Details for: RASGEF1C

Gene ID: 255426

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: RASGEF1C

Ensembl ID: ENSG00000146090

Description: RasGEF domain family member 1C

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • central nervous system macrophage CL0000878
    CSI 17.99
    rCSI 59.61%
    PRS 92.39
  • microglial cell CL0000129
    CSI 10.53
    rCSI 42.38%
    PRS 88.95
  • inhibitory interneuron CL0000498
    CSI 10.33
    rCSI 23.84%
    PRS 81.64
  • Schwann cell CL0002573
    CSI 3.62
    rCSI 10.29%
    PRS 87.25
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.51
    rCSI 4.37%
    PRS 75.77
  • neural crest cell CL0011012
    CSI 3.27
    rCSI 2.58%
    PRS 83.84
  • glycinergic amacrine cell CL4030028
    CSI 3.05
    rCSI 7.94%
    PRS 84.99
  • retinal bipolar neuron CL0000748
    CSI 2.74
    rCSI 5.13%
    PRS 82.47
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.59
    rCSI 3.1%
    PRS 77.98
  • glutamatergic neuron CL0000679
    CSI 2.5
    rCSI 5.13%
    PRS 79.24
  • interneuron CL0000099
    CSI 2.46
    rCSI 4.94%
    PRS 84.59
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.4
    rCSI 3.1%
    PRS 79.01
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 2.34
    rCSI 8.86%
    PRS 78.16
  • mature microglial cell CL0002629
    CSI 2.32
    rCSI 9.64%
    PRS 88.68
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 2.31
    rCSI 4.21%
    PRS 84.43
  • cerebellar granule cell CL0001031
    CSI 2.18
    rCSI 3.2%
    PRS 85.66
  • amacrine cell CL0000561
    CSI 1.86
    rCSI 5.39%
    PRS 82.4
  • cardiac neuron CL0010022
    CSI 1.69
    rCSI 5.41%
    PRS 89.34
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.66
    rCSI 2.94%
    PRS 77.35
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.47
    rCSI 2.46%
    PRS 77.94
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.08
    rCSI 3.37%
    PRS 79.25
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 1.06
    rCSI 3.31%
    PRS 80.91
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.06
    rCSI 2.57%
    PRS 75.74
  • dopaminergic neuron CL0000700
    CSI 0.99
    rCSI 5.61%
    PRS 80.18
  • serotonergic neuron CL0000850
    CSI 0.96
    rCSI 4.27%
    PRS 76.54
  • retinal ganglion cell CL0000740
    CSI 0.95
    rCSI 2.1%
    PRS 80.33
  • glial cell CL0000125
    CSI 0.87
    rCSI 3.32%
    PRS 84.26
  • cerebellar neuron CL1001611
    CSI 0.85
    rCSI 7.49%
    PRS 78.74
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.77
    rCSI 2.76%
    PRS 75.93
  • enteroglial cell CL4040002
    CSI 0.65
    rCSI 3.43%
    PRS 90.68
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.61
    rCSI 3.58%
    PRS 78.39

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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Comma-separated if multiple.
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  • 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 [RASGEF1C](/details-gene/255426) encodes RasGEF domain family member 1C, a guanyl-nucleotide exchange factor (GEF). Its primary molecular function is to activate Ras family proteins by promoting the exchange of GDP for GTP, a critical step in 'Ras protein signal transduction' ([GO:0007265](https://www.ebi.ac.uk/QuickGO/term/GO:0007265)). Expression data reveals a highly specialized role for [RASGEF1C](/details-gene/255426) within the central nervous system (CNS). **Overall**, it shows exceptionally high significance in resident immune cells of the brain, such as [central nervous system macrophage](/details-cell/CL0000878)s and [microglial cell](/details-cell/CL0000129)s, as well as in various neuronal populations, particularly [inhibitory interneuron](/details-cell/CL0000498)s. This specific expression pattern suggests that [RASGEF1C](/details-gene/255426) is a key regulator of neuro-immune signaling and neuronal circuit function. ## Cellular Roles and Expression Landscape The expression profile of [RASGEF1C](/details-gene/255426) is predominantly restricted to the central nervous system, indicating a specialized function in neural and neuro-immune biology. The gene exhibits its highest significance in the resident myeloid cells of the CNS. It is the top marker in [central nervous system macrophage](/details-cell/CL0000878)s (CSI: 17.99) and shows very high significance in both general [microglial cell](/details-cell/CL0000129)s (CSI: 10.53) and [mature microglial cell](/details-cell/CL0002629)s (CSI: 2.32). This strong association suggests that [RASGEF1C](/details-gene/255426) is a critical component of the signaling machinery that governs microglial surveillance, activation, and response to physiological or pathological cues. In addition to its role in CNS immune cells, [RASGEF1C](/details-gene/255426) is also highly significant in a diverse array of neurons. It is a defining marker for [inhibitory interneuron](/details-cell/CL0000498)s (CSI: 10.33) and their subtypes, including [pvalb GABAergic cortical interneuron](/details-cell/CL4023018)s and [VIP GABAergic cortical interneuron](/details-cell/CL4023016)s. Its significance extends to [glutamatergic neuron](/details-cell/CL0000679)s and specialized retinal neurons like the [glycinergic amacrine cell](/details-cell/CL4030028) and [retinal bipolar neuron](/details-cell/CL0000748). This broad yet specific neuronal expression pattern points towards a fundamental role in regulating neuronal signaling, synaptic function, and network excitability across different brain regions. The gene also shows moderate significance in other glial cell types, including [Schwann cell](/details-cell/CL0002573)s of the peripheral nervous system and [differentiation-committed oligodendrocyte precursor](/details-cell/CL4023059)s, suggesting its involvement in myelination and glial development or maintenance. ## Pathways and Molecular Function Functionally, [RASGEF1C](/details-gene/255426) acts as a 'guanyl-nucleotide exchange factor' ([GO:0005085](https://www.ebi.ac.uk/QuickGO/term/GO:0005085)), a key class of enzymes that activate small GTPases. It specifically participates in 'Ras protein signal transduction' ([GO:0007265](https://www.ebi.ac.uk/QuickGO/term/GO:0007265)), a central signaling hub that controls a wide range of cellular processes, including proliferation, differentiation, survival, and motility. As indicated by its association with the [plasma membrane](/details-cell/GO:0005886) ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO:0005886)), [RASGEF1C](/details-gene/255426) likely transduces extracellular signals received by cell surface receptors into downstream intracellular responses by activating Ras. This function is highly consistent with its cellular expression profile. In [microglial cell](/details-cell/CL0000129)s, Ras signaling is essential for mediating responses to inflammatory stimuli, such as pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), which in turn control cytokine production and phagocytosis. In neurons, Ras pathways are well-established regulators of synaptic plasticity (e.g., long-term potentiation and depression), neurite outgrowth, and neuronal survival. Therefore, [RASGEF1C](/details-gene/255426) is positioned to be a critical link between external cues and long-term functional changes in both the immune and neuronal cells of the CNS. The identification of this gene stems from large-scale cDNA sequencing projects ([Link](https://doi.org/10.1038/ng1285), [Link](https://doi.org/10.1101/gr.2596504)). ## Research Directions The specific and high-level expression of [RASGEF1C](/details-gene/255426) in microglia and neurons makes it a compelling subject for further investigation, particularly in the context of neuroinflammatory and neurodegenerative diseases. **Proposed Hypotheses:** 1. [RASGEF1C](/details-gene/255426) is a key molecular switch that dictates the polarization of [microglial cell](/details-cell/CL0000129)s. Its activity may selectively couple specific cell-surface receptors (e.g., Toll-like receptors or TREM2) to downstream Ras-effector pathways (e.g., MAPK/ERK or PI3K/AKT), thereby determining whether microglia adopt a pro-inflammatory or homeostatic phenotype. 2. In [inhibitory interneuron](/details-cell/CL0000498)s, [RASGEF1C](/details-gene/255426) plays a crucial role in activity-dependent synaptic scaling and plasticity. It may be required to translate sustained changes in neuronal activity into the structural and functional modifications of synapses that maintain network stability. **Suggested Experimental Approach:** To test the first hypothesis regarding the role of [RASGEF1C](/details-gene/255426) in microglial function, a conditional knockout mouse model could be generated by crossing a mouse with floxed *Rasgef1c* alleles with a Cx3cr1-CreERT2 line to allow for tamoxifen-inducible, microglia-specific gene deletion in adults. Following gene deletion, the mice could be subjected to a neuroinflammatory challenge, such as intraperitoneal injection of lipopolysaccharide (LPS) or stereotactic injection of amyloid-beta oligomers. The microglial response would be assessed using single-cell RNA sequencing of sorted microglia to profile transcriptomic changes, and immunohistochemistry to analyze morphological changes and the expression of activation markers like Iba1 and CD68. This approach would directly reveal the necessity of [RASGEF1C](/details-gene/255426) for microglial activation *in vivo*. **Therapeutic Potential:** Given its role as an activator of Ras signaling and its high expression in microglia, [RASGEF1C](/details-gene/255426) represents a potential therapeutic target for neurological disorders characterized by chronic neuroinflammation, such as Alzheimer's disease or multiple sclerosis. A strategy involving **inhibition** of [RASGEF1C](/details-gene/255426) activity could be beneficial for dampening excessive microglial-mediated inflammation. Its localization at the plasma membrane and its enzymatic GEF activity make it potentially druggable by small-molecule inhibitors designed to disrupt its catalytic pocket or its interaction with upstream receptors. The development of such inhibitors, particularly those capable of crossing the blood-brain barrier, could offer a targeted approach to modulate neuroinflammation.

Genular Protein ID: 103983596

Symbol: RGF1C_HUMAN

Name: Ras-GEF domain-containing family member 1C

UniProtKB Accession Codes:

Q8N431 D3DWQ7 Q7Z4T0 Q8NA49

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 3 ExpressionAtlas 1 GO 3 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 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

Sequence Information:

  • Length: 466
  • Mass: 52870
  • Checksum: DDEFC900F30612B7
  • Sequence:
    • MPQTLSASDM VTPGSLSPPP TEPTDGEQAG QPLLDGAPSS ASLETLIQHL VPTADYYPEK 
AYIFTFLLSS RLFIEPRELL ARVCHLCIEQ QQLDKPVLDK ARVRKFGPKL LQLLAEWTET 
FPRDFQEEST IGHLKDVVGR IAPCDEAYRK RMHQLLQALH QKLAALRQGP EGLVGADKPI 
SYRTKPPASI HRELLGVCSD PYTLAQQLTH VELERLRHIG PEEFVQAFVN KDPLASTKPC 
FSDKTSNLEA YVKWFNRLCY LVATEICMPA KKKQRAQVIE FFIDVARECF NIGNFNSLMA 
IISGMNMSPV SRLKKTWAKV RTAKFFILEH QMDPTGNFCN YRTALRGAAH RSLTAHSSRE 
KIVIPFFSLL IKDIYFLNEG CANRLPNGHV NFEKFLELAK QVGEFITWKQ VECPFEQDAS 
ITHYLYTAPI FSEDGLYLAS YESESPENQT EKERWKALRS SILGKT