kat6b
<div class="infobox infobox-gene">
<table>
<tr><th colspan="2">KAT6B</th></tr>
<tr><td>Symbol</td><td>KAT6B</td></tr>
<tr><td>Full Name</td><td>Lysine Acetyltransferase 6B</td></tr>
<tr><td>Chromosome</td><td>10q22.2</td></tr>
<tr><td>NCBI Gene ID</td><td>[23522](https://www.ncbi.nlm.nih.gov/gene/23522)</td></tr>
<tr><td>OMIM</td><td>[607528](https://omim.org/entry/607528)</td></tr>
<tr><td>Ensembl</td><td>[ENSG00000138311](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000138311)</td></tr>
<tr><td>UniProt</td><td>[Q9H0H5](https://www.uniprot.org/uniprot/Q9H0H5)</td></tr>
<tr><td>Aliases</td><td>MORF, MYST4, QKF</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>
Overview
KAT6B encodes lysine acetyltransferase 6B (also known as KAT6B or MORF), a member of the MYST family of histone acetyltransferases (HATs). This family includes four other members: KAT5 (TIP60), KAT6A (MOZ), KAT7 (HBO1), and KAT8 (MYST1). KAT6B plays critical roles in chromatin remodeling, transcriptional regulation, and embryonic development by catalyzing histone acetylation, particularly on histone H3 at lysine 9 (H3K9) and lysine 14 (H3K14)[@kalkhoven2013][@mills2010].
...kat6b
<div class="infobox infobox-gene">
<table>
<tr><th colspan="2">KAT6B</th></tr>
<tr><td>Symbol</td><td>KAT6B</td></tr>
<tr><td>Full Name</td><td>Lysine Acetyltransferase 6B</td></tr>
<tr><td>Chromosome</td><td>10q22.2</td></tr>
<tr><td>NCBI Gene ID</td><td>[23522](https://www.ncbi.nlm.nih.gov/gene/23522)</td></tr>
<tr><td>OMIM</td><td>[607528](https://omim.org/entry/607528)</td></tr>
<tr><td>Ensembl</td><td>[ENSG00000138311](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000138311)</td></tr>
<tr><td>UniProt</td><td>[Q9H0H5](https://www.uniprot.org/uniprot/Q9H0H5)</td></tr>
<tr><td>Aliases</td><td>MORF, MYST4, QKF</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>
Overview
KAT6B encodes lysine acetyltransferase 6B (also known as KAT6B or MORF), a member of the MYST family of histone acetyltransferases (HATs). This family includes four other members: KAT5 (TIP60), KAT6A (MOZ), KAT7 (HBO1), and KAT8 (MYST1). KAT6B plays critical roles in chromatin remodeling, transcriptional regulation, and embryonic development by catalyzing histone acetylation, particularly on histone H3 at lysine 9 (H3K9) and lysine 14 (H3K14)[@kalkhoven2013][@mills2010].
KAT6B functions as both a transcriptional co-activator and a component of chromatin-modifying complexes. It interacts with CREBBP (CBP), EP300 (p300), and other transcriptional regulators to modulate gene expression programs essential for development, cell cycle progression, and cellular identity. Mutations in KAT6B cause distinctive developmental syndromes including Genitopatellar Syndrome (GPS) and Ohdo Syndrome, highlighting its critical role in human development[@laure2012].
Normal Function
Histone Acetyltransferase Activity
KAT6B possesses intrinsic HAT activity that acetylates histone H3 and, to a lesser extent, histone H4. The catalytic domain is located in the N-terminal region and requires acetyl-CoA as a cofactor for the acetylation reaction[@chen2017]:
- H3K9 acetylation — Associated with transcriptionally active chromatin
- H3K14 acetylation — Co-occurs with H3K9ac and marks active promoters
- H4K5 acetylation — Involved in DNA replication and repair
The HAT activity is regulated by:
- Post-translational modifications (phosphorylation, ubiquitination)
- Protein-protein interactions with co-factors
- Subcellular localization
Transcriptional Co-activator Function
Beyond its catalytic activity, KAT6B functions as a transcriptional co-activator through multiple mechanisms[@bird2015]:
Recruitment to chromatin — KAT6B is recruited to specific genomic loci by transcription factors
Histone modification — Creates an open chromatin environment permissive for transcription
Interaction with transcriptional machinery — Associates with RNA polymerase II and general transcription factors
Complex formation — Part of multi-protein complexes including CREBBP, EP300, and other HATsProtein Domains and Structure
KAT6B contains several functional domains:
- N-terminal HAT domain — Catalytic activity for histone acetylation
- Proline-rich region — Mediates protein-protein interactions
- C-terminal domains — Include transcriptional activation domains and nuclear receptor interaction motifs
Mermaid diagram (expand to render)
Expression Pattern
KAT6B exhibits tissue-specific expression with highest levels in:
During Development
- Embryonic stem cells — High expression maintains pluripotency
- Neural tube — Important for early neurogenesis
- Limb buds — Critical for limb development
- Facial mesenchyme — Essential for craniofacial morphogenesis
- Genitourinary system — Important for kidney and genital development
In Adult Tissues
- Brain — Expressed in neurons and glia
- Testis — High expression in spermatogonia
- Bone marrow — Present in hematopoietic stem cells
- Uterus — Regulated during menstrual cycle
- Low expression — Most other adult tissues
Cellular Localization
- Nucleus — Primary location for chromatin functions
- Nucleolus — Some isoforms may localize here
- Cytoplasm — Minor fraction, may have non-chromatin functions
Disease Associations
Genitopatellar Syndrome (GPS)
GPS is caused by heterozygous truncating mutations in KAT6B. It is characterized by[@laure2012]:
- Genitourinary anomalies — Absent or hypoplastic kidneys, hydronephrosis
- Skeletal abnormalities — Absent or small patellae, hip dysplasia
- Craniofacial features — Broad nasal tip, anomalies
- Intellectual disability — Variable severity
- Other features — Hearing loss, dental anomalies
Ohdo Syndrome (Blepharophimosis Syndrome)
Similar but distinct from GPS, Ohdo syndrome (also called KAT6B-related syndrome) includes:
- Blepharophimosis — Narrow eye openings
- Ptosis — Drooping eyelids
- Developmental delay — Variable intellectual disability
- Facial features — Distinctive appearance
- Additional features — Dental, auditory, cardiac anomalies
Cancer
While less frequently mutated than its paralog KAT6A, KAT6B is implicated in cancer[@yang2020]:
- Chromosomal rearrangements — KAT6B fusions in some leukemias
- Dysregulated expression — Altered in various cancers
- Epigenetic reprogramming — Contributes to oncogenic transcriptional programs
Role in Neurodegeneration
Alzheimer's Disease
KAT6B and the broader HAT family are increasingly recognized in AD pathophysiology[@sun2019][@yang2022]:
Epigenetic dysregulation:
- Global histone acetylation changes are observed in AD brains
- KAT6B expression may be altered in AD
- Reduced HAT activity contributes to transcriptional dysfunction
Therapeutic implications:
- HAT inhibitors and activators are being explored
- Histone deacetylase (HDAC) inhibitors have shown promise in models
- Targeting KAT6B-specific pathways may offer new approaches
Other Neurodegenerative Disorders
- Huntington's disease — Histone acetylation deficits
- Parkinson's disease — Epigenetic changes in dopaminergic neurons
- Amyotrophic lateral sclerosis — Transcriptional dysregulation involves HATs
Epigenetic Therapy
The role of HATs in neurodegeneration suggests therapeutic strategies:
Small molecule HAT modulators — Activate or inhibit specific HATs
HDAC inhibitors — Promote histone acetylation by blocking deacetylases
Epigenetic editing — CRISPR-based approaches to modify histone marksProtein Interactions
KAT6B interacts with numerous proteins[@li2020]:
| Interactor | Function |
|------------|----------|
| CREBBP/CBP | Transcriptional co-activator, HAT complex |
| EP300/p300 | Histone acetyltransferase, transcription |
| p53 | Tumor suppressor, transcription factor |
| MLL1/2 | Histone methyltransferases, epigenetic regulation |
| RUNX1 | Transcription factor, hematopoiesis |
| Nuclear receptors | Hormone-dependent transcription |
Mermaid diagram (expand to render)
Animal Models
- Kat6b knockout mice — Show embryonic lethality or severe developmental defects
- Conditional knockout — Brain-specific deletion affects neurodevelopment
- Transgenic overexpression — Leads to tumors in some models
- Zebrafish models — Morpholino knockdowns show developmental defects
Therapeutic Implications
Targeting KAT6B and histone acetylation offers therapeutic opportunities:
HAT modulators — Small molecules that activate or inhibit specific HATs
Combination therapy — HAT modulators with other epigenetic therapies
Targeted degradation — PROTACs for specific HATsResearch is ongoing to develop:
- Brain-penetrant HAT modulators
- Selective KAT6B inhibitors
- Epigenetic combination approaches
Key Publications
[Mills AA, Human Molecular Genetics 2010](https://doi.org/10.1093/hmg/ddq142) — KAT6 family review
[Laure L et al., American Journal of Human Genetics 2012](https://doi.org/10.1016/j.ajhg.2012.03.001) — KAT6B mutation syndromes
[Chen Z et al., Nature Communications 2017](https://doi.org/10.1038/ncomms14216) — KAT6B deficiency
[Huang Y et al., JCI 2018](https://doi.org/10.1172/JCI98067) — KAT6B in stem cells
[Yang X et al., Frontiers in Oncology 2020](https://doi.org/10.3389/fonc.2020.558901) — KAT6A/B in cancerSee Also
- [KAT6A Gene](/genes/kat6a)
- [Histone Acetyltransferases](/proteins/histone-acetyltransferases)
- [Chromatin Remodeling](/mechanisms/chromatin-remodeling)
- [Epigenetics in Neurodegeneration](/mechanisms/epigenetics-neurodegeneration)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
External Links
- [NCBI Gene: KAT6B](https://www.ncbi.nlm.nih.gov/gene/23522)
- [OMIM: 607528](https://omim.org/entry/607528)
- [UniProt: Q9H0H5](https://www.uniprot.org/uniprot/Q9H0H5)
- [Ensembl: ENSG00000138311](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000138311)
References
[Kalkhoven E, Histone acetyltransferases in transcription and beyond (2013)](https://doi.org/10.1016/j.jbior.2013.05.004)
[Mills AA, The KAT6 family of histone acetyltransferases (2010)](https://doi.org/10.1093/hmg/ddq142)
[Chen Z et al., KAT6B deficiency leads to enhanced histone acetylation (2017)](https://doi.org/10.1038/ncomms14216)
[Huang Y et al., KAT6B regulates embryonic stem cell pluripotency (2018)](https://doi.org/10.1172/JCI98067)
[Ruthenburg AJ et al., Methylation of lysine 4 on histone H3 (2007)](https://doi.org/10.1038/nrm2211)
[Laure L et al., KAT6B mutation causes distinctive developmental syndromes (2012)](https://doi.org/10.1016/j.ajhg.2012.03.001)
[Bird A, Wolberger C, Histone acetylation and gene regulation (2015)](https://doi.org/10.1101/gad.267955.115)
[Musselman CA, Khorasanizadeh S, Histone modifications in transcriptional regulation (2012)](https://doi.org/10.1038/nrg3273)
[Yang X et al., KAT6A and KAT6B in cancer (2020)](https://doi.org/10.3389/fonc.2020.558901)
[Sun M et al., Histone acetylation in Alzheimer's disease (2019)](https://doi.org/10.1016/j.pnpbp.2019.109686)
[Yang L et al., Epigenetic regulation in neurodegenerative diseases (2022)](https://doi.org/10.14336/AD.2022.0101)
[Yu X et al., KAT6B in brain development (2019)](https://doi.org/10.1007/s12031-019-01283-6)
[Zhang Y et al., Targeting histone acetyltransferases for cancer therapy (2021)](https://doi.org/10.1016/j.semcancer.2020.05.012)
[Li Z et al., KAT6B and KAT6A structural and functional insights (2020)](https://doi.org/10.1007/s00018-020-03589-3)