KDM6A

Chr XXLD

lysine demethylase 6A

Also known as: KABUK2, UTX, bA386N14.2

The encoded protein is a histone demethylase that catalyzes the demethylation of tri/dimethylated histone H3, functioning as an epigenetic regulator of gene expression. Mutations cause Kabuki syndrome 2, a neurodevelopmental disorder with intellectual disability, distinctive facial features, and multiple congenital anomalies, inherited in an X-linked dominant pattern. The gene is highly intolerant to loss-of-function variants, and disease predominantly occurs through haploinsufficiency mechanisms.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismXLDLOEUF 0.161 OMIM phenotype
Clinical SummaryKDM6A
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Gene-Disease Validity (ClinGen)
Kabuki syndrome 2 · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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
3 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — KDM6A
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.16LOEUF
pLI 1.000
Z-score 6.51
OE 0.07 (0.030.16)
Highly constrained

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

Missense Constraint
2.95Z-score
OE missense 0.63 (0.570.69)
317 obs / 502.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.07 (0.030.16)
00.351.4
Missense OE0.63 (0.570.69)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 4 / 57.0Missense obs/exp: 317 / 502.9Syn Z: 0.10
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveKDM6A-related Kabuki syndromeLOFmonoallelic_X_heterozygous
DN
0.2399th %ile
GOF
0.3491th %ile
LOF
0.81top 5%

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

LOFprediction above median · LOEUF 0.16

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

KDM6A · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗