CHRDL2 Gene

Name chordin-like 2
Description This gene encodes a member of the chordin family of proteins. Chordin family members are secreted proteins that share a cysteine-rich pro-collagen repeat domain and associate with members of the transforming growth factor beta superfamily. In vitro assays demonstrate a direct interaction between the encoded protein and human activin A. This gene is expressed in many tissues including osteoblasts, where it is differentially expressed during differentiation. In addition, its expression is upregulated in human osteoarthritic joint cartilage, suggesting a role in adult cartilage regeneration. [provided by RefSeq, Jan 2015]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CHRDL2 is a secreted antagonist of bone morphogenetic protein (BMP) signaling that regulates pivotal developmental and pathological processes. Functional studies have demonstrated that CHRDL2 binds directly to BMP ligands, thereby competitively inhibiting their interaction with type I receptors and downstream signaling events. In developmental contexts, CHRDL2 is selectively expressed in chondrocytes and mesenchymal progenitor populations, where its activity negatively regulates cartilage matrix deposition, mineralization, and overall chondrocyte maturation. Such inhibitory effects suggest that CHRDL2 may contribute to impaired regeneration or aberrant differentiation in articular cartilage, as observed in osteoarthritic conditions. In addition, multiple studies have reported that CHRDL2 is upregulated in several malignancies—including osteosarcoma, colorectal cancer, and gastric cancer—where its elevated expression correlates with enhanced cell proliferation, migration, and survival via mechanisms such as modulation of the BMP9/PI3K–AKT axis and alterations in cell cycle regulators. Moreover, tissue‐specific alternative splicing may generate distinct CHRDL2 isoforms, potentially diversifying its function. Collectively, these findings establish CHRDL2 as a multifaceted modulator of BMP signaling with significant implications for cartilage homeostasis and oncogenic progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Naoki Nakayama, Chun-ya E Han, Linh Cam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel chordin-like BMP inhibitor, CHL2, expressed preferentially in chondrocytes of developing cartilage and osteoarthritic joint cartilage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.00901"}], "href": "https://doi.org/10.1242/dev.00901"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14660436"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14660436"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Houping Chen, Runsang Pan, Hao Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CHRDL2 promotes osteosarcoma cell proliferation and metastasis through the BMP-9/PI3K/AKT pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biol Int (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cbin.11507"}], "href": "https://doi.org/10.1002/cbin.11507"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33245175"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33245175"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jian Sun, Xuan Liu, Hong Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of colorectal cancer oncogene CHRDL2 predicts a poor prognosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.14039"}], "href": "https://doi.org/10.18632/oncotarget.14039"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28009989"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28009989"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xin Yu, Bin Yu, Weidan Fang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification hub genes of consensus molecular subtype correlation with immune infiltration and predict prognosis in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Discov Oncol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12672-021-00434-5"}], "href": "https://doi.org/10.1007/s12672-021-00434-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35201473"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35201473"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Anat Oren, Amir Toporik, Sharon Biton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "hCHL2, a novel chordin-related gene, displays differential expression and complex alternative splicing in human tissues and during myoblast and osteoblast maturation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2004.01.029"}], "href": "https://doi.org/10.1016/j.gene.2004.01.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15094188"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15094188"}]}]}]}
Synonyms CHL2, BNF1
Proteins CRDL2_HUMAN
NCBI Gene ID 25884
API
Download Associations
Predicted Functions View CHRDL2's ARCHS4 Predicted Functions.
Co-expressed Genes View CHRDL2's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View CHRDL2's ARCHS4 Predicted Functions.

Functional Associations

CHRDL2 has 2,712 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 82 datasets.

Click the + buttons to view associations for CHRDL2 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles tissues with high or low expression of CHRDL2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles tissue samples with high or low expression of CHRDL2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray tissue samples with high or low expression of CHRDL2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles tissues with high or low expression of CHRDL2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
BioGPS Human Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of CHRDL2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
BioGPS Mouse Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of CHRDL2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of CHRDL2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
CCLE Cell Line Gene Expression Profiles cell lines with high or low expression of CHRDL2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
CellMarker Gene-Cell Type Associations cell types associated with CHRDL2 gene from the CellMarker Gene-Cell Type Associations dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of CHRDL2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of CHRDL2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
ChEA Transcription Factor Targets 2022 transcription factors binding the promoter of CHRDL2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores cellular components containing CHRDL2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing CHRDL2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Experimental Protein Localization Evidence Scores cellular components containing CHRDL2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 cellular components containing CHRDL2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores cellular components co-occuring with CHRDL2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 cellular components co-occuring with CHRDL2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
CORUM Protein Complexes protein complexs containing CHRDL2 protein from the CORUM Protein Complexes dataset.
COSMIC Cell Line Gene CNV Profiles cell lines with high or low copy number of CHRDL2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with CHRDL2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Disease Associations diseases associated with CHRDL2 gene/protein from the curated CTD Gene-Disease Associations dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by CHRDL2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Experimental Gene-Disease Association Evidence Scores 2025 diseases associated with CHRDL2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores diseases co-occuring with CHRDL2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with CHRDL2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
DisGeNET Gene-Disease Associations diseases associated with CHRDL2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with CHRDL2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
ENCODE Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at CHRDL2 gene from the ENCODE Histone Modification Site Profiles dataset.
ENCODE Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of CHRDL2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of CHRDL2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
ESCAPE Omics Signatures of Genes and Proteins for Stem Cells PubMedIDs of publications reporting gene signatures containing CHRDL2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
GAD Gene-Disease Associations diseases associated with CHRDL2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with CHRDL2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
GeneSigDB Published Gene Signatures PubMedIDs of publications reporting gene signatures containing CHRDL2 from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of CHRDL2 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations kinase perturbations changing expression of CHRDL2 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of CHRDL2 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations transcription factor perturbations changing expression of CHRDL2 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of CHRDL2 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GlyGen Glycosylated Proteins ligands (chemical) binding CHRDL2 protein from the GlyGen Glycosylated Proteins dataset.
GO Biological Process Annotations 2015 biological processes involving CHRDL2 gene from the curated GO Biological Process Annotations 2015 dataset.
GO Biological Process Annotations 2023 biological processes involving CHRDL2 gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving CHRDL2 gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2015 cellular components containing CHRDL2 protein from the curated GO Cellular Component Annotations 2015 dataset.
GO Molecular Function Annotations 2023 molecular functions performed by CHRDL2 gene from the curated GO Molecular Function Annotations 2023 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by CHRDL2 gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of CHRDL2 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of CHRDL2 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GTEx Tissue Sample Gene Expression Profiles tissue samples with high or low expression of CHRDL2 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset.
GWAS Catalog SNP-Phenotype Associations 2025 phenotypes associated with CHRDL2 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.
GWASdb SNP-Phenotype Associations phenotypes associated with CHRDL2 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset.
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles cell lines with high or low expression of CHRDL2 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of CHRDL2 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset.
HPA Tissue Protein Expression Profiles tissues with high or low expression of CHRDL2 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset.
HPA Tissue Sample Gene Expression Profiles tissue samples with high or low expression of CHRDL2 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for CHRDL2 protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Human Transcription Factor Targets 2025 transcription factors regulating expression of CHRDL2 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset.
JASPAR Predicted Mouse Transcription Factor Targets 2025 transcription factors regulating expression of CHRDL2 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of CHRDL2 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of CHRDL2 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles cell lines with CHRDL2 gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset.
KnockTF Gene Expression Profiles with Transcription Factor Perturbations transcription factor perturbations changing expression of CHRDL2 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain CHRDL2 protein from the LOCATE Predicted Protein Localization Annotations dataset.
MiRTarBase microRNA Targets microRNAs targeting CHRDL2 gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset.
MotifMap Predicted Transcription Factor Targets transcription factors regulating expression of CHRDL2 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset.
MoTrPAC Rat Endurance Exercise Training tissue samples with high or low expression of CHRDL2 gene relative to other tissue samples from the MoTrPAC Rat Endurance Exercise Training dataset.
MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations gene perturbations changing expression of CHRDL2 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for CHRDL2 from the Pathway Commons Protein-Protein Interactions dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of CHRDL2 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations gene perturbations changing expression of CHRDL2 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles cell types and tissues with high or low DNA methylation of CHRDL2 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset.
Roadmap Epigenomics Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at CHRDL2 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of CHRDL2 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of CHRDL2 gene from the RummaGEO Gene Perturbation Signatures dataset.
Tabula Sapiens Gene-Cell Associations cell types with high or low expression of CHRDL2 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset.
TargetScan Predicted Conserved microRNA Targets microRNAs regulating expression of CHRDL2 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset.
TCGA Signatures of Differentially Expressed Genes for Tumors tissue samples with high or low expression of CHRDL2 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores tissues with high expression of CHRDL2 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 tissues with high expression of CHRDL2 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with CHRDL2 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with CHRDL2 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.