Details for: LDOC1

Gene ID: 23641

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: LDOC1

Ensembl ID: ENSG00000182195

Description: LDOC1 regulator of NFKB signaling

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • interstitial cell of Cajal CL0002088
    CSI 3.84
    rCSI 4.89%
    PRS 96.93
  • epithelial cell of lower respiratory tract CL0002632
    CSI 3.77
    rCSI 2.92%
    PRS 96.47
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 3.76
    rCSI 6.64%
    PRS 86.19
  • mesodermal cell CL0000222
    CSI 3.73
    rCSI 4.48%
    PRS 94.55
  • ON-bipolar cell CL0000749
    CSI 3.6
    rCSI 5.35%
    PRS 93.51
  • acinar cell CL0000622
    CSI 3.59
    rCSI 5.27%
    PRS 97.54
  • ionocyte CL0005006
    CSI 3.47
    rCSI 3.71%
    PRS 95.69
  • epithelial cell of lung CL0000082
    CSI 3.31
    rCSI 2.75%
    PRS 95.83
  • group 3 innate lymphoid cell CL0001071
    CSI 3.26
    rCSI 2.45%
    PRS 96.58
  • interneuron CL0000099
    CSI 3.2
    rCSI 6.43%
    PRS 91.4
  • myofibroblast cell CL0000186
    CSI 3.16
    rCSI 4.37%
    PRS 92.81
  • neural crest cell CL0011012
    CSI 3.13
    rCSI 2.48%
    PRS 90.76
  • microcirculation associated smooth muscle cell CL0008035
    CSI 2.94
    rCSI 8.5%
    PRS 94.36
  • hematopoietic stem cell CL0000037
    CSI 2.9
    rCSI 1.93%
    PRS 95.76
  • rod bipolar cell CL0000751
    CSI 2.88
    rCSI 5.18%
    PRS 91.42
  • mucus secreting cell CL0000319
    CSI 2.83
    rCSI 4.49%
    PRS 97.31
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.76
    rCSI 2.49%
    PRS 94.24
  • intestinal epithelial cell CL0002563
    CSI 2.55
    rCSI 2.67%
    PRS 93.18
  • OFF-bipolar cell CL0000750
    CSI 2.51
    rCSI 3.43%
    PRS 93.03
  • lung neuroendocrine cell CL1000223
    CSI 2.46
    rCSI 3.64%
    PRS 95.29
  • smooth muscle cell CL0000192
    CSI 2.46
    rCSI 5.86%
    PRS 91
  • pulmonary ionocyte CL0017000
    CSI 2.43
    rCSI 2.96%
    PRS 96.73
  • retinal ganglion cell CL0000740
    CSI 2.35
    rCSI 5.18%
    PRS 87.86
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 2.34
    rCSI 6.9%
    PRS 94.78
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.12
    rCSI 2.64%
    PRS 84.7
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.12
    rCSI 2.72%
    PRS 92.27
  • retina horizontal cell CL0000745
    CSI 2.08
    rCSI 3.17%
    PRS 92.72
  • stem cell CL0000034
    CSI 2.08
    rCSI 2%
    PRS 92.62
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.06
    rCSI 2.66%
    PRS 87.61
  • enteric smooth muscle cell CL0002504
    CSI 2.03
    rCSI 2.89%
    PRS 94.92
  • peripheral nervous system neuron CL2000032
    CSI 1.96
    rCSI 2.67%
    PRS 90.51
  • fallopian tube secretory epithelial cell CL4030006
    CSI 1.93
    rCSI 1.86%
    PRS 93.83
  • pancreatic ductal cell CL0002079
    CSI 1.93
    rCSI 3.74%
    PRS 95.6
  • stromal cell CL0000499
    CSI 1.88
    rCSI 5.3%
    PRS 92.28
  • radial glial cell CL0000681
    CSI 1.88
    rCSI 2.61%
    PRS 93.68
  • vascular associated smooth muscle cell CL0000359
    CSI 1.86
    rCSI 6.04%
    PRS 93.83
  • club cell CL0000158
    CSI 1.82
    rCSI 2.67%
    PRS 92.15
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.66
    rCSI 2.78%
    PRS 86.81
  • progenitor cell CL0011026
    CSI 1.61
    rCSI 3.43%
    PRS 90.11
  • type B pancreatic cell CL0000169
    CSI 1.45
    rCSI 3.2%
    PRS 94.84
  • mesenchymal cell CL0008019
    CSI 1.33
    rCSI 3.38%
    PRS 92.06
  • mammary gland epithelial cell CL0002327
    CSI 1.31
    rCSI 4.58%
    PRS 97.07
  • pancreatic PP cell CL0002275
    CSI 1.1
    rCSI 4.38%
    PRS 96.01
  • forebrain radial glial cell CL0013000
    CSI 1.05
    rCSI 3.35%
    PRS 94.59
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.98
    rCSI 3.07%
    PRS 87.65
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.93
    rCSI 2.25%
    PRS 84.83
  • Cajal-Retzius cell CL0000695
    CSI 0.54
    rCSI 4.21%
    PRS 95.34
  • blood vessel smooth muscle cell CL0019018
    CSI 0.47
    rCSI 3.84%
    PRS 93.99
  • bronchiolar smooth muscle cell CL4033017
    CSI 0.4
    rCSI 6.06%
    PRS 97.4

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 [LDOC1](/details-gene/23641) (Leucine Zipper Down-Regulated In Cancer 1) is a protein-coding gene located on the X chromosome at position Xq27.1. Functionally, [LDOC1](/details-gene/23641) is described as a regulator of NF-kappaB (NFKB) signaling and has been implicated in the negative regulation of cell proliferation, consistent with its initial discovery as a gene downregulated in various cancer cell lines ([Link](https://doi.org/10.1016/s0304-3835(99)00087-7)). The protein product is localized to the nucleus and nucleolus, suggesting a role in transcriptional regulation. Expression data reveals its significance across a diverse array of cell types, including specialized neural, epithelial, and mesenchymal cells, indicating a broad but context-specific functional importance. Its clinical relevance is noted under OMIM entry [300402](https://omim.org/entry/300402). ## Cellular Roles and Expression Landscape The expression profile of [LDOC1](/details-gene/23641) suggests a multifaceted role across various lineages, rather than being restricted to a single tissue. **Overall**, [LDOC1](/details-gene/23641) shows significant expression in several distinct cellular systems: * **Mesenchymal and Structural Cells:** The gene's highest significance is observed in [interstitial cell of Cajal](/details-cell/CL0002088) (CSI: 3.84), a key pacemaker cell in the gastrointestinal tract. It is also prominent in [mesodermal cell](/details-cell/CL0000222) (CSI: 3.73), [myofibroblast cell](/details-cell/CL0000186) (CSI: 3.16), and [microcirculation associated smooth muscle cell](/details-cell/CL0008035) (CSI: 2.94), pointing towards a role in tissue structure, contractility, and development. * **Epithelial Cells:** High significance is noted in [epithelial cell of lower respiratory tract](/details-cell/CL0002632) (CSI: 3.77), [acinar cell](/details-cell/CL0000622) (CSI: 3.59), [ionocyte](/details-cell/CL0005006) (CSI: 3.47), and [epithelial cell of lung](/details-cell/CL0000082) (CSI: 3.31), suggesting a role in the function of glandular and barrier tissues. * **Neural Cells:** The gene is a significant marker in several neuronal subtypes, including [caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064) (CSI: 3.76), [ON-bipolar cell](/details-cell/CL0000749) (CSI: 3.60), and [interneuron](/details-cell/CL0000099) (CSI: 3.20), indicating a potential role in neuronal function or development. * **Immune and Hematopoietic Cells:** While not its most prominent role, [LDOC1](/details-gene/23641) shows relevance in [group 3 innate lymphoid cell](/details-cell/CL0001071) (CSI: 3.26) and [hematopoietic stem cell](/details-cell/CL0000037) (CSI: 2.90), which aligns with its annotated functions in immune response pathways. This broad expression pattern across functionally disparate cell types highlights a potentially fundamental regulatory role, likely tailored to the specific context of each cell. ## Pathways and Molecular Function [LDOC1](/details-gene/23641) is annotated as a nuclear [protein binding](/details-go/GO:0005515) protein found within the [nucleus](/details-go/GO:0005634), [nucleoplasm](/details-go/GO:0005654), and [nucleolus](/details-go/GO:0005730). This localization is consistent with a function in regulating gene expression or other nuclear processes. Its involvement in biological processes provides further insight: * **Cell Proliferation:** The gene is associated with the [negative regulation of cell population proliferation](/details-go/GO:0008285), which corroborates early research identifying it as a potential tumor suppressor ([Link](https://doi.org/10.1016/s0304-3835(99)00087-7)). * **Innate Immunity:** [LDOC1](/details-gene/23641) is implicated in the [cellular response to lipopolysaccharide](/details-go/GO:0071222) and [cellular response to muramyl dipeptide](/details-go/GO:0071225). These processes are central to the recognition of bacterial components by the innate immune system, which aligns with its role as a regulator of NFKB signaling and its interaction with NOD2-pathway proteins ([Link](https://doi.org/10.1371/journal.pone.0165420)). This function is particularly relevant to its expression in immune cells like [group 3 innate lymphoid cell](/details-cell/CL0001071). * **Reproductive Biology:** Annotations for [maternal placenta development](/details-go/GO:0001893) and [maternal process involved in parturition](/details-go/GO:0060137) suggest a specialized role in maternal-fetal biology, although the precise mechanisms remain to be elucidated. ## Research Directions The diverse expression pattern and functional annotations of [LDOC1](/details-gene/23641) suggest it acts as a key cellular regulator, particularly at the intersection of cell proliferation and inflammation. Its downregulation in cancer offers a compelling avenue for further investigation. **Proposed Testable Hypotheses:** 1. Given its role in negatively regulating proliferation and its high significance in respiratory epithelial cells, the loss of [LDOC1](/details-gene/23641) expression in [epithelial cell of lower respiratory tract](/details-cell/CL0002632) may be an early event in lung carcinogenesis, leading to hyperactivation of the NFKB pathway and promoting malignant transformation. 2. Based on its function in responding to bacterial components and its expression in [group 3 innate lymphoid cell](/details-cell/CL0001071), [LDOC1](/details-gene/23641) may function as a critical brake on intestinal inflammation by modulating NOD2- and TLR-dependent NFKB activation in ILC3s, thereby maintaining mucosal homeostasis. **Suggested Experimental Approach:** To test the hypothesis regarding its role in lung carcinogenesis, one could employ a CRISPR-Cas9-mediated knockout of [LDOC1](/details-gene/23641) in a non-transformed human bronchial epithelial cell line (e.g., BEAS-2B). The resulting knockout cells and wild-type controls could be assessed for changes in proliferation rates (via colony formation assays), anchorage-independent growth (soft agar assay), and NFKB pathway activity (via immunoblotting for phosphorylated IKBα and p65). Further, RNA-sequencing could identify downstream transcriptional changes, and a xenograft mouse model could be used to evaluate the in vivo tumorigenic potential of [LDOC1](/details-gene/23641)-deficient epithelial cells. **Therapeutic Potential:** As a putative tumor suppressor that is downregulated in cancer, [LDOC1](/details-gene/23641) itself is not a conventional drug target for inhibition. Instead, therapeutic strategies would likely focus on restoring its function or mimicking its downstream effects. This could involve developing small molecules that stabilize [LDOC1](/details-gene/23641) protein, gene therapies aimed at re-expressing the gene in tumor cells, or targeting downstream nodes in the NFKB pathway that become overactive in its absence. Its potential role in modulating immune responses also suggests that its expression status could serve as a biomarker for predicting response to immunotherapies.

Genular Protein ID: 3937715965

Symbol: LDOC1_HUMAN

Name: Protein LDOC1

UniProtKB Accession Codes:

O95751 Q6IAR6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 GO 8 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MINT 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 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 10403563

Title: Identification of a novel gene, LDOC1, down-regulated in cancer cell lines.

PubMed ID: 10403563

DOI: 10.1016/s0304-3835(99)00087-7

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

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: 27812135

Title: Characterization and Genetic Analyses of New Genes Coding for NOD2 Interacting Proteins.

PubMed ID: 27812135

DOI: 10.1371/journal.pone.0165420

Sequence Information:

  • Length: 146
  • Mass: 16968
  • Checksum: 3D02813B2DE52DBE
  • Sequence:
    • MVDELVLLLH ALLMRHRALS IENSQLMEQL RLLVCERASL LRQVRPPSCP VPFPETFNGE 
SSRLPEFIVQ TASYMLVNEN RFCNDAMKVA FLISLLTGEA EEWVVPYIEM DSPILGDYRA 
FLDEMKQCFG WDDDEDDDDE EEEDDY