KDM6A
Lysine Demethylase 6A: A Key Epigenetic Regulator in Development and Disease
Gene Information Card
| Symbol | KDM6A |
|---|---|
| Full Name | Lysine Demethylase 6A |
| Gene Type | Protein coding |
| Chromosomal Location | Xp11.3 |
| NCBI Gene ID | 7403 ncbi.nlm.nih.gov/gene/7403 |
| Ensembl ID | ENSG00000147050 |
| UniProt ID | O15550 |
| OMIM ID | 300128 |
| HGNC ID | 12637 |
| Aliases | UTX, bA386N14.2, KABUK1 |
Description
KDM6A (lysine demethylase 6A) encodes a histone demethylase that specifically demethylates di- and tri-methylated lysine 27 of histone H3 (H3K27me2/me3), a repressive chromatin mark. It is a component of the MLL2/COMPASS-like complex and plays a critical role in transcriptional activation, embryonic development, and cell differentiation. Loss-of-function mutations in KDM6A are associated with Kabuki syndrome and various cancers, including multiple myeloma and bladder cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Kabuki syndrome | Loss-of-function mutations lead to haploinsufficiency, disrupting H3K27me3 demethylation and gene expression during development | OMIM #300867; ClinVar |
| Multiple myeloma | Somatic mutations and deletions contribute to tumorigenesis by altering epigenetic regulation | COSMIC; NCBI |
| Bladder cancer | Frequent inactivating mutations promote cancer progression through aberrant histone methylation | COSMIC; NCBI |
| Acute myeloid leukemia | Recurrent mutations impair hematopoietic differentiation | COSMIC; NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Brain | 8.3 | Low |
| Kidney | 15.2 | Medium |
| Liver | 10.1 | Medium |
| Lung | 9.7 | Low |
| Testis | 18.4 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.5 | Embryonic kidney cells |
| K562 | 11.2 | Leukemia cell line |
| MCF7 | 9.8 | Breast cancer cell line |
| HepG2 | 13.1 | Liver cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2971C>T (p.Gln991*) | Nonsense | <1% | Loss of function; truncation |
| c.3682_3683del (p.Glu1228fs) | Frameshift | <1% | Loss of function; protein truncation |
| c.1120G>A (p.Gly374Arg) | Missense | <0.5% | Likely loss of function; impaired demethylase activity |
| c.2071C>T (p.Arg691*) | Nonsense | <1% | Loss of function; nonsense-mediated decay |
Mutation functional classification
Loss of Function (LOF)
Most KDM6A mutations in Kabuki syndrome and cancer are loss-of-function, leading to reduced H3K27me3 demethylation and altered gene expression.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented for KDM6A; the gene primarily acts as a tumor suppressor.
Dominant Negative (DN)
Dominant-negative effects are not established; haploinsufficiency is the primary mechanism in Kabuki syndrome.
View complete mutation data：
Gene Ontology (GO)
| • Histone H3K27 demethylase activity (GO:0071558) | • Chromatin binding (GO:0003682) |
| • Transcription coactivator activity (GO:0003713) | • Nucleus (GO:0005634) |
| • DNA-templated (GO:0006355) |
Pathways
• Chromatin modifying enzymes (Reactome: R-HSA-3247509)
• Transcriptional regulation by MLL2/COMPASS complex (Reactome: R-HSA-8878171)
• Epigenetic regulation of gene expression (KEGG: hsa05202)
Protein Summary
KDM6A (UTX) is a 1401-amino acid protein containing a JmjC domain responsible for demethylase activity. It removes methyl groups from H3K27me2/me3, promoting an open chromatin state and gene activation. The protein interacts with multiple transcription factors and chromatin remodelers, including MLL2, and is essential for normal development. Mutations that disrupt its catalytic activity or protein stability lead to disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KDM6A Knockout HEK293 Cell Line | EDJ-KQ1956 | Human | 7403 | Details Get a Quote |
| KDM6A Knockout A-549 Cell Line | EDJ-KQ21908 | Human | 7403 | Details Get a Quote |
| KDM6A Knockout HCT 116 Cell Line | EDJ-KQ21909 | Human | 7403 | Details Get a Quote |
| KDM6A Knockout HeLa Cell Line | EDJ-KQ21910 | Human | 7403 | Details Get a Quote |
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