CNMD Gene

Name chondromodulin
Description This gene encodes a glycosylated transmembrane protein that is cleaved to form a mature, secreted protein. The N-terminus of the precursor protein shares characteristics with other surfactant proteins and is sometimes called chondrosurfactant protein although no biological activity has yet been defined for it. The C-terminus of the precursor protein contains a 25 kDa mature protein called leukocyte cell-derived chemotaxin-1 or chondromodulin-1. The mature protein promotes chondrocyte growth and inhibits angiogenesis. This gene is expressed in the avascular zone of prehypertrophic cartilage and its expression decreases during chondrocyte hypertrophy and vascular invasion. The mature protein likely plays a role in endochondral bone development by permitting cartilaginous anlagen to be vascularized and replaced by bone. It may be involved also in the broad control of tissue vascularization during development. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Chondromodulin (CNMD), particularly in the form of chondromodulin‐1 (ChM‐I), is a cartilage‐derived glycoprotein that plays dual, context‐dependent roles in tissue homeostasis. First, its potent antiangiogenic activity is critical for maintaining the avascularity of cartilage and specialized connective tissues such as cardiac valves and the inner meniscus. CNMD accomplishes this by inhibiting endothelial cell migration, tube formation, and actin cytoskeleton reorganization—processes largely mediated via attenuation of VEGF‐induced signaling cascades."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Second, CNMD supports chondrogenesis by stabilizing the chondrocyte phenotype and preventing premature hypertrophic maturation and subsequent endochondral ossification. In various experimental models, gene transfer of CNMD promoted chondrogenic differentiation and maintained a hyaline‐like cartilage matrix, whereas loss‐of‐function studies (including knockout models) have revealed defects in proper cartilage repair and fracture healing with aberrant bone remodeling and delayed callus formation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, transcriptional and epigenetic regulation of the CNMD gene—via factors such as Sp3 and modifications of its promoter methylation state—ensures its tissue‐specific expression in avascular regions, further reinforcing its role as a gatekeeper against unwanted vascular invasion."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In disease contexts, aberrant CNMD expression has broader implications. For example, overexpression of CNMD in Ewing sarcoma supports chondrogenic differentiation while dampening osteolytic signaling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", and alterations in CNMD levels have been associated with immune modulation in rheumatoid arthritis via suppression of synovial cell proliferation and T‐cell responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Additionally, polymorphisms in the chondromodulin‐II gene have been linked to increased radiographic progression in joint destruction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these studies indicate that CNMD acts as a critical factor in preserving the avascular environment necessary for cartilage integrity and proper skeletal development, while also modulating tissue repair and disease progression through its antiangiogenic and chondroprotective functions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "18"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Masatoyo Yoshioka, Shinsuke Yuasa, Keisuke Matsumura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chondromodulin-I maintains cardiac valvular function by preventing angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm1476"}], "href": "https://doi.org/10.1038/nm1476"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16980969"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16980969"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Berit Olofsson, Helena Porsch, Paraskevi Heldin "}, {"type": "b", "children": [{"type": "t", "text": "Knock-down of CD44 regulates endothelial cell differentiation via NFκB-mediated chemokine production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0090921"}], "href": "https://doi.org/10.1371/journal.pone.0090921"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24614402"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24614402"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shigenori Miura, Kaori Mitsui, Takahiro Heishi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impairment of VEGF-A-stimulated lamellipodial extensions and motility of vascular endothelial cells by chondromodulin-I, a cartilage-derived angiogenesis inhibitor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2009.12.009"}], "href": "https://doi.org/10.1016/j.yexcr.2009.12.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20026108"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20026108"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "An-Chi Tsai, Shiow-Lin Pan, Hui-Lung Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CHM-1, a new vascular targeting agent, induces apoptosis of human umbilical vein endothelial cells via p53-mediated death receptor 5 up-regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.036277"}], "href": "https://doi.org/10.1074/jbc.M109.036277"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20007968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20007968"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Patricia Klinger, Cordula Surmann-Schmitt, Matthias Brem, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chondromodulin 1 stabilizes the chondrocyte phenotype and inhibits endochondral ossification of porcine cartilage repair tissue."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Rheum (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/art.30335"}], "href": "https://doi.org/10.1002/art.30335"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21391200"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21391200"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yuko Nakamichi, Chisa Shukunami, Takashi Yamada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chondromodulin I is a bone remodeling factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.2.636-644.2003"}], "href": "https://doi.org/10.1128/MCB.23.2.636-644.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12509461"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12509461"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kiminori Yukata, Yoshito Matsui, Chisa Shukunami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered fracture callus formation in chondromodulin-I deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bone (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bone.2008.08.111"}], "href": "https://doi.org/10.1016/j.bone.2008.08.111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18793763"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18793763"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yueqian Zhu, Yingying Zhang, Yu Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The influence of Chm-I knockout on ectopic cartilage regeneration and homeostasis maintenance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tissue Eng Part A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/ten.TEA.2014.0277"}], "href": "https://doi.org/10.1089/ten.TEA.2014.0277"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25251892"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25251892"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Tomoki Aoyama, Takeshi Okamoto, Satoshi Nagayama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Methylation in the core-promoter region of the chondromodulin-I gene determines the cell-specific expression by regulating the binding of transcriptional activator Sp3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M401273200"}], "href": "https://doi.org/10.1074/jbc.M401273200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15107420"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15107420"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Tomoki Aoyama, Takeshi Okamoto, Kenichi Fukiage, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Histone modifiers, YY1 and p300, regulate the expression of cartilage-specific gene, chondromodulin-I, in mesenchymal stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.116319"}], "href": "https://doi.org/10.1074/jbc.M110.116319"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20663886"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20663886"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Tomoki Aoyama, Takeshi Okamoto, Yoshiki Kohno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cell-specific epigenetic regulation of ChM-I gene expression: crosstalk between DNA methylation and histone acetylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2007.10.135"}], "href": "https://doi.org/10.1016/j.bbrc.2007.10.135"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17980151"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17980151"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Kristina von Heyking, Julia Calzada-Wack, Stefanie Göllner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The endochondral bone protein CHM1 sustains an undifferentiated, invasive phenotype, promoting lung metastasis in Ewing sarcoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Oncol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1878-0261.12057"}], "href": "https://doi.org/10.1002/1878-0261.12057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28319320"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28319320"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Keigo Setoguchi, Yoshikata Misaki, Kimito Kawahata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Suppression of T cell responses by chondromodulin I, a cartilage-derived angiogenesis inhibitory factor: therapeutic potential in rheumatoid arthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Rheum (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/art.20193"}], "href": "https://doi.org/10.1002/art.20193"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15022325"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15022325"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Juergen Graessler, Michael Verlohren, Anett Graessler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of chondromodulin-II Val58Ile polymorphism with radiographic joint destruction in rheumatoid arthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Rheumatol (2005)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16142856"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16142856"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Jérôme E Lafont, Sonia Talma, Christine Hopfgarten, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypoxia promotes the differentiated human articular chondrocyte phenotype through SOX9-dependent and -independent pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M707729200"}], "href": "https://doi.org/10.1074/jbc.M707729200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18077449"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18077449"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Chisa Shukunami, Aki Takimoto, Shigenori Miura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chondromodulin-I and tenomodulin are differentially expressed in the avascular mesenchyme during mouse and chick development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Tissue Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00441-007-0570-8"}], "href": "https://doi.org/10.1007/s00441-007-0570-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18239943"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18239943"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Masataka Fujii, Takayuki Furumatsu, Yusuke Yokoyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chondromodulin-I derived from the inner meniscus prevents endothelial cell proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Orthop Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jor.22257"}], "href": "https://doi.org/10.1002/jor.22257"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23143879"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23143879"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Oliver Brandau, Attila Aszódi, Ernst B Hunziker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chondromodulin I is dispensable during enchondral ossification and eye development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.22.18.6627-6635.2002"}], "href": "https://doi.org/10.1128/MCB.22.18.6627-6635.2002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12192060"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12192060"}]}]}]}
NCBI Gene ID 11061
API
Download Associations
Predicted Functions View CNMD's ARCHS4 Predicted Functions.
Co-expressed Genes View CNMD's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View CNMD's ARCHS4 Predicted Functions.

Functional Associations

CNMD has 1,394 functional associations with biological entities spanning 5 categories (chemical, functional term, phrase or reference, disease, phenotype or trait, cell line, cell type or tissue, gene, protein or microRNA) extracted from 17 datasets.

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

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles tissue samples with high or low expression of CNMD gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
Carcinogenome Chemical Perturbation Carcinogenicity Signatures small molecule perturbations changing expression of CNMD gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
CM4AI KOLF21J CRISPRi Gene Perturbation Atlas gene perturbations changing expression of CNMD gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 cellular components co-occuring with CNMD protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with CNMD gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
GO Biological Process Annotations 2025 biological processes involving CNMD gene from the curated GO Biological Process Annotations2025 dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of CNMD gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
JASPAR Predicted Human Transcription Factor Targets 2025 transcription factors regulating expression of CNMD 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 CNMD gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset.
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures small molecule perturbations changing expression of CNMD gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset.
MoTrPAC Rat Endurance Exercise Training tissue samples with high or low expression of CNMD gene relative to other tissue samples from the MoTrPAC Rat Endurance Exercise Training dataset.
Rummagene Transcription Factor Associations 2026 transcription factors regulating expression of CNMD gene from the Rummagene Transcription Factor Associations 2026 dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of CNMD gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of CNMD gene from the RummaGEO Gene Perturbation Signatures dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of CNMD protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with CNMD protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.
WikiPathways Pathways 2024 pathways involving CNMD protein from the WikiPathways Pathways 2024 dataset.