Details for: KIRREL2

Gene ID: 84063

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: KIRREL2

Ensembl ID: ENSG00000126259

Description: kirre like nephrin family adhesion molecule 2

Cell Significance Landscape

Associated with

Significant Cells

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

  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 3.49
    rCSI 4.03%
    PRS 97.04
  • retinal bipolar neuron CL0000748
    CSI 2.92
    rCSI 5.47%
    PRS 96.71
  • OFF-bipolar cell CL0000750
    CSI 2.86
    rCSI 3.91%
    PRS 97.95
  • neural progenitor cell CL0011020
    CSI 1.89
    rCSI 8.3%
    PRS 94.44

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 [KIRREL2](/details-gene/84063) (kirre like nephrin family adhesion molecule 2) is a protein-coding gene located on chromosome 19q13.12. As a member of the immunoglobulin superfamily and the nephrin-like protein family, it functions as a cell adhesion molecule. Gene ontology annotations indicate its involvement in processes such as cell-cell adhesion ([GO:0098609](https://www.ebi.ac.uk/QuickGO/term/GO:0098609)) and its localization to the plasma membrane ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO:0005886)) and cell-cell junctions ([GO:0005911](https://www.ebi.ac.uk/QuickGO/term/GO:0005911)). Expression data highlight its significant role in the developing and mature nervous system, with particularly high significance in [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338) and specialized retinal neurons. ## Cellular Roles and Expression Landscape The expression profile of [KIRREL2](/details-gene/84063) suggests a highly specialized function, primarily within the nervous system. **Overall**, the gene shows the highest significance in neuronal cell types, indicating it may serve as a key marker and functional component in these cells. The top cell types where [KIRREL2](/details-gene/84063) is significantly expressed are: * [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338) (CSI: 3.49) * [retinal bipolar neuron](/details-cell/CL0000748) (CSI: 2.92) * [OFF-bipolar cell](/details-cell/CL0000750) (CSI: 2.86) * [neural progenitor cell](/details-cell/CL0011020) (CSI: 1.89) This strong enrichment in both progenitor cells ([neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338), [neural progenitor cell](/details-cell/CL0011020)) and terminally differentiated neurons ([retinal bipolar neuron](/details-cell/CL0000748)) points towards a dual role in both neurodevelopment and the maintenance of mature neural circuits. Its prominent expression in retinal neurons is consistent with studies identifying its transcript in human retina-derived cell lines ([Link](https://doi.org/10.1167/iovs.11-7479)). While the provided data point to a neural-specific role, separate research has identified its expression in beta cells of pancreatic islets, suggesting it may also play a role in endocrine tissue architecture ([Link](https://doi.org/10.1016/s0888-7543(03)00110-1)). ## Pathways and Molecular Function The molecular functions of [KIRREL2](/details-gene/84063) are centered on cell-cell interactions and adhesion, which are critical for tissue organization and integrity. Its annotation within the 'Nephrin family interactions' pathway ([R-HSA-373753](https://reactome.org/content/detail/R-HSA-373753)) and 'Cell-cell communication' ([R-HSA-1500931](https://reactome.org/content/detail/R-HSA-1500931)) highlights its role as a mediator of intercellular signaling and structural linkage. Key functional annotations include: * **Biological Process:** [KIRREL2](/details-gene/84063) is involved in cell adhesion ([GO:0007155](https://www.ebi.ac.uk/QuickGO/term/GO:0007155)), particularly homophilic (identical protein binding, [GO:0042802](https://www.ebi.ac.uk/QuickGO/term/GO:0042802)) and heterophilic (cell adhesion molecule binding, [GO:0050839](https://www.ebi.ac.uk/QuickGO/term/GO:0050839)) interactions. * **Cellular Component:** It is an integral membrane protein ([GO:0016020](https://www.ebi.ac.uk/QuickGO/term/GO:0016020)) localized to the plasma membrane ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO:0005886)), with enrichment at cell-cell junctions ([GO:0005911](https://www.ebi.ac.uk/QuickGO/term/GO:0005911)). Its homology to nephrin also suggests a potential role in specialized junctions like the slit diaphragm ([GO:0036057](https://www.ebi.ac.uk/QuickGO/term/GO:0036057)), though this may be more relevant in other tissues. This functional profile is highly consistent with its observed expression in the nervous system, where precise cell-cell adhesion is fundamental for neuronal migration, axon guidance, and synapse formation. ## Research Directions The specific and high-level expression of [KIRREL2](/details-gene/84063) in neuronal subtypes, coupled with its function as an adhesion molecule, presents several avenues for future investigation. Its role appears to be structural and developmental, but its potential contribution to neurological or metabolic disorders warrants further exploration. ### Proposed Hypotheses: 1. Given its high significance in [retinal bipolar neuron](/details-cell/CL0000748) and [OFF-bipolar cell](/details-cell/CL0000750), [KIRREL2](/details-gene/84063) is essential for the formation and/or maintenance of specific synaptic connections between bipolar cells and their post-synaptic partners (e.g., ganglion cells) in the inner plexiform layer of the retina. 2. Based on literature evidence of its expression in pancreatic beta cells ([Link](https://doi.org/10.1016/s0888-7543(03)00110-1)), [KIRREL2](/details-gene/84063) mediates homophilic adhesion that is critical for the proper clustering of beta cells within the islet of Langerhans, a process necessary for coordinated glucose sensing and insulin secretion. ### Experimental Approach: To test the first hypothesis regarding its role in retinal circuitry, a conditional knockout mouse model could be generated where [KIRREL2](/details-gene/84063) is specifically deleted in retinal bipolar cells. Retinas from these mice could be analyzed using transmission electron microscopy to quantify synaptic density and morphology in the inner plexiform layer. Functional consequences could be assessed via electroretinography (ERG) to measure deficits in the b-wave, which reflects bipolar cell activity. ### Therapeutic Potential: As a cell surface protein, [KIRREL2](/details-gene/84063) is theoretically accessible to biologic therapies. However, its primary role appears to be structural, making it a challenging target for conventional inhibition or activation. Its high specificity for certain neuronal subtypes could make it a valuable biomarker for these cells. In the context of disease, if mutations in [KIRREL2](/details-gene/84063) are linked to retinal degenerative diseases or synaptopathies, gene therapy to restore its function could be a potential long-term strategy. Furthermore, it could be explored as a target for cell-specific drug delivery systems designed to reach retinal bipolar neurons.

Genular Protein ID: 386115643

Symbol: KIRR2_HUMAN

Name: Kin of IRRE-like protein 2

UniProtKB Accession Codes:

Q6UWL6 C9JHF1 C9JJ76 F1T0I2 Q6P1R1 Q7Z5P1 Q7Z5P2 Q96IQ8 Q9H0T1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 9 Ensembl 3 ExpressionAtlas 1 GO 9 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 RNAct 1 Reactome 1 RefSeq 6 SMART 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 12837264

Title: Kirrel2, a novel immunoglobulin superfamily gene expressed primarily in beta cells of the pancreatic islets.

PubMed ID: 12837264

DOI: 10.1016/s0888-7543(03)00110-1

PubMed ID: 11230166

Title: Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.

PubMed ID: 11230166

DOI: 10.1101/gr.gr1547r

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 21697133

Title: Full-length transcriptome analysis of human retina-derived cell lines ARPE-19 and Y79 using the vector-capping method.

PubMed ID: 21697133

DOI: 10.1167/iovs.11-7479

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: 15340161

Title: Signal peptide prediction based on analysis of experimentally verified cleavage sites.

PubMed ID: 15340161

DOI: 10.1110/ps.04682504

Sequence Information:

  • Length: 708
  • Mass: 75093
  • Checksum: 97978D0F1D7E3330
  • Sequence:
    • MLRMRVPALL VLLFCFRGRA GPSPHFLQQP EDLVVLLGEE ARLPCALGAY WGLVQWTKSG 
LALGGQRDLP GWSRYWISGN AANGQHDLHI RPVELEDEAS YECQATQAGL RSRPAQLHVL 
VPPEAPQVLG GPSVSLVAGV PANLTCRSRG DARPTPELLW FRDGVLLDGA TFHQTLLKEG 
TPGSVESTLT LTPFSHDDGA TFVCRARSQA LPTGRDTAIT LSLQYPPEVT LSASPHTVQE 
GEKVIFLCQA TAQPPVTGYR WAKGGSPVLG ARGPRLEVVA DASFLTEPVS CEVSNAVGSA 
NRSTALDVLF GPILQAKPEP VSVDVGEDAS FSCAWRGNPL PRVTWTRRGG AQVLGSGATL 
RLPSVGPEDA GDYVCRAEAG LSGLRGGAAE ARLTVNAPPV VTALHSAPAF LRGPARLQCL 
VFASPAPDAV VWSWDEGFLE AGSQGRFLVE TFPAPESRGG LGPGLISVLH ISGTQESDFS 
RSFNCSARNR LGEGGAQASL GRRDLLPTVR IVAGVAAATT TLLMVITGVA LCCWRHSKAS 
ASFSEQKNLM RIPGSSDGSS SRGPEEEETG SREDRGPIVH TDHSDLVLEE EGTLETKDPT 
NGYYKVRGVS VSLSLGEAPG GGLFLPPPSP LGPPGTPTFY DFNPHLGMVP PCRLYRARAG 
YLTTPHPRAF TSYIKPTSFG PPDLAPGTPP FPYAAFPTPS HPRLQTHV

Genular Protein ID: 1989808934

Symbol: A0A0A0MQV3_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A0A0MQV3

Database IDs:

ARBA 2 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 2 ExpressionAtlas 1 GO 1 Gene3D 1 HGNC 1 InterPro 8 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PROSITE 2 PeptideAtlas 1 Pfam 3 Proteomes 2 ProteomicsDB 1 RefSeq 1 SAM 3 SMART 2 SMR 1 SUPFAM 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 15057824

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

PubMed ID: 15057824

DOI: 10.1038/nature02399

Sequence Information:

  • Length: 633
  • Mass: 67128
  • Checksum: 1AC252C19237A752
  • Sequence:
    • MLRMRVPALL VLLFCFRGRA GPSPHFLQQP EDLVVLLGEE ARLPCALGAY WGLVQWTKSG 
LALGGQRDLP GWSRYWISGN AANGQHDLHI RPVELEDEAS YECQATQAGL RSRPAQLHVL 
VPPEAPQVLG GPSVSLVAGV PANLTCRSRG DARPTPELLW FRDGVLLDGA TFHQTLLKEG 
TPGSVESTLT LTPFSHDDGA TFVCRARSQA LPTGRDTAIT LSLQYPPEVT LSASPHTVQE 
GEKVIFLCQA TAQPPVTGYR WAKGGSPVLG ARGPRLEVVA DASFLTEPVS CEVSNAVGSA 
NRSTALDVLF GPILQAKPEP VSVDVGEDAS FSCAWRGNPL PRVTWTRRGG AQVLGSGATL 
RLPSVGPEDA GDYVCRAEAG LSGLRGGAAE ARLTVNAPPV VTALHSAPAF LRGPARLQCL 
VFASPAPDAV VWSWDEGFLE AGSQGRFLVE TFPAPESRGG LGPGLISVLH ISGTQESDFS 
RSFNCSARNR LGEGGAQASL GRRDLLPTVR IVAGVAAATT TLLMVITGVA LCCWRHSKAS 
ASFSEQKNLM RIPGSSDGSS SRGPEEEETG SREDRGPIVH TDHSDLVLEE EGTLETKDPT 
NGYYKVRGVS PPASPDSRVT SFQWKSPGIS NLP

Genular Protein ID: 1332600242

Symbol: A0A0A0MRC1_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A0A0MRC1

Database IDs:

ARBA 2 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 2 ExpressionAtlas 1 GO 1 Gene3D 1 HGNC 1 InterPro 7 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PROSITE 2 PeptideAtlas 1 Pfam 2 Proteomes 2 ProteomicsDB 1 RefSeq 1 SAM 3 SMART 2 SMR 1 SUPFAM 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 15057824

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

PubMed ID: 15057824

DOI: 10.1038/nature02399

Sequence Information:

  • Length: 583
  • Mass: 61761
  • Checksum: D9A1A837AF8E78CC
  • Sequence:
    • MLRMRVPALL VLLFCFRGRA GWSRYWISGN AANGQHDLHI RPVELEDEAS YECQATQAGL 
RSRPAQLHVL VPPEAPQVLG GPSVSLVAGV PANLTCRSRG DARPTPELLW FRDGVLLDGA 
TFHQTLLKEG TPGSVESTLT LTPFSHDDGA TFVCRARSQA LPTGRDTAIT LSLQYPPEVT 
LSASPHTVQE GEKVIFLCQA TAQPPVTGYR WAKGGSPVLG ARGPRLEVVA DASFLTEPVS 
CEVSNAVGSA NRSTALDVLF GPILQAKPEP VSVDVGEDAS FSCAWRGNPL PRVTWTRRGG 
AQVLGSGATL RLPSVGPEDA GDYVCRAEAG LSGLRGGAAE ARLTVNAPPV VTALHSAPAF 
LRGPARLQCL VFASPAPDAV VWSWDEGFLE AGSQGRFLVE TFPAPESRGG LGPGLISVLH 
ISGTQESDFS RSFNCSARNR LGEGGAQASL GRRDLLPTVR IVAGVAAATT TLLMVITGVA 
LCCWRHSKAS ASFSEQKNLM RIPGSSDGSS SRGPEEEETG SREDRGPIVH TDHSDLVLEE 
EGTLETKDPT NGYYKVRGVS PPASPDSRVT SFQWKSPGIS NLP