GeneBe

MCU

protein-coding

mitochondrial calcium uniporter, the group of MicroRNA protein coding host genes

Gene summary

Enables calcium channel activity; identical protein binding activity; and uniporter activity. Involved in several processes, including cellular response to calcium ion starvation; positive regulation of mitochondrial calcium ion concentration; and positive regulation of mitochondrial fission. Located in mitochondrion. Part of uniplex complex. Is active in mitochondrial inner membrane. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:
  • C10orf42
  • CCDC109A

MANE transcript

NM_138357.3

Inheritance

—

ClinVar variants

U:35B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr10:72,692,143-72,887,694

External References & Databases

Ensembl (ENSG00000156026)NCBI Gene (90550)OMIM (614197)HGNC:23526GenCCUniProt (Q8NE86)AlphaFoldClinVar (MCU)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~195.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MCU variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 35
not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138357.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
0
missense
34
clinvar
2
clinvar
 36
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total00352037
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_138357.3RefSeqNP_612366.18MANE Select
ENST00000373053.8EnsemblENSP00000362144.38MANE Select
NM_001270679.2RefSeqNP_001257608.18Standard
NM_001270680.3RefSeqNP_001257609.18Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
mcuDanio rerio

Structure: mesodermal cell

Quality: oriented

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Calcium signaling pathway - Homo sapiens (human)
  • NOD-like receptor signaling pathway - Homo sapiens (human)
  • Cellular senescence - Homo sapiens (human)
  • Transport of small molecules
  • Mitochondrial calcium ion transport

Biological Process

  • mitochondrial calcium ion transmembrane transport
  • calcium-mediated signaling
  • positive regulation of insulin secretion
  • calcium import into the mitochondrion
  • glucose homeostasis

Molecular Function

  • calcium channel activity
  • protein binding
  • uniporter activity
  • identical protein binding

Cellular Component

  • mitochondrion
  • mitochondrial inner membrane
  • integral component of mitochondrial inner membrane
  • calcium channel complex
  • uniplex complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000373053
Coding exons
8
Length
195564
Individuals with no LoFs
125741
Homozygous LoFs
0
Heterozygous LoFs
3
Defined
125744
p
0.0000119
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.831041710.6070.000009262240
Missense (PolyPhen)1750.4530.33695589
Synonymous-0.7006760.11.110.00000292711
Loss of Function3.41319.10.1570.00000111222

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian0.0000540.000054rare
Finnish00.0absent
European (Non-Finnish)0.0000180.000018rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Mitochondrial inner membrane calcium uniporter that mediates calcium uptake into mitochondria (PubMed:21685888, PubMed:21685886, PubMed:23101630, PubMed:22904319, PubMed:23178883, PubMed:22829870, PubMed:22822213, PubMed:24332854, PubMed:23755363, PubMed:26341627). Constitutes the pore-forming and calcium-conducting subunit of the uniporter complex (uniplex) (PubMed:23755363). Activity is regulated by MICU1 and MICU2. At low Ca(2+) levels MCU activity is down- regulated by MICU1 and MICU2; at higher Ca(2+) levels MICU1 increases MCU activity (PubMed:24560927, PubMed:26903221). Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates cell bioenergetics, cytoplasmic calcium signals and activation of cell death pathways. Involved in buffering the amplitude of systolic calcium rises in cardiomyocytes (PubMed:22822213). While dispensable for baseline homeostatic cardiac function, acts as a key regulator of short- term mitochondrial calcium loading underlying a 'fight-or-flight' response during acute stress: acts by mediating a rapid increase of mitochondrial calcium in pacemaker cells (PubMed:25603276). participates in mitochondrial permeability transition during ischemia-reperfusion injury (By similarity). Regulates glucose- dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (PubMed:22904319, PubMed:22829870). Mitochondrial calcium uptake in skeletal muscle cells is involved in muscle size in adults (By similarity). Regulates synaptic vesicle endocytosis kinetics in central nerve terminal (By similarity). Involved in antigen processing and presentation (By similarity). {ECO:0000250|UniProtKB:Q3UMR5, ECO:0000269|PubMed:21685886, ECO:0000269|PubMed:21685888, ECO:0000269|PubMed:22822213, ECO:0000269|PubMed:22829870, ECO:0000269|PubMed:22904319, ECO:0000269|PubMed:23101630, ECO:0000269|PubMed:23178883, ECO:0000269|PubMed:23755363, ECO:0000269|PubMed:24332854, ECO:0000269|PubMed:24560927, ECO:0000269|PubMed:25603276, ECO:0000269|PubMed:26341627, ECO:0000269|PubMed:26903221}.;

Intolerance Scores

RVIS EVS
-0.12
RVIS percentile EVS
44.89

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.114

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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