SETD3: SET Domain Containing 3, Actin Histidine Methyltransferase
A dual-function methyltransferase involved in actin methylation and viral replication regulation
Gene Information Card
| Symbol | SETD3 |
|---|---|
| Full Name | SET Domain Containing 3, Actin Histidine Methyltransferase |
| Gene Type | Protein coding |
| Chromosomal Location | 14q32.2 |
| NCBI Gene ID | 84193 ncbi.nlm.nih.gov/gene/84193 |
| Ensembl ID | ENSG00000100804 |
| UniProt ID | Q86TU7 |
| OMIM ID | 617860 |
| HGNC ID | 26020 |
| Aliases | C14orf154, HsT16998, SETD3A, SETD3B |
Description
SETD3 encodes a methyltransferase that catalyzes the methylation of actin at histidine 73 (H73), a post-translational modification important for actin cytoskeleton dynamics. The protein also possesses a SET domain and is involved in transcriptional regulation. SETD3 has been implicated in viral replication, particularly for enteroviruses, and is associated with various cancers and developmental processes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | SETD3 overexpression or mutation may alter actin methylation and cell migration, contributing to tumor progression. | COSMIC; literature (PMID: 31073040) |
| Enterovirus infection | SETD3 is required for viral replication; loss of SETD3 reduces viral RNA synthesis. | Literature (PMID: 28296633, 31073040) |
| Developmental disorders | Rare variants in SETD3 have been reported in patients with intellectual disability and congenital anomalies. | ClinVar; literature (PMID: 31073040) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 12.5 | Medium |
| Heart | 10.8 | Medium |
| Brain | 6.2 | Low |
| Liver | 4.1 | Low |
| Testis | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 8.9 | Cervical cancer cell line |
| HEK293 | 7.3 | Embryonic kidney cell line |
| K562 | 6.1 | Leukemia cell line |
| A549 | 5.4 | Lung cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1072C>T (p.Arg358Trp) | Missense | <0.01% | Unknown; reported in ClinVar as uncertain significance |
| c.1435G>A (p.Gly479Arg) | Missense | <0.01% | Unknown; reported in ClinVar as uncertain significance |
| c.1846C>T (p.Arg616Cys) | Missense | <0.01% | Unknown; reported in ClinVar as uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in SETD3 reduce actin H73 methylation and impair enterovirus replication in vitro.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • nucleus (GO:0005634) |
| • cytoplasm (GO:0005737) | • methyltransferase activity (GO:0008168) |
| • histone-lysine N-methyltransferase activity (GO:0018024) | • methylation (GO:0032259) |
| • identical protein binding (GO:0042802) | • actin filament binding (GO:0051015) |
| • ubiquitin protein ligase activity (GO:0061630) |
Pathways
• Actin cytoskeleton regulation
• Histone methylation
• Enterovirus life cycle
Protein Summary
SETD3 is a 645-amino acid protein containing a SET domain and a methyltransferase domain. It catalyzes the methylation of actin at histidine 73, which is essential for normal actin function and cell motility. The protein also has histone methyltransferase activity and can act as a ubiquitin ligase. SETD3 is required for enterovirus replication, making it a potential antiviral target. Expression is highest in skeletal muscle and heart, with lower levels in other tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SETD3 Knockout HEK293 Cell Line | EDJ-KQ10009 | Human | 84193 | Details Get a Quote |
| SETD3 Knockout HCT 116 Cell Line | EDJ-KQ36991 | Human | 84193 | Details Get a Quote |
| SETD3 Knockout HeLa Cell Line | EDJ-KQ36992 | Human | 84193 | Details Get a Quote |
| SETD3 Knockout A-549 Cell Line | EDJ-KQ35775 | Human | 84193 | Details Get a Quote |
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