MCU

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

Basic information

Region (hg38): 10:72692143-72887694

Previous symbols: [ "C10orf42", "CCDC109A" ]

Links

ENSG00000156026NCBI:90550OMIM:614197HGNC:23526Uniprot:Q8NE86AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MCU gene.

  • not_specified (29 variants)
  • not_provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MCU gene is commonly pathogenic or not. These statistics are base on transcript: NM_000138357.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
0
missense
27
clinvar
2
clinvar
29
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
0
Total 0 0 27 2 0
Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
MCUprotein_codingprotein_codingENST00000373053 8195564
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.8330.167125741031257440.0000119
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.831041710.6070.000009262240
Missense in Polyphen1750.4530.33695589
Synonymous-0.7006760.11.110.00000292711
Loss of Function3.41319.10.1570.00000111222

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.00005440.0000544
Finnish0.000.00
European (Non-Finnish)0.00001770.0000176
Middle Eastern0.00005440.0000544
South Asian0.000.00
Other0.000.00

dbNSFP

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}.;
Pathway
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;Processing of SMDT1 (Consensus)

Intolerance Scores

loftool
rvis_EVS
-0.12
rvis_percentile_EVS
44.89

Haploinsufficiency Scores

pHI
0.560
hipred
Y
hipred_score
0.713
ghis
0.527

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.114

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Mcu
Phenotype
cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype;

Zebrafish Information Network

Gene name
mcu
Affected structure
mesodermal cell
Phenotype tag
abnormal
Phenotype quality
oriented

Gene ontology

Biological process
mitochondrial calcium ion transmembrane transport;calcium-mediated signaling;positive regulation of insulin secretion;calcium import into the mitochondrion;glucose homeostasis;protein complex oligomerization;mitochondrial calcium ion homeostasis;positive regulation of mitochondrial calcium ion concentration
Cellular component
mitochondrion;mitochondrial inner membrane;integral component of mitochondrial inner membrane;calcium channel complex;uniplex complex
Molecular function
calcium channel activity;protein binding;uniporter activity;identical protein binding