MICU1

Chr 10AR

mitochondrial calcium uptake 1

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

The protein regulates mitochondrial calcium uptake by interacting with the mitochondrial calcium uniporter to prevent calcium overload and excessive reactive oxygen species production. Mutations cause myopathy with extrapyramidal signs through autosomal recessive inheritance. Loss of function leads to impaired mitochondrial calcium homeostasis resulting in cellular stress and dysfunction.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.291 OMIM phenotype
Clinical SummaryMICU1
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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.
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ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 35 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.29LOEUF
pLI 0.000
Z-score 0.47
OE 0.90 (0.641.29)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.65Z-score
OE missense 0.70 (0.620.80)
174 obs / 247.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.90 (0.641.29)
00.351.4
Missense OE0.70 (0.620.80)
00.61.4
Synonymous OE0.88
01.21.6
LoF obs/exp: 21 / 23.4Missense obs/exp: 174 / 247.2Syn Z: 0.84
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMICU1-related myopathy with extrapyramidal signsLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.5869th %ile
GOF
0.6638th %ile
LOF
0.4528th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic2
VUS35
Likely Benign39
Benign15
Conflicting1
8
Pathogenic
2
Likely Pathogenic
35
VUS
39
Likely Benign
15
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
4
0
8
Likely Pathogenic
2
0
0
0
2
VUS
0
31
4
0
35
Likely Benign
0
0
19
20
39
Benign
0
0
14
1
15
Conflicting
1
Total6314121100

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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