RCOR1

Summary

RCOR1 (REST corepressor 1, HGNC:17441) is a protein-coding gene on chromosome 14q32.31, encoding REST corepressor 1 (Q9UKL0). Essential component of the BHC complex, a corepressor complex that represses transcription of neuron-specific genes in non-neuronal cells. It is a selective cancer dependency (DepMap: 32.2% of cell lines).

This gene encodes a protein that is well-conserved, downregulated at birth, and with a specific role in determining neural cell differentiation. The encoded protein binds to the C-terminal domain of REST (repressor element-1 silencing transcription factor).

Source: NCBI Gene 23186 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 69 total — 1 likely-pathogenic
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 32.2% of screened cell lines
• MANE Select transcript: NM_015156

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17441
Approved symbol	RCOR1
Name	REST corepressor 1
Location	14q32.31
Locus type	gene with protein product
Status	Approved
Aliases	COREST, KIAA0071
Ensembl gene	ENSG00000089902
Ensembl biotype	protein_coding
OMIM	607675
Entrez	23186

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000262241, ENST00000558495, ENST00000559597, ENST00000560472, ENST00000908570

RefSeq mRNA: 1 — MANE Select: NM_015156 NM_015156

CCDS: CCDS9974

Canonical transcript exons

ENST00000262241 — 12 exons

Exon	Start	End
ENSE00000660501	102593266	102593325
ENSE00000660506	102708465	102708583
ENSE00000660508	102714423	102714617
ENSE00000660509	102721007	102721084
ENSE00000660510	102721320	102721377
ENSE00000870514	102681895	102681978
ENSE00000870515	102710935	102711013
ENSE00001152549	102726468	102730561
ENSE00001420913	102592649	102593187
ENSE00001678988	102701278	102701330
ENSE00001719953	102707351	102707512
ENSE00003552664	102722187	102722416

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 97.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.5601 / max 3793.0765, expressed in 1823 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141668	37.4597	1823
141669	1.4747	604
141671	0.3676	65
141670	0.2581	75

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.67	gold quality
esophagus squamous epithelium	UBERON:0006920	96.75	gold quality
epithelium of esophagus	UBERON:0001976	95.28	gold quality
gingiva	UBERON:0001828	94.63	gold quality
gingival epithelium	UBERON:0001949	94.13	gold quality
squamous epithelium	UBERON:0006914	93.83	gold quality
bone marrow	UBERON:0002371	93.74	gold quality
pharyngeal mucosa	UBERON:0000355	92.47	gold quality
oocyte	CL:0000023	92.14	gold quality
palpebral conjunctiva	UBERON:0001812	91.98	gold quality
lower esophagus mucosa	UBERON:0035834	91.98	gold quality
bone marrow cell	CL:0002092	91.90	gold quality
jejunal mucosa	UBERON:0000399	91.53	gold quality
esophagus mucosa	UBERON:0002469	91.11	gold quality
upper leg skin	UBERON:0004262	91.07	gold quality
penis	UBERON:0000989	90.87	gold quality
monocyte	CL:0000576	90.81	gold quality
mononuclear cell	CL:0000842	90.76	gold quality
skin of hip	UBERON:0001554	90.76	gold quality
leukocyte	CL:0000738	90.47	gold quality
jejunum	UBERON:0002115	90.44	gold quality
oral cavity	UBERON:0000167	90.23	gold quality
tongue squamous epithelium	UBERON:0006919	89.85	gold quality
lower lobe of lung	UBERON:0008949	89.76	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.54	gold quality
eye	UBERON:0000970	89.48	gold quality
amniotic fluid	UBERON:0000173	88.92	gold quality
epithelium of nasopharynx	UBERON:0001951	88.87	gold quality
trabecular bone tissue	UBERON:0002483	88.83	gold quality
blood	UBERON:0000178	88.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.73

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
BDNF	Unknown
CSF2RB
SCN2A	Repression

miRNA regulators (miRDB)

271 targeting RCOR1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-9-5P	100.00	72.28	2361
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-4747-5P	100.00	67.90	2681
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
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

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 32.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 37)

• The shape and dimension of LSD1-CoREST crystal structure suggest its bivalent binding to nucleosomes, allowing efficient H3-K4 demethylation. (PMID:16885027)
• elevated levels of REST and CoREST in the brain of RTT patients and MeCP2 deficient mice result in downregulation of BDNF, apparently by their binding to the RE1 (element) located between the first two promoters of the BDNF gene (PMID:18075316)
• CoREST is bound to the hsp70 gene promoter under basal conditions and that its binding increases during heat shock response. (PMID:18657505)
• ZNF198, through its multiple protein-protein interaction interfaces, helps to maintain the intact LSD1-CoREST-HDAC1 complex on specific, non-REST-responsive promoters and may also prevent SUMO-dependent dissociation of HDAC1 (PMID:18806873)
• These results demonstrate that SUMO-1 modification modulates the transcriptional repression by CoREST and is needed for its full repressive activity. (PMID:18854179)
• The results indicate that both sets of events mediated by ICP0, the degradation of PML and the blocking of silencing via the HDAC1/2-CoREST-REST complex, are interdependent and in large measure dependent on events in the ND10 nuclear bodies. (PMID:18945770)
• Direct interactions between CoREST1 and SUMO-2 mediate SUMO-dependent changes in chromatin structure and transcription that are important for cell-type-specific gene expression. (PMID:19394292)
• Analysis of chromatin modification patterns shows that CoREST are recruited to the c-myc promoter leading to appearance of repressive chromatin marks. (PMID:19522008)
• PC4 interacts with heterochromatin protein 1alpha, REST/NRSF (RE1-silencing transcription factor/neuron-restrictive silencer factor) and CoREST to establish the repressed state of neural genes in nonneuronal cells. (PMID:20080105)
• CoREST does not play an influential role in regulating HSV-1 infection. (PMID:20106915)
• silencing of CoREST by siRNA transfection in normal articular cartilage may reflect CoREST repression in advanced osteoarthritic cartilage, which results in phenotypic genes modulation and suggests a homeostatic role of this transcription factor (PMID:20973059)
• Insight into the molecular basis of the interaction between scaffolding protein CoREST and histone deacetylase LSD1 may suggest a new means of inhibiting LSD1 activity by misdirecting the enzyme away from nucleosomal substrates. (PMID:21142040)
• The CoREST and REST are necessary and inimical for expression of herpes simplex virus genes. (PMID:21221247)
• Transciption factor SNAIL1 mimics the histone H3 tail and binds to the histone demethylase LSD1-transcription co-repressor (CoREST) complex. The crystal structure of the complex is given here. (PMID:21300290)
• Gfi-1B p32 isoform binds to Gfi-1B target gene promoters and associates with the LSD1-CoREST repressor complex more efficiently than the major Gfi-1B p37 isoform (PMID:22399799)
• the H3 binding pocket is a central target site to (i) switch off LSD1 amino oxidase activity, thus H3-tail demethylation; (ii) block the competitive binding of transcription factors; and (iii) prevent chromatin anchoring to LSD1/CoREST. (PMID:22802671)
• Data show that miR-22 specifically interacts with the 3’ UTRs of the Rcor1, Rgs2 and HDAC4 mRNAs. (PMID:23349832)
• a combination of virtual screening and biological approaches can lead to compounds reducing REST complex formation (PMID:23800350)
• Genomic deletions in RCOR1 are associated with a specific gene expression signature and with unfavorable clinical outcomes in diffuse large B-cell lymphoma patients. (PMID:25395426)
• results suggest that LSD1-CoREST functions as an ergonomic clamp that induces the detachment of the H3 histone tail from the nucleosomal DNA to make it available for capture by the enzyme active site. (PMID:25730864)
• The results suggest that LSD1/CoREST interacts with extranucleosomal DNA when it productively engages its nucleosome substrate. (PMID:25916846)
• Rcor1 knock-out monocytes exhibited extensive self-renewal associated with hematopoietic stem cell expansion. (PMID:26119982)
• results demonstrate that CoREST and LSD1 downregulate the Notch pathway in the developing cerebral cortex (PMID:27112428)
• ERalpha engages not only LSD1, but its partners of the CoREST corepressor complex and the molecular chaperone Hsp90. (PMID:27325688)
• Expressions of REST and RCOR1 genes may downregulate SYN1 expression in gliomas. (PMID:27685921)
• This study identified histone modification by SUMO as the first post-translational modification that stimulates intranucleosomal demethylation by the developmentally critical LSD1-CoREST complex. (PMID:28832116)
• This study showed that tetrahydrofolate stably binds to the LSD1/CoREST complex, in its open conformation, at its entrance. (PMID:29161028)
• The studies have identified members of the CoREST repression complex as key regulators of HIV latency in microglia. (PMID:29256041)
• the intact CoREST complex is targeted with dual histone deacetylase and demethylase inhibitors (PMID:29302039)
• AGS mutations in this cluster impair the interaction of RNase H2 with several members of the CoREST chromatin-silencing complex that include the histone deacetylase HDAC2 and the demethylase KDM1A, the transcriptional regulators RCOR1 and GTFII-I as well as ZMYM3, an MYM-type zinc finger protein. (PMID:30889214)
• Inhibiting the coregulator CoREST impairs Foxp3+ Treg function and promotes antitumor immunity. (PMID:31917688)
• Mechanism of Crosstalk between the LSD1 Demethylase and HDAC1 Deacetylase in the CoREST Complex. (PMID:32101746)
• MYT1 attenuates neuroblastoma cell differentiation by interacting with the LSD1/CoREST complex. (PMID:32251364)
• RCOR1 directly binds to MED28 and weakens its inducing effect on cancer stem cell-like activity of oral cavity squamous cell carcinoma cells. (PMID:32306431)
• Crystal Structure of the LSD1/CoREST Histone Demethylase Bound to Its Nucleosome Substrate. (PMID:32396821)
• Genome-wide association study suggests that variation at the RCOR1 locus is associated with tinnitus in UK Biobank. (PMID:33742053)
• GSE1 links the HDAC1/CoREST co-repressor complex to DNA damage. (PMID:37878419)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	rcor1	ENSDARG00000031434
mus_musculus	Rcor1	ENSMUSG00000037896
rattus_norvegicus	Rcor1	ENSRNOG00000049783
drosophila_melanogaster	CG16779	FBGN0037698
caenorhabditis_elegans		WBGENE00005006
caenorhabditis_elegans		WBGENE00009224
caenorhabditis_elegans		WBGENE00010012
caenorhabditis_elegans		WBGENE00013632
caenorhabditis_elegans	rcor-1	WBGENE00022278

Paralogs (5): RCOR3 (ENSG00000117625), ZNF541 (ENSG00000118156), TRERF1 (ENSG00000124496), MIDEAS (ENSG00000156030), RCOR2 (ENSG00000167771)

Protein

Protein identifiers

REST corepressor 1 — Q9UKL0 (reviewed: Q9UKL0)

Alternative names: Protein CoREST

All UniProt accessions (2): Q9UKL0, H0YNY4

UniProt curated annotations — full annotation on UniProt →

Function. Essential component of the BHC complex, a corepressor complex that represses transcription of neuron-specific genes in non-neuronal cells. The BHC complex is recruited at RE1/NRSE sites by REST and acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier. In the BHC complex, it serves as a molecular beacon for the recruitment of molecular machinery, including MeCP2 and SUV39H1, that imposes silencing across a chromosomal interval. Plays a central role in demethylation of Lys-4 of histone H3 by promoting demethylase activity of KDM1A on core histones and nucleosomal substrates. It also protects KDM1A from the proteasome. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development and controls hematopoietic differentiation.

Subunit / interactions. Interacts directly with GFI1 and GFI1B in a RCOR/GFI/KDM1A/HDAC complex. Interacts with INMS1. Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST and PHF21A/BHC80. The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. Interacts with REST. Interacts with the SMARCE1/BAF57, suggesting that the BHC complex may recruit the ATP-dependent chromatin-remodeling SWI-SNF complex. Interacts with SOX2. (Microbial infection) Interacts with herpes virus HSV-1 ICP0 protein; the interaction leads to the disruption of the BHC complex, thereby preventing the BHC complex from repressing transcription of viral genes.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Phosphorylated by HSV-1 protein kinases in case of infection.

Domain organisation. The SANT domains may bridge the nucleosomal substrates and the demethylase KDM1A.

Similarity. Belongs to the CoREST family.

RefSeq proteins (1): NP_055971* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000949	ELM2_dom	Domain
IPR001005	SANT/Myb	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017884	SANT_dom	Domain
IPR049048	REST_helical	Domain
IPR051066	Trans_reg/Corepressor	Family

Pfam: PF00249, PF01448, PF20878

UniProt features (53 total): helix 13, mutagenesis site 6, turn 6, strand 6, region of interest 6, compositionally biased region 4, domain 3, modified residue 3, cross-link 3, coiled-coil region 2, chain 1

Structure

Experimental structures (PDB)

102 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5H6Q	X-RAY DIFFRACTION	2.53
2IW5	X-RAY DIFFRACTION	2.57
5H6R	X-RAY DIFFRACTION	2.6
5L3D	X-RAY DIFFRACTION	2.6
6TUY	X-RAY DIFFRACTION	2.6
8Q1G	X-RAY DIFFRACTION	2.6
6KGM	X-RAY DIFFRACTION	2.62
6KGN	X-RAY DIFFRACTION	2.62
7CDC	X-RAY DIFFRACTION	2.64
9DBP	X-RAY DIFFRACTION	2.66
7CDE	X-RAY DIFFRACTION	2.68
7CDF	X-RAY DIFFRACTION	2.68
5X60	X-RAY DIFFRACTION	2.69
6KGK	X-RAY DIFFRACTION	2.7
6KGL	X-RAY DIFFRACTION	2.7
7ZRY	X-RAY DIFFRACTION	2.7
2UXN	X-RAY DIFFRACTION	2.72
8FRV	X-RAY DIFFRACTION	2.72
2UXX	X-RAY DIFFRACTION	2.74
8BOP	X-RAY DIFFRACTION	2.74
8UL6	X-RAY DIFFRACTION	2.74
7CDD	X-RAY DIFFRACTION	2.76
8FJ4	X-RAY DIFFRACTION	2.76
8GJ6	X-RAY DIFFRACTION	2.77
3ZN0	X-RAY DIFFRACTION	2.8
4UV8	X-RAY DIFFRACTION	2.8
4UVB	X-RAY DIFFRACTION	2.8
5L3E	X-RAY DIFFRACTION	2.8
7CDG	X-RAY DIFFRACTION	2.8
8F59	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKL0-F1	70.32	0.39

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 (6): 127, 260, 460, 122, 297, 466

Mutagenesis-validated functional residues (6):

Position	Phenotype
106	reduces bcr(kbtbd4)-mediated proteasomal degradation.
110	reduces bcr(kbtbd4)-mediated proteasomal degradation.
111	reduces bcr(kbtbd4)-mediated proteasomal degradation.
112	reduces bcr(kbtbd4)-mediated proteasomal degradation.
114	reduces bcr(kbtbd4)-mediated proteasomal degradation.
117	reduces bcr(kbtbd4)-mediated proteasomal degradation.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-3214815	HDACs deacetylate histones
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 261 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_MYELOID_CELL_HOMEOSTASIS, RORA1_01, GOBP_ERYTHROCYTE_HOMEOSTASIS, MEF2_02, CEBPB_01, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_MEGAKARYOCYTE_DIFFERENTIATION, GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_UP, IRF1_Q6, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, KEGG_HUNTINGTONS_DISEASE

GO Biological Process (6): chromatin organization (GO:0006325), regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of gene expression (GO:0010629), erythrocyte differentiation (GO:0030218), positive regulation of megakaryocyte differentiation (GO:0045654), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (4): chromatin binding (GO:0003682), transcription corepressor activity (GO:0003714), enzyme binding (GO:0019899), protein binding (GO:0005515)

GO Cellular Component (7): histone deacetylase complex (GO:0000118), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), transcription repressor complex (GO:0017053), histone methyltransferase complex (GO:0035097), DNA repair complex (GO:1990391)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Chromatin modifying enzymes	1
PTEN Regulation	1
SARS-CoV Infections	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
binding	2
nucleoplasm	2
nuclear protein-containing complex	2
catalytic complex	2
cellular component organization	1
transcription by RNA polymerase II	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
megakaryocyte differentiation	1
positive regulation of myeloid cell differentiation	1
regulation of megakaryocyte differentiation	1
DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
protein binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
protein-containing complex	1
transcription regulator complex	1
methyltransferase complex	1

Protein interactions and networks

STRING

1856 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RCOR1	KDM1A	O60341	999
RCOR1	HDAC1	Q13547	998
RCOR1	HDAC2	Q92769	998
RCOR1	REST	Q13127	996
RCOR1	CTBP1	Q13363	996
RCOR1	PHF21A	Q96BD5	996
RCOR1	SIN3A	Q96ST3	995
RCOR1	HMG20B	Q9P0W2	994
RCOR1	MECP2	P51608	992
RCOR1	ZNF217	O75362	989
RCOR1	EHMT2	Q96KQ7	985
RCOR1	NCOR1	O75376	977
RCOR1	GFI1B	Q5VTD9	964
RCOR1	CTBP2	P56545	893
RCOR1	ZNF516	Q92618	888

IntAct

231 interactions, top by confidence:

A	B	Type	Score
HDAC1	RCOR1	psi-mi:“MI:0915”(physical association)	0.950
HDAC1	KDM1A	psi-mi:“MI:0914”(association)	0.910
KDM1A	HDAC1	psi-mi:“MI:0914”(association)	0.910
KDM1A	RCOR1	psi-mi:“MI:0407”(direct interaction)	0.900
RCOR1	KDM1A	psi-mi:“MI:0915”(physical association)	0.900
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
KDM1A	HDAC2	psi-mi:“MI:0914”(association)	0.890
LLGL2	PRKCI	psi-mi:“MI:0914”(association)	0.890
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
SNAI1	KDM1A	psi-mi:“MI:0914”(association)	0.830
CTBP1	ZEB2	psi-mi:“MI:0914”(association)	0.800
CTBP1	KDM1A	psi-mi:“MI:0914”(association)	0.790
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
KDM1A	RCOR1	psi-mi:“MI:0407”(direct interaction)	0.780
HMG20A	KDM1A	psi-mi:“MI:0914”(association)	0.730
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730

BioGRID (719): KDM1A (Reconstituted Complex), RCOR1 (Affinity Capture-MS), RCOR1 (Affinity Capture-MS), RCOR1 (Affinity Capture-MS), RCOR1 (Affinity Capture-MS), RCOR1 (Affinity Capture-MS), RCOR1 (Affinity Capture-MS), RCOR1 (Affinity Capture-MS), DDX46 (Co-fractionation), RCOR1 (Co-fractionation), RCOR1 (Affinity Capture-MS), RCOR1 (Proximity Label-MS), RCOR1 (Proximity Label-MS), RCOR1 (Proximity Label-MS), RCOR1 (Proximity Label-MS)

ESM2 similar proteins: A0A286Y9D1, A3KFM7, A9X4T1, B6ZLK2, D3ZA12, E9PZM4, G5EDE2, G5EET5, I1HNB2, J9VQZ0, O14646, O14647, O70523, O94880, O97159, P05205, P23198, P29227, P40201, P40381, P45973, P51114, P83916, P83917, Q13185, Q15326, Q1JQD9, Q29NG1, Q2TBT7, Q4V3E2, Q5R6X7, Q5R737, Q5XEN5, Q5ZKY4, Q61584, Q61686, Q6INA9, Q7ZTQ5, Q8CFE3, Q8R5C8

Diamond homologs: A5PJX4, O75376, P25357, Q0GGX2, Q4KKX4, Q4R2Z8, Q55DP9, Q59E36, Q5FWT8, Q60974, Q6NRZ0, Q6P116, Q8C796, Q8CFE3, Q8IZ40, Q8QG78, Q90WN5, Q9H0D2, Q9H4R4, Q9P2K3, Q9UKL0, Q9WU42, Q9WUB5, Q9Y618, O94776, Q18919, Q5ZJ40, Q6PGA0, Q8BXJ2, Q95Y41, Q9R190, Q20733, Q4R3R9, Q7Z3K6, P34333, Q10369

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
RCOR1	“up-regulates activity”	REST	binding
RCOR1	“down-regulates quantity by repression”	SCN2A	“transcriptional regulation”
RCOR1	“form complex”	“CoREST-HDAC complex”	binding
RCOR1	“form complex”	REST-CoREST	binding
RCOR1	“form complex”	“BHC complex”	binding
RCOR1	“up-regulates activity”	KDM1A	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 179 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 PTEN gene transcription	8	12.2×	9e-05
Negative Regulation of CDH1 Gene Transcription	11	11.3×	2e-06
Deactivation of the beta-catenin transactivating complex	5	10.0×	8e-03
PTEN Regulation	5	9.8×	8e-03
HDACs deacetylate histones	8	8.2×	7e-04
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	6	7.5×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
cell fate commitment	6	10.9×	3e-03
chromatin organization	12	7.3×	2e-05
chromatin remodeling	11	4.9×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	34
Likely benign	19
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
548645	NM_015156.4(RCOR1):c.446-3C>T	Likely pathogenic

SpliceAI

2944 predictions. Top by Δscore:

Variant	Effect	Δscore
14:102593183:GCACG:G	donor_gain	1.0000
14:102593187:GGTA:G	donor_loss	1.0000
14:102593188:G:GA	donor_loss	1.0000
14:102593188:G:GG	donor_gain	1.0000
14:102593189:T:G	donor_loss	1.0000
14:102681891:CAAG:C	acceptor_loss	1.0000
14:102681892:A:AG	acceptor_gain	1.0000
14:102681893:A:AC	acceptor_loss	1.0000
14:102681893:A:AG	acceptor_gain	1.0000
14:102681894:G:A	acceptor_loss	1.0000
14:102681894:G:GG	acceptor_gain	1.0000
14:102681894:GCCA:G	acceptor_gain	1.0000
14:102681977:GT:G	donor_gain	1.0000
14:102701272:TTTCA:T	acceptor_loss	1.0000
14:102701273:TTCAG:T	acceptor_loss	1.0000
14:102701274:TCAGT:T	acceptor_loss	1.0000
14:102701275:CA:C	acceptor_loss	1.0000
14:102701276:A:AG	acceptor_gain	1.0000
14:102701276:A:C	acceptor_loss	1.0000
14:102701276:AGT:A	acceptor_gain	1.0000
14:102701276:AGTG:A	acceptor_gain	1.0000
14:102701277:G:GT	acceptor_gain	1.0000
14:102701277:GT:G	acceptor_gain	1.0000
14:102701277:GTG:G	acceptor_gain	1.0000
14:102701277:GTGG:G	acceptor_gain	1.0000
14:102701277:GTGGA:G	acceptor_gain	1.0000
14:102701328:CAG:C	donor_loss	1.0000
14:102701329:AGGTA:A	donor_loss	1.0000
14:102701330:GGTAA:G	donor_loss	1.0000
14:102701332:T:A	donor_loss	1.0000

AlphaMissense

3204 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:102593286:G:A	G108R	1.000
14:102593286:G:C	G108R	1.000
14:102593287:G:A	G108E	1.000
14:102681943:T:A	V137D	1.000
14:102681945:T:A	W138R	1.000
14:102681945:T:C	W138R	1.000
14:102681947:G:C	W138C	1.000
14:102681947:G:T	W138C	1.000
14:102701286:T:C	Y152H	1.000
14:102701286:T:G	Y152D	1.000
14:102701287:A:C	Y152S	1.000
14:102701287:A:G	Y152C	1.000
14:102701298:G:C	A156P	1.000
14:102701299:C:A	A156D	1.000
14:102701310:C:G	H160D	1.000
14:102701316:T:C	Y162H	1.000
14:102701316:T:G	Y162D	1.000
14:102701317:A:C	Y162S	1.000
14:102701325:G:A	E165K	1.000
14:102701326:A:T	E165V	1.000
14:102701329:A:C	Q166P	1.000
14:102701330:G:C	Q166H	1.000
14:102701330:G:T	Q166H	1.000
14:102707351:G:C	A167P	1.000
14:102707352:C:A	A167D	1.000
14:102707355:T:A	L168H	1.000
14:102707355:T:C	L168P	1.000
14:102707357:G:A	G169R	1.000
14:102707357:G:C	G169R	1.000
14:102707357:G:T	G169W	1.000

dbSNP variants (sampled 300 via entrez): RS1000030175 (14:102664311 C>T), RS1000069933 (14:102625670 T>C), RS1000108281 (14:102680078 C>T), RS1000146423 (14:102625493 C>T), RS1000150981 (14:102601571 G>A), RS1000153079 (14:102719069 G>T), RS1000155230 (14:102638643 G>A), RS1000181655 (14:102630710 G>T), RS1000198962 (14:102670459 C>T), RS1000227615 (14:102675878 C>T), RS1000241583 (14:102616940 G>A,T), RS1000243543 (14:102628708 C>G), RS1000262885 (14:102592382 A>C), RS1000267191 (14:102711114 A>G,T), RS1000303781 (14:102694750 T>C)

Disease associations

OMIM: gene MIM:607675 | disease phenotypes: MIM:213300

GenCC curated gene-disease

Mondo (1): Joubert syndrome (MONDO:0018772)

Orphanet (1): Isolated Joubert syndrome (Orphanet:475)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST001337_44	Platelet count	2.000000e-10
GCST004599_173	Mean platelet volume	3.000000e-12
GCST004603_144	Platelet count	3.000000e-35
GCST004607_104	Plateletcrit	6.000000e-26
GCST004628_9	Immature fraction of reticulocytes	2.000000e-12
GCST005038_88	Allergic disease (asthma, hay fever or eczema)	2.000000e-08
GCST005951_8	Body mass index	7.000000e-09
GCST009597_131	Multiple sclerosis	2.000000e-09
GCST010043_20	Asthma	8.000000e-09
GCST011541_1	Tinnitus	2.000000e-08
GCST011741_19	LDL cholesterol levels in HIV infection	9.000000e-06
GCST011741_4	LDL cholesterol levels in HIV infection	9.000000e-06
GCST011981_12	Homeostasis model assessment of insulin resistance	1.000000e-07
GCST90002385_37	High light scatter reticulocyte count	4.000000e-12
GCST90002386_586	High light scatter reticulocyte percentage of red cells	2.000000e-12
GCST90002387_2	Immature fraction of reticulocytes	3.000000e-23
GCST90002395_212	Mean platelet volume	5.000000e-24
GCST90002396_625	Mean reticulocyte volume	4.000000e-12
GCST90002400_148	Plateletcrit	8.000000e-39
GCST90002402_201	Platelet count	6.000000e-49

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0007986	reticulocyte count
EFO:0004340	body mass index
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004501	HOMA-IR
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL3137262 (PROTEIN COMPLEX), CHEMBL5169078 (PROTEIN-PROTEIN INTERACTION), CHEMBL5483007 (PROTEIN-PROTEIN INTERACTION), CHEMBL5483008 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195589 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 9,146 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3353410	OSIMERTINIB	4	8,898
CHEMBL3989843	TRANYLCYPROMINE	4	70
CHEMBL6067481	COLISTIN	4
CHEMBL3781751	IADADEMSTAT	2	178

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

ChEMBL bioactivities

232 potent at pChembl≥5 of 264 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.42	IC50	0.38	nM	IADADEMSTAT
9.22	IC50	0.6	nM	CHEMBL3906257
9.22	IC50	0.6	nM	CHEMBL6169362
8.89	IC50	1.3	nM	CHEMBL6150265
8.82	IC50	1.5	nM	CHEMBL6152761
8.80	IC50	1.6	nM	CHEMBL6132742
8.68	IC50	2.1	nM	CHEMBL4875015
8.55	IC50	2.8	nM	CHEMBL6146360
8.48	IC50	3.3	nM	CHEMBL3775474
8.41	IC50	3.9	nM	CHEMBL5291155
8.27	IC50	5.4	nM	CHEMBL5280566
8.19	IC50	6.5	nM	IADADEMSTAT
8.17	IC50	6.7	nM	CHEMBL4069817
8.14	IC50	7.2	nM	CHEMBL5277056
8.14	IC50	7.2	nM	CHEMBL5399284
8.11	IC50	7.8	nM	CHEMBL4090812
8.10	IC50	8	nM	CHEMBL6144466
8.08	IC50	8.4	nM	CHEMBL4072541
8.00	IC50	10	nM	CHEMBL5281376
7.96	IC50	11	nM	OSIMERTINIB
7.85	Kd	14	nM	CHEMBL3134377
7.85	IC50	14	nM	CHEMBL5421067
7.75	IC50	18	nM	CHEMBL4081995
7.72	IC50	19.2	nM	CHEMBL3546846
7.66	IC50	22	nM	CHEMBL4074211
7.66	IC50	22	nM	CHEMBL5276713
7.65	IC50	22.5	nM	CHEMBL3780391
7.62	IC50	24	nM	CHEMBL5270114
7.55	IC50	28	nM	CHEMBL3780374
7.54	IC50	29.2	nM	CHEMBL4080514
7.51	IC50	31	nM	CHEMBL3407602
7.50	IC50	32	nM	CHEMBL3735553
7.47	IC50	33.5	nM	CHEMBL3780524
7.46	IC50	35	nM	CHEMBL3410944
7.46	Ki	35	nM	CHEMBL3134377
7.42	IC50	38	nM	CHEMBL3407601
7.40	IC50	40	nM	CHEMBL3734779
7.40	Ki	40	nM	CHEMBL4210908
7.37	IC50	42.6	nM	CHEMBL3780674
7.34	IC50	46	nM	CHEMBL5417375
7.33	IC50	47	nM	CHEMBL3410941
7.30	Ki	50	nM	CHEMBL1797647
7.30	IC50	50	nM	CHEMBL3736264
7.29	IC50	51.2	nM	CHEMBL3781494
7.25	IC50	56	nM	CHEMBL4061143
7.22	Ki	60	nM	CHEMBL5084197
7.21	IC50	61	nM	CHEMBL3736172
7.21	IC50	61.5	nM	CHEMBL3781329
7.21	IC50	61.4	nM	CHEMBL3780542
7.19	IC50	65	nM	CHEMBL3734791

PubChem BioAssay actives

205 with measured affinity, of 424 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-N-[(1R,2S)-2-phenylcyclopropyl]cyclohexane-1,4-diamine	1441194: Inhibition of recombinant human KDM1A/CoREST complex expressed in Escherichia coli using [Lys(Me1)4]-Histone H3 (1 to 21 residues)-GGK(biotin) as substrate incubated for 20 mins measured after 1 hr by TR-FRET assay	ic50	0.0004	uM
N-[4-[(1S,2R)-2-(cyclopropylmethylamino)cyclopropyl]phenyl]-1-methylpyrazole-4-carboxamide;hydrochloride	1755610: Inhibition of N-terminal His-SUMO tagged human LSD1 (172 to 852 residues)/His-tagged CoREST (286 to 482 residues) expressed in Escherichia coli BL21 (DE3) using ART(mK)QTARKSTGGKAPRKQLAGGK-Biotin as substrate preincubated for 60 mins followed by substrate addition and measured after 15 mins by HTRF assay	ic50	0.0021	uM
5-[(1R,2R)-2-(cyclopropylmethylamino)cyclopropyl]-N-(oxan-4-yl)thiophene-3-carboxamide	1986215: Inhibition of recombinant human LSD1 (172 to 852 residues)/His-tagged human CoREST (286 to 482 residues) expressed in Escherichia coli BL21 (DE3) cells using ART(mK)QTARKSTGGKAPRKQLAGGK-Biotin as substrate assessed as increase in H3K4 methylation incubated for 40 mins	ic50	0.0033	uM
4-[(1S,2R)-2-(cyclopropylmethylamino)cyclopropyl]-N-(6-fluoro-4-methyl-3-pyridinyl)-N-methylbenzamide	1925407: Inhibition of human recombinant LSD1/CoREST using ART(mK)QTARKSTGGKAPRKQLAGGK-biotin as substrate incubated for 15 mins	ic50	0.0039	uM
4-[(1S,2R)-2-(cyclopropylmethylamino)cyclopropyl]-N-(6-fluoro-2-methyl-3-pyridinyl)-N-methylbenzamide	1925407: Inhibition of human recombinant LSD1/CoREST using ART(mK)QTARKSTGGKAPRKQLAGGK-biotin as substrate incubated for 15 mins	ic50	0.0054	uM
4-ethyl-N-[3-(methoxymethyl)-2-[[4-[[(3R)-pyrrolidin-3-yl]methoxy]phenoxy]methyl]phenyl]thieno[3,2-b]pyrrole-5-carboxamide	1441194: Inhibition of recombinant human KDM1A/CoREST complex expressed in Escherichia coli using [Lys(Me1)4]-Histone H3 (1 to 21 residues)-GGK(biotin) as substrate incubated for 20 mins measured after 1 hr by TR-FRET assay	ic50	0.0067	uM
5-[(1R,2R)-2-(cyclopropylmethylamino)cyclopropyl]-N-(5-methyl-1,3,4-thiadiazol-2-yl)thiophene-3-carboxamide	1986215: Inhibition of recombinant human LSD1 (172 to 852 residues)/His-tagged human CoREST (286 to 482 residues) expressed in Escherichia coli BL21 (DE3) cells using ART(mK)QTARKSTGGKAPRKQLAGGK-Biotin as substrate assessed as increase in H3K4 methylation incubated for 40 mins	ic50	0.0072	uM
N-[4-[(1S,2R)-2-(cyclopropylmethylamino)cyclopropyl]phenyl]-6-fluoro-4-methylpyridine-3-carboxamide	1925407: Inhibition of human recombinant LSD1/CoREST using ART(mK)QTARKSTGGKAPRKQLAGGK-biotin as substrate incubated for 15 mins	ic50	0.0072	uM
N-[3-(ethoxymethyl)-2-[[4-[[(3R)-pyrrolidin-3-yl]methoxy]phenoxy]methyl]phenyl]-4-methylthieno[3,2-b]pyrrole-5-carboxamide	1441194: Inhibition of recombinant human KDM1A/CoREST complex expressed in Escherichia coli using [Lys(Me1)4]-Histone H3 (1 to 21 residues)-GGK(biotin) as substrate incubated for 20 mins measured after 1 hr by TR-FRET assay	ic50	0.0078	uM
N-[3-(methoxymethyl)-2-[[4-[[(3R)-pyrrolidin-3-yl]methoxy]phenoxy]methyl]phenyl]-4-methylthieno[3,2-b]pyrrole-5-carboxamide	1441194: Inhibition of recombinant human KDM1A/CoREST complex expressed in Escherichia coli using [Lys(Me1)4]-Histone H3 (1 to 21 residues)-GGK(biotin) as substrate incubated for 20 mins measured after 1 hr by TR-FRET assay	ic50	0.0084	uM
N-[4-[(1S,2R)-2-(cyclopropylmethylamino)cyclopropyl]phenyl]-6-fluoropyridine-3-carboxamide	1925407: Inhibition of human recombinant LSD1/CoREST using ART(mK)QTARKSTGGKAPRKQLAGGK-biotin as substrate incubated for 15 mins	ic50	0.0100	uM
3-[(1S,2R)-2-(cyclopropylmethylamino)cyclopropyl]-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzamide	1986215: Inhibition of recombinant human LSD1 (172 to 852 residues)/His-tagged human CoREST (286 to 482 residues) expressed in Escherichia coli BL21 (DE3) cells using ART(mK)QTARKSTGGKAPRKQLAGGK-Biotin as substrate assessed as increase in H3K4 methylation incubated for 40 mins	ic50	0.0140	uM
4-[2-(4-methylphenyl)-5-[[(3R)-pyrrolidin-3-yl]methoxy]-3-pyridinyl]benzonitrile	1868492: Binding affinity to human LSD1/CoREST assessed as dissociation constant by competitive fluorescence polarization assay	kd	0.0140	uM
4-methyl-N-[2-[[4-[[(3R)-pyrrolidin-3-yl]methoxy]phenoxy]methyl]phenyl]thieno[3,2-b]pyrrole-5-carboxamide	1441194: Inhibition of recombinant human KDM1A/CoREST complex expressed in Escherichia coli using [Lys(Me1)4]-Histone H3 (1 to 21 residues)-GGK(biotin) as substrate incubated for 20 mins measured after 1 hr by TR-FRET assay	ic50	0.0180	uM
N-[4-[(1S,2R)-2-aminocyclopropyl]phenyl]benzamide	1286212: Inhibition of human recombinant KDM1A/CoREST expressed in Escherichia coli using mono-methylated H3-K4 peptide as substrate assessed as H2O2 release preincubated for 15 mins followed by substrate addition measured for 12 mins by fluorescence-based microplate reader analysis	ic50	0.0192	uM
3-[(1S,2R)-2-(cyclobutylamino)cyclopropyl]-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzamide	1964572: Inhibition of recombinant human LSD1/CoREST by SPR analysis	ic50	0.0220	uM
4-methyl-N-[2-[[4-(pyrrolidin-3-ylmethoxy)phenoxy]methyl]phenyl]thieno[3,2-b]pyrrole-5-carboxamide	1441194: Inhibition of recombinant human KDM1A/CoREST complex expressed in Escherichia coli using [Lys(Me1)4]-Histone H3 (1 to 21 residues)-GGK(biotin) as substrate incubated for 20 mins measured after 1 hr by TR-FRET assay	ic50	0.0220	uM
N-[4-[(1S,2R)-2-aminocyclopropyl]phenyl]-4-(furan-3-yl)benzamide;hydrochloride	1286212: Inhibition of human recombinant KDM1A/CoREST expressed in Escherichia coli using mono-methylated H3-K4 peptide as substrate assessed as H2O2 release preincubated for 15 mins followed by substrate addition measured for 12 mins by fluorescence-based microplate reader analysis	ic50	0.0225	uM
[4-[(1S,2R)-2-(cyclopropylmethylamino)cyclopropyl]phenyl]-(4-fluoropiperidin-1-yl)methanone	1925407: Inhibition of human recombinant LSD1/CoREST using ART(mK)QTARKSTGGKAPRKQLAGGK-biotin as substrate incubated for 15 mins	ic50	0.0240	uM
N-[4-[(1S,2R)-2-aminocyclopropyl]phenyl]-3-(2-oxo-1,3-oxazolidin-3-yl)benzamide;hydrochloride	1286212: Inhibition of human recombinant KDM1A/CoREST expressed in Escherichia coli using mono-methylated H3-K4 peptide as substrate assessed as H2O2 release preincubated for 15 mins followed by substrate addition measured for 12 mins by fluorescence-based microplate reader analysis	ic50	0.0280	uM
N-[2-[[4-(azepan-4-yloxy)phenoxy]methyl]-3-(methoxymethyl)phenyl]-4-methylthieno[3,2-b]pyrrole-5-carboxamide	1441194: Inhibition of recombinant human KDM1A/CoREST complex expressed in Escherichia coli using [Lys(Me1)4]-Histone H3 (1 to 21 residues)-GGK(biotin) as substrate incubated for 20 mins measured after 1 hr by TR-FRET assay	ic50	0.0292	uM
cis-(1S,2R)-2-(3-bromophenyl)-1-ethylcyclopropan-1-amine;hydrochloride	1196904: Inhibition of human recombinant KDM1A/CoREST complex expressed in Escherichia coli using mono-methylated H3-K4 peptide containing 21 amino acids as substrate preincubated for 15 mins followed by substrate addition measured for 12 mins by fluorescence assay	ic50	0.0310	uM
N-[4-[(1S,2R)-2-aminocyclopropyl]phenyl]-4-(2-oxo-1,3-oxazolidin-3-yl)benzamide;hydrochloride	1286212: Inhibition of human recombinant KDM1A/CoREST expressed in Escherichia coli using mono-methylated H3-K4 peptide as substrate assessed as H2O2 release preincubated for 15 mins followed by substrate addition measured for 12 mins by fluorescence-based microplate reader analysis	ic50	0.0335	uM
cis-(1S,2R)-2-(4-bromo-3-fluorophenyl)-1-ethylcyclopropan-1-amine;hydrochloride	1196904: Inhibition of human recombinant KDM1A/CoREST complex expressed in Escherichia coli using mono-methylated H3-K4 peptide containing 21 amino acids as substrate preincubated for 15 mins followed by substrate addition measured for 12 mins by fluorescence assay	ic50	0.0350	uM
cis-(1S,2R)-2-(3-chlorophenyl)-1-ethylcyclopropan-1-amine;hydrochloride	1196904: Inhibition of human recombinant KDM1A/CoREST complex expressed in Escherichia coli using mono-methylated H3-K4 peptide containing 21 amino acids as substrate preincubated for 15 mins followed by substrate addition measured for 12 mins by fluorescence assay	ic50	0.0380	uM
(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-6-amino-2-[[2-[[2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylsulfanylbutanoyl]amino]hexanoyl]amino]-3-hydroxybutanoyl]amino]propanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]acetyl]amino]hexanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]propanoic acid	1382517: Inhibition of LSD1/CoREST (unknown origin)	ki	0.0400	uM
benzyl N-[3-[[4-[(1S,2R)-2-aminocyclopropyl]phenyl]carbamoyl]phenyl]carbamate;hydrochloride	1286212: Inhibition of human recombinant KDM1A/CoREST expressed in Escherichia coli using mono-methylated H3-K4 peptide as substrate assessed as H2O2 release preincubated for 15 mins followed by substrate addition measured for 12 mins by fluorescence-based microplate reader analysis	ic50	0.0426	uM
5-[(1S,2S)-2-(cyclopropylmethylamino)cyclopropyl]-N-(oxan-4-yl)thiophene-3-carboxamide	1986215: Inhibition of recombinant human LSD1 (172 to 852 residues)/His-tagged human CoREST (286 to 482 residues) expressed in Escherichia coli BL21 (DE3) cells using ART(mK)QTARKSTGGKAPRKQLAGGK-Biotin as substrate assessed as increase in H3K4 methylation incubated for 40 mins	ic50	0.0460	uM
trans-(1S,2R)-2-(4-bromophenyl)-1-phenylcyclopropan-1-amine;hydrochloride	1196904: Inhibition of human recombinant KDM1A/CoREST complex expressed in Escherichia coli using mono-methylated H3-K4 peptide containing 21 amino acids as substrate preincubated for 15 mins followed by substrate addition measured for 12 mins by fluorescence assay	ic50	0.0470	uM
(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-6-amino-2-[[2-[[2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]propanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]acetyl]amino]hexanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]propanoic acid	1064859: Inhibition of recombinant human LSD1/CoREST complex expressed in Escherichia coli using methylated H3-K4 peptide as substrate by peroxidase-coupled assay	ki	0.0500	uM
N-[4-[(1S,2R)-2-aminocyclopropyl]phenyl]-4-(1-methylpiperidin-4-yl)benzamide;hydrochloride	1286212: Inhibition of human recombinant KDM1A/CoREST expressed in Escherichia coli using mono-methylated H3-K4 peptide as substrate assessed as H2O2 release preincubated for 15 mins followed by substrate addition measured for 12 mins by fluorescence-based microplate reader analysis	ic50	0.0512	uM
N-[3-(ethoxymethyl)-2-[(4-piperidin-4-yloxyphenoxy)methyl]phenyl]-4-methylthieno[3,2-b]pyrrole-5-carboxamide	1441194: Inhibition of recombinant human KDM1A/CoREST complex expressed in Escherichia coli using [Lys(Me1)4]-Histone H3 (1 to 21 residues)-GGK(biotin) as substrate incubated for 20 mins measured after 1 hr by TR-FRET assay	ic50	0.0560	uM
(20S,23S,26S,29S,32S,35S,38S,41S,44S)-66-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]-29-benzyl-23,38,41-tris(3-carbamimidamidopropyl)-26-(hydroxymethyl)-32-(2-methylpropyl)-15,21,24,27,30,33,36,39,42,50-decaoxo-35-propan-2-yl-2,14,51,63-tetraoxa-10,11,54,55-tetrathia-5,6,7,16,22,25,28,31,34,37,40,43,49,58,59,60-hexadecazapentacyclo[62.3.1.14,7.158,61.016,20]heptaconta-1(67),4(70),5,59,61(69),64(68),65-heptaene-44,66-dicarboxamide	1829616: Inhibition of human LSD1/CoREST	ki	0.0600	uM
benzyl N-[5-[[4-[(1S,2R)-2-aminocyclopropyl]phenyl]carbamoyl]-2-morpholin-4-ylphenyl]carbamate;hydrochloride	1286212: Inhibition of human recombinant KDM1A/CoREST expressed in Escherichia coli using mono-methylated H3-K4 peptide as substrate assessed as H2O2 release preincubated for 15 mins followed by substrate addition measured for 12 mins by fluorescence-based microplate reader analysis	ic50	0.0614	uM
N-[4-[(1S,2R)-2-aminocyclopropyl]phenyl]-4-morpholin-4-ylbenzamide;hydrochloride	1286212: Inhibition of human recombinant KDM1A/CoREST expressed in Escherichia coli using mono-methylated H3-K4 peptide as substrate assessed as H2O2 release preincubated for 15 mins followed by substrate addition measured for 12 mins by fluorescence-based microplate reader analysis	ic50	0.0615	uM
N-[2-[[4-(azepan-4-yloxy)phenoxy]methyl]phenyl]-4-methylthieno[3,2-b]pyrrole-5-carboxamide	1441194: Inhibition of recombinant human KDM1A/CoREST complex expressed in Escherichia coli using [Lys(Me1)4]-Histone H3 (1 to 21 residues)-GGK(biotin) as substrate incubated for 20 mins measured after 1 hr by TR-FRET assay	ic50	0.0640	uM
4-N-(1-benzylpiperidin-4-yl)-6,7-dimethoxy-2-N-[3-[methyl(prop-2-ynyl)amino]propyl]quinazoline-2,4-diamine	1868492: Binding affinity to human LSD1/CoREST assessed as dissociation constant by competitive fluorescence polarization assay	kd	0.0640	uM
[4-[(1S,2R)-2-(cyclopropylmethylamino)cyclopropyl]phenyl]-(3-fluoroazetidin-1-yl)methanone	1925407: Inhibition of human recombinant LSD1/CoREST using ART(mK)QTARKSTGGKAPRKQLAGGK-biotin as substrate incubated for 15 mins	ic50	0.0640	uM
4-methyl-N-[3-(morpholin-4-ylmethyl)-2-[(4-piperidin-4-yloxyphenoxy)methyl]phenyl]thieno[3,2-b]pyrrole-5-carboxamide	1441194: Inhibition of recombinant human KDM1A/CoREST complex expressed in Escherichia coli using [Lys(Me1)4]-Histone H3 (1 to 21 residues)-GGK(biotin) as substrate incubated for 20 mins measured after 1 hr by TR-FRET assay	ic50	0.0650	uM
4-methyl-N-[2-[(4-piperidin-4-yloxyphenoxy)methyl]-3-(propan-2-yloxymethyl)phenyl]thieno[3,2-b]pyrrole-5-carboxamide	1441194: Inhibition of recombinant human KDM1A/CoREST complex expressed in Escherichia coli using [Lys(Me1)4]-Histone H3 (1 to 21 residues)-GGK(biotin) as substrate incubated for 20 mins measured after 1 hr by TR-FRET assay	ic50	0.0660	uM
4-N-(1-benzylpiperidin-4-yl)-2-N-[3-(dimethylamino)propyl]-6-methoxy-7-phenylmethoxyquinazoline-2,4-diamine	1868492: Binding affinity to human LSD1/CoREST assessed as dissociation constant by competitive fluorescence polarization assay	kd	0.0670	uM
4-N-(1-benzylpiperidin-4-yl)-6,7-dimethoxy-2-N-(3-piperidin-1-ylpropyl)quinazoline-2,4-diamine	1868492: Binding affinity to human LSD1/CoREST assessed as dissociation constant by competitive fluorescence polarization assay	kd	0.0680	uM
N-[3-(methoxymethyl)-2-[(4-piperidin-4-yloxyphenoxy)methyl]phenyl]-4-methylthieno[3,2-b]pyrrole-5-carboxamide	1441194: Inhibition of recombinant human KDM1A/CoREST complex expressed in Escherichia coli using [Lys(Me1)4]-Histone H3 (1 to 21 residues)-GGK(biotin) as substrate incubated for 20 mins measured after 1 hr by TR-FRET assay	ic50	0.0746	uM
benzyl N-[4-[[4-[(1S,2R)-2-aminocyclopropyl]phenyl]carbamoyl]-2-morpholin-4-ylphenyl]carbamate;hydrochloride	1286212: Inhibition of human recombinant KDM1A/CoREST expressed in Escherichia coli using mono-methylated H3-K4 peptide as substrate assessed as H2O2 release preincubated for 15 mins followed by substrate addition measured for 12 mins by fluorescence-based microplate reader analysis	ic50	0.0750	uM
2-N-[3-(dimethylamino)propyl]-6,7-dimethoxy-4-N-[1-(naphthalen-2-ylmethyl)piperidin-4-yl]quinazoline-2,4-diamine	1868492: Binding affinity to human LSD1/CoREST assessed as dissociation constant by competitive fluorescence polarization assay	kd	0.0750	uM
cis-(1S,2R)-1-ethyl-2-(3-fluorophenyl)cyclopropan-1-amine;hydrochloride	1196904: Inhibition of human recombinant KDM1A/CoREST complex expressed in Escherichia coli using mono-methylated H3-K4 peptide containing 21 amino acids as substrate preincubated for 15 mins followed by substrate addition measured for 12 mins by fluorescence assay	ic50	0.0790	uM
(19S,22S,25S,28S,31S,34S,37S,40S,43S)-64-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]-28-benzyl-22,37,40-tris(3-carbamimidamidopropyl)-25-(hydroxymethyl)-31-(2-methylpropyl)-14,20,23,26,29,32,35,38,41,49-decaoxo-34-propan-2-yl-2,10,13,50,53,61-hexaoxa-5,6,7,15,21,24,27,30,33,36,39,42,48,56,57,58-hexadecazapentacyclo[60.3.1.14,7.156,59.015,19]octahexaconta-1(65),4(68),5,57,59(67),62(66),63-heptaene-43,64-dicarboxamide	1829616: Inhibition of human LSD1/CoREST	ki	0.0800	uM
2-N-[3-(dimethylamino)propyl]-6,7-dimethoxy-4-N-[1-[(4-phenylphenyl)methyl]piperidin-4-yl]quinazoline-2,4-diamine	1868492: Binding affinity to human LSD1/CoREST assessed as dissociation constant by competitive fluorescence polarization assay	kd	0.0810	uM
3-[(1S,2R)-2-(cyclopropylmethylamino)cyclopropyl]-N-phenylbenzamide	1986215: Inhibition of recombinant human LSD1 (172 to 852 residues)/His-tagged human CoREST (286 to 482 residues) expressed in Escherichia coli BL21 (DE3) cells using ART(mK)QTARKSTGGKAPRKQLAGGK-Biotin as substrate assessed as increase in H3K4 methylation incubated for 40 mins	ic50	0.0820	uM
4-N-(1-benzylpiperidin-4-yl)-6,7-dimethoxy-2-N-(3-pyrrolidin-1-ylpropyl)quinazoline-2,4-diamine	1868492: Binding affinity to human LSD1/CoREST assessed as dissociation constant by competitive fluorescence polarization assay	kd	0.0820	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression	2
Fulvestrant	affects cotreatment, decreases methylation, affects binding, decreases reaction, increases reaction	2
Acetaminophen	increases expression	2
Valproic Acid	increases methylation, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation, affects cotreatment	1
deoxynivalenol	increases expression	1
arsenite	affects binding, decreases reaction	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
jinfukang	decreases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	increases reaction, increases expression, affects binding, affects cotreatment, decreases reaction	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects binding, decreases reaction, increases expression	1
Folic Acid	decreases expression	1
Ivermectin	decreases expression	1
Oxygen	affects binding, decreases expression, increases reaction, increases methylation	1

ChEMBL screening assays

64 unique, capped per target: 64 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3110656	Binding	Inhibition of recombinant human LSD1/CoREST complex expressed in Escherichia coli using methylated H3-K4 peptide as substrate by peroxidase-coupled assay	Synthesis and evaluation of novel cyclic Peptide inhibitors of lysine-specific demethylase 1. — ACS Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A5U1	SEES3-1V human RCOR1, clone1	Embryonic stem cell	Male
CVCL_A5U2	SEES3-1V human RCOR1, clone2	Embryonic stem cell	Male
CVCL_A5U3	SEES3-1V human RCOR1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00873678	Not specified	COMPLETED	Assessment of the Prevalence of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)