Details for: DRP2

Gene ID: 1821

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: DRP2

Ensembl ID: ENSG00000102385

Description: dystrophin related protein 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 6.29
    rCSI 10.56%
    PRS 84.39
  • VIP GABAergic cortical interneuron CL4023016
    CSI 3.07
    rCSI 3.67%
    PRS 84.29
  • Schwann cell CL0002573
    CSI 2.37
    rCSI 6.73%
    PRS 90.89
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.2
    rCSI 2.73%
    PRS 82.16
  • direct pathway medium spiny neuron CL4023026
    CSI 1.9
    rCSI 45.55%
    PRS 82.12
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.85
    rCSI 44.75%
    PRS 82.06
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.78
    rCSI 2.3%
    PRS 85.22
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.57
    rCSI 3.81%
    PRS 82.17
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.48
    rCSI 2.37%
    PRS 85.3
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.96
    rCSI 3.47%
    PRS 82.48
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.94
    rCSI 2.94%
    PRS 85.24
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.64
    rCSI 2%
    PRS 87
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.59
    rCSI 2.24%
    PRS 84.44
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.47
    rCSI 2.8%
    PRS 84.62

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)

Loading network (please wait)...

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 Dystrophin-related protein 2, encoded by the [DRP2](/details-gene/1821) gene, is a protein-coding gene located on the X chromosome. As a member of the dystrophin family of proteins, [DRP2](/details-gene/1821) is strongly implicated in structural and signaling roles within the nervous system. The initial characterization of [DRP2](/details-gene/1821) identified it as a novel homologue of dystrophin ([Link](https://doi.org/10.1038/ng0696-223)). Expression data from the **Overall** context reveals its highly specific and significant expression in various neuronal subtypes, including a prominent role in [lamp5 GABAergic cortical interneurons](/details-cell/CL4023011), and in glial cells, particularly [Schwann cells](/details-cell/CL0002573). Its function is closely tied to developmental biology, synapse organization, and the structural integrity of the plasma membrane at synaptic junctions. ## Cellular Roles and Expression Landscape The expression profile of [DRP2](/details-gene/1821) firmly establishes its importance within the central and peripheral nervous systems. **Overall**, the gene exhibits its highest significance in diverse neuronal populations. It is a particularly strong marker for [lamp5 GABAergic cortical interneurons](/details-cell/CL4023011) (CSI: 6.29) and is also significantly expressed in other inhibitory neuron subtypes such as [VIP](/details-cell/CL4023016), [pvalb](/details-cell/CL4023018), and [sst GABAergic cortical interneurons](/details-cell/CL4023017). This suggests a key role in the function of cortical inhibitory circuits. Furthermore, its significance in both [direct pathway](/details-cell/CL4023026) and [indirect pathway medium spiny neurons](/details-cell/CL4023029) points to a role in basal ganglia function. The gene is also notable in several subtypes of excitatory glutamatergic neurons, including [L2/3-6 intratelencephalic projecting glutamatergic neurons](/details-cell/CL4023040), indicating a broad function in cortical processing. Beyond neurons, [DRP2](/details-gene/1821) is a significant marker for [Schwann cells](/details-cell/CL0002573), the myelinating glial cells of the peripheral nervous system. This expression is consistent with its known role in myelination processes, suggesting it contributes to the structural organization of the myelin sheath. ## Pathways and Molecular Function Functional annotations for [DRP2](/details-gene/1821) are consistent with its observed expression pattern in the nervous system. The gene is involved in broad biological processes such as 'central nervous system development' ([GO:0007417](https://www.ebi.ac.uk/QuickGO/term/GO:0007417)) and more specific functions like 'synapse organization' ([GO:0050808](https://www.ebi.ac.uk/QuickGO/term/GO:0050808)) and 'synaptic signaling' ([GO:0099536](https://www.ebi.ac.uk/QuickGO/term/GO:0099536)). At the cellular level, the [DRP2](/details-gene/1821) protein is localized to the 'plasma membrane' ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO:0005886)) and is a component of specialized structures including the 'postsynaptic density' ([GO:0014069](https://www.ebi.ac.uk/QuickGO/term/GO:0014069)) and 'glutamatergic synapse' ([GO:0098978](https://www.ebi.ac.uk/QuickGO/term/GO:0098978)), highlighting its role in synaptic architecture. Its involvement in the Reactome pathway 'Egr2 and sox10-mediated initiation of schwann cell myelination' ([R-HSA-9619665](https://reactome.org/content/detail/R-HSA-9619665)) directly aligns with its high significance in [Schwann cells](/details-cell/CL0002573). Its annotated molecular function as a 'zinc ion binding' protein ([GO:0008270](https://www.ebi.ac.uk/QuickGO/term/GO:0008270)) suggests a role in protein-protein interactions or structural stability that is dependent on zinc coordination. ## Research Directions The specific expression and functional annotation of [DRP2](/details-gene/1821) point toward critical roles in neuronal and glial biology, offering several avenues for future research. **Proposed Hypotheses:** 1. Given its high expression across multiple inhibitory interneuron subtypes and its localization to the postsynaptic density, [DRP2](/details-gene/1821) may be essential for the clustering and stabilization of GABA-A receptors at inhibitory synapses, thereby regulating the efficacy of cortical inhibition. 2. Based on its expression in [Schwann cells](/details-cell/CL0002573) and its link to the myelination pathway, [DRP2](/details-gene/1821) may function as a crucial scaffolding protein that links the Schwann cell plasma membrane to the underlying cytoskeleton, a role necessary for the proper wrapping and compaction of the myelin sheath around peripheral axons. **Suggested Experimental Approach:** To test the hypothesis regarding its role in peripheral myelination, a conditional knockout mouse model could be generated. By crossing a mouse with a floxed `Drp2` allele to a `Plp1-CreER` mouse line, `Drp2` could be inducibly deleted specifically in myelinating cells (Schwann cells and oligodendrocytes) upon tamoxifen administration. The resulting phenotype in peripheral nerves could be assessed through a combination of techniques. Transmission electron microscopy would allow for detailed ultrastructural analysis of myelin sheaths, including measurements of the g-ratio (axon diameter to myelinated fiber diameter) and quantification of amyelinated or dysmyelinated axons. Functional consequences could be measured via nerve conduction velocity tests on the sciatic nerve. Additionally, immunofluorescence staining for myelin-associated proteins could reveal disruptions in the molecular organization of the myelin sheath and nodes of Ranvier. **Therapeutic Potential:** The clinical association of [DRP2](/details-gene/1821) with a disorder ([OMIM: 300052](https://omim.org/entry/300052)) suggests that its dysfunction has pathological consequences. As dystrophin family members are often implicated in loss-of-function diseases, therapeutic strategies would likely focus on restoring function. Given the gene's specific expression in the nervous system, gene therapy approaches using adeno-associated virus (AAV) vectors to deliver a functional copy of [DRP2](/details-gene/1821) could be a potential long-term strategy. However, the precise role of [DRP2](/details-gene/1821) in disease pathogenesis needs to be further elucidated before its potential as a therapeutic target can be fully evaluated.

Genular Protein ID: 637519626

Symbol: DRP2_HUMAN

Name: Dystrophin-related protein 2

UniProtKB Accession Codes:

Q13474 A6ZKI5 A8K1B0 B1B1F3 B4DIZ0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 4 CTD 1 ChEBI 4 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 11 Ensembl 4 ExpressionAtlas 1 GO 9 Gene3D 4 GeneCards 1 GeneReviews 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 11 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIRSF 1 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 5 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 1 RefSeq 2 SMART 3 SMR 1 STRING 1 SUPFAM 4 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8640231

Title: Characterization of DRP2, a novel human dystrophin homologue.

PubMed ID: 8640231

DOI: 10.1038/ng0696-223

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

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: 957
  • Mass: 107962
  • Checksum: 95B26DCFF45DDE12
  • Sequence:
    • MQPMVMQGCP YTLPRCHDWQ AADQFHHSSS LRSTCPHPQV RAAVTSPAPP QDGAGVPCLS 
LKLLNGSVGA SGPLEPPAMN LCWNEIKKKS HNLRARLEAF SDHSGKLQLP LQEIIDWLSQ 
KDEELSAQLP LQGDVALVQQ EKETHAAFME EVKSRGPYIY SVLESAQAFL SQHPFEELEE 
PHSESKDTSP KQRIQNLSRF VWKQATVASE LWEKLTARCV DQHRHIERTL EQLLEIQGAM 
EELSTTLSQA EGVRATWEPI GDLFIDSLPE HIQAIKLFKE EFSPMKDGVK LVNDLAHQLA 
ISDVHLSMEN SQALEQINVR WKQLQASVSE RLKQLQDAHR DFGPGSQHFL SSSVQVPWER 
AISPNKVPYY INHQAQTTCW DHPKMTELYQ TLADLNNIKF SAYRTAMKLR RVQKALRLDL 
VTLTTALEIF NEHDLQASEH VMDVVEVIHC LTALYERLEE ERGILVNVPL CVDMSLNWLL 
NVFDSGRSGK MRALSFKTGI ACLCGTEVKE KLQYLFSQVA NSGSQCDQRH LGVLLHEAIQ 
VPRQLGEVAA FGGSNVEPSV RSCFRFSTGK PVIEASQFLE WVNLEPQSMV WLAVLHRVTI 
AEQVKHQTKC SICRQCPIKG FRYRSLKQFN VDICQTCFLT GRASKGNKLH YPIMEYYTPT 
TSSENMRDFA TTLKNKFRSK HYFSKHPQRG YLPVQSVLEA DYSETPASSP MWPHADTHSR 
IEHFASRLAE MESQNCSFFN DSLSPDDSID EDQYLLRHSS PITDREPAFG QQAPCSVATE 
SKGELQKILA HLEDENRILQ GELRRLKWQH EEAAEAPSLA DGSTEAATDH RNEELLAEAR 
ILRQHKSRLE TRMQILEDHN KQLESQLQRL RELLLQPPTE SDGSGSAGSS LASSPQQSEG 
SHPREKGQTT PDTEAADDVG SKSQDVSLCL EDIMEKLRHA FPSVRSSDVT ANTLLAS