Details for: CBLN4

Gene ID: 140689

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: CBLN4

Ensembl ID: ENSG00000054803

Description: cerebellin 4 precursor

Cell Significance Landscape

Associated with

Significant Cells

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

  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 7.7
    rCSI 12.93%
    PRS 96.52
  • pancreatic D cell CL0000173
    CSI 4.54
    rCSI 4.47%
    PRS 98.77
  • sst GABAergic cortical interneuron CL4023017
    CSI 3.05
    rCSI 3.93%
    PRS 96.7
  • cerebral cortex neuron CL0010012
    CSI 2.71
    rCSI 11.04%
    PRS 95.83
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.66
    rCSI 3.18%
    PRS 96.13
  • enteroendocrine cell CL0000164
    CSI 2.37
    rCSI 3.24%
    PRS 97.93
  • sncg GABAergic cortical interneuron CL4023015
    CSI 2.29
    rCSI 3.69%
    PRS 96.1
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.07
    rCSI 2.61%
    PRS 95.1

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):
    • 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 [CBLN4](/details-gene/140689) (cerebellin 4 precursor) is a protein-coding gene located on chromosome 20q13.2. It encodes a secreted protein belonging to the C1q/TNF superfamily, which is known to play critical roles in synapse formation and maintenance. Functional annotations strongly link [CBLN4](/details-gene/140689) to the assembly of inhibitory synapses and trans-synaptic signaling. Expression data reveals that **Overall**, [CBLN4](/details-gene/140689) is a highly specific marker for distinct neuronal populations, particularly [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011)s and other interneuron subtypes within the cerebral cortex. Its expression is also notably high in certain endocrine cells, such as [pancreatic D cell](/details-cell/CL0000173)s, suggesting a potential role in both neuronal and hormonal signaling pathways. ## Cellular Roles and Expression Landscape The expression profile of [CBLN4](/details-gene/140689) highlights its specialized function primarily within the central nervous system and select endocrine tissues. **Overall**, the gene's significance is most pronounced in neuronal subtypes critical for cortical circuitry. It is the top marker for [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011) (CSI: 7.70) and shows significant expression in other inhibitory neurons including [sst GABAergic cortical interneuron](/details-cell/CL4023017)s (CSI: 3.05), [VIP GABAergic cortical interneuron](/details-cell/CL4023016)s (CSI: 2.66), and [sncg GABAergic cortical interneuron](/details-cell/CL4023015)s (CSI: 2.29). Its presence in [L2/3-6 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4023040)s (CSI: 1.07) suggests a broader role in modulating both inhibitory and excitatory synapses. This expression pattern strongly indicates that [CBLN4](/details-gene/140689) is a key secreted factor involved in establishing and maintaining the complex synaptic architecture of the cerebral cortex. Beyond the nervous system, [CBLN4](/details-gene/140689) shows a distinct and high level of significance in specialized endocrine cells. It is a prominent marker in [pancreatic D cell](/details-cell/CL0000173)s (CSI: 4.54), which are responsible for secreting somatostatin, and also in [enteroendocrine cell](/details-cell/CL0000164)s (CSI: 2.37). The shared high expression between somatostatin-positive neuronal and endocrine cells suggests a conserved functional role for [CBLN4](/details-gene/140689) related to somatostatin signaling or the function of cells that produce it. ## Pathways and Molecular Function Functional annotations for [CBLN4](/details-gene/140689) confirm its role as an extracellular protein involved in synaptic organization. The gene's product is localized to the [extracellular region](/details-cell/GO:0005576), [extracellular space](/details-cell/GO:0005615), and the [synaptic cleft](/details-cell/GO:0043083), consistent with its identification as a secreted protein through large-scale bioinformatics efforts ([Link](https://doi.org/10.1101/gr.1293003)). Its primary biological processes involve synaptic function. [CBLN4](/details-gene/140689) is directly implicated in [Inhibitory synapse assembly](/details-cell/GO:1904862) and is a component of both [Gaba-ergic synapse](/details-cell/GO:0098982)s and [glutamatergic synapse](/details-cell/GO:0098978)s. This aligns perfectly with its high expression in various GABAergic interneurons and glutamatergic neurons. The annotation for [Trans-synaptic signaling, modulating synaptic transmission](/details-cell/GO:0099550) further suggests that it does not just play a structural role but actively participates in the dynamic regulation of neural communication. ## Research Directions The specific expression pattern and annotated functions of [CBLN4](/details-gene/140689) point toward several compelling areas for future research, particularly concerning its role in neurobiology and endocrinology. ### Proposed Hypotheses 1. **[CBLN4](/details-gene/140689) is a key organizer of specific inhibitory microcircuits in the cortex.** Given its exceptionally high expression in diverse GABAergic interneurons ([lamp5](/details-cell/CL4023011), [sst](/details-cell/CL4023017), [VIP](/details-cell/CL4023016)) and its role in [inhibitory synapse assembly](/details-cell/GO:1904862), we hypothesize that [CBLN4](/details-gene/140689) acts as a secreted synaptogenic factor that guides the formation or stabilization of synapses between specific interneuron subtypes and their postsynaptic targets. 2. **[CBLN4](/details-gene/140689) functions as a regulator of somatostatin-producing cells across different tissues.** The high expression in both [pancreatic D cell](/details-cell/CL0000173)s and [sst GABAergic cortical interneuron](/details-cell/CL4023017)s, both defined by their production of somatostatin, suggests a conserved function. We hypothesize that [CBLN4](/details-gene/140689) may act in an autocrine or paracrine manner to modulate the development, survival, or secretory function of these cells in both the pancreas and the brain. ### Key Experiment To test the hypothesis that [CBLN4](/details-gene/140689) organizes cortical inhibitory circuits, a conditional knockout (cKO) mouse model could be generated. Using a Cre-driver line specific to cortical interneurons (e.g., *Gad2*-Cre), [CBLN4](/details-gene/140689) could be selectively deleted from these cells. The consequences could be assessed using a combination of techniques: * **Immunohistochemistry:** Stain for synaptic markers (e.g., Gephyrin, VGAT) to quantify the density of inhibitory synapses on pyramidal neurons. * **Electrophysiology:** Perform whole-cell patch-clamp recordings from pyramidal neurons in cortical slices to measure the frequency and amplitude of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs). A reduction in these parameters in cKO mice would support a role for [CBLN4](/details-gene/140689) in synapse formation or maintenance. ### Therapeutic Potential As a secreted protein with a highly specific expression pattern in the central nervous system, [CBLN4](/details-gene/140689) presents an intriguing therapeutic profile. Its role in inhibitory synapse assembly suggests that dysregulation could contribute to neurological or psychiatric disorders characterized by an imbalance of excitation and inhibition, such as epilepsy or schizophrenia. Rather than being a target for inhibition, [CBLN4](/details-gene/140689) or a synthetic analog could be a candidate for protein-based replacement therapy. Administering [CBLN4](/details-gene/140689) could potentially restore inhibitory tone and correct circuit deficits in these conditions. Its specificity for certain neuronal populations might limit off-target effects, though the challenges of delivering protein therapeutics across the blood-brain barrier would need to be addressed.

Genular Protein ID: 2193134694

Symbol: CBLN4_HUMAN

Name: Cerebellin-4

UniProtKB Accession Codes:

Q9NTU7 A8K0S5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 1 GO 7 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 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 RNAct 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 11780052

Title: The DNA sequence and comparative analysis of human chromosome 20.

PubMed ID: 11780052

DOI: 10.1038/414865a

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: 201
  • Mass: 21808
  • Checksum: 2CC9B6C25A1929B7
  • Sequence:
    • MGSGRRALSA VPAVLLVLTL PGLPVWAQND TEPIVLEGKC LVVCDSNPAT DSKGSSSSPL 
GISVRAANSK VAFSAVRSTN HEPSEMSNKT RIIYFDQILV NVGNFFTLES VFVAPRKGIY 
SFSFHVIKVY QSQTIQVNLM LNGKPVISAF AGDKDVTREA ATNGVLLYLD KEDKVYLKLE 
KGNLVGGWQY STFSGFLVFP L