Details for: TMEM88

Gene ID: 92162

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: TMEM88

Ensembl ID: ENSG00000167874

Description: transmembrane protein 88

Cell Significance Landscape

Associated with

Significant Cells

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

  • capillary endothelial cell CL0002144
    CSI 9.57
    rCSI 17.55%
    PRS 93.96
  • vasa recta ascending limb cell CL1001131
    CSI 7.28
    rCSI 32.94%
    PRS 97.58
  • endothelial cell of artery CL1000413
    CSI 5.49
    rCSI 8.04%
    PRS 95.91
  • blood vessel endothelial cell CL0000071
    CSI 5.02
    rCSI 10.42%
    PRS 94.29
  • type EC enteroendocrine cell CL0000577
    CSI 4.41
    rCSI 15.67%
    PRS 95.42
  • cardiac endothelial cell CL0010008
    CSI 4.29
    rCSI 17.29%
    PRS 95.68
  • cerebral cortex endothelial cell CL1001602
    CSI 3.46
    rCSI 5.98%
    PRS 92.3
  • pulmonary artery endothelial cell CL1001568
    CSI 2.9
    rCSI 3.95%
    PRS 97.46
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.68
    rCSI 4.27%
    PRS 96.68
  • mesodermal cell CL0000222
    CSI 2.06
    rCSI 2.48%
    PRS 94.9
  • vasa recta descending limb cell CL1001285
    CSI 1.32
    rCSI 10.57%
    PRS 97.51
  • endothelial cell of vascular tree CL0002139
    CSI 1.25
    rCSI 6.86%
    PRS 92.25
  • endothelial cell of placenta CL0009092
    CSI 1.08
    rCSI 5.32%
    PRS 96.7
  • lung microvascular endothelial cell CL2000016
    CSI 0.49
    rCSI 9.44%
    PRS 97.23
  • prostate gland microvascular endothelial cell CL2000059
    CSI 0.42
    rCSI 10.1%
    PRS 96.82

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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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 [TMEM88](/details-gene/92162) is a protein-coding gene located on chromosome 17p13.1 that encodes Transmembrane protein 88. Functionally, [TMEM88](/details-gene/92162) is primarily known as a negative regulator of the canonical Wnt signaling pathway ([Link](https://doi.org/10.1074/jbc.m110.193383)), a crucial process in embryonic development and tissue homeostasis. Expression data from the **Overall** context highlights its significant role within the vascular system, showing prominent expression and high significance scores across a wide range of endothelial cell populations. Its localization to the '[plasma membrane](/details-go/GO:0005886)' is consistent with its function in modulating extracellular signals. ## Cellular Roles and Expression Landscape The expression profile of [TMEM88](/details-gene/92162) strongly suggests a specialized role within the vascular endothelium. **Overall**, it is most significant in [capillary endothelial cell](/details-cell/CL0002144) (CSI: 9.57), [vasa recta ascending limb cell](/details-cell/CL1001131) (CSI: 7.28), and [endothelial cell of artery](/details-cell/CL1000413) (CSI: 5.49). This pattern extends across various specialized endothelial beds, including those in cardiac, cerebral, pulmonary, and placental tissues, underscoring its general importance as a marker and functional component of [blood vessel endothelial cell](/details-cell/CL0000071) (CSI: 5.02). The data points to [TMEM88](/details-gene/92162) as a key constituent of the endothelial cell identity across multiple organ systems. ## Pathways and Molecular Function [TMEM88](/details-gene/92162) is an integral component of the '[Wnt signaling pathway](/details-go/GO:0016055)', where it functions primarily as a negative regulator ([GO:0090090](https://www.ebi.ac.uk/QuickGO/term/GO:0090090)). Research has shown that it acts by binding to the PDZ domain of Dishevelled, an essential scaffold protein in the Wnt pathway, thereby inhibiting downstream signaling ([Link](https://doi.org/10.1074/jbc.m110.193383)). This regulatory role is critical in developmental processes, as demonstrated by its function in specifying cardiomyocyte development ([Link](https://doi.org/10.1242/dev.094789)). Its molecular function is characterized by '[Pdz domain binding](/details-go/GO:0030165)' and general '[protein binding](/details-go/GO:0005515)'. Cellularly, it is localized to both the '[plasma membrane](/details-go/GO:0005886)' and the '[cytosol](/details-go/GO:0005829)', consistent with its role as a transmembrane protein that interacts with intracellular signaling complexes. ## Research Directions Given the established role of [TMEM88](/details-gene/92162) as a Wnt inhibitor and its high expression in endothelial cells, future research should focus on its potential role in pathologies involving aberrant vascular growth and Wnt signaling, such as cancer and cardiovascular disease. **Proposed Hypotheses:** 1. Inhibition of tumor angiogenesis: Downregulation of [TMEM88](/details-gene/92162) in tumor-associated endothelial cells may promote Wnt-driven angiogenesis, facilitating tumor growth and metastasis. Conversely, its targeted overexpression in the tumor vasculature could serve as an anti-angiogenic strategy. 2. Regulation of vascular permeability: [TMEM88](/details-gene/92162) may regulate endothelial barrier function by modulating Wnt/beta-catenin signaling, which is known to control the expression of cell-cell junction proteins. Dysregulation of [TMEM88](/details-gene/92162) could therefore contribute to vascular leakage in inflammatory conditions. **Experimental Approach:** To test the hypothesis that [TMEM88](/details-gene/92162) inhibits tumor angiogenesis (Hypothesis 1), a murine tumor model (e.g., B16 melanoma or LLC Lewis lung carcinoma) could be employed. One group of animals would receive systemic administration of an endothelial-targeted adeno-associated virus (AAV) vector driving overexpression of [TMEM88](/details-gene/92162) (e.g., using a Cdh5 promoter). A control group would receive a similar vector with a reporter gene. Tumor growth rates would be monitored, and upon sacrifice, tumors would be analyzed for vessel density (via CD31 immunohistochemistry), pericyte coverage, and Wnt pathway activity (via nuclear beta-catenin staining) to assess the impact of [TMEM88](/details-gene/92162) on the tumor vasculature. **Therapeutic Potential:** As a transmembrane protein, [TMEM88](/details-gene/92162) is a potentially druggable target. Given its role as a negative regulator of the pro-proliferative Wnt pathway, it could represent a therapeutic target for activation or agonism in diseases characterized by excessive Wnt signaling, such as colorectal cancer or fibrosis. Therapeutic strategies could involve small molecules that stabilize [TMEM88](/details-gene/92162) or enhance its interaction with Dishevelled. Conversely, in scenarios where increased Wnt signaling is desirable, such as promoting tissue regeneration after injury, transient inhibition of [TMEM88](/details-gene/92162) with an antibody or small molecule inhibitor might be beneficial.

Genular Protein ID: 1009943031

Symbol: TMM88_HUMAN

Name: Transmembrane protein 88

UniProtKB Accession Codes:

Q6PEY1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 1 ExpressionAtlas 1 GO 7 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 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 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: 21044957

Title: Identification of transmembrane protein 88 (TMEM88) as a dishevelled-binding protein.

PubMed ID: 21044957

DOI: 10.1074/jbc.m110.193383

PubMed ID: 23924634

Title: Transmembrane protein 88: a Wnt regulatory protein that specifies cardiomyocyte development.

PubMed ID: 23924634

DOI: 10.1242/dev.094789

Sequence Information:

  • Length: 159
  • Mass: 17251
  • Checksum: B77503ABB3D4295B
  • Sequence:
    • MADVPGAQRA VPGDGPEPRD PLDCWACAVL VTAQNLLVAA FNLLLLVLVL GTILLPAVTM 
LGFGFLCHSQ FLRSQAPPCT AHLRDPGFTA LLVTGFLLLV PLLVLALASY RRLCLRLRLA 
DCLVPYSRAL YRRRRAPQPR QIRASPGSQA VPTSGKVWV

Genular Protein ID: 1753273913

Symbol: I3L2J3_HUMAN

Name: N/A

UniProtKB Accession Codes:

I3L2J3

Database IDs:

ARBA 5 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 2 ExpressionAtlas 1 GO 1 GeneTree 1 HGNC 1 HOGENOM 1 InterPro 1 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Proteomes 2 ProteomicsDB 2 RefSeq 1 SAM 1 SMR 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

Sequence Information:

  • Length: 126
  • Mass: 13334
  • Checksum: 2B5B2F0105FFA776
  • Sequence:
    • MADVPGAQRA VPGDGPEPRD PLDCWACAVL VTAQNLLVAA FNLLLLVLVL GTILLPAVTM 
LGFGFLCHSQ DLKPGIFRPA LPPPLPERSP SIPLGAAASV DPVLRKAPTS RKTHFPFTTH 
ISILNI