Details for: TRAPPC2

Gene ID: 6399

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: TRAPPC2

Ensembl ID: ENSG00000196459

Description: trafficking protein particle complex subunit 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • hematopoietic precursor cell CL0008001
    CSI 5.78
    rCSI 5.95%
    PRS 89.96
  • pro-B cell CL0000826
    CSI 4.92
    rCSI 4.07%
    PRS 80.84
  • CD4-positive, alpha-beta thymocyte CL0000810
    CSI 4.52
    rCSI 3.62%
    PRS 91.52
  • activated type II NK T cell CL0000931
    CSI 3.81
    rCSI 4.29%
    PRS 90.82
  • amacrine cell CL0000561
    CSI 3.67
    rCSI 10.63%
    PRS 67.81
  • kidney connecting tubule epithelial cell CL1000768
    CSI 3.63
    rCSI 9.21%
    PRS 68.66
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 3.58
    rCSI 3.23%
    PRS 76.5
  • mesodermal cell CL0000222
    CSI 3.45
    rCSI 4.14%
    PRS 75.92
  • double negative thymocyte CL0002489
    CSI 3.39
    rCSI 2.36%
    PRS 89.23
  • interneuron CL0000099
    CSI 3.38
    rCSI 6.79%
    PRS 68.32
  • VIP GABAergic cortical interneuron CL4023016
    CSI 3.3
    rCSI 3.94%
    PRS 60.26
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 3.29
    rCSI 2.5%
    PRS 90.26
  • ON-bipolar cell CL0000749
    CSI 3.11
    rCSI 4.62%
    PRS 78.45
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 2.91
    rCSI 14.61%
    PRS 89.54
  • precursor B cell CL0000817
    CSI 2.79
    rCSI 2.44%
    PRS 85.67
  • hematopoietic stem cell CL0000037
    CSI 2.75
    rCSI 1.83%
    PRS 81.19
  • early lymphoid progenitor CL0000936
    CSI 2.66
    rCSI 2.34%
    PRS 83.34
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 2.62
    rCSI 2.58%
    PRS 91.02
  • mature B cell CL0000785
    CSI 2.57
    rCSI 2.24%
    PRS 87.68
  • epithelial cell of lung CL0000082
    CSI 2.55
    rCSI 2.12%
    PRS 78.83
  • respiratory basal cell CL0002633
    CSI 2.53
    rCSI 2.62%
    PRS 82.55
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.48
    rCSI 5.57%
    PRS 61.06
  • CD4-positive helper T cell CL0000492
    CSI 2.46
    rCSI 1.86%
    PRS 89.97
  • small pre-B-II cell CL0000954
    CSI 2.41
    rCSI 2.32%
    PRS 91.92
  • neural crest cell CL0011012
    CSI 2.37
    rCSI 1.88%
    PRS 66.76
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.35
    rCSI 4.16%
    PRS 59.48
  • T follicular helper cell CL0002038
    CSI 2.3
    rCSI 1.72%
    PRS 90.43
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.27
    rCSI 1.58%
    PRS 81.62
  • common dendritic progenitor CL0001029
    CSI 2.26
    rCSI 2.83%
    PRS 87.05
  • epithelial cell of lower respiratory tract CL0002632
    CSI 2.21
    rCSI 1.71%
    PRS 81.88
  • cerebral cortex endothelial cell CL1001602
    CSI 2.19
    rCSI 3.79%
    PRS 69.69
  • common myeloid progenitor CL0000049
    CSI 2.18
    rCSI 1.76%
    PRS 80.59
  • CD4-positive, alpha-beta cytotoxic T cell CL0000934
    CSI 2.12
    rCSI 2.91%
    PRS 93.09
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 2.11
    rCSI 1.92%
    PRS 90.08
  • Mueller cell CL0000636
    CSI 2.07
    rCSI 4.72%
    PRS 69.85
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 2.06
    rCSI 1.39%
    PRS 90.54
  • retinal bipolar neuron CL0000748
    CSI 2.06
    rCSI 3.85%
    PRS 66.61
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.01
    rCSI 1.55%
    PRS 81.01
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 1.99
    rCSI 5.87%
    PRS 79.21
  • T-helper 1 cell CL0000545
    CSI 1.79
    rCSI 3.23%
    PRS 93.26
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 1.76
    rCSI 1.79%
    PRS 88.11
  • lung ciliated cell CL1000271
    CSI 1.74
    rCSI 2.02%
    PRS 70.44
  • retina horizontal cell CL0000745
    CSI 1.72
    rCSI 2.63%
    PRS 75.21
  • ciliated epithelial cell CL0000067
    CSI 1.72
    rCSI 1.51%
    PRS 67.31
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.62
    rCSI 2.08%
    PRS 74.45
  • vascular leptomeningeal cell CL4023051
    CSI 1.58
    rCSI 2.78%
    PRS 71.79
  • alveolar type 1 fibroblast cell CL4028004
    CSI 1.58
    rCSI 1.73%
    PRS 80.35
  • peripheral nervous system neuron CL2000032
    CSI 1.56
    rCSI 2.12%
    PRS 69.81
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.56
    rCSI 1.94%
    PRS 58.12
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.51
    rCSI 5.73%
    PRS 60.7
  • enteric smooth muscle cell CL0002504
    CSI 1.5
    rCSI 2.14%
    PRS 79.22
  • megakaryocyte CL0000556
    CSI 1.49
    rCSI 6.47%
    PRS 84.31
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.48
    rCSI 1.91%
    PRS 61.32
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.39
    rCSI 2.34%
    PRS 60.25
  • tracheobronchial smooth muscle cell CL0019019
    CSI 1.36
    rCSI 2.39%
    PRS 83.66
  • pulmonary artery endothelial cell CL1001568
    CSI 1.35
    rCSI 1.84%
    PRS 86.86
  • platelet CL0000233
    CSI 1.28
    rCSI 5.29%
    PRS 76.33
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.26
    rCSI 4.52%
    PRS 58.18
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.12
    rCSI 6.59%
    PRS 60.98
  • mesenchymal cell CL0008019
    CSI 1.1
    rCSI 2.78%
    PRS 71.62
  • lung pericyte CL0009089
    CSI 1.09
    rCSI 2.88%
    PRS 85.02
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.04
    rCSI 1.67%
    PRS 61.9
  • retinal cone cell CL0000573
    CSI 0.97
    rCSI 1.56%
    PRS 68.33
  • large pre-B-II cell CL0000957
    CSI 0.88
    rCSI 2.51%
    PRS 84.33
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.86
    rCSI 2.1%
    PRS 58.23
  • retinal ganglion cell CL0000740
    CSI 0.72
    rCSI 1.58%
    PRS 64.14
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.51
    rCSI 1.59%
    PRS 61.87
  • direct pathway medium spiny neuron CL4023026
    CSI 0.29
    rCSI 6.86%
    PRS 58.69
  • cytotoxic T cell CL0000910
    CSI 0.18
    rCSI 1.01%
    PRS 82.56

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 [TRAPPC2](/details-gene/6399) (Trafficking Protein Particle Complex Subunit 2), also known as SEDL, is a protein-coding gene located on the X chromosome (Xp22.2). It encodes a core subunit of the Transport Protein Particle (TRAPP) complexes, which are essential for vesicle tethering and transport between the endoplasmic reticulum and the Golgi apparatus. This fundamental role in intracellular protein trafficking positions [TRAPPC2](/details-gene/6399) as a critical component of cellular logistics, particularly in cells with high secretory or proliferative activity. Clinically, mutations in [TRAPPC2](/details-gene/6399) are the causative factor for X-linked spondyloepiphyseal dysplasia tarda (SEDT), a genetic disorder characterized by defects in skeletal development ([Link](https://doi.org/10.1038/11976), OMIM: [313400](https://omim.org/entry/313400)). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [TRAPPC2](/details-gene/6399) highlights its fundamental importance across a diverse range of cell types, consistent with its core role in vesicle-mediated transport. The gene shows particularly high significance in cells undergoing active development, differentiation, and proliferation. Its highest significance is observed in [hematopoietic precursor cell](/details-cell/CL0008001) (CSI: 5.78), [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 3.58), and various stages of lymphocyte development, including [pro-B cell](/details-cell/CL0000826) (CSI: 4.92), [CD4-positive, alpha-beta thymocyte](/details-cell/CL0000810) (CSI: 4.52), and [double negative thymocyte](/details-cell/CL0002489) (CSI: 3.39). This pattern suggests that the high demand for protein synthesis and transport of surface receptors during hematopoiesis and lymphopoiesis makes these cells particularly reliant on efficient TRAPP complex function. Beyond the immune system, [TRAPPC2](/details-gene/6399) also demonstrates notable significance in specialized cells of the nervous system, such as [amacrine cell](/details-cell/CL0000561) (CSI: 3.67) and [interneuron](/details-cell/CL0000099) (CSI: 3.38), as well as in epithelial cells like [kidney connecting tubule epithelial cell](/details-cell/CL1000768) (CSI: 3.63). This broad but distinct expression landscape underscores its role as an essential housekeeping gene whose function is amplified in metabolically active and developing cell lineages. ## Pathways and Molecular Function The functional annotations for [TRAPPC2](/details-gene/6399) confirm its central role in the secretory pathway. As a component of the [TRAPP complex](/details-go/GO:0030008), it participates directly in [endoplasmic reticulum to golgi vesicle-mediated transport](/details-go/GO:0006888) and [COPII vesicle coating](/details-go/GO:0048208). These processes are integral parts of broader cellular logistics pathways, including [Vesicle-mediated transport](/details-pathway/R-HSA-5653656) and [Membrane Trafficking](/details-pathway/R-HSA-199991). The function of [TRAPPC2](/details-gene/6399) is upstream of crucial protein maturation events that occur in the Golgi. Consequently, it is linked to pathways such as [Asparagine N-linked glycosylation](/details-pathway/R-HSA-446203) and [Post-translational protein modification](/details-pathway/R-HSA-597592). This involvement is consistent with its high expression in immune cells, which depend on correct glycosylation for the function of cell surface receptors and secreted effector molecules. Its established role in skeletal system development ([GO:0001501](https://www.ebi.ac.uk/QuickGO/term/GO:0001501)) is directly linked to the clinical phenotype observed when the gene is mutated ([Link](https://doi.org/10.1086/320592)). ## Research Directions The established link between [TRAPPC2](/details-gene/6399) mutations and spondyloepiphyseal dysplasia tarda provides a clear basis for further investigation into its cell-specific functions. While it is a broadly expressed gene, its deficiency results in a tissue-specific pathology, suggesting that certain cell types are uniquely vulnerable to disruptions in its function. Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis 1:** The skeletal defects in spondyloepiphyseal dysplasia tarda arise from the inefficient secretion of specific, high-flux extracellular matrix proteins (e.g., type II collagen) by chondrocytes, leading to their intracellular aggregation, induction of ER stress, and eventual apoptosis. 2. **Hypothesis 2:** The high significance of [TRAPPC2](/details-gene/6399) in lymphoid progenitors suggests that sub-clinical immunological defects may exist in patients with SEDT mutations. A deficiency in [TRAPPC2](/details-gene/6399) could impair the surface expression of antigen receptors during T and B cell development, subtly compromising immune repertoire diversity or function. **Experimental Approach to Test Hypothesis 1:** To investigate the role of [TRAPPC2](/details-gene/6399) in chondrocyte protein secretion, one could utilize an *in vitro* model system. Specifically, primary human chondrocytes or an immortalized chondrocyte cell line could be subjected to CRISPR-Cas9 mediated knockout of [TRAPPC2](/details-gene/6399). The impact on cellular function would be assessed by quantifying the secretion of type II collagen and aggrecan into the culture medium using ELISA. Concurrently, intracellular levels of these proteins could be visualized via immunofluorescence microscopy to detect aggregation. The induction of ER stress pathways could be monitored by measuring the expression of markers like BiP and CHOP through quantitative PCR and western blotting. **Therapeutic Potential:** As [TRAPPC2](/details-gene/6399) is a core component of a fundamental cellular trafficking pathway, it is not a suitable target for pharmacological inhibition, which would likely lead to widespread cellular toxicity. Instead, its therapeutic potential is primarily in the context of gene therapy for monogenic disorders like SEDT. Strategies aimed at restoring functional [TRAPPC2](/details-gene/6399) protein expression in affected tissues, such as chondrocytes, using viral vectors (e.g., AAV) could represent a viable long-term therapeutic approach to correct the underlying molecular defect.

Genular Protein ID: 314775246

Symbol: TPC2A_HUMAN

Name: Trafficking protein particle complex subunit 2

UniProtKB Accession Codes:

P0DI81 A6NEG0 O14582 Q9HD16

Database IDs:

AGR 2 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CORUM 1 CTD 1 ChiTaRS 1 ComplexPortal 2 DMDM 1 DNASU 1 DisGeNET 1 EMBL 10 Ensembl 6 ExpressionAtlas 1 GO 17 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 2 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 Pumba 1 RNAct 1 Reactome 2 RefSeq 5 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10431248

Title: Identification of the gene (SEDL) causing X-linked spondyloepiphyseal dysplasia tarda.

PubMed ID: 10431248

DOI: 10.1038/11976

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

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: 11031107

Title: Gene structure and expression study of the SEDL gene for spondyloepiphyseal dysplasia tarda.

PubMed ID: 11031107

DOI: 10.1006/geno.2000.6326

PubMed ID: 11805826

Title: Functional organization of the yeast proteome by systematic analysis of protein complexes.

PubMed ID: 11805826

DOI: 10.1038/415141a

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21525244

Title: C4orf41 and TTC-15 are mammalian TRAPP components with a role at an early stage in ER-to-Golgi trafficking.

PubMed ID: 21525244

DOI: 10.1091/mbc.e10-11-0873

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 25918224

Title: TRAMM/TrappC12 plays a role in chromosome congression, kinetochore stability, and CENP-E recruitment.

PubMed ID: 25918224

DOI: 10.1083/jcb.201501090

PubMed ID: 14597397

Title: Human wild-type SEDL protein functionally complements yeast Trs20p but some naturally occurring SEDL mutants do not.

PubMed ID: 14597397

DOI: 10.1016/s0378-1119(03)00819-9

PubMed ID: 19416478

Title: TRAPPC2L is a novel, highly conserved TRAPP-interacting protein.

PubMed ID: 19416478

DOI: 10.1111/j.1600-0854.2009.00906.x

PubMed ID: 20498720

Title: SEDLIN forms homodimers: characterisation of SEDLIN mutations and their interactions with transcription factors MBP1, PITX1 and SF1.

PubMed ID: 20498720

DOI: 10.1371/journal.pone.0010646

PubMed ID: 11349230

Title: The molecular basis of X-linked spondyloepiphyseal dysplasia tarda.

PubMed ID: 11349230

DOI: 10.1086/320592

PubMed ID: 11424925

Title: A missense mutation in the SEDL gene results in delayed onset of X linked spondyloepiphyseal dysplasia in a large pedigree.

PubMed ID: 11424925

DOI: 10.1136/jmg.38.6.409

Sequence Information:

  • Length: 140
  • Mass: 16445
  • Checksum: B099943C6F88952C
  • Sequence:
    • MSGSFYFVIV GHHDNPVFEM EFLPAGKAES KDDHRHLNQF IAHAALDLVD ENMWLSNNMY 
LKTVDKFNEW FVSAFVTAGH MRFIMLHDIR QEDGIKNFFT DVYDLYIKFS MNPFYEPNSP 
IRSSAFDRKV QFLGKKHLLS