Details for: TM4SF18

Gene ID: 116441

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: TM4SF18

Ensembl ID: ENSG00000163762

Description: transmembrane 4 L six family member 18

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • pericyte CL0000669
    CSI 8.96
    rCSI 23.86%
    PRS 90.63
  • lung endothelial cell CL1001567
    CSI 8.19
    rCSI 19.09%
    PRS 99.72
  • blood vessel endothelial cell CL0000071
    CSI 8.16
    rCSI 16.94%
    PRS 98.96
  • neural progenitor cell CL0011020
    CSI 6.31
    rCSI 27.78%
    PRS 95.21
  • vasa recta ascending limb cell CL1001131
    CSI 6.26
    rCSI 28.31%
    PRS 99.6
  • endothelial cell of lymphatic vessel CL0002138
    CSI 6.02
    rCSI 11.94%
    PRS 99.15
  • cerebral cortex endothelial cell CL1001602
    CSI 6
    rCSI 10.38%
    PRS 98.02
  • endothelial cell of placenta CL0009092
    CSI 5.62
    rCSI 27.71%
    PRS 99.15
  • luminal epithelial cell of mammary gland CL0002326
    CSI 5.53
    rCSI 10.05%
    PRS 99.39
  • vein endothelial cell CL0002543
    CSI 4.59
    rCSI 12.53%
    PRS 99.39
  • endothelial cell of arteriole CL1000412
    CSI 3.81
    rCSI 21.14%
    PRS 99.7
  • retinal blood vessel endothelial cell CL0002585
    CSI 3.39
    rCSI 5.42%
    PRS 99.53
  • collagen secreting cell CL0000667
    CSI 3.36
    rCSI 19.25%
    PRS 99.28
  • endothelial cell of uterus CL0009095
    CSI 2.97
    rCSI 21.69%
    PRS 99.8
  • vein endothelial cell of respiratory system CL4033008
    CSI 2.93
    rCSI 20.14%
    PRS 99.5
  • type EC enteroendocrine cell CL0000577
    CSI 2.93
    rCSI 10.39%
    PRS 98.94
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 2.84
    rCSI 8.76%
    PRS 99.36
  • vasa recta descending limb cell CL1001285
    CSI 2.5
    rCSI 19.95%
    PRS 99.53
  • endothelial cell of vascular tree CL0002139
    CSI 2.28
    rCSI 12.47%
    PRS 97.77
  • prostate gland microvascular endothelial cell CL2000059
    CSI 1.63
    rCSI 39.06%
    PRS 99.34
  • lung microvascular endothelial cell CL2000016
    CSI 1.04
    rCSI 19.99%
    PRS 99.62

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):
    • 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 [TM4SF18](/details-gene/116441) is a protein-coding gene located on chromosome 3q25.1 that encodes Transmembrane 4 L six family member 18. As a member of the transmembrane 4 L6 family, it is annotated as an integral membrane protein. Expression data indicates that [TM4SF18](/details-gene/116441) is a significant marker predominantly for cells of the vascular system, with exceptionally high significance in [pericytes](/details-cell/CL0000669) and various types of endothelial cells. This specific expression pattern suggests a primary role in vascular biology, potentially related to vessel structure, integrity, or endothelial function. Foundational research from large-scale cDNA projects has confirmed the sequence and existence of its transcript [[Link](https://doi.org/10.1038/ng1285), [Link](https://doi.org/10.1101/gr.2596504)]. ## Cellular Roles and Expression Landscape The expression profile of [TM4SF18](/details-gene/116441) strongly points to a specialized function within the circulatory and vascular support systems. **Overall**, the gene shows its highest significance in cell types that constitute or are intimately associated with blood vessels. It is a top marker for [pericytes](/details-cell/CL0000669) (CSI: 8.96), which are critical for capillary stability. Following this, [TM4SF18](/details-gene/116441) is highly significant across a broad range of endothelial cells, including [lung endothelial cells](/details-cell/CL1001567) (CSI: 8.19), general [blood vessel endothelial cells](/details-cell/CL0000071) (CSI: 8.16), and [endothelial cells of lymphatic vessels](/details-cell/CL0002138) (CSI: 6.02). This consistent, high-level expression across endothelial populations from diverse tissues—such as the brain ([cerebral cortex endothelial cell](/details-cell/CL1001602)), placenta ([endothelial cell of placenta](/details-cell/CL0009092)), and retina ([retinal blood vessel endothelial cell](/details-cell/CL0002585))—underscores its potential role as a core component of endothelial cell identity and function. Interestingly, the gene also shows notable significance in [neural progenitor cells](/details-cell/CL0011020) (CSI: 6.31), which may suggest a secondary, context-dependent role in neurodevelopment or in the formation of the neurovascular unit. Its expression in [collagen secreting cells](/details-cell/CL0000667) further supports a role related to the structural microenvironment of tissues. The widespread and specific nature of its expression within the vasculature suggests that [TM4SF18](/details-gene/116441) is likely involved in fundamental processes common to these cell types. ## Pathways and Molecular Function The functional annotations for [TM4SF18](/details-gene/116441) are currently broad, reflecting a need for more detailed biochemical characterization. According to Gene Ontology, it is associated with the cellular component [Membrane](/details-cell/GO:0016020), which is consistent with its classification as a transmembrane protein. Its annotated molecular function is [Protein binding](/details-cell/GO:0005515), indicating that it likely interacts with other proteins, either on the cell surface or within the membrane, to exert its biological effect. The specific signaling pathways mediated by [TM4SF18](/details-gene/116441) and its precise binding partners remain to be elucidated. However, its strong co-expression with pericyte and endothelial markers suggests it may participate in pathways governing cell-cell adhesion, vascular permeability, or angiogenesis signaling. ## Research Directions The highly specific expression pattern of [TM4SF18](/details-gene/116441) in the vasculature, coupled with limited functional data, presents several clear avenues for future investigation. **Proposed Hypotheses:** 1. Given its high significance in both [pericytes](/details-cell/CL0000669) and multiple endothelial cell types, [TM4SF18](/details-gene/116441) may function as a key mediator of pericyte-endothelial cell communication, essential for maintaining blood-brain barrier integrity or regulating capillary microcirculation. 2. The expression of [TM4SF18](/details-gene/116441) in [neural progenitor cells](/details-cell/CL0011020) suggests a possible role in neuro-angiogenesis, where it could guide the development and patterning of blood vessels in the developing central nervous system. 3. As a transmembrane protein, [TM4SF18](/details-gene/116441) could be involved in mechanotransduction, sensing blood flow or shear stress and translating these physical cues into biochemical signals within endothelial cells. **Key Experimental Approach:** To test the hypothesis that [TM4SF18](/details-gene/116441) is critical for vascular stability and angiogenesis (Hypothesis 1), a co-culture experiment could be performed. Using CRISPR-Cas9 or shRNA to knock down [TM4SF18](/details-gene/116441) in primary human endothelial cells (HUVECs), these cells could then be co-cultured with primary human pericytes. The effects of [TM4SF18](/details-gene/116441) depletion could be assessed by measuring the stability of vessel-like networks in a 3D matrix, analyzing the expression of junctional proteins (e.g., VE-cadherin), and measuring trans-endothelial electrical resistance (TEER) to quantify barrier function. **Therapeutic Potential:** As a cell-surface protein with highly restricted expression to the vasculature, [TM4SF18](/details-gene/116441) presents a compelling potential therapeutic target. Its specificity for endothelial cells and pericytes makes it an attractive candidate for targeted drug delivery to blood vessels. For instance, antibodies or nanobodies targeting [TM4SF18](/details-gene/116441) could be used to deliver anti-angiogenic agents in cancer therapy or pro-angiogenic factors in ischemic diseases. Whether inhibition or activation would be the desired therapeutic strategy depends on its currently unknown function in vascular pathology. If it promotes vessel growth, inhibition would be relevant for oncology; if it stabilizes vessels, activation could be beneficial in diseases characterized by vascular leakage, such as diabetic retinopathy.

Genular Protein ID: 113275466

Symbol: T4S18_HUMAN

Name: Transmembrane 4 L6 family member 18

UniProtKB Accession Codes:

Q96CE8 B2R8K0 D3DNH5

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 5 Ensembl 2 ExpressionAtlas 1 GO 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 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 TCDB 1 TreeFam 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: 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: 201
  • Mass: 22277
  • Checksum: A49E70402164D336
  • Sequence:
    • MGSRKCGGCL SCLLIPLALW SIIVNILLYF PNGQTSYASS NKLTNYVWYF EGICFSGIMM 
LIVTTVLLVL ENNNNYKCCQ SENCSKKYVT LLSIIFSSLG IAFSGYCLVI SALGLVQGPY 
CRTLDGWEYA FEGTAGRFLT DSSIWIQCLE PAHVVEWNII LFSILITLSG LQVIICLIRV 
VMQLSKILCG SYSVIFQPGI I