Details for: NINJ2

Gene ID: 4815

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: NINJ2

Ensembl ID: ENSG00000171840

Description: ninjurin 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • T follicular helper cell CL0002038
    CSI 4.98
    rCSI 3.73%
    PRS 96.44
  • epithelial cell of lung CL0000082
    CSI 4.36
    rCSI 3.61%
    PRS 90.02
  • mature T cell CL0002419
    CSI 3.7
    rCSI 2.88%
    PRS 96.73
  • myeloid leukocyte CL0000766
    CSI 3.36
    rCSI 3.1%
    PRS 90.26
  • hematopoietic stem cell CL0000037
    CSI 3.3
    rCSI 2.19%
    PRS 90.88
  • cardiac endothelial cell CL0010008
    CSI 3.18
    rCSI 12.83%
    PRS 89.85
  • Kupffer cell CL0000091
    CSI 3.03
    rCSI 6.93%
    PRS 90.08
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 2.87
    rCSI 2.82%
    PRS 97.19
  • common myeloid progenitor CL0000049
    CSI 2.59
    rCSI 2.09%
    PRS 90.72
  • erythrocyte CL0000232
    CSI 2.46
    rCSI 5.58%
    PRS 87.88
  • promyelocyte CL0000836
    CSI 2.44
    rCSI 3.53%
    PRS 91.84
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.22
    rCSI 2.01%
    PRS 88.09
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.01
    rCSI 1.93%
    PRS 87.86
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.82
    rCSI 1.4%
    PRS 92.27
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 1.76
    rCSI 2.3%
    PRS 95.49
  • cardiac muscle cell CL0000746
    CSI 1.69
    rCSI 2.43%
    PRS 81.15
  • promonocyte CL0000559
    CSI 1.57
    rCSI 2.7%
    PRS 91.82
  • regular ventricular cardiac myocyte CL0002131
    CSI 0.71
    rCSI 4.41%
    PRS 82.66

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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  • Node Color (Target Cell CSI, relative to current network):
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    • 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 [NINJ2](/details-gene/4815) (Ninjurin 2) is a protein-coding gene located on chromosome 12p13.33 that encodes a transmembrane protein. Originally identified for its role in nerve injury and neurite outgrowth ([Link](https://doi.org/10.1523/jneurosci.20-01-00187.2000)), [NINJ2](/details-gene/4815) functions in processes such as [cell adhesion](/details-cell/GO:0007155) and potentially [cytolysis](/details-cell/GO:0019835). Its expression profile indicates a broad role beyond the nervous system, with high significance observed in various immune cell populations, including [T follicular helper cell](/details-cell/CL0002038) and [myeloid leukocyte](/details-cell/CL0000766), as well as in structural cells like [epithelial cell of lung](/details-cell/CL0000082). This suggests that [NINJ2](/details-gene/4815) is a multifunctional protein involved in cell-cell interactions and membrane dynamics across diverse physiological contexts. ## Cellular Roles and Expression Landscape The expression pattern of [NINJ2](/details-gene/4815) highlights its functional importance in both the immune system and in tissue-resident structural cells. **Overall**, the gene shows the highest significance in specialized T cell subsets, with [T follicular helper cell](/details-cell/CL0002038) (CSI: 4.98) and [mature T cell](/details-cell/CL0002419) (CSI: 3.70) ranking among the top cell types. This is consistent with its annotated role in [cell adhesion](/details-cell/GO:0007155), a critical process for T cell interactions. Beyond the adaptive immune system, [NINJ2](/details-gene/4815) is a significant marker in the myeloid lineage, including [myeloid leukocyte](/details-cell/CL0000766) (CSI: 3.36), [Kupffer cell](/details-cell/CL0000091) (CSI: 3.03), and various monocyte populations. Its expression in hematopoietic progenitors, such as [hematopoietic stem cell](/details-cell/CL0000037) (CSI: 3.30) and [common myeloid progenitor](/details-cell/CL0000049) (CSI: 2.59), suggests a role that extends from hematopoietic development through to mature effector cell function. Notably, [NINJ2](/details-gene/4815) also displays high significance in non-hematopoietic cells, including [epithelial cell of lung](/details-cell/CL0000082) (CSI: 4.36) and [cardiac endothelial cell](/details-cell/CL0010008) (CSI: 3.18). This widespread expression across diverse cell types points to a fundamental role in maintaining tissue integrity and mediating cellular interactions in multiple organ systems. ## Pathways and Molecular Function [NINJ2](/details-gene/4815) is annotated as a [plasma membrane](/details-cell/GO:0005886) protein involved in several key biological processes. Its primary documented function is in promoting [cell adhesion](/details-cell/GO:0007155), particularly homophilic adhesion in neurons, which facilitates neurite outgrowth ([Link](https://doi.org/10.1523/jneurosci.20-01-00187.2000)). This function likely extends to the immune system, where its high expression in T cells and myeloid cells may facilitate cell-cell interactions during immune surveillance and activation. The gene is also associated with [cytolysis](/details-cell/GO:0019835) and possesses [membrane destabilizing activity](/details-cell/GO:0140912). This is particularly noteworthy given that its homolog, NINJ1, has been identified as a key executioner of plasma membrane rupture during lytic cell death pathways such as pyroptosis ([Link](https://doi.org/10.1038/s41586-021-03218-7); [Link](https://doi.org/10.1016/j.cell.2024.03.008)). This suggests that [NINJ2](/details-gene/4815) may play a similar role in mediating controlled membrane disruption in specific cellular contexts. Furthermore, its association with [tissue regeneration](/details-cell/GO:0042246) is consistent with its high expression in lung epithelial cells and its original discovery in the context of nerve injury repair. ## Research Directions The diverse expression profile and functional annotations of [NINJ2](/details-gene/4815) suggest several avenues for future investigation. Its roles in both adhesion and potential membrane rupture position it as a critical regulator of cell-cell interactions and cell fate decisions. **Proposed Hypotheses:** 1. Given its high significance in [T follicular helper cell](/details-cell/CL0002038) and its function in [cell adhesion](/details-cell/GO:0007155), [NINJ2](/details-gene/4815) may be essential for stabilizing the interaction between Tfh cells and B cells within the germinal center, thereby regulating antibody production. 2. Drawing parallels with its homolog NINJ1, [NINJ2](/details-gene/4815) may function as an executioner of plasma membrane rupture during lytic cell death (e.g., pyroptosis) specifically in [myeloid leukocyte](/details-cell/CL0000766), where it is highly expressed. 3. The high expression of [NINJ2](/details-gene/4815) in [epithelial cell of lung](/details-cell/CL0000082) and its annotation for [tissue regeneration](/details-cell/GO:0042246) suggest that it plays a direct role in mediating cell migration and adhesion to restore epithelial barrier integrity following lung injury. **Experimental Approach:** To test the hypothesis that [NINJ2](/details-gene/4815) mediates lytic cell death in myeloid cells, one could utilize a CRISPR-Cas9 knockout strategy in a human monocytic cell line (e.g., THP-1). Following differentiation into macrophages, these [NINJ2](/details-gene/4815)-deficient cells and wild-type controls could be stimulated with pyroptosis-inducing agents (e.g., LPS plus nigericin). The functional consequence of [NINJ2](/details-gene/4815) loss would be assessed by measuring lactate dehydrogenase (LDH) release as a marker of cell lysis and by using live-cell imaging with membrane-impermeable dyes (e.g., propidium iodide) to directly visualize plasma membrane rupture. **Therapeutic Potential:** As a plasma membrane protein, [NINJ2](/details-gene/4815) is an accessible drug target. If it is confirmed to be a key mediator of lytic cell death in inflammatory myeloid cells, its inhibition could represent a novel therapeutic strategy for diseases characterized by excessive inflammation and pyroptosis, such as sepsis or certain autoimmune disorders. A small molecule inhibitor or a therapeutic antibody targeting the extracellular domain of [NINJ2](/details-gene/4815) could prevent cell lysis and the subsequent release of pro-inflammatory cytokines. However, its broad expression across multiple essential cell types, including hematopoietic stem cells and epithelial cells, suggests that systemic inhibition could lead to significant off-target effects, necessitating targeted drug delivery approaches.

Genular Protein ID: 551460523

Symbol: NINJ2_HUMAN

Name: Nerve injury-induced protein 2

UniProtKB Accession Codes:

Q9NZG7

Database IDs:

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

Citations:

PubMed ID: 10627596

Title: Ninjurin2, a novel homophilic adhesion molecule, is expressed in mature sensory and enteric neurons and promotes neurite outgrowth.

PubMed ID: 10627596

DOI: 10.1523/jneurosci.20-01-00187.2000

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: 33472215

Title: NINJ1 mediates plasma membrane rupture during lytic cell death.

PubMed ID: 33472215

DOI: 10.1038/s41586-021-03218-7

PubMed ID: 38614101

Title: NINJ1 mediates plasma membrane rupture by cutting and releasing membrane disks.

PubMed ID: 38614101

DOI: 10.1016/j.cell.2024.03.008

Sequence Information:

  • Length: 142
  • Mass: 15680
  • Checksum: B00A92F5EAFF6BD9
  • Sequence:
    • MESARENIDL QPGSSDPRSQ PINLNHYATK KSVAESMLDV ALFMSNAMRL KAVLEQGPSS 
HYYTTLVTLI SLSLLLQVVI GVLLVVIARL NLNEVEKQWR LNQLNNAATI LVFFTVVINV 
FITAFGAHKT GFLAARASRN PL

Genular Protein ID: 704666047

Symbol: A0A590UJR9_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A590UJR9

Database IDs:

ARBA 5 Antibodypedia 1 Bgee 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 2 GO 3 GeneTree 1 HGNC 1 InterPro 1 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 Proteomes 2 ProteomicsDB 1 RefSeq 1 SAM 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

Sequence Information:

  • Length: 188
  • Mass: 20430
  • Checksum: 1CE3F4A16E9F156A
  • Sequence:
    • MAGLSRQLCA LSHPKKAAET QTAEPGGAHA VCSRHPVRVK GLEGSEMESA RENIDLQPGS 
SDPRSQPINL NHYATKKSVA ESMLDVALFM SNAMRLKAVL EQGPSSHYYT TLVTLISLSL 
LLQVVIGVLL VVIARLNLNE VEKQWRLNQL NNAATILVFF TVVINVFITA FGAHKTGFLA 
ARASRNPL

Genular Protein ID: 3688223608

Symbol: F8WBZ3_HUMAN

Name: N/A

UniProtKB Accession Codes:

F8WBZ3

Database IDs:

ARBA 5 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 2 ExpressionAtlas 1 GO 3 GeneTree 1 HGNC 1 HOGENOM 1 InterPro 1 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 2 Pfam 1 Proteomes 2 ProteomicsDB 2 RefSeq 1 SAM 1 SMR 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

Sequence Information:

  • Length: 135
  • Mass: 14950
  • Checksum: 8C139BEBE5687861
  • Sequence:
    • MMYMPGSSDP RSQPINLNHY ATKKSVAESM LDVALFMSNA MRLKAVLEQG PSSHYYTTLV 
TLISLSLLLQ VVIGVLLVVI ARLNLNEVEK QWRLNQLNNA ATILVFFTVV INVFITAFGA 
HKTGFLAARA SRNPL

Genular Protein ID: 2491704255

Symbol: F5H3L1_HUMAN

Name: N/A

UniProtKB Accession Codes:

F5H3L1

Database IDs:

ARBA 5 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 2 ExpressionAtlas 1 GO 3 GeneTree 1 HGNC 1 HOGENOM 1 InterPro 1 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 2 Pfam 1 Proteomes 2 ProteomicsDB 2 RefSeq 1 SAM 1 SMR 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

Sequence Information:

  • Length: 106
  • Mass: 11727
  • Checksum: A4EE9C9AEC1B448F
  • Sequence:
    • MLDVALFMSN AMRLKAVLEQ GPSSHYYTTL VTLISLSLLL QVVIGVLLVV IARLNLNEVE 
KQWRLNQLNN AATILVFFTV VINVFITAFG AHKTGFLAAR ASRNPL

Genular Protein ID: 2744628309

Symbol: B4DJC1_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4DJC1

Database IDs:

ARBA 5 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 4 GO 3 InterPro 1 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 RefSeq 1 SAM 1

Sequence Information:

  • Length: 172
  • Mass: 18454
  • Checksum: 0E6425956FDCE597
  • Sequence:
    • MAGLSRQLCA LSHPKKAAET QTAEPGGAHA VCSRHPVRVK GLEGSEMESA RENIDLQPGS 
SDPRSQPINL NHYATKKSVA ESMLDVALFM SNAMRLKAVL EQGPSSHYYT TLVTLISLSL 
LLQVVIGVLL VVIGEEPSLQ SDLLPRHPWL AERPHVSPGP PCIGTGSFAT TR