Details for: RAB3D

Gene ID: 9545

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: RAB3D

Ensembl ID: ENSG00000105514

Description: RAB3D, member RAS oncogene family

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • chondrocyte CL0000138
    CSI 27.35
    rCSI 43.5%
    PRS 88.14
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 18.95
    rCSI 22.96%
    PRS 73.91
  • basal cell of epidermis CL0002187
    CSI 17.9
    rCSI 31.73%
    PRS 65.03
  • melanocyte of skin CL1000458
    CSI 17.56
    rCSI 23.93%
    PRS 64.73
  • stem cell CL0000034
    CSI 14.93
    rCSI 14.4%
    PRS 88.49
  • suprabasal keratinocyte CL4033013
    CSI 14.68
    rCSI 23.97%
    PRS 65.09
  • regulatory T cell CL0000815
    CSI 12.63
    rCSI 14.64%
    PRS 86.58
  • conventional dendritic cell CL0000990
    CSI 9.12
    rCSI 7.61%
    PRS 86.66
  • intestinal epithelial cell CL0002563
    CSI 7.7
    rCSI 8.05%
    PRS 89.92
  • enteroendocrine cell CL0000164
    CSI 7.02
    rCSI 9.59%
    PRS 90.41
  • intestine goblet cell CL0019031
    CSI 6.58
    rCSI 5.84%
    PRS 89.86
  • pancreatic acinar cell CL0002064
    CSI 6.18
    rCSI 8.22%
    PRS 94.42
  • goblet cell CL0000160
    CSI 5.97
    rCSI 5.64%
    PRS 90.14
  • common myeloid progenitor CL0000049
    CSI 5.74
    rCSI 4.64%
    PRS 93.12
  • epithelial cell CL0000066
    CSI 5.62
    rCSI 8.63%
    PRS 80.92
  • secretory cell CL0000151
    CSI 5.51
    rCSI 5.74%
    PRS 91.22
  • epithelial cell of lower respiratory tract CL0002632
    CSI 5.45
    rCSI 4.23%
    PRS 94.01
  • innate lymphoid cell CL0001065
    CSI 4.79
    rCSI 9.9%
    PRS 86.46
  • hematopoietic stem cell CL0000037
    CSI 4.57
    rCSI 3.04%
    PRS 93.3
  • granulocyte monocyte progenitor cell CL0000557
    CSI 4.44
    rCSI 3.85%
    PRS 93.95
  • myoepithelial cell CL0000185
    CSI 4.3
    rCSI 10.87%
    PRS 93.96
  • cytotoxic T cell CL0000910
    CSI 3.73
    rCSI 21.39%
    PRS 90.72
  • epithelial cell of lung CL0000082
    CSI 3.5
    rCSI 2.91%
    PRS 92.96
  • helper T cell CL0000912
    CSI 3.37
    rCSI 4.76%
    PRS 87.92
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 3.15
    rCSI 11.92%
    PRS 81.02
  • fallopian tube secretory epithelial cell CL4030006
    CSI 3.01
    rCSI 2.9%
    PRS 90.84
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.94
    rCSI 2.65%
    PRS 90.98
  • acinar cell CL0000622
    CSI 2.93
    rCSI 4.3%
    PRS 96.16
  • club cell CL0000158
    CSI 2.9
    rCSI 4.24%
    PRS 88.33
  • duct epithelial cell CL0000068
    CSI 2.88
    rCSI 4.21%
    PRS 94.88
  • mucous neck cell CL0000651
    CSI 2.77
    rCSI 3.99%
    PRS 94.28
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.7
    rCSI 2.08%
    PRS 94.81
  • peripheral nervous system neuron CL2000032
    CSI 2.63
    rCSI 3.58%
    PRS 86.23
  • lung secretory cell CL1000272
    CSI 2.61
    rCSI 6.45%
    PRS 93.03
  • promyelocyte CL0000836
    CSI 2.58
    rCSI 3.72%
    PRS 93.72
  • keratinocyte CL0000312
    CSI 2.51
    rCSI 2.11%
    PRS 91.91
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.46
    rCSI 3.49%
    PRS 90.54
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.45
    rCSI 4.33%
    PRS 80.21
  • lung macrophage CL1001603
    CSI 2.34
    rCSI 5.23%
    PRS 95.91
  • renal interstitial pericyte CL1001318
    CSI 2.18
    rCSI 6%
    PRS 90.06
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 2.16
    rCSI 3.62%
    PRS 80.85
  • paneth cell CL0000510
    CSI 2.14
    rCSI 3.16%
    PRS 96.23
  • tracheobronchial serous cell CL0019001
    CSI 1.98
    rCSI 8.54%
    PRS 93.91
  • promonocyte CL0000559
    CSI 1.91
    rCSI 3.27%
    PRS 93.7
  • intermediate monocyte CL0002393
    CSI 1.87
    rCSI 2.82%
    PRS 95.6
  • granulocyte CL0000094
    CSI 1.86
    rCSI 2.85%
    PRS 95.47
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.66
    rCSI 4.04%
    PRS 78.67
  • foveolar cell of stomach CL0002179
    CSI 1.61
    rCSI 3.42%
    PRS 93.64
  • bronchial goblet cell CL1000312
    CSI 1.08
    rCSI 4.31%
    PRS 94.66
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.86
    rCSI 3.11%
    PRS 78.94
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 0.7
    rCSI 4.23%
    PRS 96.46
  • eosinophil CL0000771
    CSI 0.62
    rCSI 4.04%
    PRS 97.29
  • peptic cell CL0000155
    CSI 0.26
    rCSI 2.56%
    PRS 94.99
  • acinar cell of salivary gland CL0002623
    CSI 0.16
    rCSI 3.71%
    PRS 96.19

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

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  • 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 [RAB3D](/details-gene/9545) is a protein-coding gene located on chromosome 19p13.2, belonging to the RAS oncogene family of small GTPases. Functionally, it is a key regulator of vesicular trafficking and exocytosis, playing a critical role in the regulated secretory pathway. Its molecular mechanism involves GTP binding and hydrolysis, which controls the docking and fusion of secretory vesicles with the plasma membrane. **Overall**, its expression profile highlights a significant role in highly secretory and specialized cell types, including [chondrocytes](/details-cell/CL0000138), various immune cells such as [CD8-positive, alpha-beta memory T cells](/details-cell/CL0001203) and [regulatory T cells](/details-cell/CL0000815), as well as epidermal cells like [basal cell of epidermis](/details-cell/CL0002187) and [melanocyte of skin](/details-cell/CL1000458). Research indicates that its expression is upregulated during myeloid differentiation, consistent with its function in the immune system ([Link](https://doi.org/10.1016/s0167-4781(98)00279-6)). ## Cellular Roles and Expression Landscape The expression pattern of [RAB3D](/details-gene/9545) underscores its fundamental role in managing and executing specialized secretory processes across diverse tissues. **Overall**, the gene shows the highest significance in cells defined by their secretory capacity. It is a top marker in [chondrocytes](/details-cell/CL0000138) (CSI: 27.35), which are responsible for secreting and maintaining the extracellular matrix of cartilage. This suggests [RAB3D](/details-gene/9545) is crucial for skeletal tissue homeostasis. A similarly vital role is indicated in epithelial and glandular tissues, with high significance in skin cells ([basal cell of epidermis](/details-cell/CL0002187), [suprabasal keratinocyte](/details-cell/CL4033013)), intestinal cells ([intestinal epithelial cell](/details-cell/CL0002563), [intestine goblet cell](/details-cell/CL0019031)), and [pancreatic acinar cells](/details-cell/CL0002064). These cells are all involved in the secretion of mucins, digestive enzymes, or other factors, a process likely coordinated by [RAB3D](/details-gene/9545). Within the immune system, [RAB3D](/details-gene/9545) is highly significant in both the adaptive and innate compartments. It is prominently expressed in [CD8-positive, alpha-beta memory T cells](/details-cell/CL0001203) and [regulatory T cells](/details-cell/CL0000815), suggesting a role in the secretion of cytotoxic granules or immunomodulatory cytokines. Its expression in [conventional dendritic cells](/details-cell/CL0000990) and [common myeloid progenitors](/details-cell/CL0000049) is consistent with its reported upregulation during myeloid differentiation and its function in antigen presentation and immune activation ([Link](https://doi.org/10.1016/s0167-4781(98)00279-6)). ## Pathways and Molecular Function The molecular functions and biological pathways associated with [RAB3D](/details-gene/9545) confirm its identity as a central coordinator of secretion. Its core functions are [Gtpase activity](/details-cell/GO:0003924) and [Gtp binding](/details-cell/GO:0005525), which allow it to act as a molecular switch in vesicle transport. The protein is primarily localized to various secretory organelles, including the [azurophil granule membrane](/details-cell/GO:0035577), [secretory vesicle](/details-cell/GO:0099503), [synaptic vesicle](/details-cell/GO:0008021), and [zymogen granule](/details-cell/GO:0042588). These molecular activities drive its participation in the broader biological process of [Exocytosis](/details-cell/GO:0006887) and the [Positive regulation of regulated secretory pathway](/details-cell/GO:1903307). This aligns perfectly with its high expression in specialized secretory cells. In the context of the immune system, this role is specified by the [Neutrophil degranulation](/details-cell/R-HSA-6798695) pathway, part of the larger [Innate immune system](/details-cell/R-HSA-168249) network. This suggests a direct role for [RAB3D](/details-gene/9545) in the release of antimicrobial contents from neutrophil granules. Furthermore, its involvement in [Bone resorption](/details-cell/GO:0045453) is consistent with its high expression in [chondrocytes](/details-cell/CL0000138) and suggests a potential role in cartilage and bone remodeling, possibly through regulating the secretion of matrix-degrading enzymes. For [RAB3D](/details-gene/9545) to function correctly, it must undergo post-translational modification, as detailed in the [Rab geranylgeranylation](/details-cell/R-HSA-8873719) pathway, which is essential for its membrane association. ## Research Directions The widespread yet specific expression of [RAB3D](/details-gene/9545) in cells with critical secretory functions presents several avenues for future investigation, particularly concerning its role in physiology and disease. **Proposed Hypotheses:** 1. Given its high significance in [CD8-positive, alpha-beta memory T cells](/details-cell/CL0001203) and its link to the [Exocytosis](/details-cell/GO:0006887) pathway, we hypothesize that **[RAB3D](/details-gene/9545) is essential for the targeted release of cytotoxic granules (e.g., perforin and granzymes) from cytotoxic T lymphocytes, and its deficiency would impair their ability to kill target cells like virus-infected or tumor cells.** 2. Based on its top-ranking significance in [chondrocytes](/details-cell/CL0000138) and its annotation for [Bone resorption](/details-cell/GO:0045453), we hypothesize that **[RAB3D](/details-gene/9545) critically regulates the secretion of extracellular matrix components (e.g., collagens, aggrecan) and matrix metalloproteinases (MMPs), and its dysregulation contributes to the pathogenesis of cartilage-degrading diseases such as osteoarthritis.** **Experimental Approach:** To test the first hypothesis regarding the role of [RAB3D](/details-gene/9545) in T cell cytotoxicity, a conditional knockout mouse model could be employed. Specifically, mice with a floxed *Rab3d* allele could be crossed with mice expressing Cre recombinase under a T-cell-specific promoter (e.g., *Cd4*-Cre or *Lck*-Cre). CD8+ T cells isolated from these knockout mice and wild-type littermates would be activated *in vitro* and co-cultured with target tumor cells. Cytotoxicity could be quantified using a chromium release assay or flow cytometry-based killing assay. Furthermore, the degranulation process itself could be measured by assessing the surface expression of CD107a (LAMP-1) on T cells following target cell engagement. **Therapeutic Potential:** As an intracellular GTPase, [RAB3D](/details-gene/9545) presents a challenging direct drug target. However, its crucial role in secretion makes its pathway a potential point of intervention. In hyperinflammatory conditions or autoimmune diseases characterized by excessive cytokine secretion or degranulation (e.g., cytokine release syndrome or hemophagocytic lymphohistiocytosis), **inhibition** of the [RAB3D](/details-gene/9545)-mediated secretory pathway could be beneficial. Due to its broad expression in other essential secretory cells (e.g., pancreatic and intestinal cells), systemic inhibitors would likely cause significant off-target toxicity. Therefore, therapeutic strategies would need to focus on cell-type-specific delivery systems (e.g., lipid nanoparticles targeted to immune cells) or on inhibiting upstream kinases or downstream effectors that are more restricted in their expression.

Genular Protein ID: 2002073087

Symbol: RAB3D_HUMAN

Name: Ras-related protein Rab-3D

UniProtKB Accession Codes:

O95716

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 5 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 2 EvolutionaryTrace 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 5 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 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 Pumba 1 RNAct 1 Reactome 2 RefSeq 1 SMART 4 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: 10023084

Title: Molecular cloning of cDNA encoding human Rab3D whose expression is upregulated with myeloid differentiation.

PubMed ID: 10023084

DOI: 10.1016/s0167-4781(98)00279-6

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: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

PubMed ID: 29125462

Title: Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis.

PubMed ID: 29125462

DOI: 10.7554/elife.31012

Sequence Information:

  • Length: 219
  • Mass: 24267
  • Checksum: 714754826C405EA7
  • Sequence:
    • MASAGDTQAG PRDAADQNFD YMFKLLLIGN SSVGKTSFLF RYADDSFTPA FVSTVGIDFK 
VKTVYRHDKR IKLQIWDTAG QERYRTITTA YYRGAMGFLL MYDIANQESF AAVQDWATQI 
KTYSWDNAQV ILVGNKCDLE DERVVPAEDG RRLADDLGFE FFEASAKENI NVKQVFERLV 
DVICEKMNES LEPSSSSGSN GKGPAVGDAP APQPSSCSC