CAPN9: Calpain 9 - Structure, Function, and Disease Associations
A comprehensive biomedical overview of the CAPN9 gene, encoding calpain-9, a calcium-dependent cysteine protease involved in gastric physiology and cancer.
Gene Information Card
| Symbol | CAPN9 |
|---|---|
| Full Name | calpain 9 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q42.2 |
| NCBI Gene ID | 10753 ncbi.nlm.nih.gov/gene/10753 |
| Ensembl ID | ENSG00000142409 |
| UniProt ID | O14815 |
| OMIM ID | 606401 |
| HGNC ID | 1484 |
| Aliases | nCL-4, calpain-9, calpain 9 (nCL-4) |
Description
CAPN9 (calpain 9) is a protein-coding gene that encodes a member of the calpain family of calcium-dependent cysteine proteases. The encoded protein, calpain-9 (also known as nCL-4), is predominantly expressed in the digestive tract, particularly the stomach, and plays a role in gastric epithelial cell differentiation, cell adhesion, and apoptosis. CAPN9 is considered a tumor suppressor candidate in gastric cancer, with downregulation or loss of expression observed in gastric carcinoma tissues. The gene spans approximately 30 kb on chromosome 1q42.2 and contains 15 exons.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gastric cancer | Loss of CAPN9 expression leads to reduced apoptosis and increased cell proliferation, contributing to tumorigenesis. | PMID: 15604205, PMID: 19030189 |
| Gastric adenocarcinoma | Hypermethylation of the CAPN9 promoter results in transcriptional silencing. | PMID: 19030189 |
| Colorectal cancer | Reduced CAPN9 expression correlates with poor prognosis and metastasis. | PMID: 23608867 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Stomach | 18.5 | High |
| Duodenum | 12.3 | Medium |
| Small intestine | 10.1 | Medium |
| Colon | 8.7 | Medium |
| Esophagus | 6.2 | Low |
| Liver | 2.1 | Low |
| Pancreas | 1.8 | Low |
| Kidney | 0.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MKN45 (gastric cancer) | 5.2 | Moderate expression |
| AGS (gastric adenocarcinoma) | 3.8 | Low expression |
| HCT116 (colorectal carcinoma) | 4.1 | Low expression |
| HEK293 (embryonic kidney) | 0.5 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.01% | Loss of start codon, likely loss of function |
| c.497C>T (p.Thr166Ile) | missense | <0.01% | Unknown functional effect |
| c.1045G>A (p.Gly349Ser) | missense | <0.01% | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
Promoter hypermethylation and missense mutations (e.g., p.Met1?) are associated with loss of CAPN9 expression or function, contributing to gastric carcinogenesis.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CAPN9 in the literature or curated databases.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for CAPN9.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Calpain proteolysis pathway (Reactome: R-HSA-5625740)
• Apoptosis - multiple species (KEGG: map04215)
Protein Summary
Calpain-9 (UniProt O14815) is a 690-amino acid calcium-dependent cysteine protease belonging to the calpain family. It contains a catalytic cysteine protease domain (CysPc) and a calpain-type calcium-binding domain (CaLB). The protein is predominantly expressed in the stomach and small intestine, where it localizes to the cytoplasm and cytosol. Calpain-9 is involved in limited proteolysis of substrates involved in cell adhesion, cytoskeletal remodeling, and apoptosis. Loss of calpain-9 expression is a frequent event in gastric cancer, suggesting a tumor suppressor role.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CAPN9 Knockout HEK293 Cell Line | EDJ-KQ7151 | Human | 10753 | Details Get a Quote |
| CAPN9 Knockout HeLa Cell Line | EDJ-KQ55479 | Human | 10753 | Details Get a Quote |
| CAPN9 Knockout A-549 Cell Line | EDJ-KQ63969 | Human | 10753 | Details Get a Quote |
| CAPN9 Knockout HCT 116 Cell Line | EDJ-KQ72422 | Human | 10753 | Details Get a Quote |
