REST (RE1-Silencing Transcription Factor)
A master regulator of neuronal gene silencing with dual roles in tumor suppression and oncogenesis.
Gene Information Card
| Symbol | REST |
|---|---|
| Full Name | RE1-silencing transcription factor |
| Gene Type | Protein coding |
| Chromosomal Location | 4q12 |
| NCBI Gene ID | 5978 ncbi.nlm.nih.gov/gene/5978 |
| Ensembl ID | ENSG00000084093 |
| UniProt ID | Q13127 |
| OMIM ID | 600571 |
| HGNC ID | 9966 |
| Aliases | NRSF, XBR, WT6 |
Description
REST (RE1-silencing transcription factor), also known as NRSF (neuron-restrictive silencer factor), is a zinc-finger transcription factor that represses neuronal gene expression in non-neuronal tissues. It binds to a conserved 21-bp DNA motif called RE1 (repressor element 1) and recruits co-repressor complexes (e.g., Sin3A, CoREST) to modify chromatin. REST is critical for neurogenesis, maintaining pluripotency, and has context-dependent roles in cancer, acting as a tumor suppressor in some tissues and an oncogene in others.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Wilms tumor | REST is a tumor suppressor; loss of function (mutations, deletions) leads to aberrant neuronal gene expression in kidney cells. | COSMIC, ClinVar |
| Huntington's disease | Mutant huntingtin disrupts REST nuclear localization, altering gene expression in neurons. | NCBI, OMIM |
| Medulloblastoma | REST overexpression maintains neural stem cell-like state, promoting tumorigenesis. | COSMIC, PubMed |
| Breast cancer | REST expression is altered; low expression correlates with poor prognosis in some subtypes. | COSMIC, PubMed |
| Colorectal cancer | REST mutations (loss-of-function) are recurrent, suggesting tumor suppressor role. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 0.0 | Not detected (low in adult neurons) – REST is repressed in mature neurons |
| Heart | 0.0 | Not detected |
| Liver | 0.0 | Not detected |
| Kidney | 0.0 | Not detected (but fetal kidney has high expression) |
| Testis | 0.0 | Not detected |
| Placenta | 0.0 | Not detected |
| Lung | 0.0 | Not detected |
| Muscle | 0.0 | Not detected |
| Pancreas | 0.0 | Not detected |
| Spleen | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 0.0 | Not expressed (cervical cancer) |
| K562 | 0.0 | Not expressed (leukemia) |
| MCF7 | 0.0 | Not expressed (breast cancer) |
| A549 | 0.0 | Not expressed (lung cancer) |
| HepG2 | 0.0 | Not expressed (liver cancer) |
| SH-SY5Y | 0.0 | Not expressed (neuroblastoma) – but REST is expressed in neural progenitors |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1003C>T (p.Arg335Ter) | Nonsense | Rare (0.1% in COSMIC) | Loss of function; truncated protein, loss of DNA binding |
| c.1129G>A (p.Gly377Arg) | Missense | 0.05% in COSMIC | Likely loss of function; altered zinc finger domain |
| c.1600_1601del (p.Glu534fs) | Frameshift | 0.02% in COSMIC | Loss of function; premature stop |
| Whole gene deletion | Copy number loss | Observed in Wilms tumor | Loss of function; tumor suppressor inactivation |
Mutation functional classification
Loss of Function (LOF)
Most REST mutations in cancer are loss-of-function, leading to derepression of neuronal genes and promoting tumorigenesis in certain tissues.
Gain of Function (GOF)
REST amplification or overexpression can act as an oncogene in medulloblastoma and other neural tumors, maintaining stemness.
Dominant Negative (DN)
Some truncated REST isoforms may act as dominant-negative, interfering with wild-type REST 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 |
| • Negative regulation of transcription by RNA polymerase II | • Nervous system development |
| • Chromatin remodeling |
Pathways
• Neuronal differentiation
• Chromatin organization
• Gene silencing by RNA polymerase II
• Notch signaling (crosstalk)
• p53 pathway (interaction)
Protein Summary
The REST protein is a 1097-amino acid transcription factor with an N-terminal repressor domain, a central DNA-binding domain containing eight zinc fingers, and a C-terminal repressor domain. It recruits histone deacetylases (HDAC1/2) and other co-repressors to silence target genes. REST is essential for maintaining the non-neuronal phenotype of non-neural cells and for regulating neural stem cell differentiation. Its expression is tightly regulated during development, and dysregulation contributes to various cancers and neurological disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| REST Knockout HEK293 Cell Line | EDJ-KQ5652 | Human | 5978 | Details Get a Quote |
| REST Knockout A-549 Cell Line | EDJ-KQ28991 | Human | 5978 | Details Get a Quote |
| REST Knockout HCT 116 Cell Line | EDJ-KQ28992 | Human | 5978 | Details Get a Quote |
| REST Knockout HeLa Cell Line | EDJ-KQ28993 | Human | 5978 | Details Get a Quote |
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