Details for: CHRDL2

Gene ID: 25884

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: CHRDL2

Ensembl ID: ENSG00000054938

Description: chordin like 2

Cell Significance Landscape

Associated with

Significant Cells

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

  • enteric smooth muscle cell CL0002504
    CSI 4.24
    rCSI 6.05%
    PRS 100
  • bronchiolar smooth muscle cell CL4033017
    CSI 0.71
    rCSI 10.59%
    PRS 100

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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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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    • 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 [CHRDL2](/details-gene/25884) (Chordin Like 2) is a protein-coding gene that encodes a secreted protein belonging to the chordin family. Functionally, it is an antagonist of Bone Morphogenetic Protein (BMP) signaling, playing a role in processes such as cartilage development, ossification, and cell differentiation. Expression data indicates that **Overall**, [CHRDL2](/details-gene/25884) is most significantly expressed in [enteric smooth muscle cell](/details-cell/CL0002504), suggesting a primary role in the biology of the gastrointestinal tract. Research has also linked its expression to myoblast and osteoblast maturation, chondrocyte development, and its overexpression has been observed in certain tumor tissues ([Link](https://doi.org/10.1016/s0378-1119(03)00563-8); [Link](https://doi.org/10.1242/dev.00901)). ## Cellular Roles and Expression Landscape The expression profile of [CHRDL2](/details-gene/25884) points towards a specialized role in smooth muscle tissues. **Overall**, its most significant expression is found in [enteric smooth muscle cell](/details-cell/CL0002504) (CSI: 4.24), with notable, albeit lower, significance in [bronchiolar smooth muscle cell](/details-cell/CL4033017) (CSI: 0.71). This strong association with smooth muscle suggests a function in regulating the development, homeostasis, or contractility of these tissues, possibly through its known role as a BMP inhibitor. While the expression data highlights its role in smooth muscle, published research expands its cellular context. Studies have demonstrated its expression in chondrocytes, particularly in developing and osteoarthritic cartilage ([Link](https://doi.org/10.1242/dev.00901)), as well as during the maturation of myoblasts and osteoblasts ([Link](https://doi.org/10.1016/j.gene.2004.01.029)). This broader expression pattern is consistent with its function in modulating BMP signaling, a critical pathway in musculoskeletal development. ## Pathways and Molecular Function [CHRDL2](/details-gene/25884) functions primarily as an extracellular antagonist of the BMP signaling pathway. Its molecular function involves direct BMP binding ([GO:0036122](https://www.ebi.ac.uk/QuickGO/term/GO:0036122)), which in turn leads to the negative regulation of BMP signaling ([GO:0030514](https://www.ebi.ac.uk/QuickGO/term/GO:0030514)). As a secreted protein found in the extracellular space ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO:0005615)), it can act locally to control the concentration and activity of BMPs. This regulatory role is crucial for several biological processes. The gene's involvement in cartilage development ([GO:0051216](https://www.ebi.ac.uk/QuickGO/term/GO:0051216)) and ossification ([GO:0001503](https://www.ebi.ac.uk/QuickGO/term/GO:0001503)) underscores its importance in skeletal formation and maintenance. Its participation in the general process of cell differentiation ([GO:0030154](https://www.ebi.ac.uk/QuickGO/term/GO:0030154)) reflects the fundamental role of BMP signaling in determining cellular fate across various lineages. ## Research Directions The specific function of [CHRDL2](/details-gene/25884) in smooth muscle and its reported deregulation in cancer present compelling avenues for future research. The protein's role as a secreted BMP inhibitor makes it a potentially tractable target for therapeutic intervention. ### Proposed Hypotheses 1. Given its high and specific expression in [enteric smooth muscle cell](/details-cell/CL0002504), [CHRDL2](/details-gene/25884) may be a critical local regulator of gastrointestinal smooth muscle homeostasis and peristalsis by modulating BMP signaling, which is known to influence smooth muscle differentiation and function. 2. Based on findings that it is overexpressed in some tumor tissues ([Link](https://doi.org/10.1016/s0378-1119(03)00563-8)), [CHRDL2](/details-gene/25884) may promote tumorigenesis by creating a microenvironment with suppressed BMP activity, thereby inhibiting BMP-induced cell differentiation and apoptosis and allowing for uncontrolled cell proliferation. ### Key Experiment To test the hypothesis regarding its role in enteric smooth muscle, a conditional knockout mouse model could be generated where [CHRDL2](/details-gene/25884) is specifically deleted in smooth muscle cells (e.g., using a *Myh11-Cre* driver). The phenotype of these mice could be assessed by measuring gut transit time, performing ex vivo contractility studies on intestinal segments, and using histology and RNA-sequencing to examine changes in smooth muscle layer morphology and the expression of BMP pathway target genes. ### Therapeutic Potential As a secreted protein that is overexpressed in certain cancers, [CHRDL2](/details-gene/25884) presents a promising therapeutic target. **Inhibition** of its function would be the primary strategy. A neutralizing monoclonal antibody that binds to CHRDL2 and prevents it from sequestering BMPs could restore tumor-suppressive BMP signaling within the tumor microenvironment. Such a therapy could be particularly relevant for tumors where loss of BMP signaling is a known driver of disease progression. Furthermore, its extracellular nature makes it an accessible target for antibody-drug conjugates or as a non-invasive biomarker in liquid biopsies.

Genular Protein ID: 2805586350

Symbol: CRDL2_HUMAN

Name: Chordin-like protein 2

UniProtKB Accession Codes:

Q6WN34 A5PKU9 Q6WN30 Q6WN31 Q6WN32 Q7Z5J3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CORUM 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 4 ExpressionAtlas 1 GO 7 Gene3D 2 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 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 5 RNAct 1 RefSeq 7 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12853144

Title: BNF-1, a novel gene encoding a putative extracellular matrix protein, is overexpressed in tumor tissues.

PubMed ID: 12853144

DOI: 10.1016/s0378-1119(03)00563-8

PubMed ID: 15094188

Title: hCHL2, a novel chordin-related gene, displays differential expression and complex alternative splicing in human tissues and during myoblast and osteoblast maturation.

PubMed ID: 15094188

DOI: 10.1016/j.gene.2004.01.029

PubMed ID: 14660436

Title: A novel chordin-like BMP inhibitor, CHL2, expressed preferentially in chondrocytes of developing cartilage and osteoarthritic joint cartilage.

PubMed ID: 14660436

DOI: 10.1242/dev.00901

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: 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

PubMed ID: 18780401

Title: Identification of N-linked glycoproteins in human milk by hydrophilic interaction liquid chromatography and mass spectrometry.

PubMed ID: 18780401

DOI: 10.1002/pmic.200701057

PubMed ID: 26091039

Title: A single kinase generates the majority of the secreted phosphoproteome.

PubMed ID: 26091039

DOI: 10.1016/j.cell.2015.05.028

Sequence Information:

  • Length: 429
  • Mass: 47495
  • Checksum: A8111F26B2EF96A4
  • Sequence:
    • MVPEVRVLSS LLGLALLWFP LDSHARARPD MFCLFHGKRY SPGESWHPYL EPQGLMYCLR 
CTCSEGAHVS CYRLHCPPVH CPQPVTEPQQ CCPKCVEPHT PSGLRAPPKS CQHNGTMYQH 
GEIFSAHELF PSRLPNQCVL CSCTEGQIYC GLTTCPEPGC PAPLPLPDSC CQACKDEASE 
QSDEEDSVQS LHGVRHPQDP CSSDAGRKRG PGTPAPTGLS APLSFIPRHF RPKGAGSTTV 
KIVLKEKHKK ACVHGGKTYS HGEVWHPAFR AFGPLPCILC TCEDGRQDCQ RVTCPTEYPC 
RHPEKVAGKC CKICPEDKAD PGHSEISSTR CPKAPGRVLV HTSVSPSPDN LRRFALEHEA 
SDLVEIYLWK LVKGIFHLTQ IKKVRKQDFQ KEAQHFRLLA GPHEGHWNVF LAQTLELKVT 
ASPDKVTKT