Details for: TMED6

Gene ID: 146456

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: TMED6

Ensembl ID: ENSG00000157315

Description: transmembrane p24 trafficking protein 6

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • ciliated epithelial cell CL0000067
    CSI 5.83
    rCSI 5.13%
    PRS 93.97
  • pancreatic D cell CL0000173
    CSI 4.38
    rCSI 4.31%
    PRS 97.86
  • mucous neck cell CL0000651
    CSI 3.77
    rCSI 5.43%
    PRS 97.95
  • type B pancreatic cell CL0000169
    CSI 3.46
    rCSI 7.66%
    PRS 97.49
  • pancreatic acinar cell CL0002064
    CSI 3.3
    rCSI 4.38%
    PRS 98.2
  • pancreatic PP cell CL0002275
    CSI 3.25
    rCSI 12.95%
    PRS 97.58
  • peptic cell CL0000155
    CSI 2.75
    rCSI 27.01%
    PRS 98.03
  • pancreatic epsilon cell CL0005019
    CSI 0.9
    rCSI 4.19%
    PRS 97.72

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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  • Node Color (Target Cell CSI, relative to current network):
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    • 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 [TMED6](/details-gene/146456), or Transmembrane p24 trafficking protein 6, is a protein-coding gene located on chromosome 16q22.1. It belongs to the transmembrane emp24 domain (TMED) family of proteins, which are critical components of the early secretory pathway. Functional annotations strongly indicate that [TMED6](/details-gene/146456) participates in vesicle-mediated protein transport between the endoplasmic reticulum and the Golgi apparatus. This role is consistent with its high expression in a variety of professional secretory cells, including pancreatic endocrine and exocrine cells, as well as gastric and epithelial cells. The gene was identified as part of large-scale initiatives to characterize the human genome and its transcribed products ([Link](https://doi.org/10.1101/gr.1293003), [Link](https://doi.org/10.1101/gr.2596504)). ## Cellular Roles and Expression Landscape **Overall**, expression analysis reveals that [TMED6](/details-gene/146456) is a significant protein in cells characterized by high secretory activity. The gene's role appears fundamental to the cellular machinery responsible for processing and exporting large quantities of proteins. Its highest significance is observed in [ciliated epithelial cell](/details-cell/CL0000067) (CSI: 5.83), suggesting a crucial function in maintaining the protein constituents of cilia or the mucus layer they propel. Furthermore, [TMED6](/details-gene/146456) is highly prominent across various cell types of the pancreas, which is consistent with the organ's extensive endocrine and exocrine functions. It is a key marker in hormone-secreting islet cells such as the [pancreatic D cell](/details-cell/CL0000173) (CSI: 4.38), [type B pancreatic cell](/details-cell/CL0000169) (CSI: 3.46), and [pancreatic PP cell](/details-cell/CL0002275) (CSI: 3.25), as well as in the enzyme-secreting [pancreatic acinar cell](/details-cell/CL0002064) (CSI: 3.30). Its significance extends to secretory cells of the stomach, including the [mucous neck cell](/details-cell/CL0000651) (CSI: 3.77) and the [peptic cell](/details-cell/CL0000155) (CSI: 2.75). This expression pattern suggests that [TMED6](/details-gene/146456) is a core component supporting the high-throughput protein trafficking required by these specialized secretory tissues. ## Pathways and Molecular Function The molecular function of [TMED6](/details-gene/146456) is centered on intracellular protein logistics. It is annotated with biological processes such as [Endoplasmic reticulum to golgi vesicle-mediated transport](/details-go/GO:0006888), [Intracellular protein transport](/details-go/GO:0006886), and [Golgi organization](/details-go/GO:0007030). These functions highlight its role as a gatekeeper and facilitator of protein movement from their site of synthesis in the ER to their processing and sorting hub in the Golgi. Its cellular localization further solidifies this role. [TMED6](/details-gene/146456) is found in the [Endoplasmic reticulum](/details-go/GO:0005783), the [Golgi apparatus](/details-go/GO:0005794), and the transitional [Endoplasmic reticulum-golgi intermediate compartment](/details-go/GO:0005793). Critically, it is a component of the [Copii-coated er to golgi transport vesicle](/details-go/GO:0030134), which are the primary carriers for anterograde transport from the ER. This places [TMED6](/details-gene/146456) at the heart of the machinery that selects and packages newly synthesized proteins for their journey through the secretory pathway, a function essential for the cell types where it is most highly expressed. ## Research Directions The well-defined role of [TMED6](/details-gene/146456) in the secretory pathway and its high expression in specialized cells provide a clear basis for further investigation, particularly concerning its specificity and potential role in disease. **Proposed Hypotheses:** 1. **Cargo-Specific Transport:** Given that TMED proteins can act as cargo receptors, it is hypothesized that [TMED6](/details-gene/146456) is responsible for the selective recognition and packaging of a specific subset of secreted proteins. Its high expression in diverse cells like pancreatic beta cells and gastric peptic cells suggests it may either recognize a common structural motif on cargo like hormones and zymogens or be part of a more general quality control mechanism for the secretory pathway. 2. **Role in Secretory Stress and Disease:** It is hypothesized that dysregulation or mutation of [TMED6](/details-gene/146456) could contribute to diseases of protein secretion or "ER stress" in high-demand tissues. In [type B pancreatic cells](/details-cell/CL0000169), for example, inefficient [TMED6](/details-gene/146456)-mediated transport could impair insulin processing and secretion, potentially contributing to metabolic disorders. Similarly, defects in [pancreatic acinar cells](/details-cell/CL0002064) could lead to pancreatitis. **Experimental Approach:** To test the hypothesis of cargo specificity (Hypothesis 1), a proximity-dependent biotinylation (BioID) experiment could be performed. By expressing a [TMED6](/details-gene/146456)-BirA* fusion protein in a relevant cell line with high secretory load (e.g., the insulin-secreting INS-1E cell line), one could identify interacting and proximal proteins within the ER and early Golgi. Proteins that are biotinylated in a stimulus-dependent manner (e.g., upon glucose stimulation to induce insulin synthesis) and subsequently identified by mass spectrometry would be strong candidates for [TMED6](/details-gene/146456)-specific cargo. **Therapeutic Potential:** As a fundamental component of protein transport, [TMED6](/details-gene/146456) presents a challenging therapeutic target due to the high risk of on-target toxicity in healthy secretory tissues. Global **inhibition** would likely disrupt essential physiological processes, such as hormone and digestive enzyme secretion. However, if [TMED6](/details-gene/146456) is found to be selectively required for the secretion of a key pathogenic protein (e.g., in certain cancers or inflammatory conditions), targeted inhibition might be a viable strategy. Conversely, strategies for **activation** or enhancement could be explored for deficiency disorders where impaired protein secretion is the underlying cause, although achieving cell-type specificity would be a significant hurdle.

Genular Protein ID: 4240726148

Symbol: TMED6_HUMAN

Name: Transmembrane emp24 domain-containing protein 6

UniProtKB Accession Codes:

Q8WW62 Q6UXN5

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 DisGeNET 1 EMBL 3 Ensembl 1 GO 9 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 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 SMART 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 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: 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

Sequence Information:

  • Length: 240
  • Mass: 27631
  • Checksum: E65B966E12533A83
  • Sequence:
    • MSPLLFGAGL VVLNLVTSAR SQKTEPLSGS GDQPLFRGAD RYDFAIMIPP GGTECFWQFA 
HQTGYFYFSY EVQRTVGMSH DRHVAATAHN PQGFLIDTSQ GVRGQINFST QETGFYQLCL 
SNQHNHFGSV QVYLNFGVFY EGPETDHKQK ERKQLNDTLD AIEDGTQKVQ NNIFHMWRYY 
NFARMRKMAD FFLIQSNYNY VNWWSTAQSL VIILSGILQL YFLKRLFNVP TTTDTKKPRC