Details for: TMEM203

Gene ID: 94107

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: TMEM203

Ensembl ID: ENSG00000187713

Description: transmembrane protein 203

Cell Significance Landscape

Associated with

Significant Cells

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

  • effector memory CD4-positive, alpha-beta T cell CL0000905
    CSI 8.57
    rCSI 11.68%
    PRS 97.3
  • multi-ciliated epithelial cell CL0005012
    CSI 6.53
    rCSI 6.51%
    PRS 81.63
  • hematopoietic precursor cell CL0008001
    CSI 5.79
    rCSI 5.95%
    PRS 94.4
  • bronchus fibroblast of lung CL2000093
    CSI 5.44
    rCSI 4.42%
    PRS 86.85
  • skin fibroblast CL0002620
    CSI 3.31
    rCSI 2.85%
    PRS 87.06
  • fibroblast of lung CL0002553
    CSI 2.96
    rCSI 2.75%
    PRS 88.44
  • mature B cell CL0000785
    CSI 2.92
    rCSI 2.54%
    PRS 94.16
  • ciliated epithelial cell CL0000067
    CSI 2.91
    rCSI 2.56%
    PRS 78.11
  • interstitial cell of Cajal CL0002088
    CSI 2.86
    rCSI 3.64%
    PRS 91.46
  • group 3 innate lymphoid cell CL0001071
    CSI 2.8
    rCSI 2.11%
    PRS 91.35
  • neural crest cell CL0011012
    CSI 2.72
    rCSI 2.15%
    PRS 78.86
  • mesodermal cell CL0000222
    CSI 2.7
    rCSI 3.24%
    PRS 85.94
  • type B pancreatic cell CL0000169
    CSI 2.69
    rCSI 5.96%
    PRS 87.26
  • pancreatic A cell CL0000171
    CSI 2.66
    rCSI 2.79%
    PRS 89.63
  • ON-bipolar cell CL0000749
    CSI 2.62
    rCSI 3.9%
    PRS 86.7
  • intestinal epithelial cell CL0002563
    CSI 2.48
    rCSI 2.59%
    PRS 84.92
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.46
    rCSI 1.71%
    PRS 90.69
  • stem cell CL0000034
    CSI 2.36
    rCSI 2.28%
    PRS 82.49
  • myeloid leukocyte CL0000766
    CSI 2.27
    rCSI 2.09%
    PRS 88.45
  • epithelial cell of lung CL0000082
    CSI 2.18
    rCSI 1.8%
    PRS 88.43
  • activated CD8-positive, alpha-beta T cell CL0000906
    CSI 2.16
    rCSI 2.12%
    PRS 95.63
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.14
    rCSI 2.75%
    PRS 73.53
  • retina horizontal cell CL0000745
    CSI 2.1
    rCSI 3.2%
    PRS 84.41
  • fallopian tube secretory epithelial cell CL4030006
    CSI 1.97
    rCSI 1.9%
    PRS 86.39
  • lung ciliated cell CL1000271
    CSI 1.96
    rCSI 2.26%
    PRS 81.12
  • radial glial cell CL0000681
    CSI 1.87
    rCSI 2.59%
    PRS 85.74
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 1.87
    rCSI 5.51%
    PRS 87.96
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 1.86
    rCSI 1.68%
    PRS 86.06
  • club cell CL0000158
    CSI 1.75
    rCSI 2.57%
    PRS 82.6
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.73
    rCSI 2.22%
    PRS 83.82
  • granulocyte monocyte progenitor cell CL0000557
    CSI 1.66
    rCSI 1.44%
    PRS 90.06
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.38
    rCSI 2.43%
    PRS 71.82
  • lung macrophage CL1001603
    CSI 1.27
    rCSI 2.83%
    PRS 92.45
  • retinal cone cell CL0000573
    CSI 1.22
    rCSI 1.96%
    PRS 78.87
  • pancreatic ductal cell CL0002079
    CSI 1.09
    rCSI 2.11%
    PRS 89.49
  • progenitor cell CL0011026
    CSI 1.05
    rCSI 2.23%
    PRS 81.48
  • mesenchymal cell CL0008019
    CSI 0.87
    rCSI 2.22%
    PRS 81.73
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.81
    rCSI 2.55%
    PRS 73.76
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.79
    rCSI 2.3%
    PRS 86.6

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 Transmembrane protein 203, encoded by the [TMEM203](/details-gene/94107) gene, is an intracellular protein primarily localized to the [endoplasmic reticulum (GO:0005783)](https://www.ebi.ac.uk/QuickGO/term/GO:0005783) and [lysosomal membranes (GO:0005765)](https://www.ebi.ac.uk/QuickGO/term/GO:0005765). It is a known regulator of critical cellular processes, including [intracellular calcium ion homeostasis (GO:0006874)](https://www.ebi.ac.uk/QuickGO/term/GO:0006874) and [spermatogenesis (GO:0007283)](https://www.ebi.ac.uk/QuickGO/term/GO:0007283) [Link](https://doi.org/10.1371/journal.pone.0127480). More recently, it has been identified as a key binding partner and modulator of STING-mediated inflammatory signaling [Link](https://doi.org/10.1073/pnas.1901090116). Expression data highlights its particular significance in the immune system, with the highest Cell Significance Index (CSI) observed in [effector memory CD4-positive, alpha-beta T cell](/details-cell/CL0000905). Its notable expression in diverse cell types such as [multi-ciliated epithelial cell](/details-cell/CL0005012) and fibroblasts suggests it plays fundamental roles across multiple tissues. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [TMEM203](/details-gene/94107) indicates a multifaceted role in both the immune system and various structural or secretory cell types. Its most significant expression is in [effector memory CD4-positive, alpha-beta T cell](/details-cell/CL0000905) (CSI: 8.57), strongly suggesting a crucial function in adaptive immune memory and T cell activation. This is complemented by its significance in other immune lineages, including [hematopoietic precursor cell](/details-cell/CL0008001), [mature B cell](/details-cell/CL0000785), and [group 3 innate lymphoid cell](/details-cell/CL0001071). This pattern is consistent with its documented role as a regulator of the STING pathway, a central component of innate immune sensing that influences adaptive responses [Link](https://doi.org/10.1073/pnas.1901090116). Beyond the immune system, [TMEM203](/details-gene/94107) shows high significance in [multi-ciliated epithelial cell](/details-cell/CL0005012) (CSI: 6.53), as well as in fibroblasts from different tissues, such as [bronchus fibroblast of lung](/details-cell/CL2000093) and [skin fibroblast](/details-cell/CL0002620). This suggests its function in regulating intracellular calcium may be important for processes like ciliary motility or extracellular matrix production. The broad but specific expression pattern across disparate cell types like [pancreatic A cell](/details-cell/CL0000171) and [ON-bipolar cell](/details-cell/CL0000749) underscores its role in a fundamental cellular process, likely calcium homeostasis, that is tailored to the specific needs of each cell. ## Pathways and Molecular Function The functions of [TMEM203](/details-gene/94107) are centered on its role as a transmembrane protein within intracellular organelles, primarily modulating signaling and ion balance. * **Intracellular Calcium Regulation:** [TMEM203](/details-gene/94107) is an established regulator of [intracellular calcium ion homeostasis (GO:0006874)](https://www.ebi.ac.uk/QuickGO/term/GO:0006874) [Link](https://doi.org/10.1371/journal.pone.0127480). Its localization to the [Endoplasmic reticulum membrane (GO:0005789)](https://www.ebi.ac.uk/QuickGO/term/GO:0005789) and [Lysosomal membrane (GO:0005765)](https://www.ebi.ac.uk/QuickGO/term/GO:0005765) places it at the hub of intracellular calcium storage and release, a process vital for T-cell activation, muscle contraction, and neurotransmission. * **Inflammatory Signaling:** Research has identified [TMEM203](/details-gene/94107) as a key regulator of the STING (Stimulator of Interferon Genes) pathway. Through its [protein binding (GO:0005515)](https://www.ebi.ac.uk/QuickGO/term/GO:0005515) function, it interacts with STING to modulate the production of type I interferons and other inflammatory cytokines, thereby controlling innate immune responses to cyclic dinucleotides from pathogens or damaged host cells [Link](https://doi.org/10.1073/pnas.1901090116). This function is highly consistent with its significant expression in multiple immune cell types. * **Specialized Physiological Processes:** The gene is essential for [spermatogenesis (GO:0007283)](https://www.ebi.ac.uk/QuickGO/term/GO:0007283), a process heavily dependent on precise calcium signaling for sperm motility and the acrosome reaction [Link](https://doi.org/10.1371/journal.pone.0127480). ## Research Directions The diverse expression profile and dual roles in both calcium homeostasis and STING signaling suggest that [TMEM203](/details-gene/94107) acts as a critical integrator of cellular stress and immune activation signals. **Testable Hypotheses:** 1. Given its high significance in [effector memory CD4-positive, alpha-beta T cell](/details-cell/CL0000905) and its functions in calcium and STING signaling, [TMEM203](/details-gene/94107) likely modulates the threshold for T cell reactivation and shapes the functional profile (e.g., cytokine production) of the memory response. 2. The high expression of [TMEM203](/details-gene/94107) in [multi-ciliated epithelial cell](/details-cell/CL0005012) suggests a role in regulating ciliary beat frequency or mucus clearance through localized control of calcium signaling in response to environmental or inflammatory stimuli in tissues like the bronchus. **Proposed Experiment:** To test the first hypothesis regarding its role in T cell memory, one could utilize CRISPR-Cas9 to knock out [TMEM203](/details-gene/94107) in primary human naive CD4+ T cells. Following *in vitro* differentiation into effector memory T cells, control and knockout cells would be restimulated through the T cell receptor. The functional consequences would be assessed by measuring key parameters such as intracellular calcium flux using a ratiometric dye, proliferation via cell trace dye dilution, and a panel of effector cytokines (e.g., IFN-gamma, IL-2, IL-17) using flow cytometry or multiplex ELISA. A significant alteration in these outputs in the knockout cells would confirm its role in modulating the T cell memory response. **Therapeutic Potential:** As an intracellular transmembrane protein, [TMEM203](/details-gene/94107) is not an ideal target for antibody-based therapies. However, its role as a modulator of the STING pathway presents a compelling opportunity for small molecule development. Overactivation of STING is implicated in autoinflammatory diseases such as lupus. Therefore, small molecule inhibitors targeting [TMEM203](/details-gene/94107) could represent a novel therapeutic strategy to dampen excessive STING-mediated inflammation. **Inhibition**, rather than activation, would likely be the therapeutic goal in such autoimmune or autoinflammatory contexts.

Genular Protein ID: 3954734011

Symbol: TM203_HUMAN

Name: Transmembrane protein 203

UniProtKB Accession Codes:

Q969S6 Q6NW08

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 GO 6 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MalaCards 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 STRING 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

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: 25996873

Title: TMEM203 is a novel regulator of intracellular calcium homeostasis and is required for spermatogenesis.

PubMed ID: 25996873

DOI: 10.1371/journal.pone.0127480

PubMed ID: 31346090

Title: TMEM203 is a binding partner and regulator of STING-mediated inflammatory signaling in macrophages.

PubMed ID: 31346090

DOI: 10.1073/pnas.1901090116

Sequence Information:

  • Length: 136
  • Mass: 15760
  • Checksum: 87CA7D87F00B16FC
  • Sequence:
    • MLFSLRELVQ WLGFATFEIF VHLLALLVFS VLLALRVDGL VPGLSWWNVF VPFFAADGLS 
TYFTTIVSVR LFQDGEKRLA VLRLFWVLTV LSLKFVFEML LCQKLAEQTR ELWFGLITSP 
LFILLQLLMI RACRVN