RCOR1

protein-coding

REST corepressor 1, the group of Myb/SANT domain containing

Gene summary

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). [provided by RefSeq, Aug 2011]

Previous symbols:

RCOR

MANE transcript

NM_015156.4

Inheritance

—

ClinVar variants

U:53B:18

Top phenotype

Joubert syndrome

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr14:102,592,649-102,730,561

External References & Databases

Ensembl (ENSG00000089902)

Transcript & Mutation Effects

hg38 • Region Span ~137.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RCOR1 variants in ClinVar

3 Conditions Cataloged

not providedTotal: 72

not specifiedTotal: 24

Joubert syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015156.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	15 clinvar	2 clinvar	20
missense			44 clinvar		1 clinvar	45
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	53	15	3	71

Highest pathogenic variant AF is 0.000006849869

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015156.4	RefSeq	NP_055971.2	12	MANE Select
ENST00000262241.7	Ensembl	ENSP00000262241.5	12	MANE Select
ENST00000560472.1	Ensembl	ENSP00000454204.1	2	Standard
ENST00000908570.1	Ensembl	ENSP00000578629.1	12	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
rcor1	Danio rerio	Structure: thrombocyte Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

rcor1

Danio rerio

Structure: thrombocyte

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Huntington,s disease - Homo sapiens (human)
miR-targeted genes in lymphocytes - TarBase
Signal Transduction
Factors involved in megakaryocyte development and platelet production
HDACs deacetylate histones

Biological Process

negative regulation of transcription by RNA polymerase II
blood coagulation
viral process
negative regulation of transcription, DNA-templated
histone H4 deacetylation

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
DNA-binding transcription factor activity
histone deacetylase activity
protein binding

Cellular Component

nucleus
nucleoplasm
transcription factor complex
transcriptional repressor complex
DNA repair complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262241
Coding exons: 12
Length: 137916
Individuals with no LoFs: 123794
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 123795
p: 0.00000404

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.87	152	232	0.655	0.0000125	3142
Missense (PolyPhen)		41	96.82	0.42347		1142
Synonymous	-0.750	89	80.4	1.11	0.00000417	891
Loss of Function	4.80	0	26.8	0.00	0.00000145	314

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00010	0.00010	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. {ECO:0000269|PubMed:11171972, ECO:0000269|PubMed:11516394, ECO:0000269|PubMed:12032298, ECO:0000269|PubMed:12399542, ECO:0000269|PubMed:12493763, ECO:0000269|PubMed:16079794, ECO:0000269|PubMed:16140033}.;

Recessive Scores

pRec: 0.161

Intolerance Scores

RVIS EVS: -0.25
RVIS percentile EVS: 35.42

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.764

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium