Details for: TMEM61

Gene ID: 199964

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: TMEM61

Ensembl ID: ENSG00000143001

Description: transmembrane protein 61

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • pulmonary ionocyte CL0017000
    CSI 17.96
    rCSI 21.86%
    PRS 97.31
  • goblet cell CL0000160
    CSI 13.78
    rCSI 13.03%
    PRS 94.29
  • ionocyte CL0005006
    CSI 13.08
    rCSI 14.02%
    PRS 96.43
  • intestine goblet cell CL0019031
    CSI 8.88
    rCSI 7.89%
    PRS 94.32
  • glial cell CL0000125
    CSI 7.79
    rCSI 29.65%
    PRS 91.5
  • renal alpha-intercalated cell CL0005011
    CSI 7.35
    rCSI 9.82%
    PRS 97.18
  • GABAergic neuron CL0000617
    CSI 6.81
    rCSI 22.81%
    PRS 86.72
  • neural progenitor cell CL0011020
    CSI 5.75
    rCSI 25.28%
    PRS 87.87
  • enteroendocrine cell CL0000164
    CSI 5.66
    rCSI 7.74%
    PRS 93.93
  • lung neuroendocrine cell CL1000223
    CSI 3.68
    rCSI 5.45%
    PRS 95.94
  • multi-ciliated epithelial cell CL0005012
    CSI 3.67
    rCSI 3.66%
    PRS 92.16
  • ependymal cell CL0000065
    CSI 3.61
    rCSI 7.33%
    PRS 83.4
  • myoepithelial cell CL0000185
    CSI 3.43
    rCSI 8.68%
    PRS 97.08
  • pancreatic D cell CL0000173
    CSI 3.18
    rCSI 3.12%
    PRS 96.34
  • epithelial cell CL0000066
    CSI 3.13
    rCSI 4.8%
    PRS 86.68
  • type L enteroendocrine cell CL0002279
    CSI 2.8
    rCSI 5.25%
    PRS 95.77
  • ciliated epithelial cell CL0000067
    CSI 2.33
    rCSI 2.05%
    PRS 90.18
  • type B pancreatic cell CL0000169
    CSI 2.31
    rCSI 5.11%
    PRS 95.74
  • enteroendocrine cell of small intestine CL0009006
    CSI 2.23
    rCSI 4.9%
    PRS 96.2
  • small intestine goblet cell CL1000495
    CSI 2.02
    rCSI 4.42%
    PRS 96.52
  • colon goblet cell CL0009039
    CSI 1.72
    rCSI 4.09%
    PRS 96.25
  • P/D1 enteroendocrine cell CL0002268
    CSI 1.06
    rCSI 5.75%
    PRS 96.12

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 Transmembrane protein 61, encoded by the [TMEM61](/details-gene/199964) gene, is a protein-coding gene located on chromosome 1 [Link](https://doi.org/10.1038/nature04727). Functional annotation is currently limited, identifying it as a membrane-bound protein involved in protein binding. **Overall**, expression data reveals a highly specific and significant role for [TMEM61](/details-gene/199964) in specialized epithelial cells responsible for ion transport and secretion, with its highest significance observed in [pulmonary ionocytes](/details-cell/CL0017000), [goblet cells](/details-cell/CL0000160), and other related ion-transporting cell types. A secondary but notable pattern of expression is also observed in several neural and neuroendocrine cell lineages, suggesting a multifaceted but specialized function. ## Cellular Roles and Expression Landscape The expression profile of [TMEM61](/details-gene/199964) points to a specialized role in maintaining homeostasis at mucosal and secretory surfaces, as well as in the nervous system. The gene's significance is highest in cell types that are critical for ion and fluid balance. **Key Roles in Epithelial and Secretory Cells:** * **Ion Transport:** [TMEM61](/details-gene/199964) is a top marker for [pulmonary ionocytes](/details-cell/CL0017000) (CSI: 17.96), [ionocytes](/details-cell/CL0005006) (CSI: 13.08), and [renal alpha-intercalated cells](/details-cell/CL0005011) (CSI: 7.35). This strong and consistent association suggests a fundamental role in regulating ion transport, potentially as a channel component, a transporter, or a regulatory protein essential for the function of these specialized cells. * **Mucus Secretion:** The gene shows high significance in [goblet cells](/details-cell/CL0000160) (CSI: 13.78) and [intestine goblet cells](/details-cell/CL0019031) (CSI: 8.88), indicating a potential involvement in the synthesis, packaging, or secretion of mucins. * **Endocrine and Exocrine Function:** Expression in [enteroendocrine cells](/details-cell/CL0000164), [lung neuroendocrine cells](/details-cell/CL1000223), and [pancreatic D cells](/details-cell/CL0000173) suggests a broader role in glandular and secretory processes beyond ion transport, possibly related to hormone or neuropeptide release. **Roles in the Nervous System:** * A distinct expression pattern is also evident within the nervous system, where [TMEM61](/details-gene/199964) is a significant marker in [glial cells](/details-cell/CL0000125) (CSI: 7.79), [GABAergic neurons](/details-cell/CL0000617) (CSI: 6.81), [neural progenitor cells](/details-cell/CL0011020) (CSI: 5.75), and [ependymal cells](/details-cell/CL0000065) (CSI: 3.61). This suggests a potential role in neural development, glial support functions, or neurotransmission. **Expression Specificity:** Notably, the gene's expression is not significant in major hematopoietic lineages, such as lymphocytes or myeloid cells, nor in structural cells like fibroblasts. This highly restricted expression pattern underscores its specialized function and makes it a specific marker for the aforementioned cell types. ## Pathways and Molecular Function The functional annotations for [TMEM61](/details-gene/199964) are currently sparse but consistent with its observed expression profile. * **Cellular Component:** Its localization to the [membrane](/details-cell/GO:0016020) ([GO:0016020](https://www.ebi.ac.uk/QuickGO/term/GO:0016020)) is consistent with a role as a channel, transporter, or receptor on the cell surface, which would be essential for cells like [ionocytes](/details-cell/CL0005006) that interface directly with the extracellular environment. * **Molecular Function:** The annotation for [protein binding](/details-cell/GO:0005515) ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)) suggests that [TMEM61](/details-gene/199964) does not function in isolation but likely acts as part of a larger protein complex to carry out its functions, such as forming a multi-subunit ion channel or scaffolding signaling proteins. The identification and characterization of this gene were part of large-scale sequencing and gene collection projects [Link](https://doi.org/10.1038/nature04727), [Link](https://doi.org/10.1101/gr.2596504), but its specific molecular pathway has yet to be elucidated. ## Research Directions The specific and high-level expression of [TMEM61](/details-gene/199964) in functionally critical cell types presents several compelling avenues for future research, particularly concerning diseases of mucosal organs and the nervous system. **Proposed Testable Hypotheses:** 1. **Role in Ion Homeostasis:** Given its prominent expression in [pulmonary ionocytes](/details-cell/CL0017000) and [renal alpha-intercalated cells](/details-cell/CL0005011), [TMEM61](/details-gene/199964) is a key component or regulator of an ion transport complex (e.g., chloride or bicarbonate transport) essential for maintaining pH and fluid balance across epithelial barriers. Its dysregulation may contribute to pathologies like cystic fibrosis or renal tubular acidosis. 2. **Involvement in Secretory Pathways:** The high significance of [TMEM61](/details-gene/199964) in both [goblet cells](/details-cell/CL0000160) and various neuroendocrine cell types suggests it may play a conserved role in regulated exocytosis, potentially by interacting with the SNARE complex or other vesicle-trafficking machinery to control the release of mucus and hormones. 3. **Function in Neural Development or Plasticity:** Its expression in [neural progenitor cells](/details-cell/CL0011020) and mature [glial cells](/details-cell/CL0000125) indicates a potential role in neurogenesis, cell fate determination, or glial-neuronal communication. **Suggested Experimental Approach:** To test the primary hypothesis of [TMEM61](/details-gene/199964)'s role in ion transport, a targeted knockdown or knockout experiment in a relevant model system is warranted. Specifically, one could use CRISPR-Cas9 to disrupt the [TMEM61](/details-gene/199964) gene in primary human bronchial epithelial cells grown in an air-liquid interface (ALI) culture, which allows for differentiation into a pseudostratified epithelium containing both [goblet cells](/details-cell/CL0000160) and [pulmonary ionocytes](/details-cell/CL0017000). Transepithelial ion transport could then be measured using Ussing chamber electrophysiology to assess changes in chloride and bicarbonate secretion. Concurrently, single-cell RNA sequencing could reveal compensatory changes in other transport-related genes and confirm the cell-type-specific impact of the knockout. **Therapeutic Potential:** As a transmembrane protein with a highly restricted expression profile, [TMEM61](/details-gene/199964) presents an attractive profile for a therapeutic target. Its specificity for certain epithelial and neuroendocrine cells could be exploited to minimize off-target effects. For diseases characterized by hypersecretion, such as certain forms of asthma or muco-secretory adenocarcinomas, a monoclonal antibody or small molecule designed to **inhibit** [TMEM61](/details-gene/199964) function could reduce pathological mucus production. Conversely, if its deficiency is linked to ion transport defects, strategies for **activation** or gene replacement therapy could be explored. Its cell surface accessibility makes it a particularly strong candidate for antibody-based therapies.

Genular Protein ID: 400036725

Symbol: TMM61_HUMAN

Name: Transmembrane protein 61

UniProtKB Accession Codes:

Q8N0U2

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 EMBL 2 Ensembl 1 GO 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 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 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 2 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 210
  • Mass: 22170
  • Checksum: 44E412BA0E8E84EF
  • Sequence:
    • MALPQMCDGS HLASTLRYCM TVSGTVVLVA GTLCFAWWSE GDATAQPGQL APPTEYPVPE 
GPSPLLRSVS FVCCGAGGLL LLIGLLWSVK ASIPGPPRWD PYHLSRDLYY LTVESSEKES 
CRTPKVVDIP TYEEAVSFPV AEGPPTPPAY PTEEALEPSG SRDALLSTQP AWPPPSYESI 
SLALDAVSAE TTPSATRSCS GLVQTARGGS