KAT6B

Chr 10AD

lysine acetyltransferase 6B

Also known as: GTPTS, MORF, MOZ2, MYST4, ZC2HC6B, qkf, querkopf

NCBI Gene: 23522ENSG00000156650UniProt: Q8WYB5

The protein encoded by this gene is a histone acetyltransferase and component of the MOZ/MORF protein complex. In addition to its acetyltransferase activity, the encoded protein has transcriptional activation activity in its N-terminal end and transcriptional repression activity in its C-terminal end. This protein is necessary for RUNX2-dependent transcriptional activation and could be involved in brain development. Mutations have been found in patients with genitopatellar syndrome. A translocation of this gene and the CREBBP gene results in acute myeloid leukemias. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]

Primary Disease Associations & Inheritance

Genitopatellar syndromeMIM #606170
AD
SBBYSS syndromeMIM #603736
AD
UniProtOhdo syndrome, SBBYS variant
1784
ClinVar variants
29
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— KAT6B
⚡
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
29 Pathogenic / Likely Pathogenic· 257 VUS of 1784 total submissions

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.
0.13LOEUF
pLI 1.000
Z-score 7.89
OE 0.06 (0.03–0.13)
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.
2.89Z-score
OE missense 0.76 (0.71–0.80)
834 obs / 1104.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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 (0.03–0.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.71–0.80)
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.0.98
0≤1.21.6
LoF obs/exp: 5 / 82.2Missense obs/exp: 834 / 1104.0Syn Z: 0.26

ClinVar Variant Classifications

1784 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic14
VUS257
Likely Benign158
Benign22
Conflicting14
15
Pathogenic
14
Likely Pathogenic
257
VUS
158
Likely Benign
22
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
9
0
15
Likely Pathogenic
8
2
4
0
14
VUS
3
231
22
1
257
Likely Benign
0
39
31
88
158
Benign
0
7
11
4
22
Conflicting
—14
Total172797793480

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

View in ClinVar →

Protein Context — Lollipop Plot

KAT6B · protein map & ClinVar variants

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

Gene2Phenotype Curations

KAT6B-related genitopatellar syndrome

definitive
ADDominant NegativeAltered Gene Product Structure
Dev. DisordersEyeSkeletal
G2P ↗

KAT6B-related Say-Barber-Biesecker-Young-Simpson syndrome

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Genitopatellar syndrome

MIM #606170

Molecular basis of disorder known

Autosomal dominant

SBBYSS syndrome

MIM #603736

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Inhibition of lysine acetyltransferase KAT6 in ER(+)HER2(-) metastatic breast cancer: a phase 1 trial.
Mukohara T et al.·Nat Med
2024Clinical trial
Further delineation of the clinical spectrum of KAT6B disorders and allelic series of pathogenic variants.
Zhang LX et al.·Genet Med
2020Review
Variable expressivity of a transmitted pathogenic KAT6B variant.
Rasmussen NB et al.·Eur J Med Genet
2025
Catalytic Inhibition of KAT6/KAT7 Enhances the Efficacy and Overcomes Primary and Acquired Resistance to Menin Inhibitors in MLL Leukemia.
Gordon SJV et al.·Cancer Discov
2025
Clinical features and underlying mechanisms of KAT6B disease in a Chinese boy.
Sun X et al.·Mol Genet Genomic Med
2023Functional
Recurrent KAT6B/A::KANSL1 Fusions Characterize a Potentially Aggressive Uterine Sarcoma Morphologically Overlapping With Low-grade Endometrial Stromal Sarcoma.
Agaimy A et al.·Am J Surg Pathol
2022
The KAT6B-related disorders genitopatellar syndrome and Ohdo/SBBYS syndrome have distinct clinical features reflecting distinct molecular mechanisms.
Campeau PM et al.·Hum Mutat
2012Review
Clinical heterogeneity of polish patients with KAT6B-related disorder.
Klaniewska M et al.·Mol Genet Genomic Med
2023Cohort
Phenotypic Characterization of Seven Pediatric Patients Diagnosed With KAT6B -Related Disorders: Case Series and Review of the Literature.
Maglione V et al.·Am J Med Genet A
2025Review
SNORD17-mediated KAT6B mRNA 2'-O-methylation regulates vasculogenic mimicry in glioblastoma cells.
Cui J et al.·Cell Biol Toxicol
2023
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools