SIX4: Sine Oculis Homeobox Homolog 4
A transcription factor involved in development, myogenesis, and cancer.
Gene Information Card
| Symbol | SIX4 |
|---|---|
| Full Name | SIX homeobox 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 14q23.1 |
| NCBI Gene ID | 51804 ncbi.nlm.nih.gov/gene/51804 |
| Ensembl ID | ENSG00000100644 |
| UniProt ID | Q9UIU6 |
| OMIM ID | 606342 |
| HGNC ID | 10891 |
| Aliases | AREC3, SIX4_HUMAN |
Description
SIX4 is a member of the SIX family of homeobox transcription factors, which are homologs of the Drosophila sine oculis gene. It plays a critical role in embryonic development, particularly in myogenesis, neurogenesis, and organogenesis. SIX4 regulates gene expression by binding to DNA as a dimer with co-factors such as EYA proteins. It is also implicated in cancer progression and metastasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | SIX4 overexpression promotes epithelial-mesenchymal transition (EMT) and metastasis via activation of TGF-β signaling. | PMID: 25944712 |
| Hepatocellular Carcinoma | SIX4 upregulation correlates with poor prognosis and enhances cell proliferation and invasion. | PMID: 28771620 |
| Rhabdomyosarcoma | SIX4 is essential for myogenic differentiation and is aberrantly expressed in rhabdomyosarcoma. | PMID: 20010870 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal Muscle | 12.5 | High |
| Heart | 8.3 | Medium |
| Kidney | 6.1 | Medium |
| Liver | 2.4 | Low |
| Brain | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung) | 5.2 | Moderate expression |
| MCF7 (Breast) | 7.8 | High expression |
| HepG2 (Liver) | 3.1 | Low expression |
| RD (Rhabdomyosarcoma) | 15.4 | Very high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.100C>T (p.Arg34Trp) | Missense | <0.01% | Unknown functional impact |
| c.457G>A (p.Glu153Lys) | Missense | <0.01% | Reported in COSMIC as likely neutral |
| c.1234_1235insA | Frameshift | <0.01% | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations are predicted to cause loss of function, potentially impairing developmental processes.
Gain of Function (GOF)
Amplification or overexpression of SIX4 in cancers may act as a gain-of-function mechanism promoting oncogenesis.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for SIX4.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • regulation of transcription by RNA polymerase II | • skeletal muscle cell differentiation |
| • positive regulation of cell migration |
Pathways
• TGF-beta signaling pathway
• Epithelial-mesenchymal transition
• Myogenesis
Protein Summary
SIX4 is a 284-amino acid protein containing a homeodomain and a SIX domain, which mediate DNA binding and protein-protein interactions. It functions as a transcriptional activator or repressor depending on co-factor binding. The protein is predominantly nuclear and is critical for muscle development and regeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIX4 Knockout HEK293 Cell Line | EDJ-KQ11223 | Human | 51804 | Details Get a Quote |
| SIX4 Knockout HeLa Cell Line | EDJ-KQ37971 | Human | 51804 | Details Get a Quote |
| SIX4 Knockout A-549 Cell Line | EDJ-KQ39293 | Human | 51804 | Details Get a Quote |
| SIX4 Knockout HCT 116 Cell Line | EDJ-KQ39294 | Human | 51804 | Details Get a Quote |
