MICU1: Mitochondrial Calcium Uptake 1
Gatekeeper of Mitochondrial Calcium Homeostasis
Gene Information Card
| Symbol | MICU1 |
|---|---|
| Full Name | Mitochondrial Calcium Uptake 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q22.1 |
| NCBI Gene ID | 10367 ncbi.nlm.nih.gov/gene/10367 |
| Ensembl ID | ENSG00000107745 |
| UniProt ID | Q9BPX6 |
| OMIM ID | 605084 |
| HGNC ID | 1530 |
| Aliases | CBARA1, EFHA3, FLJ12684, MGC2452 |
Description
MICU1 (Mitochondrial Calcium Uptake 1) encodes a protein that functions as a gatekeeper of the mitochondrial calcium uniporter (MCU) complex. It contains two EF-hand domains that sense cytosolic calcium levels, regulating MCU channel activity to prevent mitochondrial calcium overload while allowing uptake under physiological conditions. MICU1 is essential for maintaining cellular calcium homeostasis and energy metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Myopathy with extrapyramidal signs (MPXPS) | Loss-of-function mutations in MICU1 impair mitochondrial calcium uptake, leading to defective oxidative phosphorylation and muscle dysfunction. | OMIM #616673; PMID 24645143 |
| Proximal myopathy with extrapyramidal signs | Biallelic MICU1 mutations cause reduced MCU activity, resulting in mitochondrial calcium deficiency and neuromuscular symptoms. | ClinVar; PMID 24645143 |
| MICU1 deficiency | Homozygous or compound heterozygous mutations disrupt MICU1 expression, causing a syndrome of muscle weakness, learning difficulties, and movement disorders. | OMIM #616673 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 12.5 | High |
| Heart | 10.8 | High |
| Liver | 6.2 | Medium |
| Brain | 5.9 | Medium |
| Kidney | 4.7 | Medium |
| Lung | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 8.4 | Cervical cancer cell line |
| HEK293 | 7.9 | Embryonic kidney cells |
| SH-SY5Y | 6.5 | Neuroblastoma cell line |
| HepG2 | 5.8 | Hepatocellular carcinoma |
| A549 | 4.2 | Lung carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.556C>T (p.Arg186*) | Nonsense | Rare | Premature stop; loss of MICU1 function |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of translation initiation |
| c.464_465del (p.Val155Alafs*12) | Frameshift | Rare | Truncated protein; loss of function |
| c.1039C>T (p.Arg347Trp) | Missense | Rare | Impaired EF-hand calcium sensing |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (nonsense, frameshift, start loss) cause MICU1 deficiency, leading to impaired mitochondrial calcium uptake and neuromuscular disease.
Gain of Function (GOF)
No gain-of-function mutations reported in MICU1.
Dominant Negative (DN)
No dominant-negative mutations reported; MICU1 mutations are typically recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Mitochondrial calcium uniporter complex (Reactome: R-HSA-8949215)
• Calcium signaling pathway (KEGG: hsa04020)
• Oxidative phosphorylation (KEGG: hsa00190)
Protein Summary
MICU1 is a 476-amino acid protein with two EF-hand calcium-binding domains. It forms a heterodimer with MICU2 and associates with the MCU pore-forming subunit. At low cytosolic calcium, MICU1 keeps the MCU channel closed; upon calcium elevation, it undergoes a conformational change to open the channel, allowing rapid mitochondrial calcium uptake. This gating mechanism protects mitochondria from calcium overload and supports ATP production.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MICU1 Knockout HEK293 Cell Line | EDJ-KQ3217 | Human | 10367 | Details Get a Quote |
| MICU1 Knockout A-549 Cell Line | EDJ-KQ24700 | Human | 10367 | Details Get a Quote |
| MICU1 Knockout HCT 116 Cell Line | EDJ-KQ24701 | Human | 10367 | Details Get a Quote |
| MICU1 Knockout HeLa Cell Line | EDJ-KQ24702 | Human | 10367 | Details Get a Quote |
