Details for: RAB3A

Gene ID: 5864

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: RAB3A

Ensembl ID: ENSG00000105649

Description: RAB3A, member RAS oncogene family

Cell Significance Landscape

Associated with

Significant Cells

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

  • OFF-bipolar cell CL0000750
    CSI 24.71
    rCSI 33.79%
    PRS 84.41
  • amacrine cell CL0000561
    CSI 20.98
    rCSI 60.81%
    PRS 73.28
  • peripheral nervous system neuron CL2000032
    CSI 19.63
    rCSI 26.75%
    PRS 75.47
  • retina horizontal cell CL0000745
    CSI 16.98
    rCSI 25.89%
    PRS 80.28
  • retinal cone cell CL0000573
    CSI 15.2
    rCSI 24.46%
    PRS 74.05
  • ON-bipolar cell CL0000749
    CSI 11.11
    rCSI 16.52%
    PRS 82.92
  • progenitor cell CL0011026
    CSI 10.59
    rCSI 22.53%
    PRS 77.35
  • neural cell CL0002319
    CSI 9.97
    rCSI 37.61%
    PRS 66.45
  • rod bipolar cell CL0000751
    CSI 9.38
    rCSI 16.86%
    PRS 77.11
  • epithelial cell CL0000066
    CSI 5.88
    rCSI 9.04%
    PRS 72.42
  • retinal ganglion cell CL0000740
    CSI 5.63
    rCSI 12.43%
    PRS 69.97
  • interneuron CL0000099
    CSI 4.93
    rCSI 9.9%
    PRS 74.6
  • Cajal-Retzius cell CL0000695
    CSI 4.9
    rCSI 38.43%
    PRS 87.16
  • cerebellar granule cell CL0001031
    CSI 4.47
    rCSI 6.57%
    PRS 76.79
  • glutamatergic neuron CL0000679
    CSI 4.43
    rCSI 9.11%
    PRS 70.72
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 4.31
    rCSI 5.37%
    PRS 64.34
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 4.31
    rCSI 5.53%
    PRS 79.73
  • VIP GABAergic cortical interneuron CL4023016
    CSI 4.18
    rCSI 4.99%
    PRS 66.47
  • inhibitory interneuron CL0000498
    CSI 4.07
    rCSI 9.4%
    PRS 71.85
  • retinal rod cell CL0000604
    CSI 3.89
    rCSI 6.86%
    PRS 78.74
  • sncg GABAergic cortical interneuron CL4023015
    CSI 3.81
    rCSI 6.12%
    PRS 67.87
  • interstitial cell of Cajal CL0002088
    CSI 3.68
    rCSI 4.68%
    PRS 88.08
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 3.55
    rCSI 10.49%
    PRS 84.15
  • sst GABAergic cortical interneuron CL4023017
    CSI 3.47
    rCSI 4.47%
    PRS 67.6
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 3.43
    rCSI 5.76%
    PRS 66.41
  • cerebral cortex neuron CL0010012
    CSI 2.97
    rCSI 12.09%
    PRS 75.34
  • mesodermal cell CL0000222
    CSI 2.91
    rCSI 3.49%
    PRS 81.53
  • radial glial cell CL0000681
    CSI 2.8
    rCSI 3.89%
    PRS 81.91
  • GABAergic neuron CL0000617
    CSI 2.3
    rCSI 7.72%
    PRS 67.63
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.3
    rCSI 5.16%
    PRS 67.34
  • forebrain radial glial cell CL0013000
    CSI 2.2
    rCSI 7.05%
    PRS 84.49
  • dopaminergic neuron CL0000700
    CSI 2.02
    rCSI 11.39%
    PRS 69.86
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 2
    rCSI 4.86%
    PRS 64.36
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.92
    rCSI 3.38%
    PRS 65.98
  • retinal bipolar neuron CL0000748
    CSI 1.88
    rCSI 3.52%
    PRS 72.44
  • type B pancreatic cell CL0000169
    CSI 1.86
    rCSI 4.13%
    PRS 82.89
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 1.77
    rCSI 5.55%
    PRS 70.37
  • serotonergic neuron CL0000850
    CSI 1.73
    rCSI 7.73%
    PRS 67.48
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.46
    rCSI 8.59%
    PRS 66.98
  • enteric neuron CL0007011
    CSI 1.46
    rCSI 21.52%
    PRS 87.85
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.33
    rCSI 5.03%
    PRS 66.98
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 1.33
    rCSI 2.88%
    PRS 70.94
  • Purkinje cell CL0000121
    CSI 1.2
    rCSI 15.69%
    PRS 86.84
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.18
    rCSI 3.7%
    PRS 68.05
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.14
    rCSI 4.1%
    PRS 64.36
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 1.1
    rCSI 3.62%
    PRS 69.57
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 0.85
    rCSI 2.02%
    PRS 70.53
  • eye photoreceptor cell CL0000287
    CSI 0.57
    rCSI 6.47%
    PRS 89.54

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 [RAB3A](/details-gene/5864) is a protein-coding gene located on chromosome 19p13.11 that encodes Rab-3A, a member of the Ras superfamily of small GTP-binding proteins. Functionally, [RAB3A](/details-gene/5864) is a key regulator of exocytosis and vesicle trafficking, particularly in the context of neurotransmitter release at chemical synapses. Its role as a molecular switch, cycling between GTP-bound (active) and GDP-bound (inactive) states, is crucial for the docking and fusion of synaptic vesicles with the presynaptic membrane. Consistent with this function, expression data shows that [RAB3A](/details-gene/5864) is a highly significant marker in various specialized neuronal populations, especially within the retina, including [OFF-bipolar cell](/details-cell/CL0000750) and [amacrine cell](/details-cell/CL0000561). It is also implicated in other regulated secretory processes, such as acrosomal exocytosis and neutrophil degranulation. Clinically, abnormal interactions involving [RAB3A](/details-gene/5864) have been associated with neurodegenerative disorders such as Lewy body disease ([Link](https://doi.org/10.1016/j.nbd.2004.01.001)). ## Cellular Roles and Expression Landscape The expression profile of [RAB3A](/details-gene/5864) strongly indicates a specialized role in the nervous system, with a particular enrichment in the neural retina. **Overall**, the gene shows the highest significance in cell types critical for visual signal processing. It is a top marker for [OFF-bipolar cell](/details-cell/CL0000750) (CSI: 24.71), [amacrine cell](/details-cell/CL0000561) (CSI: 20.98), [retina horizontal cell](/details-cell/CL0000745) (CSI: 16.98), and [retinal cone cell](/details-cell/CL0000573) (CSI: 15.20). Its high significance extends to other bipolar cell subtypes like [ON-bipolar cell](/details-cell/CL0000749) and [rod bipolar cell](/details-cell/CL0000751), underscoring its fundamental importance across the retinal circuitry that relays photoreceptor signals. Beyond the retina, [RAB3A](/details-gene/5864) is also a significant marker for [peripheral nervous system neuron](/details-cell/CL2000032) and other central nervous system cells such as [interneuron](/details-cell/CL0000099) and [glutamatergic neuron](/details-cell/CL0000679). This broader neuronal expression is consistent with its general role in synaptic transmission. The data suggest that [RAB3A](/details-gene/5864) serves as a key operational component in neurons that rely on rapid and regulated vesicle release. ## Pathways and Molecular Function The molecular functions and biological pathways associated with [RAB3A](/details-gene/5864) are tightly aligned with its expression in secretory cells, primarily neurons. As a GTPase ([GO:0003924](https://www.ebi.ac.uk/QuickGO/term/GO:0003924)), its primary activity is to bind GTP ([GO:0005525](https://www.ebi.ac.uk/QuickGO/term/GO:0005525)) and regulate protein-protein interactions essential for membrane trafficking. **Biological Processes:** [RAB3A](/details-gene/5864) is centrally involved in the regulation of exocytosis ([GO:0006887](https://www.ebi.ac.uk/QuickGO/term/GO:0006887)), particularly [regulated exocytosis](/details-go/GO:0045055) and [evoked neurotransmitter secretion](/details-go/GO:0061670). Its function is specified to the management of synaptic vesicles, including their clustering ([GO:0097091](https://www.ebi.ac.uk/QuickGO/term/GO:0097091)), transport ([GO:0048489](https://www.ebi.ac.uk/QuickGO/term/GO:0048489)), and exocytosis ([GO:0016079](https://www.ebi.ac.uk/QuickGO/term/GO:0016079)). This aligns with its localization to the [presynapse](/details-go/GO:0098793) and [synaptic vesicle membrane](/details-go/GO:0030672). Research has confirmed its interplay with RIM and Munc13 in driving exocytosis ([Link](https://doi.org/10.1016/j.yexcr.2012.01.002)). Beyond neurotransmission, it also participates in specialized secretory events like [acrosomal vesicle exocytosis](/details-go/GO:0060478) during fertilization ([Link](https://doi.org/10.1016/j.bbamcr.2018.12.005)) and contributes to [plasma membrane repair](/details-go/GO:0001778) ([Link](https://doi.org/10.1083/jcb.201511093)). **Reactome Pathways:** The gene's role is highlighted in numerous neurotransmitter release cycles, including those for acetylcholine ([R-HSA-264642](https://reactome.org/content/detail/R-HSA-264642)), dopamine ([R-HSA-212676](https://reactome.org/content/detail/R-HSA-212676)), and glutamate ([R-HSA-210500](https://reactome.org/content/detail/R-HSA-210500)), reinforcing its broad importance in chemical synaptic transmission ([R-HSA-112315](https://reactome.org/content/detail/R-HSA-112315)). Its inclusion in the [Rab regulation of trafficking](/details-pathway/R-HSA-9007101) pathway situates it within the larger family of Rab GTPases that coordinate vesicle-mediated transport throughout the cell. Interestingly, its involvement in [Neutrophil degranulation](/details-pathway/R-HSA-6798695) suggests a conserved role in regulated secretion that extends to the [Innate immune system](/details-pathway/R-HSA-168249). ## Research Directions The well-defined role of [RAB3A](/details-gene/5864) in vesicular transport, combined with its links to neurodegenerative diseases, opens several avenues for future research. The protein is a substrate for the Parkinson's disease-associated kinase LRRK2 ([Link](https://doi.org/10.7554/elife.12813)) and interacts abnormally with alpha-synuclein in diffuse Lewy body disease ([Link](https://doi.org/10.1016/j.nbd.2004.01.001)), placing it at a critical nexus of pathogenic mechanisms. **Proposed Hypotheses:** 1. Given its exceptionally high significance in retinal interneurons and its phosphorylation by LRRK2, dysregulation of [RAB3A](/details-gene/5864) activity in the retina may be an early event in LRRK2-associated Parkinson's disease, contributing to non-motor symptoms such as visual disturbances before the onset of classic motor deficits. 2. The abnormal interaction between [RAB3A](/details-gene/5864) and alpha-synuclein may sequester [RAB3A](/details-gene/5864) away from presynaptic terminals, leading to a functional deficit in synaptic vesicle recycling and neurotransmitter release, thereby contributing to the synaptopathy characteristic of Lewy body dementias. **Experimental Approach:** To test the first hypothesis, a robust experimental plan could be implemented. One could use an LRRK2 pathogenic mutant knock-in mouse model (e.g., LRRK2-G2019S). At various ages, retinal function could be assessed *in vivo* using electroretinography (ERG) to detect deficits in bipolar cell and photoreceptor signaling. Following functional testing, retinal tissues would be harvested for phosphoproteomic analysis specifically targeting [RAB3A](/details-gene/5864) and its known phosphorylation sites to confirm hyperphosphorylation by mutant LRRK2. Furthermore, super-resolution microscopy of retinal slices could be used to quantify the localization and density of [RAB3A](/details-gene/5864)-positive vesicles at the presynaptic terminals of [bipolar cells](/details-cell/CL0000748), correlating molecular changes with subcellular structural deficits. **Therapeutic Potential:** Directly targeting a fundamental protein like [RAB3A](/details-gene/5864) with an inhibitor is likely to cause significant toxicity due to its widespread importance in neuronal function. However, its role as a downstream effector in neurodegenerative pathways suggests more nuanced therapeutic strategies. Instead of targeting [RAB3A](/details-gene/5864) itself, developing small molecules or biologics that disrupt its pathological interaction with aggregated alpha-synuclein could be a promising approach. Such a strategy would aim to restore normal [RAB3A](/details-gene/5864) function and localization without affecting its basal activity. Similarly, in the context of LRRK2-driven pathology, therapies would be better directed at inhibiting the upstream kinase (LRRK2) to prevent the aberrant phosphorylation of [RAB3A](/details-gene/5864) and other Rab GTPase substrates.

Genular Protein ID: 2970739155

Symbol: RAB3A_HUMAN

Name: Ras-related protein Rab-3A

UniProtKB Accession Codes:

P20336 A8K0J4 Q9NYE1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CTD 1 ChEBI 5 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 11 Ensembl 1 ExpressionAtlas 1 GO 54 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 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 10 RefSeq 2 SIGNOR 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: 2501306

Title: The human Rab genes encode a family of GTP-binding proteins related to yeast YPT1 and SEC4 products involved in secretion.

PubMed ID: 2501306

DOI: 10.1016/s0021-9258(18)63872-4

PubMed ID: 10574328

Title: Genomic organisation of the human cyclic AMP-specific phosphodiesterase PDE4C gene and its chromosomal localisation to 19p13.1, between RAB3A and JUND.

PubMed ID: 10574328

DOI: 10.1016/s0898-6568(99)00037-6

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

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: 1648736

Title: Isoprenoid modification of rab proteins terminating in CC or CXC motifs.

PubMed ID: 1648736

DOI: 10.1073/pnas.88.14.6264

PubMed ID: 7991565

Title: Rab geranylgeranyl transferase catalyzes the geranylgeranylation of adjacent cysteines in the small GTPases Rab1A, Rab3A, and Rab5A.

PubMed ID: 7991565

DOI: 10.1073/pnas.91.25.11963

PubMed ID: 15207266

Title: Abnormal alpha-synuclein interactions with rab3a and rabphilin in diffuse Lewy body disease.

PubMed ID: 15207266

DOI: 10.1016/j.nbd.2004.01.001

PubMed ID: 22248876

Title: RIM, Munc13, and Rab3A interplay in acrosomal exocytosis.

PubMed ID: 22248876

DOI: 10.1016/j.yexcr.2012.01.002

PubMed ID: 26824392

Title: Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases.

PubMed ID: 26824392

DOI: 10.7554/elife.12813

PubMed ID: 27325790

Title: A Rab3a-dependent complex essential for lysosome positioning and plasma membrane repair.

PubMed ID: 27325790

DOI: 10.1083/jcb.201511093

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

PubMed ID: 30599141

Title: Grab recruitment by Rab27A-Rabphilin3a triggers Rab3A activation in human sperm exocytosis.

PubMed ID: 30599141

DOI: 10.1016/j.bbamcr.2018.12.005

Sequence Information:

  • Length: 220
  • Mass: 24984
  • Checksum: 08B59F8C9BD2EB40
  • Sequence:
    • MASATDSRYG QKESSDQNFD YMFKILIIGN SSVGKTSFLF RYADDSFTPA FVSTVGIDFK 
VKTIYRNDKR IKLQIWDTAG QERYRTITTA YYRGAMGFIL MYDITNEESF NAVQDWSTQI 
KTYSWDNAQV LLVGNKCDME DERVVSSERG RQLADHLGFE FFEASAKDNI NVKQTFERLV 
DVICEKMSES LDTADPAVTG AKQGPQLSDQ QVPPHQDCAC