Details for: BCORL1

Gene ID: 63035

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: BCORL1

Ensembl ID: ENSG00000085185

Description: BCL6 corepressor like 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • neural crest cell CL0011012
    CSI 4.01
    rCSI 3.17%
    PRS 95.6
  • blood vessel endothelial cell CL0000071
    CSI 3.13
    rCSI 6.49%
    PRS 96.91
  • astrocyte of the cerebral cortex CL0002605
    CSI 3.09
    rCSI 6.93%
    PRS 92.93
  • extravillous trophoblast CL0008036
    CSI 2.61
    rCSI 3.23%
    PRS 96.62
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.53
    rCSI 3.15%
    PRS 91.25
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.43
    rCSI 3.14%
    PRS 93.12
  • basal cell CL0000646
    CSI 2.3
    rCSI 3.08%
    PRS 96.15
  • placental villous trophoblast CL2000060
    CSI 2.08
    rCSI 3.22%
    PRS 96.65
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.9
    rCSI 3.36%
    PRS 92.56
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.83
    rCSI 3.07%
    PRS 92.86
  • syncytiotrophoblast cell CL0000525
    CSI 1.5
    rCSI 4.33%
    PRS 96.67
  • dopaminergic neuron CL0000700
    CSI 0.84
    rCSI 4.76%
    PRS 91.95
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.75
    rCSI 2.69%
    PRS 91.38

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [BCORL1](/details-gene/63035) (BCL6 Corepressor Like 1) is a protein-coding gene located on the X chromosome that functions as a transcriptional corepressor. It plays a crucial role in epigenetic regulation, primarily through its involvement in [Chromatin organization](/details-go/GO:0006325) and [Negative regulation of transcription by rna polymerase ii](/details-go/GO:0000122). Consistent with a role in developmental processes, **Overall** expression data shows [BCORL1](/details-gene/63035) is a significant marker in cell types of neurodevelopmental and placental origin, including [neural crest cell](/details-cell/CL0011012), [blood vessel endothelial cell](/details-cell/CL0000071), and various neuronal subtypes. Its function is mediated by its interaction with other regulatory proteins in the [Nucleus](/details-go/GO:0005634), and mutations in the gene are associated with inherited developmental disorders ([300688](https://omim.org/entry/300688), [301029](https://omim.org/entry/301029)). ## Cellular Roles and Expression Landscape The expression profile of [BCORL1](/details-gene/63035) highlights its specialized role in neurogenesis, vasculogenesis, and placental development. **Overall**, the gene shows the highest significance in [neural crest cell](/details-cell/CL0011012) (CSI: 4.01), a multipotent cell population critical for the development of the peripheral nervous system and other tissues. This is further supported by its high significance in multiple differentiated neuronal subtypes, including [astrocyte of the cerebral cortex](/details-cell/CL0002605) (CSI: 3.09), [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 2.53), and [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 2.43), suggesting a sustained role in the maturation and function of the central nervous system. In parallel, [BCORL1](/details-gene/63035) is a key marker for [blood vessel endothelial cell](/details-cell/CL0000071) (CSI: 3.13), indicating a potential function in angiogenesis or the maintenance of vascular integrity. Its significance is also prominent in placental cells such as [extravillous trophoblast](/details-cell/CL0008036) (CSI: 2.61) and [placental villous trophoblast](/details-cell/CL2000060) (CSI: 2.08), which are essential for embryonic implantation and development. This dual expression pattern across neural and vascular/placental lineages suggests that [BCORL1](/details-gene/63035) is a core regulatory factor governing the gene expression programs essential for these complex developmental processes. ## Pathways and Molecular Function Functionally, [BCORL1](/details-gene/63035) operates as a transcriptional corepressor, a role defined by its [Transcription corepressor activity](/details-go/GO:0003714) and its localization to the [Nucleus](/details-go/GO:0005634) and [Nucleoplasm](/details-go/GO:0005654). Its primary mechanism involves the recruitment of chromatin-modifying complexes to specific gene promoters, leading to transcriptional silencing. Research has demonstrated that [BCORL1](/details-gene/63035) can repress transcription through direct interaction with the C-terminal binding protein (CtBP) ([Link](https://doi.org/10.1074/jbc.m700246200)). Furthermore, [BCORL1](/details-gene/63035) is a component of the non-canonical Polycomb Repressive Complex 1.1 (PRC1.1), where it collaborates with PCGF1 to recruit the KDM2B subunit, which is critical for the complex's function in gene repression ([Link](https://doi.org/10.1016/j.str.2016.07.011), [Link](https://doi.org/10.1016/j.str.2013.02.013)). This places [BCORL1](/details-gene/63035) as a key player in Polycomb-mediated gene silencing, a fundamental process for maintaining cell identity and regulating development. Its involvement in [Chromatin organization](/details-go/GO:0006325) is therefore central to its function in the diverse cell types where it is highly expressed. ## Research Directions The specific and high expression of [BCORL1](/details-gene/63035) in distinct developmental lineages, combined with its known function as a transcriptional corepressor, points toward several avenues for future research. The clinical associations with intellectual disability ([300688](https://omim.org/entry/300688)) underscore the critical importance of its function in the central nervous system. **Testable Hypotheses:** 1. Given its high significance in multiple classes of cortical interneurons and their precursors ([neural crest cell](/details-cell/CL0011012)), [BCORL1](/details-gene/63035) likely acts as a key epigenetic regulator that represses alternative cell fates during interneuron specification. Loss-of-function mutations may disrupt the precise gene expression programs required for their proper differentiation and migration, leading to neurodevelopmental disorders. 2. The high CSI of [BCORL1](/details-gene/63035) in [blood vessel endothelial cell](/details-cell/CL0000071) and various trophoblast subtypes suggests it plays a critical role in coordinating gene expression during angiogenesis and placentation. It may repress anti-angiogenic factors or genes that restrict trophoblast invasion, and its dysregulation could contribute to vascular abnormalities or placental insufficiency. **Proposed Experiment:** To test the role of [BCORL1](/details-gene/63035) in cortical interneuron development (Hypothesis 1), a CRISPR interference (CRISPRi) system could be used to specifically knock down its expression in human pluripotent stem cells (hPSCs). These modified hPSCs would then be directed to differentiate towards caudal ganglionic eminence-derived cortical interneurons. Single-cell RNA-sequencing (scRNA-seq) at multiple time points during differentiation would reveal alterations in cell fate trajectories and gene regulatory networks. Concurrently, CUT&RUN or ChIP-seq for BCORL1 and key histone marks (e.g., H3K27me3) in wild-type cells would identify the direct genomic targets of [BCORL1](/details-gene/63035)-mediated repression during this process. **Therapeutic Potential:** As a transcriptional corepressor, [BCORL1](/details-gene/63035) presents a challenging therapeutic target. Direct inhibition or activation is difficult. However, in pathologies driven by its loss-of-function (e.g., certain developmental disorders), therapies aimed at modulating downstream pathways or compensating for the epigenetic dysregulation could be explored. Conversely, if [BCORL1](/details-gene/63035) overexpression were found to drive certain cancers by aberrantly repressing tumor suppressor genes, developing small molecule inhibitors that disrupt its key protein-protein interactions (e.g., with PCGF1 or CtBP) could represent a viable therapeutic strategy. This approach would be highly specific and focus on inhibiting the formation of the repressive complex rather than the protein itself.

Genular Protein ID: 362037711

Symbol: BCORL_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q5H9F3 B5MDQ8 Q5H9F2 Q5H9F4 Q6ZVE0 Q8TEN3 Q9Y528

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 9 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 6 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HPA 1 IDEAL 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 11 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

PubMed ID: 12693554

Title: Characterization of long cDNA clones from human adult spleen. II. The complete sequences of 81 cDNA clones.

PubMed ID: 12693554

DOI: 10.1093/dnares/10.1.49

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 17379597

Title: A novel corepressor, BCoR-L1, represses transcription through an interaction with CtBP.

PubMed ID: 17379597

DOI: 10.1074/jbc.m700246200

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 25218447

Title: Uncovering global SUMOylation signaling networks in a site-specific manner.

PubMed ID: 25218447

DOI: 10.1038/nsmb.2890

PubMed ID: 25755297

Title: System-wide analysis of SUMOylation dynamics in response to replication stress reveals novel small ubiquitin-like modified target proteins and acceptor lysines relevant for genome stability.

PubMed ID: 25755297

DOI: 10.1074/mcp.o114.044792

PubMed ID: 28112733

Title: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

PubMed ID: 28112733

DOI: 10.1038/nsmb.3366

PubMed ID: 23523425

Title: Structure of the polycomb group protein PCGF1 in complex with BCOR reveals basis for binding selectivity of PCGF homologs.

PubMed ID: 23523425

DOI: 10.1016/j.str.2013.02.013

PubMed ID: 27568929

Title: KDM2B Recruitment of the Polycomb Group Complex, PRC1.1, Requires Cooperation between PCGF1 and BCORL1.

PubMed ID: 27568929

DOI: 10.1016/j.str.2016.07.011

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

PubMed ID: 24123876

Title: Identification of pathogenic gene variants in small families with intellectually disabled siblings by exome sequencing.

PubMed ID: 24123876

DOI: 10.1136/jmedgenet-2013-101644

PubMed ID: 26933038

Title: Exome sequencing identified a splice site mutation in FHL1 that causes Uruguay Syndrome, an X-linked disorder with skeletal muscle hypertrophy and premature cardiac death.

PubMed ID: 26933038

DOI: 10.1161/circgenetics.115.001193

PubMed ID: 30941876

Title: Variants in the transcriptional corepressor BCORL1 are associated with an X-linked disorder of intellectual disability, dysmorphic features, and behavioral abnormalities.

PubMed ID: 30941876

DOI: 10.1002/ajmg.a.61118

Sequence Information:

  • Length: 1785
  • Mass: 190561
  • Checksum: DD62FFFEC2DE1E9C
  • Sequence:
    • MISTAPLYSG VHNWTSSDRI RMCGINEERR APLSDEESTT GDCQHFGSQE FCVSSSFSKV 
ELTAVGSGSN ARGADPDGSA TEKLGHKSED KPDDPQPKMD YAGNVAEAEG LLVPLSSPGD 
GLKLPASDSA EASNSRADCS WTPLNTQMSK QVDCSPAGVK ALDSRQGVGE KNTFILATLG 
TGVPVEGTLP LVTTNFSPLP APICPPAPGS ASVPHSVPDA FQVPLSVPAP VPHSGLVPVQ 
VATSVPAPSP PLAPVPALAP APPSVPTLIS DSNPLSVSAS VLVPVPASAP PSGPVPLSAP 
APAPLSVPVS APPLALIQAP VPPSAPTLVL APVPTPVLAP MPASTPPAAP APPSVPMPTP 
TPSSGPPSTP TLIPAFAPTP VPAPTPAPIF TPAPTPMPAA TPAAIPTSAP IPASFSLSRV 
CFPAAQAPAM QKVPLSFQPG TVLTPSQPLV YIPPPSCGQP LSVATLPTTL GVSSTLTLPV 
LPSYLQDRCL PGVLASPELR SYPYAFSVAR PLTSDSKLVS LEVNRLPCTS PSGSTTTQPA 
PDGVPGPLAD TSLVTASAKV LPTPQPLLPA PSGSSAPPHP AKMPSGTEQQ TEGTSVTFSP 
LKSPPQLERE MASPPECSEM PLDLSSKSNR QKLPLPNQRK TPPMPVLTPV HTSSKALLST 
VLSRSQRTTQ AAGGNVTSCL GSTSSPFVIF PEIVRNGDPS TWVKNSTALI STIPGTYVGV 
ANPVPASLLL NKDPNLGLNR DPRHLPKQEP ISIIDQGEPK GTGATCGKKG SQAGAEGQPS 
TVKRYTPARI APGLPGCQTK ELSLWKPTGP ANIYPRCSVN GKPTSTQVLP VGWSPYHQAS 
LLSIGISSAG QLTPSQGAPI RPTSVVSEFS GVPSLSSSEA VHGLPEGQPR PGGSFVPEQD 
PVTKNKTCRI AAKPYEEQVN PVLLTLSPQT GTLALSVQPS GGDIRMNQGP EESESHLCSD 
STPKMEGPQG ACGLKLAGDT KPKNQVLATY MSHELVLATP QNLPKMPELP LLPHDSHPKE 
LILDVVPSSR RGSSTERPQL GSQVDLGRVK MEKVDGDVVF NLATCFRADG LPVAPQRGQA 
EVRAKAGQAR VKQESVGVFA CKNKWQPDDV TESLPPKKMK CGKEKDSEEQ QLQPQAKAVV 
RSSHRPKCRK LPSDPQESTK KSPRGASDSG KEHNGVRGKH KHRKPTKPES QSPGKRADSH 
EEGSLEKKAK SSFRDFIPVV LSTRTRSQSG SICSSFAGMA DSDMGSQEVF PTEEEEEVTP 
TPAKRRKVRK TQRDTQYRSH HAQDKSLLSQ GRRHLWRARE MPWRTEAARQ MWDTNEEEEE 
EEEEGLLKRK KRRRQKSRKY QTGEYLTEQE DEQRRKGRAD LKARKQKTSS SQSLEHRLRN 
RNLLLPNKVQ GISDSPNGFL PNNLEEPACL ENSEKPSGKR KCKTKHMATV SEEAKGKGRW 
SQQKTRSPKS PTPVKPTEPC TPSKSRSASS EEASESPTAR QIPPEARRLI VNKNAGETLL 
QRAARLGYKD VVLYCLQKDS EDVNHRDNAG YTALHEACSR GWTDILNILL EHGANVNCSA 
QDGTRPVHDA VVNDNLETIW LLLSYGADPT LATYSGQTAM KLASSDTMKR FLSDHLSDLQ 
GRAEGDPGVS WDFYSSSVLE EKDGFACDLL HNPPGSSDQE GDDPMEEDDF MFELSDKPLL 
PCYNLQVSVS RGPCNWFLFS DVLKRLKLSS RIFQARFPHF EITTMPKAEF YRQVASSQLL 
TPAERPGGLD DRSPPGSSET VELVRYEPDL LRLLGSEVEF QSCNS