurodevelopmental syndrome, which follows an autosomal recessive inheritance pattern. This gene is extremely intolerant to loss-of-function variants, indicating that functional copies are critical for normal development.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
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
397 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 | 4 | 1 | 61 | 0 | 66 |
Likely Pathogenic | 3 | 2 | 3 | 0 | 8 |
VUS | 9 | 197 | 25 | 0 | 231 |
Likely Benign | 0 | 4 | 13 | 17 | 34 |
Benign | 0 | 7 | 2 | 3 | 12 |
Conflicting | — | 2 | |||
| Total | 16 | 211 | 104 | 20 | 353 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KDM5A · 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