Details for: ORC6

Gene ID: 23594

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: ORC6

Ensembl ID: ENSG00000091651

Description: origin recognition complex subunit 6

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • pro-B cell CL0000826
    CSI 7.98
    rCSI 6.61%
    PRS 95.58
  • erythroblast CL0000765
    CSI 5.4
    rCSI 14.33%
    PRS 94.8
  • large pre-B-II cell CL0000957
    CSI 4.82
    rCSI 13.77%
    PRS 93.97
  • transit amplifying cell of colon CL0009011
    CSI 4.22
    rCSI 4.95%
    PRS 94.94
  • neural crest cell CL0011012
    CSI 4.17
    rCSI 3.3%
    PRS 90.64
  • common myeloid progenitor CL0000049
    CSI 3.53
    rCSI 2.85%
    PRS 95.6
  • early lymphoid progenitor CL0000936
    CSI 3.38
    rCSI 2.97%
    PRS 96.82
  • stem cell CL0000034
    CSI 3.37
    rCSI 3.25%
    PRS 92.55
  • intestinal epithelial cell CL0002563
    CSI 3.19
    rCSI 3.33%
    PRS 93.09
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 3.08
    rCSI 3.56%
    PRS 89.23
  • fraction A pre-pro B cell CL0002045
    CSI 3.06
    rCSI 3.5%
    PRS 96.65
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 3.05
    rCSI 5.39%
    PRS 86.01
  • mesodermal cell CL0000222
    CSI 2.95
    rCSI 3.54%
    PRS 94.43
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.88
    rCSI 2.6%
    PRS 94.12
  • placental villous trophoblast CL2000060
    CSI 2.83
    rCSI 4.38%
    PRS 93.46
  • promonocyte CL0000559
    CSI 2.81
    rCSI 4.82%
    PRS 95.71
  • glioblast CL0000030
    CSI 2.77
    rCSI 4.41%
    PRS 89.37
  • promyelocyte CL0000836
    CSI 2.57
    rCSI 3.71%
    PRS 95.72
  • radial glial cell CL0000681
    CSI 2.52
    rCSI 3.5%
    PRS 93.57
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.48
    rCSI 2.14%
    PRS 95.93
  • erythrocyte CL0000232
    CSI 2.26
    rCSI 5.12%
    PRS 93.12
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.23
    rCSI 2.15%
    PRS 93.71
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.94
    rCSI 2.49%
    PRS 92.14
  • ependymal cell CL0000065
    CSI 1.91
    rCSI 3.88%
    PRS 81.33
  • erythroid progenitor cell CL0000038
    CSI 1.85
    rCSI 10.6%
    PRS 95.79
  • neural progenitor cell CL0011020
    CSI 1.76
    rCSI 7.76%
    PRS 86.31
  • common dendritic progenitor CL0001029
    CSI 1.58
    rCSI 1.99%
    PRS 97.4
  • primitive red blood cell CL0002355
    CSI 1.33
    rCSI 7.17%
    PRS 95.26
  • myeloid lineage restricted progenitor cell CL0000839
    CSI 1.18
    rCSI 6.08%
    PRS 98.63
  • forebrain radial glial cell CL0013000
    CSI 1.17
    rCSI 3.76%
    PRS 94.51
  • pluripotent stem cell CL0002248
    CSI 1.01
    rCSI 30.4%
    PRS 97.06
  • epithelial cell of nephron CL1000449
    CSI 0.93
    rCSI 8.82%
    PRS 98.79
  • mesenchymal stem cell CL0000134
    CSI 0.63
    rCSI 6.89%
    PRS 96.15

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.

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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 [ORC6](/details-gene/23594) (Origin Recognition Complex Subunit 6) is a protein-coding gene located on chromosome 16q11.2. It encodes a crucial component of the six-subunit origin recognition complex (ORC), which is essential for the initiation of DNA replication in eukaryotic cells. The ORC complex binds to origins of replication on DNA, serving as a platform for the assembly of the pre-replicative complex (pre-RC). Consistent with this fundamental role in cell division, expression of [ORC6](/details-gene/23594) is most significant in highly proliferative cell populations, including hematopoietic progenitors such as [pro-B cell](/details-cell/CL0000826)s and [erythroblast](/details-cell/CL0000765)s, as well as various tissue-specific stem and progenitor cells. Mutations in [ORC6](/details-gene/23594) have been causally linked to Meier-Gorlin syndrome, a rare primordial dwarfism disorder, highlighting its critical importance in normal human development ([Link](https://doi.org/10.1038/ng.775)). ## Cellular Roles and Expression Landscape The expression profile of [ORC6](/details-gene/23594) strongly underscores its central function in cell cycle progression and proliferation. **Overall**, the gene shows the highest significance in cell types characterized by rapid division and differentiation. This is particularly evident in the hematopoietic system, where [ORC6](/details-gene/23594) is a top marker for multiple progenitor populations, including [pro-B cell](/details-cell/CL0000826)s (CSI: 7.98), [erythroblast](/details-cell/CL0000765)s (CSI: 5.40), [large pre-B-II cell](/details-cell/CL0000957)s (CSI: 4.82), and [common myeloid progenitor](/details-cell/CL0000049)s (CSI: 3.53). This pattern of high expression in progenitor cells extends to other tissues. For instance, [ORC6](/details-gene/23594) is highly significant in the [transit amplifying cell of colon](/details-cell/CL0009011) (CSI: 4.22), which are responsible for the rapid renewal of the intestinal epithelium. Similarly, it is prominent in developing neural tissues, as shown by its high CSI in [neural crest cell](/details-cell/CL0011012)s (CSI: 4.17) and [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338)s (CSI: 3.08). The gene's general importance in development and tissue maintenance is further supported by its high significance in undifferentiated [stem cell](/details-cell/CL0000034)s (CSI: 3.37) and [placental villous trophoblast](/details-cell/CL2000060)s (CSI: 2.83). This landscape suggests that [ORC6](/details-gene/23594) is a key operational component for any cell lineage undergoing expansion or renewal. ## Pathways and Molecular Function Functionally, [ORC6](/details-gene/23594) is integral to the molecular machinery governing DNA replication and cell cycle control. As a subunit of the [origin recognition complex](/details-go/GO:0000808), it participates directly in [Dna replication initiation](/details-go/GO:0006270) through its [Dna binding](/details-go/GO:0003677) and [protein binding](/details-go/GO:0005515) activities. It localizes primarily to the [nucleus](/details-go/GO:0005634), where it functions within the [nuclear origin of replication recognition complex](/details-go/GO:0005664). Structural studies have revealed that the protein shares homology with the general transcription factor TFIIB, suggesting a potential ancestral link between transcription and replication initiation ([Link](https://doi.org/10.1073/pnas.1013676108)). The Reactome pathway analysis further details its involvement across the entire cell cycle. [ORC6](/details-gene/23594) is a key player in the '[Assembly of the orc complex at the origin of replication](/details-reactome/R-HSA-68616)' and the subsequent '[Activation of the pre-replicative complex](/details-reactome/R-HSA-68962)'. Its function is tightly regulated during the '[G1/s transition](/details-reactome/R-HSA-69206)' and is essential for progression into the '[S phase](/details-reactome/R-HSA-69242)'. Furthermore, its participation in pathways such as '[Activation of atr in response to replication stress](/details-reactome/R-HSA-176187)' and '[G2/m checkpoints](/details-reactome/R-HSA-69481)' indicates a role not only in initiating DNA synthesis but also in maintaining genome integrity through cell cycle checkpoint control. This extensive involvement is consistent with its phosphorylation being responsive to DNA damage ([Link](https://doi.org/10.1126/science.1140321)). ## Research Directions The fundamental role of [ORC6](/details-gene/23594) in DNA replication makes it a critical gene for both normal development and pathological conditions like cancer. Its established link to Meier-Gorlin syndrome via mutations that impair pre-replicative complex function confirms its non-redundant role in human growth ([Link](https://doi.org/10.1038/ng.775)). Future research should focus on how quantitative variations in [ORC6](/details-gene/23594) expression or subtle functional alterations contribute to disease states beyond rare developmental syndromes. Based on its expression and function, several testable hypotheses can be proposed: 1. **Hypothesis 1:** The precise expression level of [ORC6](/details-gene/23594) in hematopoietic stem and progenitor cells acts as a rheostat for cell cycle speed, thereby influencing the balance between self-renewal and differentiation into specific lineages like B-cells or erythrocytes. 2. **Hypothesis 2:** In cancer cells experiencing high replicative stress, dysregulation of [ORC6](/details-gene/23594) expression or post-translational modifications may contribute to genomic instability by altering the fidelity of replication origin firing, creating a specific vulnerability. A key experiment to test the second hypothesis could be designed as follows: To investigate the role of [ORC6](/details-gene/23594) in genomic instability under replicative stress, one could use CRISPR-Cas9 to knockdown [ORC6](/details-gene/23594) in cancer cell lines with known oncogene-driven replication stress (e.g., MYC-overexpressing lymphomas, reflecting its high expression in B-cell precursors). These modified cells could then be analyzed using DNA fiber assays to measure changes in inter-origin distances and replication fork speed. Furthermore, whole-genome sequencing could be employed to quantify increases in structural variants or specific mutational signatures, which would directly link [ORC6](/details-gene/23594) insufficiency to a loss of genome maintenance under oncogenic stress. **Therapeutic Potential:** As a core component of the DNA replication machinery, [ORC6](/details-gene/23594) represents a potential therapeutic target for hyperproliferative diseases like cancer. The therapeutic strategy would involve **inhibition** to halt the uncontrolled division of tumor cells. However, its essential function in all dividing healthy cells, such as hematopoietic progenitors and intestinal epithelial cells, poses a significant challenge, suggesting a narrow therapeutic window and a high risk of on-target toxicity. Future approaches may require the development of inhibitors that target cancer-specific protein-protein interactions involving [ORC6](/details-gene/23594) or exploiting synthetic lethality in tumors with pre-existing DNA damage response defects.

Genular Protein ID: 2031690660

Symbol: ORC6_HUMAN

Name: Origin recognition complex subunit 6

UniProtKB Accession Codes:

Q9Y5N6 B3KN89

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CORUM 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 9 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 2 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 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 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 7 RefSeq 1 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 17081983

Title: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

PubMed ID: 17081983

DOI: 10.1016/j.cell.2006.09.026

PubMed ID: 17716973

Title: ATP-dependent assembly of the human origin recognition complex.

PubMed ID: 17716973

DOI: 10.1074/jbc.m705905200

PubMed ID: 17525332

Title: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.

PubMed ID: 17525332

DOI: 10.1126/science.1140321

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 22427655

Title: Leucine-rich repeat and WD repeat-containing protein 1 is recruited to pericentric heterochromatin by trimethylated lysine 9 of histone H3 and maintains heterochromatin silencing.

PubMed ID: 22427655

DOI: 10.1074/jbc.m111.337980

PubMed ID: 23186163

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

PubMed ID: 23186163

DOI: 10.1021/pr300630k

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: 21502537

Title: Structural analysis of human Orc6 protein reveals a homology with transcription factor TFIIB.

PubMed ID: 21502537

DOI: 10.1073/pnas.1013676108

PubMed ID: 21358632

Title: Mutations in the pre-replication complex cause Meier-Gorlin syndrome.

PubMed ID: 21358632

DOI: 10.1038/ng.775

Sequence Information:

  • Length: 252
  • Mass: 28107
  • Checksum: 78840387605F45FE
  • Sequence:
    • MGSELIGRLA PRLGLAEPDM LRKAEEYLRL SRVKCVGLSA RTTETSSAVM CLDLAASWMK 
CPLDRAYLIK LSGLNKETYQ SCLKSFECLL GLNSNIGIRD LAVQFSCIEA VNMASKILKS 
YESSLPQTQQ VDLDLSRPLF TSAALLSACK ILKLKVDKNK MVATSGVKKA IFDRLCKQLE 
KIGQQVDREP GDVATPPRKR KKIVVEAPAK EMEKVEEMPH KPQKDEDLTQ DYEEWKRKIL 
ENAASAQKAT AE