# REST

Source: https://onco.cc/targets/rest/  
OnCo record `rest` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

REST (RE1-silencing transcription factor) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Wilms tumour.

## Summary

Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells. Restricts the expression of neuronal genes by associating with two distinct corepressors, SIN3A and RCOR1, which in turn recruit histone deacetylase to the promoters of REST-regulated genes. Mediates repression by recruiting the BHC complex at RE1/NRSE sites which acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier.

Open Targets scores its association with cancer at 0.63 (direct and indirect evidence; datatypes literature 0.99, genetic association 0.70, somatic mutation 0.47, genetic literature 0.58). IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Wilms' Tumour.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: RE1 silencing transcription factor; RE1-silencing transcription factor; DFNA27
- Tags: cancer-genes-wave
- Symbol: REST
- Class: tumor-suppressor
- Biology: Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells. Restricts the expression of neuronal genes by associating with two distinct corepressors, SIN3A and RCOR1, which in turn recruit histone deacetylase to the promoters of REST-regulated genes. Mediates repression by recruiting the BHC complex at RE1/NRSE sites which acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier. Transcriptional repression by REST-CDYL via the recruitment of histone methyltransferase EHMT2 may be important in transformation suppression. Represses the expression of SRRM4 in non-neural cells to prevent the activation of neural-specific splicing events and to prevent production of REST isoform 3. Repressor activity may be inhibited by forming heterodimers with isoform 3, thereby preventing binding to NRSE or binding to corepressors and leading to derepression of target genes. Location: Nucleus; Cytoplasm (UniProt). Locus 4q12 (HGNC).
- Where found: Wilms tumour: IntOGen driver in 1 cohort (WT)

## Notes

- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it a loss-of-function (LoF) driver in 1 cohort. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.

## Sources

- HGNC HGNC:9966: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9966
- UniProt Q13127: https://www.uniprot.org/uniprotkb/Q13127/entry
- NCBI Gene 5978: https://www.ncbi.nlm.nih.gov/gene/5978
- Ensembl ENSG00000084093: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000084093

## Connected records

- collections: [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Wilms tumour (nephroblastoma)](https://onco.cc/cancers/wilms-tumor/)

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JSON: https://onco.cc/api/v1/entities/rest.json