M6PR (Cation-Dependent Mannose-6-Phosphate Receptor)
Key regulator of lysosomal enzyme trafficking and cellular homeostasis
Gene Information Card
| Symbol | M6PR |
|---|---|
| Full Name | Mannose-6-Phosphate Receptor, Cation Dependent |
| Gene Type | Protein coding |
| Chromosomal Location | 12p13.31 |
| NCBI Gene ID | 4074 ncbi.nlm.nih.gov/gene/4074 |
| Ensembl ID | ENSG00000103056 |
| UniProt ID | P20645 |
| OMIM ID | 154540 |
| HGNC ID | 6752 |
| Aliases | CD-MPR, MPR46, M6P/IGF2R binding protein |
Description
The M6PR gene encodes the cation-dependent mannose-6-phosphate receptor (CD-MPR), a transmembrane protein that binds mannose-6-phosphate (M6P) tags on newly synthesized lysosomal hydrolases in the Golgi apparatus. This binding facilitates the transport of these enzymes to lysosomes, a critical process for cellular degradation and recycling. The receptor also interacts with insulin-like growth factor 2 (IGF2) and other ligands, influencing growth signaling. Mutations or dysregulation of M6PR are linked to lysosomal storage disorders and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mucolipidosis III Gamma | Impaired lysosomal enzyme trafficking due to defective M6P recognition; M6PR dysfunction contributes to the phenotype. | ClinVar; NCBI Gene Reviews |
| Hepatocellular carcinoma | Reduced M6PR expression leads to increased IGF2 signaling, promoting tumor growth and metastasis. | COSMIC; PubMed studies |
| Prostate cancer | Loss of M6PR heterozygosity and altered splicing variants associated with aggressive disease. | COSMIC; OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 9.8 | Medium |
| Placenta | 8.2 | Medium |
| Brain | 6.1 | Low |
| Lung | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 14.2 | High expression |
| HEK293 (embryonic kidney) | 11.0 | Moderate expression |
| MCF7 (breast) | 7.5 | Low expression |
| A549 (lung) | 6.3 | 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.112C>T (p.Arg38Cys) | Missense | 0.02% | Impaired M6P binding; reduced lysosomal targeting |
| c.407G>A (p.Arg136His) | Missense | 0.01% | Altered receptor recycling; associated with mucolipidosis III gamma |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt M6P binding or receptor trafficking lead to lysosomal enzyme misrouting and accumulation of undegraded substrates.
Gain of Function (GOF)
Not well documented; some variants may enhance IGF2 binding, potentially promoting oncogenic signaling.
Dominant Negative (DN)
Heterozygous missense mutations may interfere with wild-type receptor function in dimerization or ligand binding.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Lysosome (KEGG: hsa04142)
• Mannose-6-phosphate receptor mediated transport (Reactome: R-HSA-9634600)
• Insulin-like growth factor 2 signaling (Reactome: R-HSA-2428924)
Protein Summary
The cation-dependent mannose-6-phosphate receptor (CD-MPR) is a 46 kDa transmembrane glycoprotein that cycles between the Golgi apparatus and endosomes. It binds M6P-tagged lysosomal enzymes in a cation-dependent manner (requires Mn2+ or Ca2+), ensuring their delivery to lysosomes. The receptor also interacts with IGF2, modulating growth factor availability. Structurally, it contains an N-terminal signal sequence, a single M6P-binding luminal domain, a transmembrane helix, and a short cytoplasmic tail with sorting signals for intracellular trafficking. CD-MPR functions as a dimer and is essential for maintaining lysosomal function and cellular homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| M6PR Knockout HEK293T Cell Line | EDJ-KQ206 | Human | 4074 | Details Get a Quote |
| M6PR Knockout HEK293 Cell Line | EDJ-KQ1892 | Human | 4074 | Details Get a Quote |
| M6PR Knockout A-549 Cell Line | EDJ-KQ21794 | Human | 4074 | Details Get a Quote |
| M6PR Knockout HCT 116 Cell Line | EDJ-KQ21795 | Human | 4074 | Details Get a Quote |
| M6PR Knockout HeLa Cell Line | EDJ-KQ21796 | Human | 4074 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
