Details for: RHEX

Gene ID: 440712

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: RHEX

Ensembl ID: ENSG00000263961

Description: regulator of hemoglobinization and erythroid cell expansion

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 26.82
    rCSI 38.01%
    PRS 89.49
  • epithelial cell of proximal tubule CL0002306
    CSI 15.86
    rCSI 38.73%
    PRS 85.43
  • parietal epithelial cell CL1000452
    CSI 15.79
    rCSI 42.21%
    PRS 86.61
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 9.38
    rCSI 24.24%
    PRS 89.04
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 8.38
    rCSI 7.56%
    PRS 90.21
  • basophil CL0000767
    CSI 8.21
    rCSI 17.38%
    PRS 95.5
  • kidney collecting duct principal cell CL1001431
    CSI 7.15
    rCSI 35.97%
    PRS 86.96
  • fallopian tube secretory epithelial cell CL4030006
    CSI 6.9
    rCSI 6.64%
    PRS 89.98
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 6.32
    rCSI 16.47%
    PRS 92.9
  • granulocyte monocyte progenitor cell CL0000557
    CSI 6.3
    rCSI 5.45%
    PRS 93.41
  • granulocyte CL0000094
    CSI 5.44
    rCSI 8.31%
    PRS 94.89
  • kidney connecting tubule epithelial cell CL1000768
    CSI 4.96
    rCSI 12.59%
    PRS 85.85
  • epithelial cell CL0000066
    CSI 4.71
    rCSI 7.23%
    PRS 80.22
  • mast cell CL0000097
    CSI 4.65
    rCSI 10.04%
    PRS 89.79
  • IgA plasma cell CL0000987
    CSI 4.51
    rCSI 4.62%
    PRS 92.85
  • renal interstitial pericyte CL1001318
    CSI 4.24
    rCSI 11.67%
    PRS 89.02
  • promyelocyte CL0000836
    CSI 3.44
    rCSI 4.96%
    PRS 93.29
  • podocyte CL0000653
    CSI 3.3
    rCSI 14.67%
    PRS 91.66
  • plasmablast CL0000980
    CSI 3.03
    rCSI 2.38%
    PRS 93.43
  • hematopoietic multipotent progenitor cell CL0000837
    CSI 2.87
    rCSI 6.9%
    PRS 97.08
  • mature B cell CL0000785
    CSI 2.76
    rCSI 2.4%
    PRS 96.34
  • kidney loop of Henle thick ascending limb epithelial cell CL1001106
    CSI 2.63
    rCSI 22.72%
    PRS 86.38
  • renal principal cell CL0005009
    CSI 2.63
    rCSI 6.83%
    PRS 90.83
  • intrahepatic cholangiocyte CL0002538
    CSI 2.11
    rCSI 5.05%
    PRS 91.32
  • eosinophil CL0000771
    CSI 2.03
    rCSI 13.32%
    PRS 97.1
  • glandular epithelial cell CL0000150
    CSI 1.82
    rCSI 4.8%
    PRS 96.59
  • myeloid lineage restricted progenitor cell CL0000839
    CSI 1.41
    rCSI 7.27%
    PRS 97.57
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 1.32
    rCSI 14.02%
    PRS 87.91

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.

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 [RHEX](/details-gene/440712) (Regulator of Hemoglobinization and Erythroid cell Expansion) is a protein-coding gene located on chromosome 1q32.1. It is characterized as a key regulator of red blood cell development, specifically influencing the expansion of human erythroid progenitor cells and subsequent erythroblast maturation ([Link](https://doi.org/10.1084/jem.20130624)). Functional annotations indicate its involvement in the erythropoietin (EPO) signaling pathway and binding to the EPO receptor at the plasma membrane. While its role in erythropoiesis is established, expression data reveals its most significant expression occurs in various specialized epithelial cells of the kidney, suggesting potentially uncharacterized functions in renal physiology. ## Cellular Roles and Expression Landscape The expression profile of [RHEX](/details-gene/440712) highlights a notable dichotomy between its established function and its tissue-specific abundance. **Overall**, the gene demonstrates its highest significance in specialized kidney epithelial cells. It is a particularly strong marker for [kidney loop of Henle thin descending limb epithelial cell](/details-cell/CL1001111) (CSI: 26.82), [epithelial cell of proximal tubule](/details-cell/CL0002306) (CSI: 15.86), and [parietal epithelial cell](/details-cell/CL1000452) (CSI: 15.79), with significant expression also noted in other tubular and collecting duct cells. Consistent with its known biological role, [RHEX](/details-gene/440712) also shows moderate to high significance in hematopoietic progenitors, including [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 8.38) and [granulocyte monocyte progenitor cell](/details-cell/CL0000557) (CSI: 6.30). Its presence in mature myeloid lineage cells such as [basophil](/details-cell/CL0000767) (CSI: 8.21), [granulocyte](/details-cell/CL0000094) (CSI: 5.44), and [mast cell](/details-cell/CL0000097) (CSI: 4.65) suggests a broader, albeit less prominent, role within the hematopoietic system. The data strongly implies that while [RHEX](/details-gene/440712) is a functional component of erythropoiesis, its most pronounced and specific expression signature is within the renal epithelium. ## Pathways and Molecular Function The functional annotations for [RHEX](/details-gene/440712) are tightly linked to red blood cell formation. It is implicated in biological processes such as [positive regulation of erythrocyte differentiation](/details-cell/GO:0045648), [erythrocyte maturation](/details-cell/GO:0043249), and the [cellular response to erythropoietin](/details-cell/GO:0036018). These functions are consistent with its identified role as a key regulator in late-stage erythropoiesis ([Link](https://doi.org/10.1084/jem.20130624)). At the molecular level, [RHEX](/details-gene/440712) is known to participate in [protein binding](/details-cell/GO:0005515) and specifically [erythropoietin receptor binding](/details-cell/GO:0005128). Its localization to the [plasma membrane](/details-cell/GO:0005886) suggests it functions as a cell surface protein, likely acting as a co-receptor or modulator of the EPO receptor to mediate downstream signaling events in the [erythropoietin-mediated signaling pathway](/details-cell/GO:0038162). While these pathways clearly explain its function in hematopoietic progenitors, they do not inherently account for its high level of expression in kidney cells, which are the primary site of erythropoietin production. ## Research Directions The striking disparity between the established erythroid function of [RHEX](/details-gene/440712) and its maximal expression in the kidney epithelium is a key area for future investigation. The current data prompts several testable hypotheses. 1. **Hypothesis 1: [RHEX](/details-gene/440712) has a pleiotropic, uncharacterized role in renal epithelial cell physiology.** Its high expression in various segments of the nephron, such as the proximal tubule and loop of Henle, may indicate involvement in processes like solute transport, fluid balance, or maintenance of epithelial integrity, entirely independent of its hematopoietic function. 2. **Hypothesis 2: [RHEX](/details-gene/440712) functions in an autocrine or paracrine feedback loop regulating erythropoietin (EPO) production in the kidney.** As a plasma membrane protein, it could modulate the sensing of hypoxia or other stimuli that trigger EPO synthesis in renal interstitial fibroblasts and tubular epithelial cells. **Proposed Experiment:** To test the hypothesis of a novel renal function (Hypothesis 1), one could perform a CRISPR-Cas9-mediated knockout of [RHEX](/details-gene/440712) in a human kidney proximal tubule cell line (e.g., HK-2 cells). Subsequent transcriptomic analysis (RNA-seq) could identify dysregulated pathways related to renal function. Functional assays, such as measuring transepithelial electrical resistance (TEER) and solute transport, could directly assess the impact of [RHEX](/details-gene/440712) loss on epithelial barrier function and transport physiology. **Therapeutic Potential:** Given its role as a plasma membrane protein that positively regulates erythroid progenitor expansion, [RHEX](/details-gene/440712) could represent a therapeutic target for hematological disorders. Agonistic antibodies or small molecules that activate [RHEX](/details-gene/440712) signaling could potentially be used to stimulate red blood cell production in certain types of anemia. Conversely, inhibitory strategies might be explored for conditions of erythrocyte overproduction, such as polycythemia vera. However, its high expression in the kidney necessitates caution, as targeting this protein could lead to unforeseen renal side effects.

Genular Protein ID: 135076057

Symbol: RHEX_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q6ZWK4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 EMBL 3 Ensembl 3 ExpressionAtlas 1 GO 6 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 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 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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 25092874

Title: RHEX, a novel regulator of human erythroid progenitor cell expansion and erythroblast development.

PubMed ID: 25092874

DOI: 10.1084/jem.20130624

Sequence Information:

  • Length: 172
  • Mass: 19405
  • Checksum: 2AE0407D9F05457B
  • Sequence:
    • MLTEVMEVWH GLVIAVVSLF LQACFLTAIN YLLSRHMAHK SEQILKAASL QVPRPSPGHH 
HPPAVKEMKE TQTERDIPMS DSLYRHDSDT PSDSLDSSCS SPPACQATED VDYTQVVFSD 
PGELKNDSPL DYENIKEITD YVNVNPERHK PSFWYFVNPA LSEPAEYDQV AM