Details for: TMEM233

Gene ID: 387890

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: TMEM233

Ensembl ID: ENSG00000224982

Description: transmembrane protein 233

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • granulocyte CL0000094
    CSI 6.4
    rCSI 9.77%
    PRS 99.09
  • blood vessel endothelial cell CL0000071
    CSI 2.94
    rCSI 6.1%
    PRS 98.35
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 2.42
    rCSI 4.07%
    PRS 96.19
  • endothelial cell of vascular tree CL0002139
    CSI 1.94
    rCSI 10.61%
    PRS 96.75
  • skeletal muscle satellite stem cell CL0008011
    CSI 1.52
    rCSI 6.76%
    PRS 99.46
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.05
    rCSI 3.28%
    PRS 95.97
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.96
    rCSI 3.47%
    PRS 95.18
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.49
    rCSI 2.91%
    PRS 95.49

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 [TMEM233](/details-gene/387890) is a protein-coding gene located on chromosome 12 that encodes Transmembrane protein 233, a member of the ancient dispanin family of proteins ([Link](https://doi.org/10.1371/journal.pone.0031961)). Functional annotations indicate it is localized to the [plasma membrane](/details-go/GO:0005886) where it participates in [protein binding](/details-go/GO:0005515). Expression data reveals a diverse cellular landscape, with its highest significance observed in [granulocytes](/details-cell/CL0000094), suggesting a role in innate immunity. It is also significantly expressed in various endothelial and neuronal cell types. Recent research has provided a key functional insight, demonstrating that [TMEM233](/details-gene/387890) acts as a modulator of the voltage-gated sodium channel NaV1.7, thereby playing a critical role in pain sensation ([Link](https://doi.org/10.1038/s41467-023-37963-2)). ## Cellular Roles and Expression Landscape The expression profile of [TMEM233](/details-gene/387890) suggests it performs distinct functions in multiple biological systems. **Overall**, its most significant expression is in [granulocytes](/details-cell/CL0000094) (CSI: 6.40), pointing towards a potentially important, yet currently uncharacterized, role in the function of these key innate immune cells. Beyond its role in the immune system, [TMEM233](/details-gene/387890) shows notable significance in the vasculature, with high expression in both [blood vessel endothelial cell](/details-cell/CL0000071) (CSI: 2.94) and the broader category of [endothelial cell of vascular tree](/details-cell/CL0002139) (CSI: 1.94). This suggests a potential involvement in regulating endothelial cell biology, such as vascular permeability or tone. Furthermore, [TMEM233](/details-gene/387890) is expressed in several distinct neuronal subtypes within the cortex, including [lamp5 GABAergic cortical interneurons](/details-cell/CL4023011) (CSI: 2.42) as well as multiple glutamatergic neuron populations such as [L6b](/details-cell/CL4023038) and [L5](/details-cell/CL4023041) projecting neurons. This neuronal expression pattern is consistent with its recently discovered function in modulating ion channels involved in nociception ([Link](https://doi.org/10.1038/s41467-023-37963-2)). The gene also shows significance in [skeletal muscle satellite stem cells](/details-cell/CL0008011) (CSI: 1.52), hinting at a possible role in muscle development or repair. ## Pathways and Molecular Function Functionally, [TMEM233](/details-gene/387890) is an integral [membrane](/details-go/GO:0016020) protein whose primary known molecular function is [protein binding](/details-go/GO:0005515). While this annotation is broad, a crucial specific interaction has been identified. Research demonstrates that [TMEM233](/details-gene/387890) directly targets and modulates the activity of the NaV1.7 voltage-gated sodium channel, a key protein in the transmission of pain signals in the peripheral nervous system ([Link](https://doi.org/10.1038/s41467-023-37963-2)). This interaction provides a mechanistic basis for its role in pain sensation and is a clear example of its protein binding capacity. It is plausible that [TMEM233](/details-gene/387890)'s function in other cell types, such as [granulocytes](/details-cell/CL0000094) and endothelial cells, may also be mediated by similar interactions with other membrane-bound proteins, potentially including other ion channels or signaling receptors. ## Research Directions The diverse expression pattern of [TMEM233](/details-gene/387890) alongside its defined role in modulating ion channel function presents several avenues for future investigation. **Proposed Hypotheses:** 1. Given its top significance score in [granulocytes](/details-cell/CL0000094), [TMEM233](/details-gene/387890) may regulate key effector functions of these immune cells, such as chemotaxis, degranulation, or the respiratory burst, by modulating the activity of specific ion channels required for these processes. 2. The expression of [TMEM233](/details-gene/387890) in [blood vessel endothelial cells](/details-cell/CL0000071) suggests it could be involved in regulating vascular homeostasis, potentially by interacting with channels that control calcium signaling, which is critical for endothelial-dependent vasodilation and barrier function. 3. In [skeletal muscle satellite stem cells](/details-cell/CL0008011), [TMEM233](/details-gene/387890) may influence myogenesis by modulating ion channel activities that are known to be critical for stem cell differentiation and fusion. **Experimental Approach:** To test the hypothesis regarding its role in granulocyte function (Hypothesis 1), a conditional knockout mouse model could be generated with [TMEM233](/details-gene/387890) deleted specifically in the myeloid lineage (e.g., via Lyz2-Cre). Neutrophils isolated from these knockout mice and wild-type littermates could then be subjected to a battery of functional assays. These would include *in vitro* migration assays to assess chemotaxis, quantification of myeloperoxidase release to measure degranulation, and measurement of reactive oxygen species production to evaluate the respiratory burst. Parallel electrophysiological studies, such as patch-clamp analysis, could be used to identify any alterations in ion channel currents in the knockout cells. **Therapeutic Potential:** The established role of [TMEM233](/details-gene/387890) in modulating NaV1.7 makes it a compelling target for the development of novel non-opioid analgesics. As a transmembrane protein, it is accessible to both small molecule inhibitors and biologic therapies like monoclonal antibodies. The therapeutic strategy would likely focus on **inhibition** of TMEM233 function or its interaction with NaV1.7 to dampen pain signaling. However, its significant expression in immune and endothelial cells raises the possibility of off-target effects. Therefore, a successful therapeutic approach might require developing agents that selectively disrupt the TMEM233-NaV1.7 interaction in nociceptive neurons without affecting its potential functions in other tissues.

Genular Protein ID: 2839981492

Symbol: TM233_HUMAN

Name: Transmembrane protein 233

UniProtKB Accession Codes:

B4DJY2

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 3 Ensembl 1 GO 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 2 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 1 STRING 1 SignaLink 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 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: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

PubMed ID: 22363774

Title: The dispanins: a novel gene family of ancient origin that contains 14 human members.

PubMed ID: 22363774

DOI: 10.1371/journal.pone.0031961

PubMed ID: 37117223

Title: Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function.

PubMed ID: 37117223

DOI: 10.1038/s41467-023-37963-2

Sequence Information:

  • Length: 109
  • Mass: 12074
  • Checksum: 4D43CDE84A8F9E3C
  • Sequence:
    • MSQYAPSPDF KRALDSSPEA NTEDDKTEED VPMPKNYLWL TIVSCFCPAY PINIVALVFS 
IMSLNSYNDG DYEGARRLGR NAKWVAIASI IIGLLIIGIS CAVHFTRNA