MICU3
Chr 8mitochondrial calcium uptake 3
Also known as: EFHA2, hMICU3
MICU3 encodes a tissue-specific calcium sensor that regulates the mitochondrial calcium uniporter channel in the central nervous system and skeletal muscle, forming a heterodimer with MICU1 to control mitochondrial calcium uptake based on cellular calcium levels. Mutations cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities, typically presenting in infancy or early childhood. The gene is not highly constrained against loss-of-function variants, suggesting that complete loss of protein function may be tolerated in some contexts.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
215 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 76 | 0 | 76 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 0 | 102 | 11 | 0 | 113 |
Likely Benign | 0 | 3 | 0 | 0 | 3 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 105 | 91 | 0 | 196 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MICU3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools