CD109 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the CD109 gene, including its genomic location, protein function, expression patterns, associated diseases, and mutational landscape.
Gene Information Card
| Symbol | CD109 |
|---|---|
| Full Name | CD109 molecule |
| Gene Type | Protein coding |
| Chromosomal Location | 6q13 |
| NCBI Gene ID | 135228 ncbi.nlm.nih.gov/gene/135228 |
| Ensembl ID | ENSG00000156535 |
| UniProt ID | Q6YHK3 |
| OMIM ID | 618569 |
| HGNC ID | 21685 |
| Aliases | CPAMD5, GP175, p180 |
Description
The CD109 gene encodes a glycosylphosphatidylinositol (GPI)-anchored glycoprotein that is a member of the alpha-2-macroglobulin/complement protein family. It is known to act as a co-receptor and negative regulator of transforming growth factor-beta (TGF-beta) signaling. CD109 is expressed on a subset of hematopoietic stem/progenitor cells, activated T-cells, and platelets, and is also found in various tissues and cell lines. Its expression is frequently upregulated in several cancers, where it is associated with tumor progression and poor prognosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (Various) | Overexpression of CD109 in tumors promotes cancer cell proliferation, migration, and invasion. It modulates the tumor microenvironment by inhibiting TGF-beta signaling, which can lead to reduced growth inhibition and enhanced tumor aggressiveness. | High expression levels are reported in squamous cell carcinomas (lung, esophageal, oral), glioblastoma, and breast cancer. Studies show a correlation with poor patient survival and metastasis. |
| Pulmonary Fibrosis | CD109 is upregulated in lung tissue from patients with idiopathic pulmonary fibrosis (IPF). It is thought to contribute to fibrosis by modulating TGF-beta signaling in fibroblasts and epithelial cells. | Gene expression profiling and immunohistochemistry studies show increased CD109 in fibrotic lung tissue compared to normal controls. |
| Autoimmune Diseases | CD109 is expressed on activated T-cells and may play a role in regulating immune responses. Its altered expression has been observed in conditions like rheumatoid arthritis, though the exact mechanism is still under investigation. | Preliminary studies indicate differential expression of CD109 in immune cells from patients with autoimmune conditions, suggesting a potential immunomodulatory role. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.3 | Medium |
| Lung | 8.5 | Low |
| Breast | 6.1 | Low |
| Prostate | 5.2 | Low |
| Ovary | 4.8 | Low |
| Brain | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung Carcinoma) | 15.2 | High expression, associated with invasive phenotype. |
| MCF7 (Breast Carcinoma) | 9.8 | Moderate expression, linked to TGF-beta resistance. |
| HaCaT (Keratinocyte) | 22.5 | Very high expression, used as a model for skin biology. |
| U87MG (Glioblastoma) | 18.7 | High expression, promotes tumor growth. |
| HUVEC (Endothelial) | 3.4 | Low expression, may play a role in angiogenesis. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Ter) | Nonsense | <0.1% | Predicted to result in a truncated, non-functional protein, potentially leading to loss of TGF-beta regulation. |
| c.456G>A (p.Val152Ile) | Missense | <0.1% | A rare variant of uncertain significance; may alter protein stability or interaction with TGF-beta. |
| c.789_790insA (p.Leu264ThrfsTer5) | Frameshift | <0.1% | Predicted to cause premature termination of translation, likely resulting in a loss-of-function allele. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CD109 are rare and not well-characterized. They are predicted to impair the protein's ability to negatively regulate TGF-beta signaling, potentially leading to enhanced TGF-beta activity and altered cellular responses.
Gain of Function (GOF)
Gain-of-function is primarily observed at the expression level rather than through specific mutations. Overexpression of wild-type CD109 in cancers acts as a functional 'gain' by excessively inhibiting TGF-beta signaling, promoting tumor progression.
Dominant Negative (DN)
No dominant-negative mutations have been described for CD109. The protein functions as a monomer, and its inhibitory effect on TGF-beta is likely dependent on its expression level rather than a dominant-negative mechanism.
View complete mutation data：
Gene Ontology (GO)
| • negative regulation of transforming growth factor beta receptor signaling pathway | • cell surface receptor signaling pathway |
| • protease binding | • extracellular region |
| • anchored component of membrane | • cell differentiation |
| • cell proliferation |
Pathways
• TGF-beta signaling pathway
• Regulation of epithelial to mesenchymal transition (EMT)
Protein Summary
The CD109 protein is a large (~180 kDa) glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein. It is synthesized as a precursor that is cleaved into a heavy chain and a light chain, which remain associated. CD109 is a member of the alpha-2-macroglobulin (A2M) family and contains a thioester domain. It functions as a co-receptor for TGF-beta, binding to the TGF-beta receptor complex and promoting its degradation. This action negatively regulates TGF-beta signaling, which is crucial for controlling cell growth, differentiation, and immune responses. CD109 is also involved in cell adhesion and migration. Its expression is tightly regulated, and aberrant overexpression is a hallmark of several aggressive cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CD109 Knockout HEK293 Cell Line | EDJ-KQ9358 | Human | 135228 | Details Get a Quote |
| CD109 Knockout A-549 Cell Line | EDJ-KQ36002 | Human | 135228 | Details Get a Quote |
| CD109 Knockout HCT 116 Cell Line | EDJ-KQ36003 | Human | 135228 | Details Get a Quote |
| CD109 Knockout HeLa Cell Line | EDJ-KQ36004 | Human | 135228 | Details Get a Quote |
| CD109 Overexpression Huh-7 Stable Cell Line | EDC90337 | Human | 135228 | Details Get a Quote |
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