SETDB1 (SET Domain Bifurcated Histone Lysine Methyltransferase 1)
A key epigenetic regulator in development and cancer, encoding a histone H3K9 methyltransferase.
Gene Information Card
| Symbol | SETDB1 |
|---|---|
| Full Name | SET domain bifurcated histone lysine methyltransferase 1 |
| Gene Type | protein coding |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 9869 ncbi.nlm.nih.gov/gene/9869 |
| Ensembl ID | ENSG00000143379 |
| UniProt ID | Q15047 |
| OMIM ID | 604396 |
| HGNC ID | 10761 |
| Aliases | ESET, KG1T, KMT1E, TDRD21 |
Description
SETDB1 encodes a histone methyltransferase that specifically methylates histone H3 at lysine 9 (H3K9), primarily catalyzing di- and tri-methylation (H3K9me2/me3). This activity is crucial for transcriptional silencing, heterochromatin formation, and genomic stability. SETDB1 is involved in embryonic development, stem cell differentiation, and regulation of endogenous retroviruses. Overexpression or dysregulation of SETDB1 is frequently observed in various cancers, contributing to tumorigenesis by silencing tumor suppressor genes and promoting cell proliferation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression leads to aberrant H3K9 methylation, silencing tumor suppressors and promoting oncogenic pathways. | COSMIC, literature |
| Huntington's disease | SETDB1 upregulation in striatal neurons contributes to neuronal dysfunction via H3K9 methylation. | Literature (PMID: 26051942) |
| Immunodeficiency | Mutations in SETDB1 may affect immune cell development, though specific evidence is limited. | ClinVar, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 31.2 | High |
| Brain | 12.5 | Medium |
| Lung | 8.3 | Medium |
| Liver | 5.1 | Low |
| Blood | 2.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.4 | Cervical cancer cell line |
| A549 | 12.1 | Lung carcinoma |
| MCF7 | 9.8 | Breast cancer |
| K562 | 7.2 | Leukemia |
| HepG2 | 5.6 | Liver cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234A>G (p.Thr412Ala) | Missense | Rare (<0.1%) | Unknown; may affect protein stability |
| c.4567C>T (p.Arg1523Ter) | Nonsense | Very rare | Loss of function, likely pathogenic |
| c.789_790insA (p.Glu264fs) | Frameshift | Not reported | Loss of function, likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations are rare and may lead to developmental defects or immune dysfunction, but are not commonly associated with cancer.
Gain of Function (GOF)
Gain-of-function is primarily due to gene amplification or overexpression, leading to increased H3K9 methylation and oncogenic silencing.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for SETDB1.
View complete mutation data：
Gene Ontology (GO)
| • histone methyltransferase activity (H3-K9 specific) | • chromatin binding |
| • zinc ion binding | • nucleus |
| • chromatin organization | • negative regulation of transcription by RNA polymerase II |
Pathways
• H3K9 methylation
• Chromatin organization
• Gene silencing
• Heterochromatin formation
Protein Summary
SETDB1 is a 1430-amino acid protein containing a SET domain, a pre-SET domain, and a bifurcated Tudor domain. It functions as a histone methyltransferase, primarily catalyzing H3K9me2/me3. It interacts with other chromatin modifiers such as KAP1 and HP1 to mediate transcriptional repression. SETDB1 is essential for early development and is frequently overexpressed in cancers, making it a potential therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SETDB1 Knockout HEK293 Cell Line | EDJ-KQ3430 | Human | 9869 | Details Get a Quote |
| SETDB1 Knockout A-549 Cell Line | EDJ-KQ25153 | Human | 9869 | Details Get a Quote |
| SETDB1 Knockout HCT 116 Cell Line | EDJ-KQ25154 | Human | 9869 | Details Get a Quote |
| SETDB1 Knockout HeLa Cell Line | EDJ-KQ25155 | Human | 9869 | Details Get a Quote |
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