KDM4B

Chr 19AD

lysine demethylase 4B

The protein functions as a histone demethylase that removes methyl groups from H3K36 and H3K9me2/H3K9me3, regulating chromatin structure and gene expression during brain development. Loss-of-function mutations cause autosomal dominant intellectual developmental disorder 65. The gene is highly intolerant to loss-of-function variants, indicating haploinsufficiency as the likely mechanism of pathogenicity.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.171 OMIM phenotype
Clinical SummaryKDM4B
🧬
Gene-Disease Validity (ClinGen)
intellectual developmental disorder, autosomal dominant 65 · ADStrong

Strong evidence — appropriate for clinical testing

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.17LOEUF
pLI 1.000
Z-score 6.27
OE 0.07 (0.040.17)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.48Z-score
OE missense 0.64 (0.590.69)
469 obs / 734.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.07 (0.040.17)
00.351.4
Missense OE0.64 (0.590.69)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 4 / 53.5Missense obs/exp: 469 / 734.8Syn Z: -0.65
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongKDM4B-related developmental disorderLOFAD
DN
0.2499th %ile
GOF
0.3491th %ile
LOF
0.74top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.17

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

KDM4B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →