This histone demethylase specifically removes methyl groups from lysine 27 of histone H3, playing a central role in gene expression regulation and chromatin remodeling during development. Mutations cause Stolerman neurodevelopmental syndrome with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants, indicating critical developmental importance.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.141 OMIM phenotype
Clinical SummaryKDM6B
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Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ARLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

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.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.14LOEUF
pLI 1.000
Z-score 7.02
OE 0.06 (0.030.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
1.32Z-score
OE missense 0.89 (0.840.94)
924 obs / 1043.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.06 (0.030.14)
00.351.4
Missense OE0.89 (0.840.94)
00.61.4
Synonymous OE1.31
01.21.6
LoF obs/exp: 4 / 65.2Missense obs/exp: 924 / 1043.6Syn Z: -5.07
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongKDM6B-related developmental disorderLOFAD
limitedKDM6B-related intellectual developmental disorderOTHERAR
DN
0.18100th %ile
GOF
0.2795th %ile
LOF
0.87top 5%

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

LOFprediction above median · 1 literature citation · LOEUF 0.14

Literature Evidence

LOFKdm6b Haploinsufficiency Causes ASD/ADHD-Like Behavioral Deficits in MicePMID:35711692

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

KDM6B · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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