Details for: LRRTM3

Gene ID: 347731

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: LRRTM3

Ensembl ID: ENSG00000198739

Description: leucine rich repeat transmembrane neuronal 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • pvalb GABAergic cortical interneuron CL4023018
    CSI 56.55
    rCSI 70.36%
    PRS 98.11
  • sst GABAergic cortical interneuron CL4023017
    CSI 52.09
    rCSI 67.16%
    PRS 98.68
  • VIP GABAergic cortical interneuron CL4023016
    CSI 47.86
    rCSI 57.17%
    PRS 98.36
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 38.83
    rCSI 65.18%
    PRS 98.5
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 36.7
    rCSI 66.69%
    PRS 98.81
  • oligodendrocyte precursor cell CL0002453
    CSI 35.36
    rCSI 77.8%
    PRS 96.62
  • sncg GABAergic cortical interneuron CL4023015
    CSI 33.8
    rCSI 54.36%
    PRS 98.28
  • cerebellar granule cell CL0001031
    CSI 27.87
    rCSI 40.97%
    PRS 98.71
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 27.75
    rCSI 60.19%
    PRS 97.46
  • cardiac muscle cell CL0000746
    CSI 27.67
    rCSI 39.7%
    PRS 98.41
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 26.73
    rCSI 64.96%
    PRS 97.74
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 26.35
    rCSI 63.02%
    PRS 97.82
  • glioblast CL0000030
    CSI 25.38
    rCSI 40.48%
    PRS 98.72
  • neuron CL0000540
    CSI 25.1
    rCSI 66.85%
    PRS 97.29
  • Bergmann glial cell CL0000644
    CSI 24.53
    rCSI 33.56%
    PRS 98.79
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 22.58
    rCSI 26.07%
    PRS 98.85
  • inhibitory interneuron CL0000498
    CSI 21.76
    rCSI 50.22%
    PRS 98.5
  • L6b glutamatergic cortical neuron CL4023038
    CSI 21.11
    rCSI 65.97%
    PRS 98.36
  • interneuron CL0000099
    CSI 20.68
    rCSI 41.52%
    PRS 99.03
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 19.95
    rCSI 62.39%
    PRS 98.55
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 19.8
    rCSI 34.97%
    PRS 98.4
  • glutamatergic neuron CL0000679
    CSI 19.76
    rCSI 40.62%
    PRS 96.94
  • cerebral cortex endothelial cell CL1001602
    CSI 19.57
    rCSI 33.85%
    PRS 99.01
  • neural cell CL0002319
    CSI 18.97
    rCSI 71.61%
    PRS 97.26
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 18.51
    rCSI 66.61%
    PRS 98.02
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 18.19
    rCSI 59.77%
    PRS 97.54
  • vascular leptomeningeal cell CL4023051
    CSI 18.04
    rCSI 31.63%
    PRS 99.12
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 17.2
    rCSI 64.99%
    PRS 98.01
  • GABAergic neuron CL0000617
    CSI 14.22
    rCSI 47.63%
    PRS 96.76
  • cerebral cortex neuron CL0010012
    CSI 14.14
    rCSI 57.62%
    PRS 98.33
  • macroglial cell CL0000126
    CSI 14.14
    rCSI 36.35%
    PRS 99.08
  • amacrine cell CL0000561
    CSI 14.09
    rCSI 40.83%
    PRS 98.51
  • oligodendrocyte CL0000128
    CSI 12.82
    rCSI 37.89%
    PRS 98.45
  • glycinergic amacrine cell CL4030028
    CSI 12.05
    rCSI 31.38%
    PRS 98.33
  • serotonergic neuron CL0000850
    CSI 11.16
    rCSI 49.85%
    PRS 96.76
  • GABAergic amacrine cell CL4030027
    CSI 10.81
    rCSI 37.02%
    PRS 97.53
  • astrocyte of the cerebral cortex CL0002605
    CSI 10.58
    rCSI 23.72%
    PRS 98.49
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 10.53
    rCSI 62.03%
    PRS 98.15
  • Schwann cell CL0002573
    CSI 9.53
    rCSI 27.08%
    PRS 99.17
  • regular atrial cardiac myocyte CL0002129
    CSI 9.33
    rCSI 30.02%
    PRS 98.87
  • dopaminergic neuron CL0000700
    CSI 8.84
    rCSI 49.93%
    PRS 97.98
  • glial cell CL0000125
    CSI 8.66
    rCSI 32.99%
    PRS 98.31
  • central nervous system neuron CL2000029
    CSI 8.3
    rCSI 61.01%
    PRS 98.66
  • medium spiny neuron CL1001474
    CSI 8.21
    rCSI 70.75%
    PRS 98.49
  • lung neuroendocrine cell CL1000223
    CSI 7.8
    rCSI 11.54%
    PRS 99.35
  • mesothelial cell CL0000077
    CSI 7.79
    rCSI 30.48%
    PRS 98.09
  • retinal ganglion cell CL0000740
    CSI 7.77
    rCSI 17.16%
    PRS 98.39
  • regular ventricular cardiac myocyte CL0002131
    CSI 5.81
    rCSI 36.32%
    PRS 98.58
  • basal cell of epidermis CL0002187
    CSI 5.45
    rCSI 9.66%
    PRS 91.6
  • forebrain radial glial cell CL0013000
    CSI 5.1
    rCSI 16.37%
    PRS 99.66
  • cerebellar neuron CL1001611
    CSI 4.94
    rCSI 43.5%
    PRS 97.38
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 4.67
    rCSI 5.66%
    PRS 93.83
  • type B pancreatic cell CL0000169
    CSI 4.1
    rCSI 9.07%
    PRS 99.33
  • melanocyte of skin CL1000458
    CSI 4.08
    rCSI 5.56%
    PRS 93.12
  • ON parasol ganglion cell CL4033052
    CSI 3.76
    rCSI 53.3%
    PRS 98.34
  • starburst amacrine cell CL0004232
    CSI 3.22
    rCSI 27.14%
    PRS 97.12
  • midbrain dopaminergic neuron CL2000097
    CSI 3.02
    rCSI 19.34%
    PRS 98.41
  • direct pathway medium spiny neuron CL4023026
    CSI 2.47
    rCSI 59.21%
    PRS 97.19
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.45
    rCSI 59.01%
    PRS 97.19
  • blood vessel smooth muscle cell CL0019018
    CSI 1.24
    rCSI 10.12%
    PRS 99.65
  • OFF midget ganglion cell CL4033047
    CSI 1.01
    rCSI 20.64%
    PRS 98.29

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 [LRRTM3](/details-gene/347731) (leucine rich repeat transmembrane neuronal 3) is a protein-coding gene that encodes a member of the LRRTM family of transmembrane proteins, which are primarily expressed in the nervous system [[Link](https://doi.org/10.1016/s0888-7543(03)00030-2)]. Functionally, [LRRTM3](/details-gene/347731) is implicated in synaptic organization, particularly at the `[glutamatergic synapse](/details-go/GO:0098978)`, where it participates in pathways involving `[Neurexins and neuroligins](/details-pathway/R-HSA-6794361)`. Expression data reveals its high significance in a wide array of neuronal subtypes, especially various classes of GABAergic cortical interneurons and glutamatergic neurons, suggesting a fundamental role in establishing and maintaining synaptic circuits. Notably, it is also linked to the `[positive regulation of amyloid-beta formation](/details-go/GO:1902004)`, pointing towards a potential role in neurodegenerative disease pathogenesis. ## Cellular Roles and Expression Landscape The expression profile of [LRRTM3](/details-gene/347731) strongly indicates a specialized function within the central nervous system. * **Key Role in Cortical Interneurons:** **Overall**, the gene shows its highest significance in multiple subtypes of GABAergic cortical interneurons, including `[pvalb GABAergic cortical interneuron](/details-cell/CL4023018)` (CSI: 56.55), `[sst GABAergic cortical interneuron](/details-cell/CL4023017)` (CSI: 52.09), `[VIP GABAergic cortical interneuron](/details-cell/CL4023016)` (CSI: 47.86), and `[lamp5 GABAergic cortical interneuron](/details-cell/CL4023011)` (CSI: 38.83). This suggests a critical function in the development, connectivity, or function of inhibitory circuits that regulate cortical activity. * **Involvement in Excitatory Neurons and Glia:** [LRRTM3](/details-gene/347731) is also a significant marker in excitatory neuronal populations such as `[L2/3 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4030059)` and `[cerebellar granule cell](/details-cell/CL0001031)`. Its expression extends to glial cells, including `[differentiation-committed oligodendrocyte precursor](/details-cell/CL4023059)`, `[oligodendrocyte precursor cell](/details-cell/CL0002453)`, and `[Bergmann glial cell](/details-cell/CL0000644)`, suggesting a broader role in the neuronal microenvironment, potentially related to myelination or glial-neuronal communication. * **Expression in Pathological Contexts:** The notable significance of [LRRTM3](/details-gene/347731) in `[glioblast](/details-cell/CL0000030)` (CSI: 25.38) indicates its potential involvement in the biology of this aggressive brain tumor. ## Pathways and Molecular Function Functional annotations for [LRRTM3](/details-gene/347731) are tightly linked to its role at the synapse. As a transmembrane protein localized to the `[postsynaptic density membrane](/details-go/GO:0098839)` and `[extracellular space](/details-go/GO:0005615)`, it is a key component of the `[Neuronal system](/details-pathway/R-HSA-112316)`. Its function in `[positive regulation of synapse assembly](/details-go/GO:0051965)` is consistent with its involvement in the `[Neurexins and neuroligins](/details-pathway/R-HSA-6794361)` pathway, which mediates cell-cell adhesion and signaling at the synapse. This biological role aligns with its high expression across diverse neuronal subtypes essential for forming complex neural networks. Clinically, the most significant annotation is its participation in the `[positive regulation of amyloid-beta formation](/details-go/GO:1902004)`, directly linking its molecular function to a key pathological process in Alzheimer's disease. ## Research Directions The specific expression pattern and functional annotations of [LRRTM3](/details-gene/347731) suggest several avenues for future research, particularly concerning its roles in synaptic regulation and neuro-pathology. **Proposed Hypotheses:** 1. Given its high expression across multiple inhibitory interneuron subtypes, [LRRTM3](/details-gene/347731) may be a critical factor in establishing the specificity of inhibitory synapses, thereby maintaining the excitatory/inhibitory balance in the cerebral cortex. 2. The established role of [LRRTM3](/details-gene/347731) in the `[positive regulation of amyloid-beta formation](/details-go/GO:1902004)` suggests that its overexpression or dysregulation in specific neuronal populations, such as glutamatergic neurons, could be a risk factor that accelerates the onset or progression of Alzheimer's disease. 3. The significant expression of [LRRTM3](/details-gene/347731) in `[glioblast](/details-cell/CL0000030)` may promote tumor progression by facilitating synaptic-like intercellular communication between cancer cells or with surrounding neurons, enhancing tumor invasion and survival. **Experimental Approach:** To test the hypothesis that [LRRTM3](/details-gene/347731) is essential for inhibitory synapse function (Hypothesis 1), one could perform a targeted knockdown of [LRRTM3](/details-gene/347731) in primary cortical cultures using shRNA or CRISPR/Cas9. The effects on inhibitory synapse density could be quantified via immunofluorescence staining for presynaptic (e.g., VGAT) and postsynaptic (e.g., Gephyrin) markers. Functional consequences could be assessed using whole-cell patch-clamp electrophysiology to measure changes in the frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs). **Therapeutic Potential:** [LRRTM3](/details-gene/347731)'s involvement in amyloid-beta formation makes it a potential therapeutic target for Alzheimer's disease. As a transmembrane protein that positively regulates this pathological process, it is an attractive candidate for **inhibition** using monoclonal antibodies or small molecule inhibitors that could block its interaction with components of the amyloid precursor protein (APP) processing machinery. Furthermore, its expression in glioblastoma may present an opportunity for targeted cancer therapies, such as antibody-drug conjugates, assuming its cell surface accessibility on tumor cells.

Genular Protein ID: 589878970

Symbol: LRRT3_HUMAN

Name: Leucine-rich repeat transmembrane neuronal protein 3

UniProtKB Accession Codes:

Q86VH5 A8K2A3 Q2NKX7 Q6N0A3

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 7 Ensembl 1 GO 7 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 1 RefSeq 1 SMART 3 SMR 1 STRING 1 SUPFAM 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 12676565

Title: A novel gene family encoding leucine-rich repeat transmembrane proteins differentially expressed in the nervous system.

PubMed ID: 12676565

DOI: 10.1016/s0888-7543(03)00030-2

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 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: 581
  • Mass: 65896
  • Checksum: A025CF13AA663730
  • Sequence:
    • MGFNVIRLLS GSAVALVIAP TVLLTMLSSA ERGCPKGCRC EGKMVYCESQ KLQEIPSSIS 
AGCLGLSLRY NSLQKLKYNQ FKGLNQLTWL YLDHNHISNI DENAFNGIRR LKELILSSNR 
ISYFLNNTFR PVTNLRNLDL SYNQLHSLGS EQFRGLRKLL SLHLRSNSLR TIPVRIFQDC 
RNLELLDLGY NRIRSLARNV FAGMIRLKEL HLEHNQFSKL NLALFPRLVS LQNLYLQWNK 
ISVIGQTMSW TWSSLQRLDL SGNEIEAFSG PSVFQCVPNL QRLNLDSNKL TFIGQEILDS 
WISLNDISLA GNIWECSRNI CSLVNWLKSF KGLRENTIIC ASPKELQGVN VIDAVKNYSI 
CGKSTTERFD LARALPKPTF KPKLPRPKHE SKPPLPPTVG ATEPGPETDA DAEHISFHKI 
IAGSVALFLS VLVILLVIYV SWKRYPASMK QLQQRSLMRR HRKKKRQSLK QMTPSTQEFY 
VDYKPTNTET SEMLLNGTGP CTYNKSGSRE CEIPLSMNVS TFLAYDQPTI SYCGVHHELL 
SHKSFETNAQ EDTMETHLET ELDLSTITTA GRISDHKQQL A