SOX4 Gene: SRY-Box Transcription Factor 4 - Function, Disease Associations, and Expression
A comprehensive biomedical overview of SOX4, a key developmental transcription factor implicated in cancer and congenital disorders.
Gene Information Card
| Symbol | SOX4 |
|---|---|
| Full Name | SRY-box transcription factor 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 6p22.3 |
| NCBI Gene ID | 6659 ncbi.nlm.nih.gov/gene/6659 |
| Ensembl ID | ENSG00000124766 |
| UniProt ID | Q06945 |
| OMIM ID | 602903 |
| HGNC ID | 11200 |
| Aliases | EVI16, MGC119586, MGC119587, MGC119588, MGC119589 |
Description
SOX4 (SRY-box transcription factor 4) is a member of the SOX (SRY-related HMG-box) family of transcription factors. It plays a critical role in embryonic development, particularly in the heart, nervous system, and immune system. SOX4 is involved in cell fate determination, differentiation, and proliferation. It is frequently overexpressed in various cancers and has been implicated in tumor progression and metastasis. Additionally, mutations in SOX4 are associated with neurodevelopmental disorders and congenital anomalies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression of SOX4 promotes tumor cell proliferation, migration, and invasion through regulation of target genes involved in epithelial-mesenchymal transition (EMT) and apoptosis. | High expression observed in breast, prostate, lung, and colorectal cancers; functional studies in cell lines and animal models. |
| Congenital heart disease | SOX4 is essential for cardiac outflow tract and valve development; mutations or dysregulation lead to cardiac malformations. | Mouse knockout models show embryonic lethality with heart defects; human studies link SOX4 variants to congenital heart disease. |
| Neurodevelopmental disorders | De novo mutations in SOX4 cause intellectual disability and developmental delay, likely due to haploinsufficiency or dominant-negative effects. | Exome sequencing studies in patients with neurodevelopmental phenotypes. |
| Autoimmune diseases | SOX4 regulates immune cell differentiation and function; altered expression is associated with autoimmune conditions like rheumatoid arthritis and systemic lupus erythematosus. | Gene expression studies and animal models. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 10.2 | Medium |
| Brain | 8.5 | Medium |
| Lung | 6.3 | Low |
| Liver | 3.1 | Low |
| Kidney | 7.8 | Medium |
| Testis | 12.4 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 15.3 | High expression |
| MCF7 (breast cancer) | 18.7 | High expression |
| A549 (lung cancer) | 9.2 | Medium expression |
| HepG2 (liver cancer) | 4.5 | Low expression |
| K562 (leukemia) | 11.8 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.470G>A (p.Arg157His) | Missense | Rare (0.01%) | Loss of DNA-binding activity, leading to reduced transcriptional activity. |
| c.541C>T (p.Arg181Trp) | Missense | Rare (0.005%) | Disrupts HMG domain, affecting DNA binding and protein stability. |
| c.1A>G (p.Met1Val) | Start codon loss | Very rare | Loss of translation initiation, likely causing haploinsufficiency. |
| c.622_623del (p.Leu208ValfsTer3) | Frameshift | Rare | Premature truncation, loss of function. |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations in SOX4 are loss-of-function, leading to haploinsufficiency or dominant-negative effects, particularly in neurodevelopmental disorders.
Gain of Function (GOF)
In cancer, SOX4 overexpression acts as a gain-of-function, promoting oncogenic pathways, but somatic mutations are rarely gain-of-function.
Dominant Negative (DN)
Some missense mutations in the HMG domain may act as dominant-negative by binding DNA but failing to activate transcription, interfering with wild-type SOX4 function.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • chromatin binding | • protein dimerization activity |
| • regulation of transcription by RNA polymerase II | • cell differentiation |
| • embryonic development | • heart development |
| • nervous system development | • immune system development |
Pathways
• Wnt signaling pathway
• TGF-beta signaling pathway
• Apoptosis regulation
• Epithelial-mesenchymal transition (EMT)
• Notch signaling pathway
Protein Summary
The SOX4 protein is a 474-amino acid transcription factor containing a highly conserved HMG (high mobility group) DNA-binding domain. It binds to the consensus sequence (A/T)(A/T)CAA(A/T)G and regulates gene expression by interacting with other transcription factors and co-activators. SOX4 is involved in chromatin remodeling and transcriptional activation or repression. It is phosphorylated and ubiquitinated, affecting its stability and activity. The protein is predominantly nuclear and is expressed in various tissues during development and in adult stem cells.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SOX4 Knockout HEK293 Cell Line | EDJ-KQ1107 | Human | 6659 | Details Get a Quote |
| SOX4 Knockout A-549 Cell Line | EDJ-KQ20288 | Human | 6659 | Details Get a Quote |
| SOX4 Knockout HCT 116 Cell Line | EDJ-KQ20289 | Human | 6659 | Details Get a Quote |
| SOX4 Knockout HeLa Cell Line | EDJ-KQ20290 | Human | 6659 | Details Get a Quote |
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