Details for: TMEM196

Gene ID: 256130

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: TMEM196

Ensembl ID: ENSG00000173452

Description: transmembrane protein 196

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • rod bipolar cell CL0000751
    CSI 44.91
    rCSI 80.71%
    PRS 86.31
  • sst GABAergic cortical interneuron CL4023017
    CSI 29.32
    rCSI 37.8%
    PRS 79.58
  • retinal bipolar neuron CL0000748
    CSI 26.6
    rCSI 49.81%
    PRS 82.97
  • ON-bipolar cell CL0000749
    CSI 25.62
    rCSI 38.08%
    PRS 89.98
  • microglial cell CL0000129
    CSI 24.15
    rCSI 97.2%
    PRS 89.29
  • interneuron CL0000099
    CSI 13.26
    rCSI 26.62%
    PRS 85.07
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 12.58
    rCSI 22.21%
    PRS 77.94
  • sncg GABAergic cortical interneuron CL4023015
    CSI 11.89
    rCSI 19.11%
    PRS 79.39
  • glioblast CL0000030
    CSI 11.33
    rCSI 18.07%
    PRS 83.8
  • VIP GABAergic cortical interneuron CL4023016
    CSI 11.06
    rCSI 13.21%
    PRS 78.56
  • GABAergic amacrine cell CL4030027
    CSI 10.49
    rCSI 35.92%
    PRS 78.84
  • inhibitory interneuron CL0000498
    CSI 9.8
    rCSI 22.63%
    PRS 82.09
  • diffuse bipolar 3b cell CL4033030
    CSI 9.67
    rCSI 64.21%
    PRS 85.28
  • OFFx cell CL4033036
    CSI 9.59
    rCSI 45.14%
    PRS 81.65
  • diffuse bipolar 2 cell CL4033028
    CSI 9.15
    rCSI 70.86%
    PRS 83.94
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 7.52
    rCSI 9.64%
    PRS 87.46
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 6.94
    rCSI 16.59%
    PRS 80.95
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 6.37
    rCSI 10.68%
    PRS 78.51
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 6.26
    rCSI 15.2%
    PRS 76.36
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 6.05
    rCSI 22.85%
    PRS 78.67
  • glycinergic amacrine cell CL4030028
    CSI 6.04
    rCSI 15.73%
    PRS 85.3
  • L6b glutamatergic cortical neuron CL4023038
    CSI 5.87
    rCSI 18.35%
    PRS 79.83
  • OFF-bipolar cell CL0000750
    CSI 5.39
    rCSI 7.37%
    PRS 89.55
  • GABAergic neuron CL0000617
    CSI 5.36
    rCSI 17.97%
    PRS 78.04
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 4.86
    rCSI 15.2%
    PRS 81.48
  • flat midget bipolar cell CL4033033
    CSI 4.55
    rCSI 32.54%
    PRS 81.89
  • amacrine cell CL0000561
    CSI 3.86
    rCSI 11.18%
    PRS 83.01
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 3.74
    rCSI 8.11%
    PRS 80.17
  • pancreatic A cell CL0000171
    CSI 3.26
    rCSI 3.42%
    PRS 92.74
  • diffuse bipolar 4 cell CL4033031
    CSI 2.65
    rCSI 30.37%
    PRS 78.89
  • pancreatic D cell CL0000173
    CSI 2.4
    rCSI 2.36%
    PRS 92.63
  • retinal ganglion cell CL0000740
    CSI 2.17
    rCSI 4.8%
    PRS 80.88
  • diffuse bipolar 1 cell CL4033027
    CSI 2.11
    rCSI 15.83%
    PRS 80.5
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 1.95
    rCSI 3.54%
    PRS 84.84
  • direct pathway medium spiny neuron CL4023026
    CSI 1.89
    rCSI 45.24%
    PRS 76.34
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.81
    rCSI 6.5%
    PRS 76.55
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.75
    rCSI 42.32%
    PRS 76.5
  • central nervous system neuron CL2000029
    CSI 1.53
    rCSI 11.24%
    PRS 82.96
  • ON parasol ganglion cell CL4033052
    CSI 1.26
    rCSI 17.93%
    PRS 83.71
  • type B pancreatic cell CL0000169
    CSI 1.23
    rCSI 2.72%
    PRS 91.02
  • cone retinal bipolar cell CL0000752
    CSI 0.42
    rCSI 5.48%
    PRS 87.91

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 [TMEM196](/details-gene/256130), or Transmembrane Protein 196, is a protein-coding gene located on chromosome 7p21.1. Functionally, [TMEM196](/details-gene/256130) is implicated as a tumor suppressor, primarily through its roles in the negative regulation of the canonical Wnt signaling pathway, cell proliferation, and migration, as well as the positive regulation of apoptosis ([Link](https://doi.org/10.18632/oncotarget.4237), [Link](https://doi.org/10.1007/s00432-022-04363-w)). Expression data from the **Overall** context reveals a highly specific enrichment in the central nervous system, with particularly strong significance in neuronal subtypes of the retina, such as the '[rod bipolar cell](/details-cell/CL0000751)', and various cortical interneurons. This suggests a primary role in neuronal function and maintenance, in addition to its more broadly studied role in cancer biology. ## Cellular Roles and Expression Landscape The expression profile of [TMEM196](/details-gene/256130) indicates a specialized function within the nervous system. **Overall**, it exhibits its highest cell significance in retinal neurons, most notably in the '[rod bipolar cell](/details-cell/CL0000751)' (CSI: 44.91) and '[retinal bipolar neuron](/details-cell/CL0000748)' (CSI: 26.60), highlighting a potentially crucial role in visual signal processing. Beyond the retina, [TMEM196](/details-gene/256130) is a significant marker for various inhibitory interneuron populations in the cortex. This includes high significance in '[sst GABAergic cortical interneuron](/details-cell/CL4023017)' (CSI: 29.32), '[interneuron](/details-cell/CL0000099)' (CSI: 13.26), and other GABAergic subtypes. This consistent pattern suggests that [TMEM196](/details-gene/256130) may be involved in regulating the development, maintenance, or function of inhibitory circuits in the brain. Furthermore, its notable expression in the '[microglial cell](/details-cell/CL0000129)' (CSI: 24.15) suggests a potential secondary role in neuro-immune processes or brain homeostasis. The specificity of its expression within these neural and glial cell types points towards a highly specialized, rather than ubiquitous, function. ## Pathways and Molecular Function The established functions of [TMEM196](/details-gene/256130) are consistent with a regulatory role in cell fate and behavior. Gene Ontology annotations reveal its participation in several key negative regulatory processes, including '[negative regulation of canonical wnt signaling pathway](/details-cell/GO:0090090)', '[negative regulation of cell growth](/details-cell/GO:0030308)', '[negative regulation of cell migration](/details-cell/GO:0030336)', and '[negative regulation of cell population proliferation](/details-cell/GO:0008285)'. Concurrently, it is annotated for '[positive regulation of apoptotic process](/details-cell/GO:0043065)'. These functions are supported by molecular studies demonstrating that [TMEM196](/details-gene/256130) can inhibit lung cancer metastasis by modulating the Wnt/beta-catenin pathway ([Link](https://doi.org/10.1007/s00432-022-04363-w)). Its high expression in terminally differentiated cells like neurons is consistent with its role in suppressing proliferation. The involvement in Wnt signaling is particularly relevant in the nervous system, as this pathway is critical for neural development, synaptic plasticity, and adult neurogenesis. The protein is known to localize to the '[membrane](/details-cell/GO:0016020)' and '[cytoplasm](/details-cell/GO:0005737)' and participates in '[protein binding](/details-cell/GO:0005515)'. ## Research Directions While research has established [TMEM196](/details-gene/256130) as a tumor suppressor in lung cancer ([Link](https://doi.org/10.18632/oncotarget.4237)), its highly specific and significant expression within the central nervous system remains largely unexplored. The strong association with retinal bipolar cells and cortical interneurons suggests its physiological roles in the brain are of primary importance. Based on the available data, several testable hypotheses can be proposed: 1. Given its role in negatively regulating Wnt signaling—a key pathway for neuronal development and migration—[TMEM196](/details-gene/256130) is essential for the correct lamination and circuit integration of specific cortical interneuron subtypes during brain development. 2. In the retina, the exceptionally high expression of [TMEM196](/details-gene/256130) in bipolar cells, combined with its pro-apoptotic function, suggests it may play a role in developmental synaptic pruning or in protecting these neurons from excitotoxicity by modulating cell survival thresholds. 3. The significant expression of [TMEM196](/details-gene/256130) in microglia suggests it may function as a regulator of microglial activation states, potentially by modulating Wnt-dependent responses to inflammation or neuronal damage. To test the first hypothesis, a compelling experimental approach would be to perform a conditional knockout of [TMEM196](/details-gene/256130) in developing interneuron precursors in a mouse model (e.g., using a *Dlx5/6-Cre* or *Nkx2-1-Cre* driver line). Subsequent analysis of the adult cortex using immunohistochemistry and patch-clamp electrophysiology would allow for the assessment of interneuron positioning, morphology, and synaptic function, thereby clarifying the gene's role in establishing inhibitory circuits. From a therapeutic standpoint, [TMEM196](/details-gene/256130) presents a potential target for **activation** or expression restoration, not inhibition. Because its loss via DNA methylation is associated with cancer progression, strategies aimed at reactivating its expression, such as treatment with demethylating agents or developing small molecules that stabilize the TMEM196 protein, could be beneficial in cancers where it is silenced. However, its high specificity in critical neuronal populations would require careful consideration of potential neurological off-target effects for any systemic therapy.

Genular Protein ID: 1121413761

Symbol: TM196_HUMAN

Name: Transmembrane protein 196

UniProtKB Accession Codes:

Q5HYL7 Q8N6I6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 2 ExpressionAtlas 1 GO 7 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 NCBI Taxonomy 1 OpenTargets 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 2 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

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: 26056045

Title: TMEM196 acts as a novel functional tumour suppressor inactivated by DNA methylation and is a potential prognostic biomarker in lung cancer.

PubMed ID: 26056045

DOI: 10.18632/oncotarget.4237

PubMed ID: 36355209

Title: TMEM196 inhibits lung cancer metastasis by regulating the Wnt/beta-catenin signaling pathway.

PubMed ID: 36355209

DOI: 10.1007/s00432-022-04363-w

Sequence Information:

  • Length: 178
  • Mass: 19025
  • Checksum: E73C72CD628CE960
  • Sequence:
    • MCTSGQIIGS LLVLSVLEIG LGVSSVAVGA VSFSLALREH KPQLGDSSPV WSGVCFLLCG 
ICGILCAKKK SGLVMILFSA CCICGLIGGI LNFQFLRAVT KKTSSLYPLH LASMSLACIG 
IGGCTLSSWL TCRLASYEQR RMFSEREHSL HHSHEMAEKE ITDNMSNGGP QLIFNGRV