Details for: TMEM86A

Gene ID: 144110

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: TMEM86A

Ensembl ID: ENSG00000151117

Description: transmembrane protein 86A

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • myeloid leukocyte CL0000766
    CSI 4.78
    rCSI 4.41%
    PRS 99.98
  • neural progenitor cell CL0011020
    CSI 2.97
    rCSI 13.06%
    PRS 98.88
  • basal cell of epidermis CL0002187
    CSI 2.75
    rCSI 4.87%
    PRS 98.76

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 Transmembrane protein 86A, encoded by the [TMEM86A](/details-gene/144110) gene, is a protein localized to the endoplasmic reticulum membrane. Functionally, it is characterized as a lysoplasmalogenase, an enzyme with alkenylglycerophosphocholine hydrolase activity ([GO:0047408](https://www.ebi.ac.uk/QuickGO/term/GO:0047408)) that plays a role in lipid metabolism ([GO:0006629](https://www.ebi.ac.uk/QuickGO/term/GO:0006629)). **Overall**, expression data highlights its high significance in [myeloid leukocyte](/details-cell/CL0000766), suggesting a key role in the innate immune system. Recent research has specifically implicated [TMEM86A](/details-gene/144110) in coupling Liver X Receptor (LXR) signaling to the regulation of lysoplasmalogens within macrophages [[Link](https://doi.org/10.1016/j.jlr.2022.100325)]. ## Cellular Roles and Expression Landscape The expression profile of [TMEM86A](/details-gene/144110) points to a primary function within the hematopoietic system, with its most significant expression observed in [myeloid leukocyte](/details-cell/CL0000766) (CSI: 4.78). This is consistent with its identified role in macrophage lipid metabolism [[Link](https://doi.org/10.1016/j.jlr.2022.100325)]. The high significance in this cell lineage suggests that [TMEM86A](/details-gene/144110) is a crucial component of myeloid cell biology, likely contributing to membrane composition and signaling functions. Beyond the immune system, the data also indicate notable significance in [neural progenitor cell](/details-cell/CL0011020) (CSI: 2.97) and [basal cell of epidermis](/details-cell/CL0002187) (CSI: 2.75). This suggests that the role of [TMEM86A](/details-gene/144110)-mediated lipid metabolism may extend to processes such as neurodevelopment and skin tissue homeostasis, areas that warrant further investigation. ## Pathways and Molecular Function [TMEM86A](/details-gene/144110) functions as a hydrolase, specifically acting on ether lipids as a lysoplasmalogenase. Its annotation with molecular functions such as 'alkenylglycerophosphocholine hydrolase activity' ([GO:0047408](https://www.ebi.ac.uk/QuickGO/term/GO:0047408)) and 'hydrolase activity' ([GO:0016787](https://www.ebi.ac.uk/QuickGO/term/GO:0016787)) defines its enzymatic role within the broader 'lipid metabolic process' ([GO:0006629](https://www.ebi.ac.uk/QuickGO/term/GO:0006629)). The protein is an integral component of the 'endoplasmic reticulum membrane' ([GO:0005789](https://www.ebi.ac.uk/QuickGO/term/GO:0005789)), a primary site for lipid synthesis and modification. A key study has placed [TMEM86A](/details-gene/144110) within a specific regulatory network in macrophages, demonstrating that it is a sterol-regulated protein that links LXR signaling, a critical pathway for cholesterol homeostasis and inflammation, to the direct control of lysoplasmalogen levels [[Link](https://doi.org/10.1016/j.jlr.2022.100325)]. This finding directly connects its molecular function to cellular physiology, suggesting that [TMEM86A](/details-gene/144110) helps macrophages adjust their membrane lipid composition in response to metabolic cues. ## Research Directions The specific function of [TMEM86A](/details-gene/144110) in lipid metabolism, particularly in myeloid cells, opens several avenues for future research into its role in both health and disease. **Proposed Hypotheses:** 1. Given its regulation by LXR and its role in macrophage lipid metabolism [[Link](https://doi.org/10.1016/j.jlr.2022.100325)], dysregulation of [TMEM86A](/details-gene/144110) activity in macrophages contributes to the pathogenesis of metabolic diseases like atherosclerosis by altering the cellular lipidome and promoting foam cell formation. 2. The significant expression of [TMEM86A](/details-gene/144110) in [neural progenitor cell](/details-cell/CL0011020) suggests that its lysoplasmalogenase activity is essential for maintaining the specific lipid environment required for proper neural stem cell differentiation and neuronal maturation. **Experimental Approach:** To test the first hypothesis, a combination of in vitro and in vivo studies could be employed. A CRISPR-Cas9-mediated knockout of [TMEM86A](/details-gene/144110) could be generated in a human macrophage cell line (e.g., THP-1) and in a mouse model of atherosclerosis (e.g., ApoE-/- mice). In vitro, knockout macrophages could be loaded with oxidized LDL, followed by lipidomic analysis via mass spectrometry to quantify changes in lysoplasmalogen and cholesterol ester content. In vivo, bone marrow from [TMEM86A](/details-gene/144110) knockout mice could be transplanted into irradiated ApoE-/- mice, which would then be placed on a high-fat diet to induce atherosclerosis. The extent of aortic plaque formation and the composition of plaque-infiltrating macrophages could then be compared between mice with and without myeloid-specific [TMEM86A](/details-gene/144110) deletion. **Therapeutic Potential:** As an enzyme central to lipid metabolism in macrophages, [TMEM86A](/details-gene/144110) presents a potential therapeutic target for diseases characterized by lipid dysregulation and inflammation, such as atherosclerosis or certain neuroinflammatory disorders. Its enzymatic nature makes it amenable to targeting by small molecule inhibitors or activators. In the context of atherosclerosis, where excess lipid accumulation in macrophages is detrimental, developing specific inhibitors of [TMEM86A](/details-gene/144110) could represent a novel strategy to modulate macrophage lipid content and reduce inflammatory responses within atherosclerotic plaques.

Genular Protein ID: 2122107427

Symbol: TM86A_HUMAN

Name: Lysoplasmalogenase TMEM86A

UniProtKB Accession Codes:

Q8N2M4 Q96AJ0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 8 DMDM 1 DNASU 1 DisGeNET 1 EC 2 EMBL 3 Ensembl 1 GO 5 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MINT 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 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 Rhea 2 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 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

PubMed ID: 36592658

Title: Sterol-regulated transmembrane protein TMEM86a couples LXR signaling to regulation of lysoplasmalogens in macrophages.

PubMed ID: 36592658

DOI: 10.1016/j.jlr.2022.100325

Sequence Information:

  • Length: 240
  • Mass: 26398
  • Checksum: 2FABCC64A964BAA9
  • Sequence:
    • MVSPVTVVKS EGPKLVPFFK ATCVYFVLWL PSSSPSWVST LIKCLPIFCL WLFLLAHGLG 
FLLAHPSATR IFVGLVFSAV GDAFLIWQDQ GYFVHGLLMF AVTHMFYASA FGMQPLALRT 
GLVMAALSGL CYALLYPCLS GAFTYLVGVY VALIGFMGWR AMAGLRLAGA DWRWTELAAG 
SGALFFIISD LTIALNKFCF PVPYSRALIM STYYVAQMLV ALSAVESREP VEHYRLTKAN