KDM6B

Chr 17AD

lysine demethylase 6B

NCBI Gene: 23135ENSG00000132510UniProt: O15054

Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code (PubMed:17713478, PubMed:17825402, PubMed:17851529, PubMed:18003914). Demethylates trimethylated and dimethylated H3 'Lys-27' (PubMed:17713478, PubMed:17825402, PubMed:17851529, PubMed:18003914). Plays a central role in regulation of posterior development, by regulating HOX gene expression (PubMed:17851529). Involved in inflammatory response by participating in macrophage differentiation in case of inflammation by regulating gene expression and macrophage differentiation (PubMed:17825402). Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression by acting as a link between T-box factors and the SMARCA4-containing SWI/SNF remodeling complex (By similarity)

Primary Disease Associations & Inheritance

Stolerman neurodevelopmental syndromeMIM #618505
AD
846
ClinVar variants
45
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— KDM6B
⚡
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.
📋
ClinVar Variants
45 Pathogenic / Likely Pathogenic· 271 VUS of 846 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.14LOEUF
pLI 1.000
Z-score 7.02
OE 0.06 (0.03–0.14)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.32Z-score
OE missense 0.89 (0.84–0.94)
924 obs / 1043.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.06 (0.03–0.14)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.84–0.94)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.31
0≤1.21.6
LoF obs/exp: 4 / 65.2Missense obs/exp: 924 / 1043.6Syn Z: -5.07

ClinVar Variant Classifications

846 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic12
VUS271
Likely Benign99
Benign11
Conflicting4
33
Pathogenic
12
Likely Pathogenic
271
VUS
99
Likely Benign
11
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
1
20
0
33
Likely Pathogenic
4
3
5
0
12
VUS
9
235
25
2
271
Likely Benign
0
45
12
42
99
Benign
0
6
3
2
11
Conflicting
—4
Total252906546430

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

Gene2Phenotype Curations

KDM6B-related developmental disorder

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

KDM6B-related intellectual developmental disorder

limited
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Stolerman neurodevelopmental syndrome

MIM #618505

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The clinical and molecular spectrum of the KDM6B-related neurodevelopmental disorder.
Rots D et al.·Am J Hum Genet
2023
Iron-loaded cancer-associated fibroblasts induce immunosuppression in prostate cancer.
Zhang K et al.·Nat Commun
2024
De novo variants underlying monogenic syndromes with intellectual disability in a neurodevelopmental cohort from India.
Pande S et al.·Eur J Hum Genet
2024Cohort
Myeloid-specific KDM6B inhibition sensitizes glioblastoma to PD1 blockade.
Goswami S et al.·Nat Cancer
2023
N6-methyladenosine RNA modification regulates the transcription of SLC7A11 through KDM6B and GATA3 to modulate ferroptosis.
Zhang H et al.·J Biomed Sci
2025
KDM6B (JMJD3) and its dual role in cancer.
Lagunas-Rangel FA·Biochimie
2021Review
Identification of novel autoantibodies in Sjögren's disease.
Engelke F et al.·Front Immunol
2025
Epigenetic targets and their inhibitors in the treatment of idiopathic pulmonary fibrosis.
Miao X et al.·Eur J Med Chem
2025Review
KDM6B drives epigenetic reprogramming associated with lymphoid stromal cell early commitment and immune properties.
Sylvestre M et al.·Sci Adv
2023
The KDM6B mutation: Phenotype and clinical characteristics-Report of a case.
Insa Pineda I et al.·Rev Psiquiatr Salud Ment (Engl Ed)
2022Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools