Details for: DGCR6

Gene ID: 8214

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: DGCR6

Ensembl ID: ENSG00000183628

Description: DiGeorge syndrome critical region gene 6

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • epithelial cell of lung CL0000082
    CSI 3.76
    rCSI 3.12%
    PRS 99.55
  • myeloid leukocyte CL0000766
    CSI 3.39
    rCSI 3.12%
    PRS 99.51
  • intestine goblet cell CL0019031
    CSI 3.2
    rCSI 2.84%
    PRS 98.72
  • keratinocyte CL0000312
    CSI 3.13
    rCSI 2.62%
    PRS 98.47
  • lung ciliated cell CL1000271
    CSI 3.04
    rCSI 3.51%
    PRS 97.8
  • multi-ciliated epithelial cell CL0005012
    CSI 2.98
    rCSI 2.98%
    PRS 97.75
  • intestinal epithelial cell CL0002563
    CSI 2.86
    rCSI 2.99%
    PRS 98.67
  • ciliated cell CL0000064
    CSI 2.85
    rCSI 4.62%
    PRS 97.11
  • retina horizontal cell CL0000745
    CSI 2.51
    rCSI 3.82%
    PRS 98.22
  • club cell CL0000158
    CSI 2.19
    rCSI 3.21%
    PRS 99.08
  • peripheral nervous system neuron CL2000032
    CSI 2.09
    rCSI 2.85%
    PRS 97.97
  • mesenchymal cell CL0008019
    CSI 1.27
    rCSI 3.23%
    PRS 98.78
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.27
    rCSI 2.9%
    PRS 96.91

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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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 [DGCR6](/details-gene/8214), or DiGeorge syndrome critical region gene 6, is a protein-coding gene located on human chromosome 22q11.21. As its name suggests, it is situated within a chromosomal region whose deletion is associated with DiGeorge syndrome ([601279](https://omim.org/entry/601279)). Functional annotations link [DGCR6](/details-gene/8214) to fundamental biological processes such as animal organ morphogenesis ([GO:0009887](https://www.ebi.ac.uk/QuickGO/term/GO:0009887)) and cell adhesion ([GO:0007155](https://www.ebi.ac.uk/QuickGO/term/GO:0007155)). The protein product is associated with both the nucleus and the extracellular matrix. **Overall**, expression data reveals its high significance in a variety of epithelial and mucosal cells, particularly [epithelial cell of lung](/details-cell/CL0000082) and [intestine goblet cell](/details-cell/CL0019031), as well as in [myeloid leukocyte](/details-cell/CL0000766), suggesting a key role in tissue structure, barrier function, and potentially immune processes at these sites. ## Cellular Roles and Expression Landscape The expression profile of [DGCR6](/details-gene/8214) strongly indicates a primary role in maintaining the structure and function of barrier tissues. **Overall**, the gene shows the highest significance in cell types that form mucosal linings and protective layers. It is a top marker for [epithelial cell of lung](/details-cell/CL0000082) (CSI: 3.76), [intestine goblet cell](/details-cell/CL0019031) (CSI: 3.20), and [keratinocyte](/details-cell/CL0000312) (CSI: 3.13). This pattern is further reinforced by its high significance in multiple types of ciliated cells, including [lung ciliated cell](/details-cell/CL1000271) (CSI: 3.04) and [multi-ciliated epithelial cell](/details-cell/CL0005012) (CSI: 2.98), which are critical for mucociliary clearance in the respiratory tract. Interestingly, [DGCR6](/details-gene/8214) is also highly significant in [myeloid leukocyte](/details-cell/CL0000766) (CSI: 3.39). The co-expression in both epithelial barrier cells and a major immune cell lineage suggests a potential function at the interface of host defense and tissue integrity, possibly related to immune cell trafficking or adhesion within these tissues. The gene's broad significance across diverse cell types like [retina horizontal cell](/details-cell/CL0000745) and [peripheral nervous system neuron](/details-cell/CL2000032) points towards a more general role in cellular organization and adhesion beyond epithelial tissues. ## Pathways and Molecular Function The functions of [DGCR6](/details-gene/8214) are consistent with its observed expression pattern in structurally important cell types. The gene is annotated with biological processes including animal organ morphogenesis ([GO:0009887](https://www.ebi.ac.uk/QuickGO/term/GO:0009887)) and cell adhesion ([GO:0007155](https://www.ebi.ac.uk/QuickGO/term/GO:0007155)), which aligns with its high significance in epithelial cells that form the architecture of organs like the lung and intestine. Early research highlighted its homology to genes involved in cell adhesion and the extracellular matrix, such as *LAMC1* ([Link](https://doi.org/10.1093/hmg/5.5.633)). At the molecular level, [DGCR6](/details-gene/8214) is involved in protein binding ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)). Its protein product has been localized to both the extracellular matrix ([GO:0031012](https://www.ebi.ac.uk/QuickGO/term/GO:0031012)) and the nucleus ([GO:0005634](https://www.ebi.ac.uk/QuickGO/term/GO:0005634)), as detailed in biochemical studies ([Link](https://doi.org/10.1007/s00439-005-1267-2)). This dual localization suggests it may have a complex role, potentially mediating signals from the extracellular environment to the nucleus, in addition to contributing directly to tissue structure. ## Research Directions The widespread expression of [DGCR6](/details-gene/8214) in barrier tissues and its link to a critical developmental syndrome present several avenues for future investigation. Based on the available data, several testable hypotheses can be proposed: 1. **Epithelial Barrier Integrity:** [DGCR6](/details-gene/8214) is essential for maintaining the physical integrity of the respiratory and intestinal mucosa by mediating cell-matrix or cell-cell adhesion. Its loss-of-function would lead to compromised barrier function. 2. **Myeloid Cell Function:** The high significance in [myeloid leukocyte](/details-cell/CL0000766) suggests that [DGCR6](/details-gene/8214) regulates myeloid cell adhesion and migration, facilitating their recruitment to and retention within epithelial tissues during homeostasis or inflammation. 3. **Ciliary Function:** Given its high expression across multiple ciliated cell types, [DGCR6](/details-gene/8214) may play a role in ciliogenesis or in coordinating ciliary beating, thereby contributing to mucociliary clearance mechanisms. To test the first hypothesis regarding its role in epithelial barrier function, a key experiment could be proposed: * **Proposed Experiment:** A CRISPR-Cas9-mediated knockdown of [DGCR6](/details-gene/8214) could be performed in primary human bronchial epithelial cells grown in an air-liquid interface (ALI) culture. The impact on barrier integrity could be quantitatively measured by transepithelial electrical resistance (TEER) and paracellular flux assays. Concurrently, immunofluorescence microscopy could be used to assess changes in the organization and localization of key junctional proteins like E-cadherin and ZO-1. **Therapeutic Potential:** Given that [DGCR6](/details-gene/8214) is associated with DiGeorge syndrome, a condition caused by haploinsufficiency, therapeutic strategies would likely focus on restoring function rather than inhibition. It is therefore not a conventional drug target for inhibition. The development of therapies to augment its expression or function, such as through gene therapy or small molecule activators, would be the conceptual goal. However, its broad expression in essential barrier tissues raises potential challenges for systemic therapies, which would require precise targeting to avoid off-target effects.

Genular Protein ID: 31532536

Symbol: DGCR6_HUMAN

Name: Protein DGCR6

UniProtKB Accession Codes:

Q14129 B2RCH5 D3DX15 G5E9J8 Q9BY28

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 2 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 9 Ensembl 2 ExpressionAtlas 1 GO 4 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 2 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 11157784

Title: Two functional copies of the DGCR6 gene are present on human chromosome 22q11 due to a duplication of an ancestral locus.

PubMed ID: 11157784

DOI: 10.1101/gr.gr-1431r

PubMed ID: 15821931

Title: Biochemical characterisation of the proteins encoded by the DiGeorge critical region 6 (DGCR6) genes.

PubMed ID: 15821931

DOI: 10.1007/s00439-005-1267-2

PubMed ID: 8733130

Title: Isolation of a novel gene from the DiGeorge syndrome critical region with homology to Drosophila gdl and to human LAMC1 genes.

PubMed ID: 8733130

DOI: 10.1093/hmg/5.5.633

PubMed ID: 24722188

Title: Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism.

PubMed ID: 24722188

DOI: 10.1038/ncomms4650

PubMed ID: 15461802

Title: A genome annotation-driven approach to cloning the human ORFeome.

PubMed ID: 15461802

DOI: 10.1186/gb-2004-5-10-r84

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 10591208

Title: The DNA sequence of human chromosome 22.

PubMed ID: 10591208

DOI: 10.1038/990031

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

Sequence Information:

  • Length: 220
  • Mass: 24989
  • Checksum: DF68DEAF5BF6B8BB
  • Sequence:
    • MERYAGALEE VADGARQQER HYQLLSALQS LVKELPSSFQ QRLSYTTLSD LALALLDGTV 
FEIVQGLLEI QHLTEKSLYN QRLRLQNEHR VLRQALRQKH QEAQQACRPH NLPVLQAAQQ 
RELEAVEHRI REEQRAMDQK IVLELDRKVA DQQSTLEKAG VAGFYVTTNP QELMLQMNLL 
ELIRKLQQRG CWAGKAALGL GGPWQLPAAQ CDQKGSPVPP