Details for: CIB4

Gene ID: 130106

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: CIB4

Ensembl ID: ENSG00000157884

Description: calcium and integrin binding family member 4

Cell Significance Landscape

Associated with

Significant Cells

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

  • ependymal cell CL0000065
    CSI 3.38
    rCSI 6.85%
    PRS 99.51

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

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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 [CIB4](/details-gene/130106) (Calcium And Integrin Binding Family Member 4) is a protein-coding gene located on chromosome 2p23.3. As a member of the CIB family, its primary molecular function involves binding cations, specifically calcium and magnesium ions ([Link](https://doi.org/10.1139/o2012-021)). Expression data analysis highlights its significant role in specialized cells of the central nervous system. **Overall**, [CIB4](/details-gene/130106) shows its most significant expression in the [ependymal cell](/details-cell/CL0000065), a cell type that lines the ventricles of the brain and the central canal of the spinal cord. This suggests a potential function related to cerebrospinal fluid homeostasis or ciliary activity. The gene was identified as part of the Mammalian Gene Collection, a large-scale effort to sequence full-length human and mouse cDNAs ([Link](https://doi.org/10.1101/gr.2596504)). ## Cellular Roles and Expression Landscape The expression profile of [CIB4](/details-gene/130106) points to a highly specialized role within the central nervous system. Analysis of its **Overall** expression pattern across numerous cell types reveals that its significance is most pronounced in the [ependymal cell](/details-cell/CL0000065) (CSI: 3.38). Ependymal cells are critical for forming the barrier between cerebrospinal fluid (CSF) and the brain parenchyma, and they play active roles in CSF production and circulation through the motility of their cilia. The high significance of [CIB4](/details-gene/130106) in this cell type suggests its involvement in processes that are fundamental to ependymal cell function, potentially linking intracellular calcium signaling to the regulation of ciliary movement or ion transport across the ependymal lining. The lack of significant expression in other cell types suggests a focused, rather than ubiquitous, function. ## Pathways and Molecular Function The known molecular functions of [CIB4](/details-gene/130106) are consistent with its identity as a calcium-binding protein. Gene Ontology annotations indicate that the CIB4 protein is involved in: * [Calcium ion binding (GO:0005509)](https://www.ebi.ac.uk/QuickGO/term/GO:0005509) * [Magnesium ion binding (GO:0000287)](https://www.ebi.ac.uk/QuickGO/term/GO:0000287) * [Protein binding (GO:0005515)](https://www.ebi.ac.uk/QuickGO/term/GO:0005515) Proteins in the CIB family, including CIB4, typically contain EF-hand motifs that are responsible for their calcium-binding properties. This ability to bind calcium suggests [CIB4](/details-gene/130106) acts as a calcium sensor or buffer, transducing changes in intracellular calcium concentration into downstream cellular responses. Biophysical studies of the human CIB protein family support their role in mediating calcium-dependent signaling events ([Link](https://doi.org/10.1139/o2012-021)). Given its prominent expression in [ependymal cells](/details-cell/CL0000065), it is plausible that [CIB4](/details-gene/130106) links calcium signals, potentially originating from the CSF or adjacent neurons, to the regulation of ciliary function or epithelial transport. ## Research Directions The specific expression of [CIB4](/details-gene/130106) in [ependymal cells](/details-cell/CL0000065) provides a strong foundation for investigating its role in central nervous system physiology. The current data supports several testable hypotheses. **Proposed Hypotheses:** 1. [CIB4](/details-gene/130106) is a critical regulator of ciliary beat frequency in [ependymal cells](/details-cell/CL0000065). Its function as a calcium-binding protein may allow it to modulate the dynein motors of cilia in a calcium-dependent manner, thereby controlling the flow of cerebrospinal fluid. 2. [CIB4](/details-gene/130106) functions as a sensor for ionic fluctuations within the cerebrospinal fluid. By binding calcium and magnesium, it may initiate signaling cascades within [ependymal cells](/details-cell/CL0000065) that regulate the composition and volume of the CSF. **Experimental Approach:** To test the hypothesis that [CIB4](/details-gene/130106) regulates ciliary function, one could utilize an *in vitro* model of primary ependymal cell culture derived from mouse brain ventricles. Using CRISPR-Cas9 or shRNA to specifically knock down [CIB4](/details-gene/130106) expression, the ciliary beat frequency could be measured using high-speed video microscopy and compared to control cells. Furthermore, these cultures could be exposed to varying concentrations of extracellular calcium to determine if CIB4-deficient cells exhibit an altered ciliary response to calcium stimuli, thus directly linking its calcium-binding function to a physiological output. **Therapeutic Potential:** Given the current data, the therapeutic potential of [CIB4](/details-gene/130106) is speculative but may be relevant to neurological disorders involving CSF dynamics, such as hydrocephalus. If [CIB4](/details-gene/130106) is found to be a key regulator of CSF circulation, its modulation could present a novel therapeutic avenue. However, as its expression pattern and role in disease are not yet well-defined, its viability as a drug target is low. Further research is required to determine if its function is dysregulated in pathological states and whether it can be targeted without causing adverse effects on normal brain function. Targeting would likely involve small molecules to modulate its activity, but a much deeper understanding of its structure and interactions is necessary first.

Genular Protein ID: 3282499872

Symbol: CIB4_HUMAN

Name: Calcium and integrin-binding family member 4

UniProtKB Accession Codes:

A0PJX0 B2RU18

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 9 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 GO 2 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 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: 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: 22779914

Title: Biophysical and structural studies of the human calcium- and integrin-binding protein family: understanding their functional similarities and differences.

PubMed ID: 22779914

DOI: 10.1139/o2012-021

Sequence Information:

  • Length: 185
  • Mass: 21745
  • Checksum: A0DB9D75BF8F9724
  • Sequence:
    • MGQCLRYQMH WEDLEEYQAL TFLTRNEILC IHDTFLKLCP PGKYYKEATL TMDQVSSLPA 
LRVNPFRDRI CRVFSHKGMF SFEDVLGMAS VFSEQACPSL KIEYAFRIYD FNENGFIDEE 
DLQRIILRLL NSDDMSEDLL MDLTNHVLSE SDLDNDNMLS FSEFEHAMAK SPDFMNSFRI 
HFWGC