Details for: DIRAS2

Gene ID: 54769

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: DIRAS2

Ensembl ID: ENSG00000165023

Description: DIRAS family GTPase 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • L6b glutamatergic cortical neuron CL4023038
    CSI 16.19
    rCSI 50.6%
    PRS 79.95
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 13.52
    rCSI 51.1%
    PRS 78.81
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 8.36
    rCSI 49.23%
    PRS 79.06
  • interneuron CL0000099
    CSI 7.63
    rCSI 15.32%
    PRS 85.16
  • retinal bipolar neuron CL0000748
    CSI 6.53
    rCSI 12.23%
    PRS 83.07
  • cerebellar granule cell CL0001031
    CSI 6.39
    rCSI 9.39%
    PRS 86.18
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 5.97
    rCSI 10.02%
    PRS 78.66
  • OFF-bipolar cell CL0000750
    CSI 5.77
    rCSI 7.89%
    PRS 89.62
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 5.28
    rCSI 19%
    PRS 76.67
  • retina horizontal cell CL0000745
    CSI 4.14
    rCSI 6.31%
    PRS 88.01
  • cerebral cortex neuron CL0010012
    CSI 4
    rCSI 16.3%
    PRS 84.04
  • rod bipolar cell CL0000751
    CSI 3.66
    rCSI 6.57%
    PRS 86.35
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.32
    rCSI 4.13%
    PRS 76.49
  • retinal rod cell CL0000604
    CSI 3.26
    rCSI 5.75%
    PRS 87.14
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 2.95
    rCSI 7.17%
    PRS 76.48
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.87
    rCSI 3.7%
    PRS 79.73
  • glutamatergic neuron CL0000679
    CSI 2.59
    rCSI 5.32%
    PRS 79.76
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.46
    rCSI 2.94%
    PRS 78.7
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 2.4
    rCSI 5.73%
    PRS 81.04
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 2.39
    rCSI 7.85%
    PRS 79.89
  • peripheral nervous system neuron CL2000032
    CSI 2.32
    rCSI 3.16%
    PRS 85.06
  • OFFx cell CL4033036
    CSI 2.25
    rCSI 10.58%
    PRS 81.71
  • vascular leptomeningeal cell CL4023051
    CSI 2.1
    rCSI 3.69%
    PRS 87.54
  • retinal ganglion cell CL0000740
    CSI 1.99
    rCSI 4.39%
    PRS 80.97
  • diffuse bipolar 3a cell CL4033029
    CSI 1.94
    rCSI 13.23%
    PRS 83.32
  • amacrine cell CL0000561
    CSI 1.78
    rCSI 5.16%
    PRS 83.06
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 1.68
    rCSI 3.65%
    PRS 80.24
  • glycinergic amacrine cell CL4030028
    CSI 1.67
    rCSI 4.35%
    PRS 85.36
  • retinal cone cell CL0000573
    CSI 1.55
    rCSI 2.5%
    PRS 83.64
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.53
    rCSI 2.7%
    PRS 78.05
  • GABAergic amacrine cell CL4030027
    CSI 1.51
    rCSI 5.19%
    PRS 78.92
  • diffuse bipolar 6 cell CL4033032
    CSI 1.45
    rCSI 7.61%
    PRS 81.49
  • H1 horizontal cell CL0004217
    CSI 1.38
    rCSI 5.46%
    PRS 84.9
  • central nervous system neuron CL2000029
    CSI 1.27
    rCSI 9.33%
    PRS 83.07
  • diffuse bipolar 1 cell CL4033027
    CSI 1.08
    rCSI 8.12%
    PRS 80.64
  • starburst amacrine cell CL0004232
    CSI 0.61
    rCSI 5.13%
    PRS 78.15
  • P/D1 enteroendocrine cell CL0002268
    CSI 0.43
    rCSI 2.32%
    PRS 93.42
  • cone retinal bipolar cell CL0000752
    CSI 0.35
    rCSI 4.61%
    PRS 88.03

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 [DIRAS2](/details-gene/54769) (DIRAS family GTPase 2) is a protein-coding gene located on chromosome 9q22.2 that encodes a small GTP-binding protein belonging to the Di-Ras subgroup of the Ras superfamily ([Link](https://doi.org/10.1074/jbc.m202150200)). Functionally, it is involved in signal transduction, specifically as a GTPase that positively regulates MAP kinase activity. Expression data indicates that **Overall**, [DIRAS2](/details-gene/54769) is a highly significant marker for various neuronal subtypes, particularly glutamatergic neurons within the cerebral cortex and specialized neurons of the retina, suggesting a primary role in the central nervous system. ## Cellular Roles and Expression Landscape The expression profile of [DIRAS2](/details-gene/54769) demonstrates a strong and specific enrichment within the nervous system. The **Overall** context shows its highest significance in cortical neurons, including [L6b glutamatergic cortical neuron](/details-cell/CL4023038) (CSI: 16.19), [near-projecting glutamatergic cortical neuron](/details-cell/CL4023012) (CSI: 13.52), and [corticothalamic-projecting glutamatergic cortical neuron](/details-cell/CL4023013) (CSI: 8.36). This enrichment extends to cortical [interneuron](/details-cell/CL0000099) populations, such as [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011) and [pvalb GABAergic cortical interneuron](/details-cell/CL4023018), highlighting its importance across both excitatory and inhibitory circuits in the cortex. Beyond the cerebral cortex, [DIRAS2](/details-gene/54769) is also a significant marker in the retina, with notable expression in [retinal bipolar neuron](/details-cell/CL0000748), [OFF-bipolar cell](/details-cell/CL0000750), [retina horizontal cell](/details-cell/CL0000745), and [retinal rod cell](/details-cell/CL0000604). This pattern suggests a specialized role in visual signal processing. The consistent and high significance across these diverse neuronal populations establishes [DIRAS2](/details-gene/54769) as a key molecular component of mature neural circuits. ## Pathways and Molecular Function [DIRAS2](/details-gene/54769) functions as a small monomeric GTPase. Its molecular activities include [Gtp binding](/details-gene/GO:0005525), [Gdp binding](/details-gene/GO:0019003), and intrinsic [Gtpase activity](/details-gene/GO:0003924), which allow it to cycle between active (GTP-bound) and inactive (GDP-bound) states to regulate downstream cellular processes. The primary annotated biological process for [DIRAS2](/details-gene/54769) is the [positive regulation of map kinase activity](/details-gene/GO:0043406), a critical pathway for cell proliferation, differentiation, and survival. Its localization to the [plasma membrane](/details-gene/GO:0005886) is consistent with its role in transducing extracellular signals. This function in MAPK signaling is highly relevant to its expression in neurons, where this pathway governs synaptic plasticity, neuronal survival, and neurite outgrowth. ## Research Directions While the expression data strongly points to a primary role for [DIRAS2](/details-gene/54769) in the central nervous system, recent research has implicated it in pathology outside of this context, such as its role in an oncogene and tumor suppressor cascade in pancreatic cancer ([Link](https://doi.org/10.1016/j.devcel.2024.03.018)). This dichotomy between its neuro-specific expression profile and its function in cancer progression presents a compelling area for future investigation. **Proposed Hypotheses:** 1. Given its high significance in specific cortical neuron subtypes like [L6b glutamatergic cortical neuron](/details-cell/CL4023038) and its role in MAPK signaling, [DIRAS2](/details-gene/54769) may be essential for activity-dependent synaptic plasticity and the structural maintenance of dendritic spines in these deep-layer cortical neurons. 2. The oncogenic role of [DIRAS2](/details-gene/54769) in pancreatic cancer may result from its aberrant, context-inappropriate activation of MAPK signaling pathways, hijacking a normally neuro-specific developmental or plasticity program to drive uncontrolled cell proliferation. **Key Experimental Approach:** To test the first hypothesis regarding its role in synaptic plasticity, a suitable experiment would involve the use of conditional knockout mouse models. Specifically, generating a mouse line where [DIRAS2](/details-gene/54769) is selectively deleted in deep-layer cortical neurons (e.g., using a *Fezf2-Cre* driver line). Electrophysiological recordings (e.g., whole-cell patch-clamp) could then be performed on acute brain slices from these animals to measure long-term potentiation (LTP) and long-term depression (LTD). Concurrently, super-resolution microscopy could be used to analyze dendritic spine density and morphology in the targeted neurons, providing a direct link between [DIRAS2](/details-gene/54769) function and the structural basis of synaptic plasticity. **Therapeutic Potential:** Based on its described role as part of an oncogenic axis in pancreatic cancer, [DIRAS2](/details-gene/54769) presents a potential therapeutic target for **inhibition**. Its function as a GTPase suggests it could be amenable to small molecule inhibitors that lock it in an inactive, GDP-bound state, similar to strategies used for other Ras family members. However, its highly specific and significant expression in the central nervous system presents a major challenge. A successful therapeutic would likely require tumor-specific delivery mechanisms or the development of inhibitors that target a cancer-specific conformation or protein-protein interaction of [DIRAS2](/details-gene/54769) to avoid significant on-target neurological side effects.

Genular Protein ID: 2874420509

Symbol: DIRA2_HUMAN

Name: GTP-binding protein Di-Ras2

UniProtKB Accession Codes:

Q96HU8 B3KVM2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 10 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 5 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 Rhea 1 SMART 3 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12194967

Title: Di-Ras, a distinct subgroup of ras family GTPases with unique biochemical properties.

PubMed ID: 12194967

DOI: 10.1074/jbc.m202150200

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

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: 38574733

Title: The UBE2F-CRL5ASB11-DIRAS2 axis is an oncogene and tumor suppressor cascade in pancreatic cancer cells.

PubMed ID: 38574733

DOI: 10.1016/j.devcel.2024.03.018

Sequence Information:

  • Length: 199
  • Mass: 22485
  • Checksum: 429D17026CC3EADC
  • Sequence:
    • MPEQSNDYRV AVFGAGGVGK SSLVLRFVKG TFRESYIPTV EDTYRQVISC DKSICTLQIT 
DTTGSHQFPA MQRLSISKGH AFILVYSITS RQSLEELKPI YEQICEIKGD VESIPIMLVG 
NKCDESPSRE VQSSEAEALA RTWKCAFMET SAKLNHNVKE LFQELLNLEK RRTVSLQIDG 
KKSKQQKRKE KLKGKCVIM