MICU3: Mitochondrial Calcium Uptake Family Member 3
A key regulator of mitochondrial calcium homeostasis with emerging roles in neuronal function and disease
Gene Information Card
| Symbol | MICU3 |
|---|---|
| Full Name | Mitochondrial Calcium Uptake Family Member 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 8p22 |
| NCBI Gene ID | 286343 ncbi.nlm.nih.gov/gene/286343 |
| Ensembl ID | ENSG00000155970 |
| UniProt ID | Q86Y78 |
| OMIM ID | 620477 |
| HGNC ID | 26782 |
| Aliases | EFHA2, FLJ22662 |
Description
MICU3 (Mitochondrial Calcium Uptake Family Member 3) encodes a protein belonging to the MICU family of mitochondrial calcium uptake regulators. It contains EF-hand domains that sense cytosolic calcium and modulate the activity of the mitochondrial calcium uniporter (MCU) complex. MICU3 is predominantly expressed in the nervous system and is thought to fine-tune mitochondrial calcium uptake in neurons, influencing synaptic activity and neuronal survival.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with microcephaly and seizures | Impaired mitochondrial calcium handling due to MICU3 loss-of-function variants | ClinVar; OMIM |
| Epileptic encephalopathy | Dysregulation of neuronal calcium homeostasis leading to hyperexcitability | ClinVar; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | High |
| Cerebellum | 10.8 | High |
| Spinal cord | 8.2 | Medium |
| Heart | 2.1 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | Neuronal model |
| U-87 MG (glioblastoma) | 9.7 | Glial model |
| HEK293 (embryonic kidney) | 1.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.556C>T (p.Arg186Trp) | Missense | Rare | Loss of calcium-binding affinity; reduced MCU activity |
| c.1021_1023del (p.Lys341del) | In-frame deletion | Rare | Impaired protein stability and complex assembly |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function variants in MICU3 reduce mitochondrial calcium uptake capacity, leading to neuronal calcium dyshomeostasis and synaptic dysfunction.
Gain of Function (GOF)
No gain-of-function mutations have been reported for MICU3 in the literature or curated databases.
Dominant Negative (DN)
Dominant-negative effects have not been described for MICU3; all reported pathogenic variants are recessive or de novo loss-of-function.
View complete mutation data：
Gene Ontology (GO)
| • calcium ion binding (GO:0005509) | • mitochondrion (GO:0005739) |
| • integral component of membrane (GO:0016021) | • mitochondrial calcium ion transport (GO:0006851) |
| • metal ion binding (GO:0046872) |
Pathways
• Mitochondrial calcium transport (Reactome: R-HSA-8949215)
• Calcium signaling pathway (KEGG: hsa04020)
Protein Summary
MICU3 is a 476-amino acid protein with two canonical EF-hand calcium-binding domains. It localizes to the mitochondrial inner membrane and associates with the MCU complex. Unlike the ubiquitously expressed MICU1, MICU3 is enriched in the central nervous system, where it modulates calcium-dependent mitochondrial metabolism and neuronal excitability. Structural studies indicate that MICU3 forms heterodimers with MICU1 to regulate the threshold and kinetics of mitochondrial calcium uptake.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MICU3 Knockout HEK293 Cell Line | EDJ-KQ14262 | Human | 286097 | Details Get a Quote |
| MICU3 Knockout A-549 Cell Line | EDJ-KQ44274 | Human | 286097 | Details Get a Quote |
| MICU3 Knockout HeLa Cell Line | EDJ-KQ59544 | Human | 286097 | Details Get a Quote |
| MICU3 Knockout HCT 116 Cell Line | EDJ-KQ76388 | Human | 286097 | Details Get a Quote |
