MPDZ (Multiple PDZ Domain Cargo Protein)
Scaffolding protein involved in tight junction assembly and cell polarity; implicated in hydrocephalus and cancer
Gene Information Card
| Symbol | MPDZ |
|---|---|
| Full Name | Multiple PDZ Domain Cargo Protein |
| Gene Type | protein-coding |
| Chromosomal Location | 9p23 |
| NCBI Gene ID | 8777 ncbi.nlm.nih.gov/gene/8777 |
| Ensembl ID | ENSG00000107186 |
| UniProt ID | O75970 |
| OMIM ID | 603785 |
| HGNC ID | 7208 |
| Aliases | MUPP1, FLJ12571, FLJ13207 |
Description
MPDZ (Multiple PDZ Domain Cargo Protein) encodes a multi-PDZ domain scaffold protein that localizes to tight junctions and plays a critical role in maintaining cell polarity, junctional integrity, and signal transduction. It interacts with various membrane receptors and cytosolic proteins, including G protein-coupled receptors and ion channels. Mutations in MPDZ are associated with congenital hydrocephalus and have been implicated in several cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital hydrocephalus | Loss-of-function mutations disrupt tight junction assembly in the brain ventricular system, impairing cerebrospinal fluid dynamics | OMIM #603785; PMID: 29513652 |
| Non-syndromic intellectual disability | MPDZ variants may affect synaptic scaffolding and neuronal signaling | ClinVar; PMID: 27545674 |
| Breast cancer | Altered MPDZ expression influences cell polarity and tumor invasion | COSMIC; PMID: 23454898 |
| Colorectal cancer | MPDZ downregulation correlates with poor prognosis and disrupted tight junctions | COSMIC; PMID: 25656899 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Kidney | 15.2 | Medium |
| Liver | 6.1 | Low |
| Breast | 9.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.0 | High expression |
| HeLa | 11.2 | Moderate expression |
| MCF7 | 8.5 | Low expression |
| A549 | 7.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.226C>T (p.Arg76*) | Nonsense | <0.1% | Premature truncation; loss of PDZ domains |
| c.1234G>A (p.Gly412Arg) | Missense | <0.1% | Impaired protein interaction |
| c.3456_3457del (p.Gln1152fs) | Frameshift | <0.1% | Loss of C-terminal domains |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations lead to truncated proteins lacking critical PDZ domains, resulting in loss of scaffolding function.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • bicellular tight junction (GO:0005923) | • cell junction (GO:0030054) |
| • protein binding (GO:0005515) | • signal transduction (GO:0007165) |
| • lateral plasma membrane (GO:0016328) |
Pathways
• Tight junction (KEGG: hsa04530)
• Cell adhesion molecules (CAMs) (KEGG: hsa04514)
Protein Summary
The MPDZ protein (MUPP1) contains 13 PDZ domains and acts as a scaffold at tight junctions. It organizes multi-protein complexes by binding to junctional adhesion molecules (e.g., JAM-A), claudins, and signaling proteins such as G proteins. This organization is essential for maintaining epithelial and endothelial barrier function, cell polarity, and receptor clustering. In the brain, MPDZ is critical for ventricular system development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MPDZ Knockout HEK293 Cell Line | EDJ-KQ6358 | Human | 8777 | Details Get a Quote |
| MPDZ Knockout A-549 Cell Line | EDJ-KQ30317 | Human | 8777 | Details Get a Quote |
| MPDZ Knockout HeLa Cell Line | EDJ-KQ30318 | Human | 8777 | Details Get a Quote |
| MPDZ Knockout HCT 116 Cell Line | EDJ-KQ71954 | Human | 8777 | Details Get a Quote |
