RCOR2

Summary

RCOR2 (REST corepressor 2, HGNC:27455) is a protein-coding gene on chromosome 11q13.1, encoding REST corepressor 2 (Q8IZ40). May act as a component of a corepressor complex that represses transcription.

Predicted to enable transcription corepressor activity. Predicted to be involved in negative regulation of DNA-templated transcription and regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of histone deacetylase complex and transcription regulator complex.

Source: NCBI Gene 283248 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 91 total
• Transcription factor: yes — 18 downstream targets (CollecTRI)
• MANE Select transcript: NM_173587

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27455
Approved symbol	RCOR2
Name	REST corepressor 2
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000167771
Ensembl biotype	protein_coding
OMIM	616019
Entrez	283248

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000301459, ENST00000473926, ENST00000489217, ENST00000864867, ENST00000917267, ENST00000917268, ENST00000917269, ENST00000958233, ENST00000958234

RefSeq mRNA: 2 — MANE Select: NM_173587 NM_001363648, NM_173587

CCDS: CCDS8052

Canonical transcript exons

ENST00000301459 — 12 exons

Exon	Start	End
ENSE00001116859	63912870	63912947
ENSE00001116860	63912305	63912534
ENSE00001278199	63911230	63912179
ENSE00001278208	63913954	63914169
ENSE00001289663	63915178	63915258
ENSE00001290949	63914655	63914816
ENSE00001291194	63914417	63914541
ENSE00001293358	63916330	63917164
ENSE00001311715	63914261	63914330
ENSE00001315505	63915555	63915611
ENSE00001743033	63914902	63914954
ENSE00003686779	63912676	63912733

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 96.90.

FANTOM5 (CAGE): breadth broad, TPM avg 9.0630 / max 251.4906, expressed in 876 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120340	8.9294	874
120339	0.0911	42
120341	0.0426	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
embryo	UBERON:0000922	96.90	gold quality
ganglionic eminence	UBERON:0004023	96.90	gold quality
kidney epithelium	UBERON:0004819	92.27	gold quality
upper arm skin	UBERON:0004263	89.03	gold quality
pancreatic ductal cell	CL:0002079	88.05	gold quality
parotid gland	UBERON:0001831	87.79	gold quality
ventricular zone	UBERON:0003053	87.17	gold quality
vena cava	UBERON:0004087	87.03	silver quality
cortical plate	UBERON:0005343	86.03	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	85.78	gold quality
epithelial cell of pancreas	CL:0000083	85.66	silver quality
heart right ventricle	UBERON:0002080	85.28	silver quality
cerebellar vermis	UBERON:0004720	84.38	silver quality
left ventricle myocardium	UBERON:0006566	84.23	gold quality
buccal mucosa cell	CL:0002336	82.83	silver quality
cardiac muscle of right atrium	UBERON:0003379	82.51	gold quality
pericardium	UBERON:0002407	82.13	gold quality
superior surface of tongue	UBERON:0007371	80.78	silver quality
pons	UBERON:0000988	80.62	silver quality
inferior vagus X ganglion	UBERON:0005363	80.60	silver quality
lateral globus pallidus	UBERON:0002476	80.35	gold quality
substantia nigra pars reticulata	UBERON:0001966	80.21	gold quality
lateral nuclear group of thalamus	UBERON:0002736	80.17	gold quality
pharyngeal mucosa	UBERON:0000355	80.07	silver quality
globus pallidus	UBERON:0001875	80.05	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	79.99	gold quality
trachea	UBERON:0003126	79.95	silver quality
substantia nigra pars compacta	UBERON:0001965	79.83	gold quality
saphenous vein	UBERON:0007318	79.83	silver quality
medial globus pallidus	UBERON:0002477	79.76	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-10485	yes	381.46
E-ANND-3	no	2.28

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

18 targets.

Target	Regulation
APC
CBX5
CDKN2B
CKM
CTNNA1
GFI1B
HLA-E
HSPA4	Repression
KDM1A
MYC	Repression
NACC1
SCN1A
SLC8A1	Repression
SLU7
SUB1
SUMO1
TNF
TSC1

miRNA regulators (miRDB)

25 targeting RCOR2, 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-4775	99.98	75.00	6394
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-4999-3P	99.11	65.55	424
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-654-3P	98.38	67.61	905
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-874-5P	96.93	63.92	1014
HSA-MIR-632	96.08	67.17	798
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280
HSA-MIR-2114-5P	96.00	64.56	617

Literature-anchored findings (GeneRIF, showing 2)

• Ectopic expression of Rcor2 in both mouse and human somatic cells effectively substituted the requirement for exogenous Sox2 expression in somatic cell reprogramming. (PMID:21433225)
• Revealing RCOR2 as a regulatory component of nuclear speckles. (PMID:34819154)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	rcor2	ENSDARG00000008278
mus_musculus	Rcor2	ENSMUSG00000024968
rattus_norvegicus	Rcor2	ENSRNOG00000060849
rattus_norvegicus		ENSRNOG00000073105
drosophila_melanogaster	CoRest	FBGN0261573
caenorhabditis_elegans		WBGENE00005006
caenorhabditis_elegans		WBGENE00009224
caenorhabditis_elegans		WBGENE00013632
caenorhabditis_elegans	rcor-1	WBGENE00022278

Paralogs (5): RCOR1 (ENSG00000089902), RCOR3 (ENSG00000117625), ZNF541 (ENSG00000118156), TRERF1 (ENSG00000124496), MIDEAS (ENSG00000156030)

Protein

Protein identifiers

REST corepressor 2 — Q8IZ40 (reviewed: Q8IZ40)

All UniProt accessions (1): Q8IZ40

UniProt curated annotations — full annotation on UniProt →

Function. May act as a component of a corepressor complex that represses transcription.

Subcellular location. Nucleus.

Similarity. Belongs to the CoREST family.

RefSeq proteins (2): NP_001350577, NP_775858* (*=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 (22 total): modified residue 6, compositionally biased region 5, domain 3, region of interest 3, chain 1, cross-link 1, sequence variant 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZ40-F1	68.20	0.34

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 (7): 31, 35, 36, 63, 202, 479, 88

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 138 (showing top): RNGTGGGC_UNKNOWN, E2F_Q4_01, PEREZ_TP63_TARGETS, MAZ_Q6, TGACCTY_ERR1_Q2, TAL1ALPHAE47_01, GGGTGGRR_PAX4_03, chr11q13, CAGCTG_AP4_Q5, SP1_Q2_01, SREBP1_02, TCF4_Q5, MYCMAX_01, OCT1_03, ZIC1_01

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (3): transcription corepressor activity (GO:0003714), enzyme binding (GO:0019899), protein binding (GO:0005515)

GO Cellular Component (3): histone deacetylase complex (GO:0000118), transcription regulator complex (GO:0005667), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	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
binding	1
nucleoplasm	1
nuclear protein-containing complex	1
catalytic complex	1
protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

794 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RCOR2	KDM1A	O60341	864
RCOR2	NCOR2	Q9Y618	649
RCOR2	NCOR1	O75376	637
RCOR2	INSM1	Q01101	570
RCOR2	REST	Q13127	551
RCOR2	PHF21A	Q96BD5	513
RCOR2	HDAC1	Q13547	507
RCOR2	HMG20B	Q9P0W2	494
RCOR2	HDAC2	Q92769	492
RCOR2	GFI1B	Q5VTD9	488
RCOR2	RCOR3	Q9P2K3	487
RCOR2	EHMT2	Q96KQ7	436
RCOR2	MECP2	P51608	427
RCOR2	ZMYND8	Q9ULU4	417
RCOR2	TRIM67	Q6ZTA4	414

IntAct

44 interactions, top by confidence:

A	B	Type	Score
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
HMG20A	KDM1A	psi-mi:“MI:0914”(association)	0.730
HDAC1	ZNF609	psi-mi:“MI:0914”(association)	0.730
CTBP1	CBX4	psi-mi:“MI:0914”(association)	0.700
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
DCAF12L2	CETN3	psi-mi:“MI:0914”(association)	0.640
RCOR2	KDM1A	psi-mi:“MI:0914”(association)	0.560
RCOR2	KDM1A	psi-mi:“MI:0915”(physical association)	0.560
PDGFRL	ANKRD28	psi-mi:“MI:0914”(association)	0.530
HMG20B	KDM1A	psi-mi:“MI:0914”(association)	0.530
ZSCAN5A	KDM1A	psi-mi:“MI:0914”(association)	0.530
KDM1A	SMARCA4	psi-mi:“MI:0914”(association)	0.480
ZMYM2	HDAC3	psi-mi:“MI:0914”(association)	0.480
HMG20A	KDM1A	psi-mi:“MI:0914”(association)	0.350
ZSCAN5A	HDAC3	psi-mi:“MI:0914”(association)	0.350
HMG20B	KDM1A	psi-mi:“MI:0914”(association)	0.350
HDAC2		psi-mi:“MI:0914”(association)	0.350
S100B	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ZNF174	FAM171A2	psi-mi:“MI:0914”(association)	0.350
NOL4	ZNF195	psi-mi:“MI:0914”(association)	0.350

BioGRID (50): RCOR2 (Reconstituted Complex), RCOR2 (Affinity Capture-MS), RCOR2 (Affinity Capture-MS), RCOR2 (Affinity Capture-MS), RCOR2 (Affinity Capture-MS), RCOR2 (Affinity Capture-MS), RCOR2 (Affinity Capture-MS), RCOR2 (Affinity Capture-MS), RCOR2 (Affinity Capture-MS), RCOR2 (Affinity Capture-MS), RCOR2 (Affinity Capture-MS), RCOR2 (Affinity Capture-MS), RCOR2 (Affinity Capture-MS), RCOR2 (Affinity Capture-MS), RCOR2 (Proximity Label-MS)

ESM2 similar proteins: B2KF05, B2RRD7, D3ZQL6, E1BBG2, E9Q0S6, F6P6X0, O88665, O95475, P0C865, P39880, P49848, P53564, P53565, P55201, Q04205, Q3UHC7, Q5FWT8, Q5T124, Q5ZJ40, Q62311, Q63618, Q63801, Q6DFC8, Q6NRZ0, Q6P116, Q6P4L9, Q6P4R8, Q6P730, Q6PGA0, Q6PIJ4, Q6ZQF7, Q8BGT6, Q8C033, Q8C796, Q8CFE3, Q8CIP4, Q8IZ40, Q8K382, Q8N3F8, Q8TEH3

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 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	5	31.9×	2e-05
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	6	31.4×	3e-06
Negative Regulation of CDH1 Gene Transcription	7	30.1×	5e-07
HDACs deacetylate histones	5	21.5×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
chromatin organization	5	12.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1847 predictions. Top by Δscore:

Variant	Effect	Δscore
11:63912315:T:TA	donor_gain	1.0000
11:63912390:T:TA	donor_gain	1.0000
11:63912408:T:TA	donor_gain	1.0000
11:63912420:T:TA	donor_gain	1.0000
11:63912530:GATGG:G	acceptor_gain	1.0000
11:63912531:ATGG:A	acceptor_gain	1.0000
11:63912532:TGG:T	acceptor_gain	1.0000
11:63912533:GG:G	acceptor_gain	1.0000
11:63912535:C:CC	acceptor_gain	1.0000
11:63912538:C:CT	acceptor_gain	1.0000
11:63912671:CCCA:C	donor_loss	1.0000
11:63912673:CA:C	donor_loss	1.0000
11:63912674:ACC:A	donor_loss	1.0000
11:63912699:T:C	donor_gain	1.0000
11:63912729:TTGGC:T	acceptor_gain	1.0000
11:63912730:TGGC:T	acceptor_gain	1.0000
11:63912731:GGC:G	acceptor_gain	1.0000
11:63912732:GC:G	acceptor_gain	1.0000
11:63912732:GCC:G	acceptor_loss	1.0000
11:63912733:CC:C	acceptor_gain	1.0000
11:63912733:CCTGG:C	acceptor_loss	1.0000
11:63912734:C:CC	acceptor_gain	1.0000
11:63912734:C:CG	acceptor_loss	1.0000
11:63912734:C:T	acceptor_gain	1.0000
11:63912742:C:CT	acceptor_gain	1.0000
11:63912743:A:T	acceptor_gain	1.0000
11:63912867:TACC:T	donor_loss	1.0000
11:63912868:A:AC	donor_gain	1.0000
11:63912868:ACCT:A	donor_gain	1.0000
11:63912869:C:CC	donor_gain	1.0000

AlphaMissense

3370 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:63912479:C:A	K361N	1.000
11:63912479:C:G	K361N	1.000
11:63912481:T:C	K361E	1.000
11:63912519:C:A	G348V	1.000
11:63912681:A:T	V341D	1.000
11:63912684:G:T	A340D	1.000
11:63912690:A:G	L338P	1.000
11:63912696:T:A	E336V	1.000
11:63912707:C:A	W332C	1.000
11:63912707:C:G	W332C	1.000
11:63912708:C:G	W332S	1.000
11:63912709:A:G	W332R	1.000
11:63912709:A:T	W332R	1.000
11:63914491:C:A	K177N	1.000
11:63914491:C:G	K177N	1.000
11:63914493:T:C	K177E	1.000
11:63914494:C:A	W176C	1.000
11:63914494:C:G	W176C	1.000
11:63914496:A:G	W176R	1.000
11:63914496:A:T	W176R	1.000
11:63914502:A:C	Y174D	1.000
11:63914502:A:G	Y174H	1.000
11:63914505:A:C	Y173D	1.000
11:63914505:A:G	Y173H	1.000
11:63914505:A:T	Y173N	1.000
11:63914508:A:C	Y172D	1.000
11:63914513:A:T	V170E	1.000
11:63914516:A:G	L169P	1.000
11:63914516:A:T	L169Q	1.000
11:63914530:C:A	K164N	1.000

dbSNP variants (sampled 300 via entrez): RS1000036365 (11:63924887 G>T), RS1000242364 (11:63912822 T>A), RS1000892680 (11:63923807 C>T), RS1000942507 (11:63920423 G>A), RS1000971965 (11:63920610 T>C), RS1001136290 (11:63926559 T>C), RS1001233847 (11:63926849 T>A,G), RS1001502456 (11:63917440 G>A), RS1002037513 (11:63925349 C>T), RS1002156863 (11:63912405 C>CA), RS1002459198 (11:63922804 A>G), RS1002598884 (11:63917151 C>T), RS1002656561 (11:63915871 G>A), RS1002745640 (11:63927163 T>C), RS1002761282 (11:63911317 C>G)

Disease associations

OMIM: gene MIM:616019 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008972_94	Urate levels	4.000000e-26
GCST009600_98	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	8.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases methylation	6
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
FR900359	decreases phosphorylation	1
propionaldehyde	increases expression	1
sulforaphane	decreases expression	1
butyraldehyde	increases expression	1
coumarin	affects phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
jinfukang	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Aldehydes	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Caffeine	increases phosphorylation	1
Camptothecin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Naled	affects expression	1
Niclosamide	increases expression	1
Rotenone	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2IX	HAP1 RCOR2 (-) 1	Cancer cell line	Male
CVCL_E2IY	HAP1 RCOR2 (-) 2	Cancer cell line	Male
CVCL_E2IZ	HAP1 RCOR2 (-) 3	Cancer cell line	Male
CVCL_E2J0	HAP1 RCOR2 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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