Details for: HRCT1

Gene ID: 646962

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: HRCT1

Ensembl ID: ENSG00000196196

Description: histidine rich carboxyl terminus 1

Cell Significance Landscape

Associated with

Significant Cells

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

  • colon epithelial cell CL0011108
    CSI 16.48
    rCSI 17.26%
    PRS 90.88
  • BEST4+ enteroycte CL4030026
    CSI 8.95
    rCSI 11.13%
    PRS 92.45
  • myofibroblast cell CL0000186
    CSI 4.56
    rCSI 6.31%
    PRS 90.26
  • intestine goblet cell CL0019031
    CSI 3.83
    rCSI 3.4%
    PRS 90.89
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.65
    rCSI 4.23%
    PRS 94.71
  • colon goblet cell CL0009039
    CSI 2.55
    rCSI 6.06%
    PRS 93.94
  • skin fibroblast CL0002620
    CSI 2.51
    rCSI 2.16%
    PRS 92.38
  • goblet cell CL0000160
    CSI 2.46
    rCSI 2.32%
    PRS 90.88
  • enterocyte CL0000584
    CSI 2.21
    rCSI 3.57%
    PRS 90.24
  • cerebral cortex endothelial cell CL1001602
    CSI 2.18
    rCSI 3.77%
    PRS 88.68
  • myoepithelial cell CL0000185
    CSI 2.17
    rCSI 5.5%
    PRS 94.64
  • pulmonary artery endothelial cell CL1001568
    CSI 2.15
    rCSI 2.93%
    PRS 96.19
  • colonocyte CL1000347
    CSI 1.89
    rCSI 2.7%
    PRS 91.13
  • paneth cell of colon CL0009009
    CSI 1.84
    rCSI 18.12%
    PRS 94.95
  • vasa recta ascending limb cell CL1001131
    CSI 1.65
    rCSI 7.48%
    PRS 95.65
  • fallopian tube secretory epithelial cell CL4030006
    CSI 1.51
    rCSI 1.45%
    PRS 91.79

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)

Loading network (please wait)...

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 [HRCT1](/details-gene/646962), or *histidine rich carboxyl terminus 1*, is a protein-coding gene located on chromosome 9p13.3. The gene product is predicted to be a membrane-associated protein, a classification supported by its annotation to the [Membrane (GO:0016020)](https://www.ebi.ac.uk/QuickGO/term/GO:0016020) cellular component and its initial identification as a putative transmembrane protein ([Link](https://doi.org/10.1101/gr.1293003)). **Overall**, expression data reveals that [HRCT1](/details-gene/646962) is a highly specific and significant marker for epithelial cells of the gastrointestinal tract, with its most profound expression observed in [colon epithelial cell](/details-cell/CL0011108)s, [BEST4+ enteroycte](/details-cell/CL4030026)s, and [intestine goblet cell](/details-cell/CL0019031)s. This strongly suggests a primary function related to the biology of the intestinal lining. ## Cellular Roles and Expression Landscape The expression profile of [HRCT1](/details-gene/646962) points to a specialized role within structural and barrier tissues, particularly in the colon and intestine. In the **Overall** biological context, [HRCT1](/details-gene/646962) demonstrates its most significant expression in a range of cell types that constitute the intestinal epithelial barrier. Its highest significance score (CSI: 16.48) is in [colon epithelial cell](/details-cell/CL0011108)s, with other key intestinal cell types such as [BEST4+ enteroycte](/details-cell/CL4030026), [intestine goblet cell](/details-cell/CL0019031), [enterocyte](/details-cell/CL0000584), and [colonocyte](/details-cell/CL1000347) also showing high significance. This colocalization within the gut lining suggests a functional role in absorption, secretion, or maintenance of the barrier itself. Beyond the intestine, [HRCT1](/details-gene/646962) shows moderate but consistent significance in several other cell types associated with structural or barrier functions. These include [myofibroblast cell](/details-cell/CL0000186)s and [skin fibroblast](/details-cell/CL0002620)s, as well as various endothelial cells such as [retinal blood vessel endothelial cell](/details-cell/CL0002585) and [cerebral cortex endothelial cell](/details-cell/CL1001602). This pattern suggests that its function, while most prominent in the gut, may extend to other tissues requiring specialized barrier or structural support. Notably, the top expressed cell list lacks representation from hematopoietic lineages, indicating a specific role outside of the adaptive and innate immune systems. ## Pathways and Molecular Function The functional annotation for [HRCT1](/details-gene/646962) is currently sparse, with its primary annotation being a localization to the [Membrane (GO:0016020)](https://www.ebi.ac.uk/QuickGO/term/GO:0016020). This is consistent with a bioinformatics-driven study that first identified it as a novel human secreted or transmembrane protein ([Link](https://doi.org/10.1101/gr.1293003)). Its localization to the cell membrane in intestinal epithelial cells, where it is most abundant, suggests potential roles in cell-cell adhesion, transmembrane transport, or as a receptor in signaling pathways that regulate epithelial cell function. The protein's name, highlighting a "histidine rich carboxyl terminus," may imply a capacity for binding metal ions or participating in specific protein-protein interactions, which could be central to its molecular function at the cell surface. ## Research Directions The highly specific expression of [HRCT1](/details-gene/646962) in the intestinal epithelium makes it a compelling subject for further investigation, particularly concerning diseases of the gastrointestinal tract. **Proposed Hypotheses:** 1. Given its membrane localization and high specificity in [colon epithelial cell](/details-cell/CL0011108)s, [HRCT1](/details-gene/646962) may be a critical component of the intestinal epithelial barrier, potentially interacting with tight junction or adherens junction proteins to regulate paracellular permeability. 2. The histidine-rich domain of the [HRCT1](/details-gene/646962) protein could function as a transmembrane transporter or channel specific for certain ions or small molecules, contributing to the absorptive or secretory functions of enterocytes. 3. [HRCT1](/details-gene/646962) may act as a cell surface receptor or co-receptor that responds to luminal signals (e.g., from the microbiome) to modulate epithelial cell differentiation, proliferation, or immune homeostasis. **Key Experimental Approach:** To test the hypothesis that [HRCT1](/details-gene/646962) is crucial for intestinal barrier integrity (Hypothesis 1), a CRISPR-Cas9 knockout could be generated in a human colonic organoid model. The functional consequence of the gene deletion would be assessed by measuring transepithelial electrical resistance (TEER) and paracellular flux of fluorescently-labeled dextran to quantify barrier function. Immunofluorescence microscopy and quantitative western blotting for key junctional proteins (e.g., ZO-1, E-cadherin, Occludin) would determine if the loss of [HRCT1](/details-gene/646962) disrupts the organization of these critical barrier complexes. **Therapeutic Potential:** The remarkable specificity of [HRCT1](/details-gene/646962) for the intestinal epithelium makes it an attractive therapeutic target with a potentially wide therapeutic window and minimal off-target effects. If found to be crucial for maintaining barrier integrity, modulating its function could be a novel strategy for treating inflammatory bowel disease (IBD) or other conditions characterized by a "leaky gut." As a putative cell surface protein, it is amenable to targeting by monoclonal antibodies or other biologics. An activating antibody or small molecule agonist that enhances its barrier-promoting function could represent a targeted therapeutic approach. Conversely, if its expression is dysregulated in colorectal cancer, it could serve as a target for antibody-drug conjugates.

Genular Protein ID: 431913796

Symbol: HRCT1_HUMAN

Name: Histidine-rich carboxyl terminus protein 1

UniProtKB Accession Codes:

Q6UXD1 B7ZBJ1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 1 GO 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 1 KEGG 1 MANE-Select 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 RNAct 1 RefSeq 1 STRING 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

Sequence Information:

  • Length: 115
  • Mass: 13183
  • Checksum: 8EE498C8AA1DE8D6
  • Sequence:
    • MLGLLGSTAL VGWITGAAVA VLLLLLLLAT CLFHGRQDCD VERNRTAAGG NRVRRAQPWP 
FRRRGHLGIF HHHRHPGHVS HVPNVGLHHH HHPRHTPHHL HHHHHPHRHH PRHAR