Details for: RHOJ

Gene ID: 57381

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: RHOJ

Ensembl ID: ENSG00000126785

Description: ras homolog family member J

Cell Significance Landscape

Associated with

Significant Cells

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

  • retinal blood vessel endothelial cell CL0002585
    CSI 11.49
    rCSI 18.35%
    PRS 87.61
  • vascular leptomeningeal cell CL4023051
    CSI 9.38
    rCSI 16.44%
    PRS 79.3
  • Bergmann glial cell CL0000644
    CSI 7.39
    rCSI 10.12%
    PRS 76.01
  • Mueller cell CL0000636
    CSI 7.31
    rCSI 16.69%
    PRS 76.68
  • glioblast CL0000030
    CSI 6.74
    rCSI 10.74%
    PRS 76.35
  • bronchus fibroblast of lung CL2000093
    CSI 5.91
    rCSI 4.8%
    PRS 83.86
  • mesenchymal cell CL0008019
    CSI 5.36
    rCSI 13.6%
    PRS 78.32
  • fibroblast of lung CL0002553
    CSI 5.15
    rCSI 4.79%
    PRS 85.41
  • innate lymphoid cell CL0001065
    CSI 4.81
    rCSI 9.93%
    PRS 80.44
  • endothelial cell of lymphatic vessel CL0002138
    CSI 4.72
    rCSI 9.35%
    PRS 87.98
  • neural crest cell CL0011012
    CSI 4.43
    rCSI 3.5%
    PRS 75.01
  • cytotoxic T cell CL0000910
    CSI 3.95
    rCSI 22.66%
    PRS 86.31
  • Schwann cell CL0002573
    CSI 3.9
    rCSI 11.1%
    PRS 80.31
  • cerebral cortex endothelial cell CL1001602
    CSI 3.75
    rCSI 6.49%
    PRS 77.01
  • hepatic stellate cell CL0000632
    CSI 3.22
    rCSI 12.07%
    PRS 77.91
  • lung endothelial cell CL1001567
    CSI 3.18
    rCSI 7.41%
    PRS 92.55
  • helper T cell CL0000912
    CSI 3.08
    rCSI 4.36%
    PRS 82.36
  • endothelial cell of placenta CL0009092
    CSI 3
    rCSI 14.8%
    PRS 90.46
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.95
    rCSI 6.62%
    PRS 69.07
  • endothelial cell of vascular tree CL0002139
    CSI 2.94
    rCSI 16.08%
    PRS 80.65
  • melanocyte CL0000148
    CSI 2.81
    rCSI 2.08%
    PRS 78.97
  • forebrain radial glial cell CL0013000
    CSI 2.79
    rCSI 8.96%
    PRS 85.33
  • mature astrocyte CL0002627
    CSI 2.79
    rCSI 11.84%
    PRS 77.04
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 2.73
    rCSI 8.41%
    PRS 87.79
  • endothelial cell of arteriole CL1000412
    CSI 2.7
    rCSI 15%
    PRS 91.24
  • pulmonary capillary endothelial cell CL4028001
    CSI 2.7
    rCSI 5.14%
    PRS 92.1
  • blood vessel endothelial cell CL0000071
    CSI 2.58
    rCSI 5.34%
    PRS 81.64
  • alveolar type 1 fibroblast cell CL4028004
    CSI 2.46
    rCSI 2.7%
    PRS 86.21
  • adipocyte CL0000136
    CSI 2.16
    rCSI 2.78%
    PRS 75.21
  • basal cell of epidermis CL0002187
    CSI 2.13
    rCSI 3.77%
    PRS 53.9
  • pulmonary artery endothelial cell CL1001568
    CSI 2.1
    rCSI 2.86%
    PRS 91.17
  • enteric smooth muscle cell CL0002504
    CSI 2.06
    rCSI 2.94%
    PRS 85.24
  • vein endothelial cell CL0002543
    CSI 2.04
    rCSI 5.57%
    PRS 89.61
  • mesodermal cell CL0000222
    CSI 2.03
    rCSI 2.44%
    PRS 82.76
  • endocardial cell CL0002350
    CSI 1.93
    rCSI 9.25%
    PRS 80.57
  • prostate gland microvascular endothelial cell CL2000059
    CSI 1.88
    rCSI 44.92%
    PRS 90.34
  • chondrocyte CL0000138
    CSI 1.87
    rCSI 2.98%
    PRS 78.29
  • adventitial cell CL0002503
    CSI 1.87
    rCSI 4.47%
    PRS 87.65
  • fibroblast of cardiac tissue CL0002548
    CSI 1.75
    rCSI 8.4%
    PRS 84.6
  • cardiac endothelial cell CL0010008
    CSI 1.52
    rCSI 6.13%
    PRS 84.78
  • renal interstitial pericyte CL1001318
    CSI 1.46
    rCSI 4.01%
    PRS 80.29
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.33
    rCSI 3.22%
    PRS 66.01
  • melanocyte of skin CL1000458
    CSI 1.22
    rCSI 1.67%
    PRS 52.31
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.22
    rCSI 1.48%
    PRS 65.04
  • alveolar adventitial fibroblast CL4028006
    CSI 1.22
    rCSI 1.92%
    PRS 85.71
  • cardiac blood vessel endothelial cell CL0010006
    CSI 1.05
    rCSI 7.39%
    PRS 77.6
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.02
    rCSI 5.99%
    PRS 68.64
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1
    rCSI 3.13%
    PRS 69.69
  • mesangial cell CL0000650
    CSI 0.87
    rCSI 3.56%
    PRS 91.22
  • stromal cell CL0000499
    CSI 0.86
    rCSI 2.43%
    PRS 79.73
  • glial cell CL0000125
    CSI 0.82
    rCSI 3.12%
    PRS 76.26
  • endothelial cell of venule CL1000414
    CSI 0.75
    rCSI 6.66%
    PRS 90.05
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.68
    rCSI 1.98%
    PRS 83.71
  • endothelial cell of uterus CL0009095
    CSI 0.67
    rCSI 4.92%
    PRS 90.48
  • blood vessel smooth muscle cell CL0019018
    CSI 0.65
    rCSI 5.29%
    PRS 79.68
  • vein endothelial cell of respiratory system CL4033008
    CSI 0.56
    rCSI 3.85%
    PRS 89.33

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 [RHOJ](/details-gene/57381) (Ras Homolog Family Member J) is a protein-coding gene located on chromosome 14q23.2. It encodes a small GTPase belonging to the Cdc42-related subgroup of the Rho family of proteins. Functionally, [RHOJ](/details-gene/57381) is a critical regulator of the actin cytoskeleton, playing a key role in signal transduction pathways that control cell shape, migration, and polarity. Its expression is highly enriched in vascular endothelial cells, such as [retinal blood vessel endothelial cell](/details-cell/CL0002585), where it is a key mediator of angiogenesis and vascular morphogenesis, a role supported by extensive research [Link](https://doi.org/10.1182/blood-2010-10-315275). The gene's activity is also significant in various glial and mesenchymal cell types, suggesting broader roles in tissue development and pathology. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [RHOJ](/details-gene/57381) strongly points to a primary function within the vascular system and associated stromal and glial tissues. The most significant expression is observed in endothelial lineages. It is a top marker in [retinal blood vessel endothelial cell](/details-cell/CL0002585) (CSI: 11.49), [vascular leptomeningeal cell](/details-cell/CL4023051) (CSI: 9.38), [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 3.75), and [endothelial cell of lymphatic vessel](/details-cell/CL0002138) (CSI: 4.72). This specific and high expression is consistent with studies identifying it as an endothelial-restricted GTPase essential for vascular development [Link](https://doi.org/10.1182/blood-2010-10-315275). Beyond the endothelium, [RHOJ](/details-gene/57381) shows significant expression in several glial and mesenchymal cell types. It is highly expressed in specialized retinal glia like [Mueller cell](/details-cell/CL0000636) (CSI: 7.31) and cerebellar [Bergmann glial cell](/details-cell/CL0000644) (CSI: 7.39), as well as [Schwann cell](/details-cell/CL0002573) (CSI: 3.90), suggesting a potential role in the development or function of the nervous system's supportive architecture. Its presence in [bronchus fibroblast of lung](/details-cell/CL2000093) (CSI: 5.91) and [mesenchymal cell](/details-cell/CL0008019) (CSI: 5.36) indicates a role in stromal biology. Notably, [RHOJ](/details-gene/57381) is also a significant marker for [glioblast](/details-cell/CL0000030) (CSI: 6.74), a malignant brain tumor cell, which aligns with its documented role in pathological angiogenesis [Link](https://doi.org/10.1016/j.ccr.2013.12.010). Moderate expression in immune cells like [innate lymphoid cell](/details-cell/CL0001065) and [cytotoxic T cell](/details-cell/CL0000910) suggests a secondary role in immune cell trafficking or function. The absence of high expression in major epithelial or hematopoietic progenitor populations underscores its specialized function. ## Pathways and Molecular Function [RHOJ](/details-gene/57381) functions as a molecular switch, cycling between an active GTP-bound and an inactive GDP-bound state, as defined by its involvement in the [Rho gtpase cycle](/details-pathway/R-HSA-9012999) pathway. Its core molecular functions include [Gtp binding](/details-go/GO0005525) and [Gtpase activity](/details-go/GO0003924). Upon activation, it participates in downstream [Signal transduction](/details-pathway/R-HSA-162582), primarily by influencing the organization of the cytoskeleton. This activity directly translates into its biological roles. The gene is a key component of pathways governing [Actin cytoskeleton organization](/details-go/GO0030036) and [Regulation of cell shape](/details-go/GO0008360). These fundamental processes are essential for its well-documented role in [Angiogenesis](/details-go/GO0001525), particularly the [Positive regulation of cell migration involved in sprouting angiogenesis](/details-go/GO0090050) and [Regulation of endothelial cell migration](/details-go/GO0010594). Its localization to the [Plasma membrane](/details-go/GO0005886) is crucial for this function, allowing it to respond to extracellular cues and regulate cell movement and polarity, a process whose mechanics have been previously investigated [Link](https://doi.org/10.1074/jbc.m116.750026). ## Research Directions The established role of [RHOJ](/details-gene/57381) in endothelial cell biology, combined with its high expression in malignant [glioblast](/details-cell/CL0000030) cells, presents compelling avenues for translational research, particularly in oncology. ### Testable Hypotheses 1. **Given its high expression in [glioblast](/details-cell/CL0000030) and its function in promoting angiogenesis, targeted inhibition of [RHOJ](/details-gene/57381) will suppress glioblastoma growth by disrupting tumor vascularization and inducing endothelial cell apoptosis, thereby limiting the tumor's nutrient and oxygen supply.** 2. **The significant expression of [RHOJ](/details-gene/57381) in retinal glial cells ([Mueller cell](/details-cell/CL0000636) and [Bergmann glial cell](/details-cell/CL0000644)) suggests it plays a critical role in retinal homeostasis and neuro-vascular coupling. Its dysregulation may contribute to the pathology of retinopathies characterized by abnormal neovascularization, such as diabetic retinopathy.** ### Proposed Experiment To test the first hypothesis, an *in vivo* study using an orthotopic glioblastoma mouse model would be highly informative. Human [glioblast](/details-cell/CL0000030) cells, engineered with a doxycycline-inducible shRNA targeting [RHOJ](/details-gene/57381], would be implanted into the brains of immunodeficient mice. Following tumor establishment, mice would be treated with doxycycline to induce [RHOJ](/details-gene/57381) knockdown. Tumor growth would be monitored longitudinally via bioluminescence imaging. At the experimental endpoint, brains would be harvested for histological analysis to quantify tumor volume, vascular density (via CD31 staining), and markers of apoptosis (via TUNEL staining) in the tumor-associated endothelium. This experiment would directly assess whether inhibiting [RHOJ](/details-gene/57381) has a therapeutic anti-angiogenic effect in a relevant pre-clinical cancer model. ### Therapeutic Potential [RHOJ](/details-gene/57381) represents a highly promising therapeutic target, primarily for anti-cancer therapies focused on disrupting angiogenesis. Its expression is largely restricted to the endothelium, suggesting that systemic **inhibition** would have a favorable safety profile with limited on-target toxicity in non-vascular tissues. This selectivity makes it a more attractive target than broadly expressed angiogenic factors. As demonstrated in prior studies, targeting vascular [RHOJ](/details-gene/57381) can be an effective strategy for disrupting tumor blood supply [Link](https://doi.org/10.1016/j.ccr.2013.12.010). Therapeutic modalities could include small molecule inhibitors designed to lock [RHOJ](/details-gene/57381) in its inactive GDP-bound state or nanoparticle-formulated siRNAs to specifically silence its expression in the tumor neovasculature.

Genular Protein ID: 2308115626

Symbol: RHOJ_HUMAN

Name: Ras-like protein family member 7B

UniProtKB Accession Codes:

Q9H4E5 Q96KC1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 5 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 1 ExpressionAtlas 1 GO 16 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 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 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 2 RNAct 1 Reactome 1 RefSeq 1 SMART 3 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10967094

Title: Characterization of TCL, a new GTPase of the Rho family related to TC10 and Cdc42.

PubMed ID: 10967094

DOI: 10.1074/jbc.m003487200

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

PubMed ID: 21628409

Title: RhoJ is an endothelial cell-restricted Rho GTPase that mediates vascular morphogenesis and is regulated by the transcription factor ERG.

PubMed ID: 21628409

DOI: 10.1182/blood-2010-10-315275

PubMed ID: 24434213

Title: Vascular RhoJ is an effective and selective target for tumor angiogenesis and vascular disruption.

PubMed ID: 24434213

DOI: 10.1016/j.ccr.2013.12.010

PubMed ID: 27660391

Title: TCL/RhoJ plasma membrane localization and nucleotide exchange is coordinately regulated by amino acids within the n terminus and a distal loop region.

PubMed ID: 27660391

DOI: 10.1074/jbc.m116.750026

PubMed ID: 30158707

Title: Role of glutamine synthetase in angiogenesis beyond glutamine synthesis.

PubMed ID: 30158707

DOI: 10.1038/s41586-018-0466-7

Sequence Information:

  • Length: 214
  • Mass: 23821
  • Checksum: AAD2E2CED036F48C
  • Sequence:
    • MNCKEGTDSS CGCRGNDEKK MLKCVVVGDG AVGKTCLLMS YANDAFPEEY VPTVFDHYAV 
TVTVGGKQHL LGLYDTAGQE DYNQLRPLSY PNTDVFLICF SVVNPASYHN VQEEWVPELK 
DCMPHVPYVL IGTQIDLRDD PKTLARLLYM KEKPLTYEHG VKLAKAIGAQ CYLECSALTQ 
KGLKAVFDEA ILTIFHPKKK KKRCSEGHSC CSII

Genular Protein ID: 3810196829

Symbol: Q7Z513_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q7Z513

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 6 Gene3D 1 InterPro 4 KEGG 1 NCBI Taxonomy 1 NCBIfam 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 3 PeptideAtlas 1 Pfam 1 RefSeq 1 SMART 3 SMR 1 SUPFAM 1

Sequence Information:

  • Length: 214
  • Mass: 23705
  • Checksum: BDCCAB8C9028B6CC
  • Sequence:
    • MNCKEGTDSS CGSGGNDEKK MLKCVVVGDG AVGKTCLLMS YANDAFPEEY VPTVFDHYAV 
TVTVGGKQHL LGLYDTAGQE DYNQLRPLSY PNTDVFLICF SVVNPASYHN VQEEWVPELK 
DCMPHVPYVL IGTQIDLRDD PKTLARLLYM KEKPLTYEHG VKLAKAIGAQ CYLECSALTQ 
KGLKAVFDEA ILTIFHPKKK KKRCSEGHSC CSII