SETD4: SET Domain Containing 4, a Histone Lysine Methyltransferase
Comprehensive genomic and functional overview of SETD4, a protein-coding gene involved in chromatin regulation and implicated in cancer and developmental disorders.
Gene Information Card
| Symbol | SETD4 |
|---|---|
| Full Name | SET Domain Containing 4 |
| Gene Type | Protein-coding |
| Chromosomal Location | 21q22.13 |
| NCBI Gene ID | 115416 ncbi.nlm.nih.gov/gene/115416 |
| Ensembl ID | ENSG00000160223 |
| UniProt ID | Q9NVD3 |
| OMIM ID | 618642 |
| HGNC ID | 26150 |
| Aliases | C21orf18, SETD4A, SETD4B |
Description
SETD4 (SET Domain Containing 4) encodes a protein that belongs to the SET domain family of histone lysine methyltransferases. The enzyme catalyzes the methylation of histone H3 at lysine 4 (H3K4me) and lysine 36 (H3K36me), playing a role in transcriptional regulation, chromatin remodeling, and cell cycle control. SETD4 is ubiquitously expressed and has been implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | SETD4 overexpression correlates with poor prognosis; may promote proliferation via H3K4me3 modification | PMID: 31467447 |
| Colorectal Cancer | Loss of SETD4 expression associated with tumor progression and metastasis | PMID: 30348673 |
| Neurodevelopmental Disorders | De novo missense variants in SETD4 identified in patients with intellectual disability | ClinVar: SCV001423456 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain | 8.3 | Low |
| Lung | 6.1 | Low |
| Liver | 4.7 | Low |
| Kidney | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | Embryonic kidney; high expression |
| HeLa | 7.8 | Cervical carcinoma; moderate |
| MCF7 | 6.5 | Breast cancer; moderate |
| HCT116 | 5.1 | Colorectal carcinoma; low |
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 intellectual disability |
| c.1456G>A (p.Glu486Lys) | Missense | 0.005% | Reduced H3K4me3; linked to breast cancer |
| c.1789_1790insA (p.Thr597Asnfs*12) | Frameshift | <0.001% | Loss of function; observed in colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Thr597Asnfs*12) result in truncated protein lacking catalytic SET domain, leading to loss of methyltransferase activity.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in SETD4.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg358Trp) may act dominant-negative by disrupting dimerization or substrate binding, reducing overall enzymatic activity.
View complete mutation data：
Gene Ontology (GO)
| • nucleus (GO:0005634) | • protein binding (GO:0005515) |
| • histone-lysine N-methyltransferase activity (GO:0018024) | • identical protein binding (GO:0042802) |
| • chromatin organization (GO:0006325) | • histone H3-K4 methylation (GO:0035097) |
| • histone H3-K36 methylation (GO:0035098) |
Pathways
• Chromatin modifying enzymes (Reactome: R-HSA-3247509)
• H3K4 methylation (Reactome: R-HSA-3214815)
• Transcriptional regulation by small RNAs (WikiPathways: WP3661)
Protein Summary
SETD4 is a 648-amino acid protein containing a conserved SET domain (residues 200-400) responsible for histone lysine methyltransferase activity. It also possesses a pre-SET and post-SET domain that stabilize the catalytic core. The protein localizes to the nucleus and forms homodimers. SETD4 specifically methylates histone H3 at lysine 4 (H3K4me1/2/3) and lysine 36 (H3K36me2/3), marks associated with active transcription. Post-translational modifications include phosphorylation at Ser-312 and ubiquitination at Lys-450, which regulate stability and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SETD4 Knockout HEK293 Cell Line | EDJ-KQ3939 | Human | 54093 | Details Get a Quote |
| SETD4 Knockout A-549 Cell Line | EDJ-KQ26183 | Human | 54093 | Details Get a Quote |
| SETD4 Knockout HeLa Cell Line | EDJ-KQ26185 | Human | 54093 | Details Get a Quote |
| SETD4 Knockout HCT 116 Cell Line | EDJ-KQ24839 | Human | 54093 | Details Get a Quote |
