Details for: CORT

Gene ID: 1325

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: CORT

Ensembl ID: ENSG00000241563

Description: cortistatin

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • sst GABAergic cortical interneuron CL4023017
    CSI 3.76
    rCSI 4.85%
    PRS 99.27
  • GABAergic neuron CL0000617
    CSI 1.22
    rCSI 4.07%
    PRS 97.66

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

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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 [CORT](/details-gene/1325), also known as cortistatin, is a protein-coding gene located on chromosome 1p36.22. It encodes a neuropeptide that plays a significant role in neuronal signaling. Functional annotations indicate that [CORT](/details-gene/1325) is involved in G protein-coupled receptor (GPCR) binding, particularly through inhibitory G alpha (i) signaling pathways, and is crucial for chemical synaptic transmission. Expression data highlights its highly specific role within the central nervous system, where it is a defining marker for specific inhibitory neuronal subtypes, most notably [sst GABAergic cortical interneurons](/details-cell/CL4023017). Early research identified and characterized this peptide, mapping its expression and chromosomal location ([Link](https://doi.org/10.1006/bbrc.1997.6252), [Link](https://doi.org/10.1006/geno.1997.4763)). Its association with OMIM entry [602784](https://omim.org/entry/602784) underscores its clinical relevance. ## Cellular Roles and Expression Landscape The expression profile of [CORT](/details-gene/1325) reveals a highly specialized function within the nervous system. **Overall**, the gene exhibits its most significant expression in specific subsets of inhibitory neurons. It is most prominently expressed in [sst GABAergic cortical interneurons](/details-cell/CL4023017) (CSI: 3.76), suggesting it is a key functional component and specific marker for this cell population. Its significance is also high in the broader category of [GABAergic neurons](/details-cell/CL0000617) (CSI: 1.22). This restricted expression pattern strongly implies a specialized role for [CORT](/details-gene/1325) in modulating cortical circuits, likely by regulating the activity of other neurons through inhibitory signaling. The data does not show significant expression outside of these neuronal subtypes, underscoring its focused biological role. ## Pathways and Molecular Function The molecular functions of [CORT](/details-gene/1325) are consistent with its role as a secreted neuropeptide that modulates neuronal activity. As a ligand, it is involved in [GPCR ligand binding](/details-gene/R-HSA-500792) and acts upon [Class a/1 (rhodopsin-like receptors)](https://reactome.org/content/detail/R-HSA-373076). Its signaling mechanism proceeds via [GPCR downstream signalling](https://reactome.org/content/detail/R-HSA-388396), specifically engaging [G alpha (i) signalling events](https://reactome.org/content/detail/R-HSA-418594). This is consistent with its role in the [adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway](/details-cell/GO:0007193), which typically results in a reduction of intracellular cAMP and a net inhibitory effect on the cell. Its localization to the [extracellular region](/details-cell/GO:0005576) and its function within the [synapse](/details-cell/GO:0045202) are central to its role in [chemical synaptic transmission](/details-cell/GO:0007268). Additionally, its annotation for the [regulation of cell migration](/details-cell/GO:0030334) suggests potential roles in neurodevelopment or neuronal plasticity beyond its immediate function in synaptic modulation. ## Research Directions The highly specific expression of [CORT](/details-gene/1325) in inhibitory interneurons suggests it is a critical regulator of cortical network function. Its role as an inhibitory neuromodulator positions it as a key player in maintaining the excitatory/inhibitory balance essential for normal brain function. Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis:** The selective expression of [CORT](/details-gene/1325) in [sst GABAergic cortical interneurons](/details-cell/CL4023017) indicates that its primary function is to mediate specific forms of local circuit inhibition, potentially by acting on presynaptic terminals of pyramidal neurons to suppress neurotransmitter release. 2. **Hypothesis:** Given its role in regulating cell migration, [CORT](/details-gene/1325) may be crucial during cortical development for the proper laminar positioning and integration of somatostatin-positive interneurons into nascent neural circuits. **Experimental Approach:** To test the first hypothesis regarding its role in circuit modulation, a conditional knockout of [CORT](/details-gene/1325) could be generated in a mouse model using a Cre-driver line specific for somatostatin-expressing neurons (e.g., Sst-Cre). Brain slices from these knockout animals could then be analyzed using electrophysiology. Patch-clamp recordings from pyramidal neurons could assess whether the loss of [CORT](/details-gene/1325) alters the frequency or amplitude of spontaneous or evoked inhibitory postsynaptic currents (IPSCs), providing direct evidence of its role in synaptic modulation. **Therapeutic Potential:** As a neuromodulator that enhances inhibitory tone, the [CORT](/details-gene/1325) signaling pathway represents a potential therapeutic target for neurological and psychiatric disorders characterized by cortical hyperexcitability, such as epilepsy or certain aspects of schizophrenia. The development of small molecule agonists targeting the specific GPCRs that cortistatin binds to could offer a strategy to selectively dampen excessive neuronal activity. Such a strategy would focus on activation of its inhibitory signaling pathway, making it a promising avenue for developing novel therapeutics.

Genular Protein ID: 2233170570

Symbol: CORT_HUMAN

Name: Cortistatin

UniProtKB Accession Codes:

O00230 Q5T6G0 Q6UX11

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 7 EMDB 3 Ensembl 1 GO 8 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 5 PDBsum 5 PIR 1 PIRSF 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 Reactome 2 RefSeq 1 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 UCSC 1 UniProtKB 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9125122

Title: Identification and characterization of a novel human cortistatin-like peptide.

PubMed ID: 9125122

DOI: 10.1006/bbrc.1997.6252

PubMed ID: 9205124

Title: Cloning, mRNA expression, and chromosomal mapping of mouse and human preprocortistatin.

PubMed ID: 9205124

DOI: 10.1006/geno.1997.4763

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 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

Sequence Information:

  • Length: 105
  • Mass: 11532
  • Checksum: 09578F4520201551
  • Sequence:
    • MPLSPGLLLL LLSGATATAA LPLEGGPTGR DSEHMQEAAG IRKSSLLTFL AWWFEWTSQA 
SAGPLIGEEA REVARRQEGA PPQQSARRDR MPCRNFFWKT FSSCK

Genular Protein ID: 2858329919

Symbol: Q8IUV6_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q8IUV6

Database IDs:

ARBA 3 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 GO 2 InterPro 2 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PIRSF 1 PIRSR 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 1 SAM 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

Sequence Information:

  • Length: 122
  • Mass: 13369
  • Checksum: A1279CA09CB0CB44
  • Sequence:
    • GRKSSSRVGE KLQSAHKMPL SPGLLLLLLS GATATAALPL EGGPTGRDSE HMQEAAGIRK 
SSLLTFLAWW FEWTSQASAG PLIGEEAREV ARRQEGAPPQ QSARRDRMPC RNFFWKTFSS 
CK