MCU Gene: Mitochondrial Calcium Uniporter
A comprehensive guide to the MCU gene, its function, expression, and clinical significance.
Gene Information Card
| Symbol | MCU |
|---|---|
| Full Name | Mitochondrial Calcium Uniporter |
| Gene Type | Protein coding |
| Chromosomal Location | 10q22.1 |
| NCBI Gene ID | 90550 ncbi.nlm.nih.gov/gene/90550 |
| Ensembl ID | ENSG00000156030 |
| UniProt ID | Q8NE86 |
| OMIM ID | 614197 |
| HGNC ID | 27556 |
| Aliases | C10orf42, FLJ20400, Hs.533282 |
Description
The MCU gene encodes the mitochondrial calcium uniporter, a pore-forming subunit of the mitochondrial calcium uniporter complex. This complex mediates the uptake of calcium ions (Ca2+) into the mitochondrial matrix, playing a critical role in cellular metabolism, ATP production, and apoptosis. MCU is essential for mitochondrial calcium homeostasis and is implicated in various physiological and pathological processes, including muscle function, neuronal signaling, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial calcium uniporter deficiency | Loss-of-function mutations in MCU lead to impaired mitochondrial calcium uptake, causing a rare autosomal recessive disorder characterized by muscle weakness, developmental delay, and metabolic abnormalities. | OMIM #614197; PMID: 29217573 |
| Cancer | Altered MCU expression affects mitochondrial calcium dynamics, influencing apoptosis resistance and tumor progression. Overexpression in some cancers promotes proliferation, while downregulation may enhance metastasis. | COSMIC; PMID: 28991257 |
| Neurodegenerative diseases | Dysregulation of MCU-mediated calcium uptake contributes to neuronal cell death in conditions like Alzheimer's and Parkinson's disease, though direct causal mutations are not yet established. | PMID: 30318147 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal Muscle | 12.5 | High |
| Heart | 10.2 | High |
| Liver | 5.3 | Medium |
| Brain | 4.8 | Medium |
| Kidney | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | High expression; commonly used for MCU studies |
| HEK293 | 12.8 | High expression; model for calcium signaling |
| HepG2 | 8.4 | Moderate expression |
| SH-SY5Y | 6.1 | Low expression; neuronal model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.260C>T (p.Ala87Val) | Missense | Rare | Reduced MCU activity; associated with mitochondrial calcium uniporter deficiency |
| c.463G>A (p.Gly155Ser) | Missense | Not reported | Predicted damaging; functional impact unknown |
| c.703C>T (p.Arg235Trp) | Missense | Rare | Loss of function; impairs calcium uptake |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in MCU impair mitochondrial calcium uptake, leading to cellular energy deficits and clinical phenotypes such as myopathy and developmental delay.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented; however, overexpression of MCU can increase mitochondrial calcium overload, triggering apoptosis or necrosis.
Dominant Negative (DN)
Dominant-negative effects have been proposed for some missense mutations that disrupt the uniporter complex assembly, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • calcium ion transmembrane transporter activity | • mitochondrial calcium ion transmembrane transport |
| • mitochondrial inner membrane | • regulation of mitochondrial membrane potential |
| • apoptotic process |
Pathways
• Calcium signaling pathway
• Apoptosis
• Mitochondrial calcium regulation
Protein Summary
The MCU protein is a 40 kDa transmembrane protein located in the inner mitochondrial membrane. It forms a tetrameric channel that selectively transports Ca2+ into the mitochondrial matrix. The protein contains a coiled-coil domain and a DIME motif essential for ion selectivity. MCU activity is regulated by accessory subunits such as MICU1 and MICU2, which set the threshold for calcium uptake. The protein is critical for buffering cytosolic calcium spikes and linking calcium signals to metabolic outputs.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MCU Knockout HEK293 Cell Line | EDC90701 | Human | 90550 | Details Get a Quote |
| MCUR1 Knockout HEK293 Cell Line | EDJ-KQ11980 | Human | 63933 | Details Get a Quote |
| MCUB Knockout HEK293 Cell Line | EDJ-KQ14223 | Human | 55013 | Details Get a Quote |
| MCUB Knockout A-549 Cell Line | EDJ-KQ44186 | Human | 55013 | Details Get a Quote |
| MCUB Knockout HCT 116 Cell Line | EDJ-KQ44187 | Human | 55013 | Details Get a Quote |
| MCUB Knockout HeLa Cell Line | EDJ-KQ44188 | Human | 55013 | Details Get a Quote |
| MCU Knockout A-549 Cell Line | EDJ-KQ21327 | Human | 90550 | Details Get a Quote |
| MCU Knockout HCT 116 Cell Line | EDJ-KQ21328 | Human | 90550 | Details Get a Quote |
| MCU Knockout HeLa Cell Line | EDJ-KQ21329 | Human | 90550 | Details Get a Quote |
| MCUR1 Knockout A-549 Cell Line | EDJ-KQ40540 | Human | 63933 | Details Get a Quote |
| MCUR1 Knockout HCT 116 Cell Line | EDJ-KQ40541 | Human | 63933 | Details Get a Quote |
| MCUR1 Knockout HeLa Cell Line | EDJ-KQ40542 | Human | 63933 | Details Get a Quote |
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