MICU1

Chr 10AR

mitochondrial calcium uptake 1

Also known as: CALC, CBARA1, EFHA3, MPXPS, ara CALC

NCBI Gene: 10367ENSG00000107745UniProt: Q9BPX6

This gene encodes an essential regulator of mitochondrial Ca2+ uptake under basal conditions. The encoded protein interacts with the mitochondrial calcium uniporter, a mitochondrial inner membrane Ca2+ channel, and is essential in preventing mitochondrial Ca2+ overload, which can cause excessive production of reactive oxygen species and cell stress. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Mar 2013]

Primary Disease Associations & Inheritance

Myopathy with extrapyramidal signsMIM #615673
AR
374
ClinVar variants
65
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MICU1
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
65 Pathogenic / Likely Pathogenic· 118 VUS of 374 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.29LOEUF
pLI 0.000
Z-score 0.47
OE 0.90 (0.64–1.29)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.65Z-score
OE missense 0.70 (0.62–0.80)
174 obs / 247.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.90 (0.64–1.29)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.62–0.80)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 21 / 23.4Missense obs/exp: 174 / 247.2Syn Z: 0.84

ClinVar Variant Classifications

374 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic18
VUS118
Likely Benign154
Benign34
Conflicting3
47
Pathogenic
18
Likely Pathogenic
118
VUS
154
Likely Benign
34
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
0
34
0
47
Likely Pathogenic
14
1
3
0
18
VUS
0
100
16
2
118
Likely Benign
0
1
85
68
154
Benign
0
1
32
1
34
Conflicting
—3
Total2710317071374

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MICU1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

MICU1-related myopathy with extrapyramidal signs

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Myopathy with extrapyramidal signs

MIM #615673

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The Genetic Landscape of Complex Childhood-Onset Hyperkinetic Movement Disorders.
Pérez-Dueñas B et al.·Mov Disord
2022
Endothelial MICU1 protects against vascular inflammation and atherosclerosis by inhibiting mitochondrial calcium uptake.
Sun L et al.·J Clin Invest
2025
Interaction of the mitochondrial calcium/proton exchanger TMBIM5 with MICU1.
Zhang L et al.·Commun Biol
2025
Molecular pathophysiology of human MICU1 deficiency.
Kohlschmidt N et al.·Neuropathol Appl Neurobiol
2021
MICU1 attenuates neuronal apoptosis after subarachnoid hemorrhage by inhibiting mitochondrial calcium overload and damage.
Wang J et al.·Cell Calcium
2025
MicroRNA-195 controls MICU1 expression and tumor growth in ovarian cancer.
Rao G et al.·EMBO Rep
2020
Cold stress-induced ferroptosis in liver sinusoidal endothelial cells determines liver transplant injury and outcomes.
Kojima H et al.·JCI Insight
2024
Myocardial transcriptomic analysis of diabetic patients with aortic stenosis: key role for mitochondrial calcium signaling.
Cherpaz M et al.·Cardiovasc Diabetol
2024Cohort
Uncontrolled mitochondrial calcium uptake underlies the pathogenesis of neurodegeneration in MICU1-deficient mice and patients.
Singh R et al.·Sci Adv
2022Cohort
Altered composition of the mitochondrial Ca(2+)uniporter in the failing human heart.
Paillard M et al.·Cell Calcium
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools