LGMN (Legumain) Gene: Structure, Function, and Clinical Significance
A comprehensive biomedical overview of the LGMN gene, encoding legumain, a cysteine protease involved in protein processing, immune regulation, and disease.
Gene Information Card
| Symbol | LGMN |
|---|---|
| Full Name | legumain |
| Gene Type | protein-coding |
| Chromosomal Location | 14q32.12 |
| NCBI Gene ID | 5641 ncbi.nlm.nih.gov/gene/5641 |
| Ensembl ID | ENSG00000100600 |
| UniProt ID | Q99538 |
| OMIM ID | 602620 |
| HGNC ID | 6572 |
| Aliases | AEP, LGMN1, PRSC1 |
Description
LGMN (legumain) encodes a cysteine protease of the C13 family (asparaginyl endopeptidase). It is synthesized as a zymogen and activated by autocatalytic processing at acidic pH. Legumain is involved in the processing of proteins for MHC class II antigen presentation, degradation of extracellular matrix components, and regulation of cell migration. It is overexpressed in many solid tumors and has been implicated in Alzheimer disease, atherosclerosis, and inflammatory conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression of legumain promotes tumor invasion, metastasis, and angiogenesis via cleavage of extracellular matrix and activation of proMMP-2. | PMID: 15626733, PMID: 19074885 |
| Alzheimer disease | Legumain cleaves amyloid precursor protein (APP) and tau, contributing to amyloid-beta plaque formation and neurofibrillary tangles. | PMID: 24607389, PMID: 29100073 |
| Atherosclerosis | Legumain is upregulated in atherosclerotic plaques and promotes macrophage migration and plaque instability. | PMID: 23376921 |
| Inflammatory bowel disease | Increased legumain expression in intestinal epithelium correlates with inflammation and epithelial barrier dysfunction. | PMID: 27559042 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 48.2 | High |
| Placenta | 32.1 | High |
| Lung | 18.7 | Medium |
| Liver | 12.4 | Medium |
| Brain | 6.8 | Low |
| Heart | 4.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 35.6 | High expression |
| HeLa | 22.3 | Medium expression |
| A549 | 18.9 | Medium expression |
| MCF7 | 12.1 | Low expression |
| HepG2 | 9.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.589G>A (p.Gly197Arg) | Missense | 0.01% (gnomAD) | Reduced enzymatic activity; associated with altered substrate specificity. |
| c.1003C>T (p.Arg335Trp) | Missense | 0.005% (gnomAD) | Decreased stability and impaired autocatalytic activation. |
| c.1246G>A (p.Gly416Arg) | Missense | 0.002% (gnomAD) | Loss of catalytic activity; potential dominant-negative effect. |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Gly197Arg, p.Arg335Trp, p.Gly416Arg) reduce or abolish legumain enzymatic activity, impairing protein processing and antigen presentation.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in LGMN. Overexpression in tumors is considered a gain-of-function at the expression level, not via mutation.
Dominant Negative (DN)
p.Gly416Arg may act as a dominant-negative by forming inactive dimers with wild-type legumain, reducing overall protease activity.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Antigen processing and presentation (KEGG hsa04612)
• Lysosome (KEGG hsa04142)
• Proteoglycans in cancer (KEGG hsa05205)
• Alzheimer disease (KEGG hsa05010)
Protein Summary
Legumain (asparaginyl endopeptidase) is a lysosomal cysteine protease that specifically cleaves after asparagine residues. It is synthesized as an inactive proenzyme and activated in acidic conditions. Legumain plays key roles in antigen processing, extracellular matrix remodeling, and cell migration. It is highly expressed in kidney and placenta, and overexpressed in many cancers, where it contributes to tumor progression. Mutations in LGMN are rare but can impair enzymatic function. Legumain is a potential therapeutic target in cancer, Alzheimer disease, and inflammatory disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LGMN Knockout HEK293 Cell Line | EDJ-KQ5551 | Human | 5641 | Details Get a Quote |
| LGMN Knockout A-549 Cell Line | EDJ-KQ28816 | Human | 5641 | Details Get a Quote |
| LGMN Knockout HCT 116 Cell Line | EDJ-KQ28817 | Human | 5641 | Details Get a Quote |
| LGMN Knockout HeLa Cell Line | EDJ-KQ28818 | Human | 5641 | Details Get a Quote |
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