MICU1

Chr 10AR

mitochondrial calcium uptake 1

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

NCBI Gene: 10367 ENSG00000107745 UniProt: Q9BPX6 OMIM: 605084

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.291 OMIM phenotype

Clinical Summary— MICU1

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

52 unique Pathogenic / Likely Pathogenic· 114 VUS of 357 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

1.65Z-score

OE missense 0.70 (0.62–0.80)

174 obs / 247.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.90 (0.64–1.29)

0≤0.351.4

Missense OE?0.70 (0.62–0.80)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

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

This gene — mechanism propensity

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

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

357 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33

Likely Pathogenic19

VUS114

Likely Benign154

Benign34

Conflicting3

Pathogenic

Likely Pathogenic

114

VUS

154

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	22	0	11	0	33
Likely Pathogenic	18	1	0	0	19
VUS	0	103	9	2	114
Likely Benign	0	1	85	68	154
Benign	0	1	32	1	34
Conflicting	—				3
Total	40	106	137	71	357

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap MICU1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →