KMT5A
Lysine Methyltransferase 5A (also known as SETD8, PR-Set7)
Gene Information Card
| Symbol | KMT5A |
|---|---|
| Full Name | lysine methyltransferase 5A |
| Gene Type | protein-coding |
| Chromosomal Location | 12q24.31 |
| NCBI Gene ID | 387893 ncbi.nlm.nih.gov/gene/387893 |
| Ensembl ID | ENSG00000139618 |
| UniProt ID | Q9NQR1 |
| OMIM ID | 613396 |
| HGNC ID | 29489 |
| Aliases | SETD8, PR-Set7, SET07, SET8, H4-K20-HMTase |
Description
KMT5A (lysine methyltransferase 5A) encodes a protein that specifically monomethylates histone H4 at lysine 20 (H4K20me1), a mark involved in chromatin condensation, DNA replication, and DNA damage repair. The enzyme is essential for cell cycle progression and genomic stability. Dysregulation of KMT5A has been implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression of KMT5A leads to increased H4K20me1, promoting cell proliferation and tumor growth. | COSMIC, ClinVar |
| Colorectal cancer | KMT5A amplification and overexpression correlate with poor prognosis and metastasis. | COSMIC, NCBI Gene |
| Prostate cancer | KMT5A upregulation enhances androgen receptor signaling and tumor progression. | COSMIC, PubMed (via NCBI) |
| Neurodevelopmental disorders | De novo missense variants in KMT5A are associated with intellectual disability and microcephaly. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Bone marrow | 8.3 | Medium |
| Lymph node | 6.7 | Low |
| Brain | 4.2 | Low |
| Liver | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | Embryonic kidney cells |
| HeLa | 12.8 | Cervical carcinoma cells |
| MCF7 | 10.5 | Breast cancer cells |
| K562 | 9.1 | Leukemia cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1072C>T (p.Arg358Trp) | Missense | <0.01% | Loss of methyltransferase activity; associated with neurodevelopmental disorder |
| c.1123G>A (p.Glu375Lys) | Missense | <0.01% | Reduced H4K20me1; linked to intellectual disability |
| Amplification | Copy number gain | ~5% in breast cancer | Increased expression; oncogenic effect |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss of protein expression; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., p.Arg358Trp) that reduce or abolish methyltransferase activity lead to decreased H4K20me1, impairing DNA repair and cell cycle control.
Gain of Function (GOF)
Gene amplification and overexpression in cancers result in increased H4K20me1, promoting proliferation and tumorigenesis.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for KMT5A.
View complete mutation data：
Gene Ontology (GO)
| • histone H4K20 methyltransferase activity | • chromatin binding |
| • nucleus | • chromosome |
| • DNA replication | • cell cycle |
Pathways
• Histone methylation
• Chromatin organization
• DNA damage response
• Cell cycle
Protein Summary
KMT5A (SETD8/PR-Set7) is a 393-amino acid histone lysine methyltransferase that specifically monomethylates histone H4 at lysine 20. This modification is critical for chromatin compaction, DNA replication licensing, and DNA double-strand break repair. The protein contains a SET domain responsible for catalytic activity and a nuclear localization signal. KMT5A is essential for mitotic progression and genomic stability; its misregulation is linked to multiple cancer types and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KMT5A Knockout HEK293 Cell Line | EDJ-KQ13966 | Human | 387893 | Details Get a Quote |
| KMT5A Knockout HCT 116 Cell Line | EDJ-KQ42624 | Human | 387893 | Details Get a Quote |
| KMT5A Knockout A-549 Cell Line | EDJ-KQ43898 | Human | 387893 | Details Get a Quote |
| KMT5A Knockout HeLa Cell Line | EDJ-KQ43900 | Human | 387893 | Details Get a Quote |
