REST

Summary

REST (RE1 silencing transcription factor, HGNC:9966) is a protein-coding gene on chromosome 4q12, encoding RE1-silencing transcription factor (Q13127). Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells.

This gene was initially identified as a transcriptional repressor that represses neuronal genes in non-neuronal tissues. However, depending on the cellular context, this gene can act as either an oncogene or a tumor suppressor. The encoded protein is a member of the Kruppel-type zinc finger transcription factor family. It represses transcription by binding a DNA sequence element called the neuron-restrictive silencer element. The protein is also found in undifferentiated neuronal progenitor cells and it is thought that this repressor may act as a master negative regulator of neurogenesis. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 5978 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Wilms tumor 6 (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 23
• Clinical variants (ClinVar): 782 total — 16 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 35
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Transcription factor: yes — 92 downstream targets (CollecTRI)
• MANE Select transcript: NM_005612

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9966
Approved symbol	REST
Name	RE1 silencing transcription factor
Location	4q12
Locus type	gene with protein product
Status	Approved
Aliases	NRSF, XBR
Ensembl gene	ENSG00000084093
Ensembl biotype	protein_coding
OMIM	600571
Entrez	5978

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 16 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000309042, ENST00000514063, ENST00000611211, ENST00000616975, ENST00000619101, ENST00000622863, ENST00000638187, ENST00000640168, ENST00000640343, ENST00000675105, ENST00000675249, ENST00000675341, ENST00000878529, ENST00000931527, ENST00000931528, ENST00000931529, ENST00000931530, ENST00000946695

RefSeq mRNA: 3 — MANE Select: NM_005612 NM_001193508, NM_001363453, NM_005612

CCDS: CCDS3509

Canonical transcript exons

ENST00000309042 — 4 exons

Exon	Start	End
ENSE00001187189	56910630	56911536
ENSE00001187202	56907900	56908213
ENSE00001187204	56929841	56935844
ENSE00003691951	56919787	56919870

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 92.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.2323 / max 242.9265, expressed in 1812 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47743	30.4303	1809
47747	2.8771	1293
47742	1.7866	1087
47746	0.7171	407
47745	0.2709	142
203182	0.1503	64

Top tissues by expression

291 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.86	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.50	gold quality
adrenal tissue	UBERON:0018303	89.19	gold quality
calcaneal tendon	UBERON:0003701	88.59	gold quality
epithelium of nasopharynx	UBERON:0001951	88.15	gold quality
nasopharynx	UBERON:0001728	88.13	gold quality
colonic epithelium	UBERON:0000397	87.83	gold quality
choroid plexus epithelium	UBERON:0003911	87.48	gold quality
pigmented layer of retina	UBERON:0001782	87.11	gold quality
retina	UBERON:0000966	87.09	gold quality
bone marrow cell	CL:0002092	87.05	gold quality
oral cavity	UBERON:0000167	86.89	gold quality
endometrium	UBERON:0001295	86.86	gold quality
tendon	UBERON:0000043	86.56	gold quality
bone marrow	UBERON:0002371	86.32	gold quality
corpus epididymis	UBERON:0004359	86.28	gold quality
tonsil	UBERON:0002372	86.23	gold quality
superficial temporal artery	UBERON:0001614	86.09	gold quality
buccal mucosa cell	CL:0002336	85.94	gold quality
cauda epididymis	UBERON:0004360	85.93	gold quality
caput epididymis	UBERON:0004358	85.90	gold quality
germinal epithelium of ovary	UBERON:0001304	85.76	gold quality
mammary duct	UBERON:0001765	85.34	gold quality
esophagus squamous epithelium	UBERON:0006920	85.32	gold quality
ventricular zone	UBERON:0003053	85.25	gold quality
epithelium of mammary gland	UBERON:0003244	85.25	gold quality
jejunal mucosa	UBERON:0000399	85.24	gold quality
amniotic fluid	UBERON:0000173	85.15	gold quality
bone element	UBERON:0001474	85.14	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6819	no	1027.51
E-CURD-135	no	622.42
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

92 targets.

Target	Regulation
ACTA1
ADCYAP1	Unknown
APRT
AR	Unknown
AVP	Activation
BCL2L1	Repression
BDNF	Repression
BRINP1	Repression
BSX	Unknown
CACNA1H	Unknown
CALB1
CARTPT	Repression
CD59	Repression
CD74
CDH17
CEL
CELSR3	Repression
CHAT
CHGA	Unknown
CHGB	Unknown
CHRM4
CHRNB2
CRH	Unknown
CYP11B1	Unknown
CYP11B2	Repression
CYP1A1
CYP21A1P	Repression
CYP2E1
DGCR5	Repression
DYRK1A	Unknown

JASPAR motifs

Motif	Name	Family
MA0138.1	REST	Factors with multiple dispersed zinc fingers
MA0138.2	REST	Factors with multiple dispersed zinc fingers
MA0138.3	REST	Factors with multiple dispersed zinc fingers

JASPAR matrix evidence (PMIDs): PMID:17540862

Upstream regulators (CollecTRI, top): AR, CREB1, CTNNB1, HES1, HIP1, NEUROD2, SP1, SP3, STAT1, YY1, ZEB1, ZNF335

miRNA regulators (miRDB)

228 targeting REST, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4803	99.98	71.99	3117

Literature-anchored findings (GeneRIF, showing 40)

• role in blocking the expression of neuronal phenotypic traits in non-neuronal cells (PMID:12192000)
• we have identified a functional binding site for REST in the first intron of the human synaptophysin gene indicating that REST blocks human synaptophysin gene transcription through an intronic neuron-specific silencer element (PMID:12492469)
• Role in the regulation of cholinergic gene expression (PMID:12628452)
• Regulates the expression of Pax4 protein. (PMID:12829700)
• the transcriptional repressor NRSF/REST regulates connexin36 (PMID:14565956)
• NRSF, a transcriptional repressor, selectively regulates expression of multiple fetal cardiac genes, including those for atrial natriuretic peptide, brain natriuretic peptide and alpha-skeletal actin (PMID:14633990)
• REST-dependent proteins are comparably expressed in fetal Down syndrome (DS) and control brains by studies in the 18/19th week of gestation at the protein level; therefore, the REST-hypothesis in DS is not confirmed. (PMID:15068239)
• individual RE1/NRSE sites interact differentially with REST/NRSF within a particular cell type. (PMID:15240883)
• NRSF can function as a repressor of MOR transcription in specific cells, via a mechanism dependent on the mu opioid receptor gene neuron-restrictive silencer element (PMID:15322094)
• interplay between REST and Sp1 determines the cell-specific expression of REST target genes (PMID:15528196)
• results show that REST/NRSF recruits SCPs to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells (PMID:15681389)
• REST is overexpressed in human medulloblastoma tumors (PMID:15767543)
• derepression of NRSF-regulated genes including these neuron-specific genes could contribute to enhance tumorigenicity and also would provide selective markers for Brm/BRG1-deficient tumors (PMID:16247481)
• HES-1 is an upstream negative regulator of REST expression. (PMID:16253247)
• Down-regulation of NRP1 by NRSF overexpression reduced Sema3A activity. It was concluded that NRSF is a transcription factor that silences NRP1 expression and thereby diminishes the Sema3A mediated inhibition of HaCaT keratinocyte migration (PMID:16330548)
• REST/NRSF-interacting LIM domain protein (RILP) is required for REST/NRSF nuclear targeting and function. (PMID:16417580)
• Data suggest that REST/NRSF contains a NLS around ZFD-5, while the putative NLS at residues 512-522 is non-functional. (PMID:16442230)
• abnormal expression of REST/NRSF and MYC in undifferentiated neural stem/progenitor cells causes cerebellum-specific tumors. Furthermore, these results suggest that such a mechanism plays a role in the formation of human medulloblastoma. (PMID:16478988)
• BRG1 facilitates REST repression by increasing the interaction between REST and chromatin (PMID:17023429)
• loss of SMCX activity impairs REST-mediated neuronal gene regulation, thereby contributing to SMCX-associated X-linked mental retardation (PMID:17468742)
• sequence census method was used to map in vivo binding of the neuron-restrictive silencer factor to 1946 locations in the human genome (PMID:17540862)
• these results suggest that REST/NRSF may have an important role in the establishment and/or maintenance of HSV-1 gene silencing during latency by targeting ICP4 expression. (PMID:17555596)
• These findings show abnormal regulation of NRSF/REST as a mechanism associated with the aberrant expression of selected neuron-related proteins, which in turn accumulate in abnormal protein aggregates, in myotilinopathy. (PMID:17823282)
• in undifferentiated human neural stem cells, neuronal genes encoding synaptic vesicle proteins are accessible for the REST mutant and are sensitive to enhanced histone acetylation (PMID:18234667)
• genome-wide scan identified significant evidence for linkage (maximum LOD) score = 4.67 at theta = 0 for D4S398) to markers in a 5.7-cM interval on chromosome 4q12-13.1. The DFNA27 interval spans 8.85 Mb & includes at least 61 predicted and 8 known genes. (PMID:18279434)
• The transcription factor REST is found to modulate transcriptional activation of mu-opioid receptor gene by insulin-like growth factor-I. (PMID:18284609)
• The high levels of REST or its truncated variants found in certain human tumours may contribute to cellular transformation by promoting genomic instability. (PMID:18354482)
• REST is a key target in beta-TRCP-driven transformation and the beta-TRCP-REST axis is a new regulatory pathway controlling neurogenesis (PMID:18354483)
• critical role of REST target genes in pancreatic beta cells; evidence that the downregulation is detrimental for the exocytosis of large dense core vesicles. (PMID:18385973)
• The REST haplotypes in combination with the BDNF Met66 polymorphism did not reduce cognitive performance more than the independent influence of the Met66 allele. (PMID:18518926)
• Results demonstrate that NRSF silencing can activate some neuronal genes and induce neuronal differentiation of mesenchymal stem cells. (PMID:18570921)
• This study shows REST as the limiting gene in the generation of functional mature neurons from MSCs. (PMID:18691653)
• DYRK1A-mediated deregulation of REST is a very early pathological consequence of trisomy 21 with potential to disturb the development of all embryonic lineages. (PMID:18771760)
• REST/NRSF, dynactin p150(Glued), huntingtin, HAP1, and RILP form a complex involved in the translocation of REST/NRSF into the nucleus and HAP1 controls REST/NRSF cellular localization in neurons (PMID:18922795)
• REST is a transcriptional repressor of neuronal genes. (PMID:18959489)
• The change in expression of sNRSF and TAC1 mRNA following mechanical stimulation in osteoarthritic (OA) but not normal chondrocytes suggests that sNRSF may be involved in the regulation of substance P production in OA cartilage. (PMID:18990442)
• Chromodomain on Y-like (CDYL) is identified as a REST corepressor that physically bridges REST and the histone methylase G9a to repress transcription. (PMID:19061646)
• the activity of the REST sites is dysfunctional in Huntington diseaes (PMID:19134002)
• relevant in the development of dopaminergic and peptidergic neurons from mesenchymal stem cells (PMID:19149626)
• REST-mediated chromatin remodeling is dynamic and complex, with novel histone modifying enzymes (PMID:19173732)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	rest	ENSDARG00000103046
mus_musculus	Rest	ENSMUSG00000029249
rattus_norvegicus	Rest	ENSRNOG00000002074
drosophila_melanogaster	hb	FBGN0001180
drosophila_melanogaster	CG12391	FBGN0033581
caenorhabditis_elegans		WBGENE00001824
caenorhabditis_elegans		WBGENE00012385

Paralogs (29): ZNF446 (ENSG00000083838), ZNF174 (ENSG00000103343), OVOL3 (ENSG00000105261), PLAGL1 (ENSG00000118495), ZSCAN18 (ENSG00000121413), ZNF576 (ENSG00000124444), OVOL2 (ENSG00000125850), PLAGL2 (ENSG00000126003), ZSCAN5A (ENSG00000131848), ZSCAN29 (ENSG00000140265), ZSCAN32 (ENSG00000140987), ZSCAN1 (ENSG00000152467), ZNF18 (ENSG00000154957), ZKSCAN2 (ENSG00000155592), ZNF496 (ENSG00000162714), ZNF202 (ENSG00000166261), ZNF641 (ENSG00000167528), ZNF444 (ENSG00000167685), SCAND1 (ENSG00000171222), ZNF274 (ENSG00000171606), ZNF131 (ENSG00000172262), OVOL1 (ENSG00000172818), ZNF518A (ENSG00000177853), ZNF518B (ENSG00000178163), PLAG1 (ENSG00000181690), ZSCAN5B (ENSG00000197213), ZNF770 (ENSG00000198146), PEG3 (ENSG00000198300), ZSCAN5C (ENSG00000204532)

Protein

Protein identifiers

RE1-silencing transcription factor — Q13127 (reviewed: Q13127)

Alternative names: Neural-restrictive silencer factor, X2 box repressor

All UniProt accessions (8): Q13127, A0A087X1C2, A0A1W2PQA1, A0A6Q8PH19, L0B1S6, L0B1V4, L0B2V9, L0B3M6

UniProt curated annotations — full annotation on UniProt →

Function. 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. Also maintains repression of neuronal genes in neural stem cells, and allows transcription and differentiation into neurons by dissociation from RE1/NRSE sites of target genes. Thereby is involved in maintaining the quiescent state of adult neural stem cells and preventing premature differentiation into mature neurons. Plays a role in the developmental switch in synaptic NMDA receptor composition during postnatal development, by repressing GRIN2B expression and thereby altering NMDA receptor properties from containing primarily GRIN2B to primarily GRIN2A subunits. Acts as a regulator of osteoblast differentiation. Key repressor of gene expression in hypoxia; represses genes in hypoxia by direct binding to an RE1/NRSE site on their promoter regions. May also function in stress resistance in the brain during aging; possibly by regulating expression of genes involved in cell death and in the stress response. Repressor of gene expression in the hippocampus after ischemia by directly binding to RE1/NRSE sites and recruiting SIN3A and RCOR1 to promoters of target genes, thereby promoting changes in chromatin modifications and ischemia-induced cell death. After ischemia, might play a role in repression of miR-132 expression in hippocampal neurons, thereby leading to neuronal cell death. Negatively regulates the expression of SRRM3 in breast cancer cell lines. Binds to the 3’ region of the neuron-restrictive silencer element (NRSE), with lower affinity than full-length REST isoform 1. Exhibits weaker repressor activity compared to isoform 1. May negatively regulate the repressor activity of isoform 1 by binding to isoform 1, thereby preventing its binding to NRSE and leading to derepression of target genes. However, in another study, does not appear to be implicated in repressor activity of a NRSE motif-containing reporter construct nor in inhibitory activity on the isoform 1 transcriptional repressor activity. Post-transcriptional inactivation of REST by SRRM4-dependent alternative splicing into isoform 3 is required in mechanosensory hair cells in the inner ear for derepression of neuronal genes and hearing.

Subunit / interactions. Isoform 1 and isoform 3 form heterodimers. Isoform 3: Forms homodimers and homooligomers; binds to the neuron-restrictive silencer element (NRSE) as monomer. Interacts with SIN3A, SIN3B and RCOR1. Interacts with CDYL. Interacts with EHMT1 and EHMT2 only in the presence of CDYL. Part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2. Interacts (via zinc-finger DNA-binding domain) with ZFP90 (via N- and C-termini); the interaction inhibits REST repressor activity. Interacts (via C2H2-type zinc finger 5) with PRICKLE1. Interacts with FBXW11 and BTRC. Interacts with USP7.

Subcellular location. Nucleus. Cytoplasm Cytoplasm Nucleus Cytoplasm.

Tissue specificity. Expressed in neurons of the prefrontal cortex, in hippocampal pyramidal neurons, dentate gyrus granule neurons and cerebellar Purkinje and granule neurons (at protein level). Expressed in dopaminergic neurons of the substantia nigra (at protein level). Expressed in neural progenitor cells (at protein level). In patients suffering from Alzheimer disease, frontotemporal dementia or dementia with Lewy bodies, decreased nuclear levels have been observed in neurons of the prefrontal cortex and the hippocampus, but not in neurons of the dentate gyrus and cerebellum (at protein level). In patients with Parkinson disease or dementia with Lewy bodies, decreased nuclear levels have been observed in dopaminergic neurons and in cortical neurons and localization to Lewy bodies and pale bodies was detected (at protein level). Expressed at higher levels in weakly invasive breast cancer cell lines and at lower levels in highly invasive breast cancer lines (at protein level). Ubiquitous. Expressed at higher levels in the tissues of the lymphocytic compartment, including spleen, thymus, peripheral blood lymphocytes and ovary.

Post-translational modifications. O-glycosylated. Phosphorylated; phosphorylation is required for ubiquitination. Ubiquitinated; ubiquitination is mediated by BTRC and leads to proteasomal degradation in G2 phase. Ubiquitination increases during neuronal differentiation. Deubiquitinated by USP7; leading to its stabilization and promoting the maintenance of neural progenitor cells.

Disease relevance. Wilms tumor 6 (WT6) [MIM:616806] A pediatric malignancy of kidney, and the most common childhood abdominal malignancy. It is caused by the uncontrolled multiplication of renal stem, stromal, and epithelial cells. Disease susceptibility is associated with variants affecting the gene represented in this entry. Fibromatosis, gingival, 5 (GINGF5) [MIM:617626] An autosomal dominant form of hereditary gingival fibromatosis, a rare condition characterized by a slow, progressive overgrowth of the gingiva. The excess gingival tissue can cover part of or the entire crown, and can result in diastemas, teeth displacement, or retention of primary or impacted teeth. The disease is caused by variants affecting the gene represented in this entry. An intronic variant that affects alternative splicing of REST into isoform 3 and inactivation of REST repressor activity is associated with progressive hearing loss and deafness. Deafness, autosomal dominant, 27 (DFNA27) [MIM:612431] A form of non-syndromic deafness characterized by postlingual, progressive, moderate to profound sensorineural hearing loss. The disease may be caused by variants affecting the gene represented in this entry. An intronic variant that affects alternative splicing of REST and inactivation of REST repressor activity fully segregates with deafness in a 3-generation family.

Domain organisation. The C2H2-type zinc finger 5 is required for nuclear localization.

Induction. Up-regulated by Wnt signaling. Up-regulated in the brain of aging individuals but not in Alzheimer disease patients. Up-regulated by oxidative stress. Down-regulated during neural progenitor cell differentiation.

Miscellaneous. Produced by SRRM4-dependent alternative splicing in neurons and inner ear hair cells. Lacks the four C-terminal zinc fingers and the RCOR1 corepressor interaction site found in full length REST isoform 1, which are required for full DNA-binding and repressive activity.

Isoforms (4)

UniProt ID	Names	Canonical?
Q13127-1	1, REST1	yes
Q13127-2	2
Q13127-3	3, N4, REST4
Q13127-4	4

RefSeq proteins (3): NP_001180437, NP_001350382, NP_005603* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050688	Zinc_finger/UBP_domain	Family
IPR057281	Zfn-C2H2_REST	Domain

Pfam: PF00096, PF24540

UniProt features (62 total): mutagenesis site 13, region of interest 11, zinc finger region 9, sequence variant 9, compositionally biased region 8, splice variant 5, sequence conflict 3, modified residue 2, chain 1, helix 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6DU2	X-RAY DIFFRACTION	2.5
6DU3	X-RAY DIFFRACTION	2.58
2CZY	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13127-F1	49.53	0.02

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 864, 971

Mutagenesis-validated functional residues (13):

Position	Phenotype
91	does not change transcriptional repression activity.
313	lack of deubiquitination by usp7.
420	inhibits transcriptional repression activity.
512–522	no effect on nuclear localization.
512–522	reduced nuclear localization.
593	does not change transcriptional repression activity.
642	does not change transcriptional repression activity.
918	does not change transcriptional repression activity.
1009–1013	loss of interaction with btrc. reduced ubiquitination. decreased proteasomal degradation in g2. decreased average time f
1009	loss of interaction with btrc.
1013	loss of interaction with btrc.
1042	no impact on deubiquitination by usp7.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-3214815	HDACs deacetylate histones
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9031628	NGF-stimulated transcription
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9768777	Regulation of NPAS4 gene transcription

MSigDB gene sets: 0 (showing top):

GO Biological Process (42): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of alternative mRNA splicing, via spliceosome (GO:0000381), response to hypoxia (GO:0001666), hematopoietic progenitor cell differentiation (GO:0002244), response to ischemia (GO:0002931), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), negative regulation of aldosterone biosynthetic process (GO:0032348), cellular response to stress (GO:0033554), somatic stem cell population maintenance (GO:0035019), positive regulation of programmed cell death (GO:0043068), host-mediated suppression of viral transcription (GO:0043922), negative regulation of neuron differentiation (GO:0045665), positive regulation of neuron differentiation (GO:0045666), regulation of osteoblast differentiation (GO:0045667), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of calcium ion-dependent exocytosis (GO:0045955), negative regulation of insulin secretion (GO:0046676), negative regulation of neurogenesis (GO:0050768), nervous system process (GO:0050877), neuromuscular process controlling balance (GO:0050885), detection of mechanical stimulus involved in sensory perception of sound (GO:0050910), auditory receptor cell stereocilium organization (GO:0060088), cardiac muscle cell myoblast differentiation (GO:0060379), cellular response to electrical stimulus (GO:0071257), cellular response to glucocorticoid stimulus (GO:0071385), neuronal stem cell population maintenance (GO:0097150), modification of synaptic structure (GO:0099563), positive regulation of stem cell population maintenance (GO:1902459), negative regulation of miRNA transcription (GO:1902894), negative regulation of cortisol biosynthetic process (GO:2000065), negative regulation of dense core granule biogenesis (GO:2000706), negative regulation of mesenchymal stem cell differentiation (GO:2000740), negative regulation of amniotic stem cell differentiation (GO:2000798), response to stress (GO:0006950), regulation of gene expression (GO:0010468)

GO Molecular Function (13): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), RNA polymerase II core promoter sequence-specific DNA binding (GO:0000979), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), transcription repressor complex (GO:0017053)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Chromatin modifying enzymes	1
PTEN Regulation	1
Nuclear Events (kinase and transcription factor activation)	1
SARS-CoV Infections	1
Regulation of NPAS4 gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to stress	3
DNA-templated transcription	3
regulation of gene expression	3
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
gene expression	2
neuron differentiation	2
regulation of neuron differentiation	2
binding	2
negative regulation of DNA-templated transcription	1
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
response to decreased oxygen levels	1
hemopoiesis	1
cell differentiation	1
chromatin organization	1
regulation of RNA biosynthetic process	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
aldosterone biosynthetic process	1
regulation of aldosterone biosynthetic process	1
negative regulation of steroid hormone biosynthetic process	1
negative regulation of alcohol biosynthetic process	1
cellular response to stimulus	1
stem cell population maintenance	1
programmed cell death	1
regulation of programmed cell death	1
positive regulation of cellular process	1
host-mediated perturbation of viral transcription	1
host-mediated suppression of viral proces	1
negative regulation of cell differentiation	1
positive regulation of cell differentiation	1
osteoblast differentiation	1
regulation of cell differentiation	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1

Protein interactions and networks

STRING

2132 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
REST	RCOR1	Q9UKL0	996
REST	KDM1A	O60341	978
REST	HDAC1	Q13547	948
REST	HTT	P42858	911
REST	EHMT2	Q96KQ7	844
REST	CTDSP1	Q9GZU7	830
REST	KDM5C	P41229	795
REST	DYRK1A	Q13627	791
REST	MECP2	P51608	763
REST	HDAC2	Q92769	758
REST	STMN2	Q93045	740
REST	CTDSP2	O14595	736
REST	CTDSPL	O15194	732
REST	SIN3A	Q96ST3	726
REST	CTBP1	Q13363	718

IntAct

32 interactions, top by confidence:

A	B	Type	Score
BTRC	REST	psi-mi:“MI:0914”(association)	0.770
BTRC	REST	psi-mi:“MI:0915”(physical association)	0.770
REST	BTRC	psi-mi:“MI:0915”(physical association)	0.770
REST	BTRC	psi-mi:“MI:0407”(direct interaction)	0.770
REST	FBXW11	psi-mi:“MI:0914”(association)	0.620
FBXW11	REST	psi-mi:“MI:0914”(association)	0.620
REST	FBXW11	psi-mi:“MI:0915”(physical association)	0.620
E2F6	KDM5C	psi-mi:“MI:0914”(association)	0.600
REST	HSP90AA1	psi-mi:“MI:0915”(physical association)	0.570
KDM5C	REST	psi-mi:“MI:0915”(physical association)	0.560
REST		psi-mi:“MI:0915”(physical association)	0.400
REST	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
REST	H2BC5	psi-mi:“MI:0915”(physical association)	0.400
REST	CHD8	psi-mi:“MI:0915”(physical association)	0.400
REST	SMARCE1	psi-mi:“MI:0915”(physical association)	0.400
SMARCA4	REST	psi-mi:“MI:0915”(physical association)	0.400
SMARCC2	REST	psi-mi:“MI:0915”(physical association)	0.400
KDM5C	NCOR1	psi-mi:“MI:0914”(association)	0.350
REST	NCOR1	psi-mi:“MI:0914”(association)	0.350
RCOR1	REST	psi-mi:“MI:0914”(association)	0.350
KEAP1	SEC16A	psi-mi:“MI:0914”(association)	0.350

BioGRID (335): REST (Co-localization), REST (Affinity Capture-Western), BTRC (Affinity Capture-Western), REST (Affinity Capture-MS), REST (Affinity Capture-MS), PLK1 (Affinity Capture-Western), REST (Biochemical Activity), TEX14 (Affinity Capture-Western), SCYL1 (Affinity Capture-Western), BTRC (Affinity Capture-Western), REST (Affinity Capture-MS), REST (Affinity Capture-Western), REST (Affinity Capture-Western), REST (Affinity Capture-MS), REST (Affinity Capture-Western)

ESM2 similar proteins: A0A8I5ZN27, A6X8Z5, E1AZ71, F1N8V3, O35668, O54963, O70318, P20689, P48165, P51954, P54256, P54257, P55917, P62025, P70278, Q01538, Q13029, Q13127, Q14028, Q16799, Q28139, Q28181, Q2M1Z3, Q3SYS4, Q3UH66, Q4KMM3, Q4V8B0, Q5DW34, Q5IS59, Q5TCY1, Q62100, Q63HN8, Q640N3, Q64548, Q6IR42, Q6PCN3, Q7Z6I6, Q811Q2, Q8BYM7, Q8C5W0

Diamond homologs: O54963, Q13127, Q2EI20, Q2EI21, Q8VIG1, Q9PVG3

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
RCOR1	“up-regulates activity”	REST	binding
REST	“down-regulates quantity by repression”	SCN2A	“transcriptional regulation”
REST	“form complex”	REST-CoREST	binding
REST	“down-regulates quantity by repression”	CARTPT	“transcriptional regulation”
REST	“down-regulates quantity by repression”	PENK	“transcriptional regulation”
REST	“down-regulates quantity by repression”	BDNF	“transcriptional regulation”
HIP1	“up-regulates quantity by expression”	REST	“transcriptional regulation”
REST	down-regulates	Epigenetic_regulation
PLK1	“down-regulates activity”	REST	phosphorylation
REST	“down-regulates quantity by repression”	HCN1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 17 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	5	36.8×	4e-05
Chromatin organization	5	25.5×	1e-04
Chromatin modifying enzymes	5	22.6×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
chromatin remodeling	5	22.8×	7e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — WT.

Clinical variants and AI predictions

ClinVar

782 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	10
Uncertain significance	481
Likely benign	198
Benign	32

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1189032	NM_005612.5(REST):c.2771_2793dup (p.Glu932delinsLysThrTer)	Pathogenic
1423378	NM_005612.5(REST):c.425del (p.Pro142fs)	Pathogenic
1435178	NM_005612.5(REST):c.274G>T (p.Gly92Ter)	Pathogenic
222002	NM_005612.5(REST):c.831_832del (p.Cys278fs)	Pathogenic
2429888	NM_005612.5(REST):c.2809A>T (p.Lys937Ter)	Pathogenic
2706001	NM_005612.5(REST):c.830_831del (p.Thr277fs)	Pathogenic
2706886	NM_005612.5(REST):c.177_181del (p.Asn59fs)	Pathogenic
2850900	NM_005612.5(REST):c.679C>T (p.Arg227Ter)	Pathogenic
3370397	REST, 2-BP DEL, 1901AG	Pathogenic
3660060	NM_005612.5(REST):c.663C>A (p.Cys221Ter)	Pathogenic
3728050	NM_005612.5(REST):c.666del (p.Tyr223fs)	Pathogenic
4726804	NM_005612.5(REST):c.319G>T (p.Glu107Ter)	Pathogenic
620429	NM_005612.5(REST):c.2227G>T (p.Glu743Ter)	Pathogenic
661428	NM_005612.5(REST):c.265dup (p.Glu89fs)	Pathogenic
694373	NM_005612.5(REST):c.983-2247C>G	Pathogenic
839965	NM_005612.5(REST):c.440_441dup (p.Glu148fs)	Pathogenic
1686854	NM_005612.5(REST):c.1244G>C (p.Cys415Ser)	Likely pathogenic
1951202	NM_005612.5(REST):c.851_866del (p.Phe284fs)	Likely pathogenic
2632513	NM_005612.5(REST):c.764del (p.Tyr255fs)	Likely pathogenic
2635523	NM_005612.5(REST):c.908del (p.Pro303fs)	Likely pathogenic
3344722	NM_005612.5(REST):c.2284_2287del (p.Val761_Lys762insTer)	Likely pathogenic
3347323	NM_005612.5(REST):c.2615T>G (p.Leu872Ter)	Likely pathogenic
427772	NM_005612.5(REST):c.1310T>A (p.Leu437Ter)	Likely pathogenic
427773	NM_005612.5(REST):c.2413del (p.Leu805fs)	Likely pathogenic
521809	NM_005612.5(REST):c.2515G>T (p.Glu839Ter)	Likely pathogenic
807670	NM_005612.5(REST):c.2770C>T (p.Gln924Ter)	Likely pathogenic

SpliceAI

1472 predictions. Top by Δscore:

Variant	Effect	Δscore
4:56908209:GGCCG:G	donor_gain	1.0000
4:56908210:GCCG:G	donor_gain	1.0000
4:56908210:GCCGG:G	donor_gain	1.0000
4:56908214:G:A	donor_loss	1.0000
4:56908214:G:GG	donor_gain	1.0000
4:56908215:T:A	donor_loss	1.0000
4:56911458:A:T	donor_gain	1.0000
4:56964530:CCAA:C	acceptor_gain	1.0000
4:56964531:C:CT	acceptor_gain	1.0000
4:56964532:A:T	acceptor_gain	1.0000
4:56964533:A:AC	acceptor_gain	1.0000
4:56964533:A:C	acceptor_gain	1.0000
4:56964538:A:AC	acceptor_gain	1.0000
4:56908206:G:GT	donor_gain	0.9900
4:56908211:CCG:C	donor_gain	0.9900
4:56908212:CG:C	donor_gain	0.9900
4:56908213:GG:G	donor_gain	0.9900
4:56910623:A:AG	acceptor_gain	0.9900
4:56910629:GA:G	acceptor_gain	0.9900
4:56911533:ACAGG:A	donor_loss	0.9900
4:56911535:AGGT:A	donor_loss	0.9900
4:56911536:GGTAA:G	donor_loss	0.9900
4:56911537:GTA:G	donor_loss	0.9900
4:56911538:T:G	donor_loss	0.9900
4:56919867:TCAG:T	donor_loss	0.9900
4:56919868:CAG:C	donor_loss	0.9900
4:56919870:GG:G	donor_loss	0.9900
4:56919871:GTTG:G	donor_gain	0.9900
4:56929827:T:TA	acceptor_gain	0.9900
4:56932003:G:GT	donor_gain	0.9900

AlphaMissense

7295 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:56911119:T:A	C161S	1.000
4:56911119:T:C	C161R	1.000
4:56911120:G:A	C161Y	1.000
4:56911120:G:C	C161S	1.000
4:56911121:T:G	C161W	1.000
4:56911128:T:A	C164S	1.000
4:56911128:T:C	C164R	1.000
4:56911129:G:A	C164Y	1.000
4:56911129:G:C	C164S	1.000
4:56911130:C:G	C164W	1.000
4:56911159:T:C	F174S	1.000
4:56911167:C:A	H177N	1.000
4:56911167:C:G	H177D	1.000
4:56911168:A:C	H177P	1.000
4:56911169:C:A	H177Q	1.000
4:56911169:C:G	H177Q	1.000
4:56911179:C:G	H181D	1.000
4:56911181:C:A	H181Q	1.000
4:56911181:C:G	H181Q	1.000
4:56911290:T:A	C218S	1.000
4:56911290:T:C	C218R	1.000
4:56911291:G:C	C218S	1.000
4:56911299:T:A	C221S	1.000
4:56911299:T:C	C221R	1.000
4:56911300:G:C	C221S	1.000
4:56911338:C:G	H234D	1.000
4:56911342:T:C	L235P	1.000
4:56911350:C:G	H238D	1.000
4:56911352:C:A	H238Q	1.000
4:56911352:C:G	H238Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000090843 (4:56933449 G>A), RS1000173060 (4:56932222 C>T), RS1000342658 (4:56916899 G>A,C), RS1000375041 (4:56917157 CTT>C,CT,CTTT), RS1000710062 (4:56918282 A>G), RS1000722978 (4:56909150 C>T), RS1000785002 (4:56908837 C>A,G,T), RS1000846470 (4:56914589 A>G), RS1000982042 (4:56906987 T>TA), RS1001071790 (4:56909022 C>T), RS1001086356 (4:56918032 A>G), RS1001176139 (4:56913455 G>A), RS1001228492 (4:56913688 C>T), RS1001288850 (4:56934042 TTCTTC>T), RS1001306227 (4:56924905 C>A,T)

Disease associations

OMIM: gene MIM:600571 | disease phenotypes: MIM:612431, MIM:616806, MIM:617626, MIM:124900, MIM:135300

GenCC curated gene-disease

Disease	Classification	Inheritance
Wilms tumor 6	Strong	Autosomal dominant
fibromatosis, gingival, 5	Strong	Autosomal dominant
autosomal dominant nonsyndromic hearing loss 27	Moderate	Autosomal dominant
hereditary gingival fibromatosis	Supportive	Autosomal dominant

Mondo (8): autosomal dominant nonsyndromic hearing loss 27 (MONDO:0012902), Wilms tumor 6 (MONDO:0014779), fibromatosis, gingival, 5 (MONDO:0033493), autosomal dominant nonsyndromic hearing loss (MONDO:0019587), primary ovarian failure (MONDO:0005387), childhood kidney Wilms tumor (MONDO:0024676), fibromatosis, gingival, 1 (MONDO:0007609), hereditary gingival fibromatosis (MONDO:0016070)

Orphanet (4): Nephroblastoma (Orphanet:654), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Hereditary gingival fibromatosis (Orphanet:2024), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000085	Horseshoe kidney
HP:0000086	Ectopic kidney
HP:0000169	Gingival fibromatosis
HP:0000212	Gingival overgrowth
HP:0000407	Sensorineural hearing impairment
HP:0000526	Aniridia
HP:0000766	Abnormal sternum morphology
HP:0000822	Hypertension
HP:0001528	Hemihypertrophy
HP:0001824	Weight loss
HP:0001901	Polycythemia
HP:0001903	Anemia
HP:0001945	Fever
HP:0002027	Abdominal pain
HP:0002094	Dyspnea
HP:0002664	Neoplasm
HP:0002667	Nephroblastoma
HP:0002716	Lymphadenopathy
HP:0002896	Neoplasm of the liver
HP:0002907	Microscopic hematuria
HP:0003072	Hypercalcemia
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0005580	Duplication of renal pelvis
HP:0008330	Reduced von Willebrand factor activity
HP:0011463	Childhood onset
HP:0012587	Macroscopic hematuria

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST000882_3	Response to bleomycin (chromatid breaks)	9.000000e-07
GCST001232_2	Age-related macular degeneration	2.000000e-08
GCST002702_46	Height	3.000000e-09
GCST003116_1	Coronary artery disease	5.000000e-08
GCST003720_40	Migraine	3.000000e-09
GCST004599_88	Mean platelet volume	4.000000e-10
GCST004787_2	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	8.000000e-08
GCST005991_80	Platelet count	2.000000e-11
GCST006979_433	Heel bone mineral density	2.000000e-22
GCST007323_22	Risk-taking tendency (4-domain principal component model)	1.000000e-08
GCST007324_15	Adventurousness	1.000000e-10
GCST007325_144	General risk tolerance (MTAG)	2.000000e-12
GCST008367_9	Plasma anti-thyroglobulin and anti-thyroid peroxidase levels (bivariate analysis)	3.000000e-06
GCST008810_60	Smoking initiation (ever regular vs never regular)	2.000000e-09
GCST008839_241	Height	2.000000e-25
GCST010479_66	Coronary artery disease	3.000000e-08
GCST010866_52	Coronary artery disease	1.000000e-15
GCST010867_57	Coronary artery disease	4.000000e-09
GCST011365_125	Myocardial infarction	3.000000e-06
GCST90000025_266	Appendicular lean mass	3.000000e-18
GCST90002396_225	Mean reticulocyte volume	3.000000e-23
GCST90002400_430	Plateletcrit	1.000000e-09
GCST90002407_431	White blood cell count	1.000000e-19

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007593	chromatid break measurement
EFO:0004309	platelet count
EFO:0009270	heel bone mineral density
EFO:0008579	risk-taking behaviour
EFO:0005670	smoking initiation
EFO:0004980	appendicular lean mass
EFO:0010701	mean reticulocyte volume
EFO:0007985	platelet crit

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, decreases expression	3
sodium arsenite	increases abundance, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Vehicle Emissions	increases abundance, increases methylation, affects expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
trichostatin A	decreases activity	1
2,2’,3,5’,6-pentachlorobiphenyl	increases expression, decreases reaction	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide	decreases reaction, increases reaction, decreases expression, increases expression, affects binding	1
Resveratrol	affects binding, decreases reaction, increases reaction, decreases expression, increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	decreases expression	1
Leflunomide	increases expression	1
Air Pollutants	increases abundance, affects expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Carbamazepine	increases expression, decreases reaction	1
Estradiol	affects expression	1
Fluorouracil	affects expression	1
Folic Acid	decreases expression	1
Methylmercury Compounds	increases expression	1
Ozone	increases abundance, affects expression	1

Cellosaurus cell lines

10 cell lines: 6 cancer cell line, 3 embryonic stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A5V0	SEES3-1V human REST, clone1	Embryonic stem cell	Male
CVCL_A5V1	SEES3-1V human REST, clone2	Embryonic stem cell	Male
CVCL_A5V2	SEES3-1V human REST, clone3	Embryonic stem cell	Male
CVCL_B8NS	Abcam HCT 116 REST KO	Cancer cell line	Male
CVCL_B9B4	Abcam MCF-7 REST KO	Cancer cell line	Female
CVCL_B9R4	Abcam A-549 REST KO	Cancer cell line	Male
CVCL_B9VT	Abcam HeLa REST KO	Cancer cell line	Female
CVCL_HC91	HEK293 eGFP-REST	Transformed cell line	Female
CVCL_TI83	HAP1 REST (-) 1	Cancer cell line	Male
CVCL_XS24	HAP1 REST (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

154 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00336531	PHASE4	COMPLETED	Efficacy of Prophylactic Itraconazole in High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00352534	PHASE3	ACTIVE_NOT_RECRUITING	Vincristine, Dactinomycin, and Doxorubicin With or Without Radiation Therapy or Observation Only in Treating Younger Patients Who Are Undergoing Surgery for Newly Diagnosed Stage I, Stage II, or Stage III Wilms’ Tumor
NCT00379340	PHASE3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy With or Without Radiation Therapy in Treating Young Patients With Newly Diagnosed Stage III or Stage IV Wilms’ Tumor
NCT00945009	PHASE3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT00141765	PHASE2	COMPLETED	Study of High-Dose Chemotherapy With Bone Marrow or Stem Cell Transplant for Rare Poor-Prognosis Cancers
NCT00187031	PHASE2	COMPLETED	A Phase II Study of Topotecan in Children With Recurrent Wilms Tumor
NCT01095926	PHASE2	COMPLETED	Pharmacokinetic Study of Doxorubicin in Children With Cancer
NCT02452554	PHASE2	COMPLETED	Lorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma
NCT02624388	PHASE2	TERMINATED	Study of Genistein in Pediatric Oncology Patients (UVA-Gen001)
NCT02689336	PHASE2	WITHDRAWN	Erlotinib in Combination With Temozolomide in Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors
NCT02867592	PHASE2	ACTIVE_NOT_RECRUITING	Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03210714	PHASE2	ACTIVE_NOT_RECRUITING	Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652	PHASE2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213665	PHASE2	COMPLETED	Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03213678	PHASE2	COMPLETED	Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213704	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03220035	PHASE2	COMPLETED	Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
NCT03233204	PHASE2	COMPLETED	Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
NCT03526250	PHASE2	COMPLETED	Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)
NCT03698994	PHASE2	ACTIVE_NOT_RECRUITING	Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCT04195555	PHASE2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04284774	PHASE2	ACTIVE_NOT_RECRUITING	Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04320888	PHASE2	ACTIVE_NOT_RECRUITING	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04322318	PHASE2	RECRUITING	A Study of Combination Chemotherapy for Patients With Newly Diagnosed DAWT and Relapsed FHWT
NCT04791228	PHASE2	WITHDRAWN	A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors
NCT04968990	PHASE2	RECRUITING	Treatment of Newly Diagnosed Patient’s With Wilm’s Tumor Requiring Abdominal Radiation Delivered With Proton Beam Irradiation