MICU3

Chr 8

mitochondrial calcium uptake 3

Also known as: EFHA2, hMICU3

NCBI Gene: 286097 ENSG00000155970 UniProt: Q86XE3 OMIM: 610633

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables calcium ion sensor activity and protein heterodimerization activity. Involved in calcium import into the mitochondrion and cellular response to calcium ion. Located in mitochondrion. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

—

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.02

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.02LOEUF

pLI 0.000

Z-score 1.49

OE 0.68 (0.46–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.22Z-score

OE missense 0.96 (0.86–1.07)

228 obs / 237.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.68 (0.46–1.02)

0≤0.351.4

Missense OE?0.96 (0.86–1.07)

0≤0.61.4

Synonymous OE?1.26

0≤1.21.6

LoF obs/exp: 17 / 25.1Missense obs/exp: 228 / 237.5Syn Z: -1.80

Background carrier burden — how many people carry a rare variant somewhere in MICU3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 60

892 rare PASS variants

Rare truncating (LoF)

1 in 870

161 rare PASS variants

Rare synonymous (reference)

1 in 79

349 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MICU3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 81	1 in 970
South Asian	~43k	1 in 64	1 in 550
Remaining (unassigned)	~30k	1 in 60	1 in 910
European (Finnish)	~27k	1 in 160	1 in 740
Admixed American	~22k	1 in 66	1 in 710
African / African American	~21k	1 in 47	1 in 770
East Asian	~20k	1 in 55	1 in 1,100
Ashkenazi Jewish	~13k	1 in 190	≈ 1 in 2,700
Middle Eastern	~2,884	1 in 56	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 14 coding exons well covered in gnomAD exomes; exon 5 poorly covered; exons 1, 3, 6, 7, 10 and 3 more marginal. Genomes: all 14.? see exons ↓