MCU
mitochondrial calcium uniporter, the group of MicroRNA protein coding host genes
Basic information
Region (hg38): 10:72692143-72887694
Previous symbols: [ "C10orf42", "CCDC109A" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
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.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 17 | 17 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 17 | 0 | 0 |
Variants in MCU
This is a list of pathogenic ClinVar variants found in the MCU region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 10-72692173-T-A | not specified | Uncertain significance (Jan 03, 2024) | ||
| 10-72692218-G-A | not specified | Uncertain significance (Sep 10, 2024) | ||
| 10-72692219-C-T | not specified | Uncertain significance (Jun 26, 2024) | ||
| 10-72692224-G-A | not specified | Uncertain significance (Dec 06, 2024) | ||
| 10-72692230-G-A | not specified | Uncertain significance (Jan 16, 2024) | ||
| 10-72692258-G-C | not specified | Uncertain significance (Apr 07, 2023) | ||
| 10-72834381-G-C | not specified | Uncertain significance (Apr 25, 2022) | ||
| 10-72834422-T-C | not specified | Uncertain significance (Jun 18, 2021) | ||
| 10-72860513-G-A | not specified | Uncertain significance (Feb 10, 2023) | ||
| 10-72868837-A-G | not specified | Uncertain significance (Aug 04, 2024) | ||
| 10-72871395-A-G | not specified | Uncertain significance (Aug 13, 2021) | ||
| 10-72871421-G-T | not specified | Uncertain significance (Sep 08, 2024) | ||
| 10-72871440-G-A | not specified | Uncertain significance (Oct 06, 2022) | ||
| 10-72871474-G-A | not specified | Uncertain significance (Oct 03, 2023) | ||
| 10-72885800-G-A | not specified | Uncertain significance (Jan 31, 2023) | ||
| 10-72885805-A-T | not specified | Uncertain significance (May 26, 2024) | ||
| 10-72885817-G-A | not specified | Uncertain significance (Oct 05, 2022) | ||
| 10-72885820-T-A | Benign (Jul 05, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MCU | protein_coding | protein_coding | ENST00000373053 | 8 | 195564 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.833 | 0.167 | 125741 | 0 | 3 | 125744 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.83 | 104 | 171 | 0.607 | 0.00000926 | 2240 |
| Missense in Polyphen | 17 | 50.453 | 0.33695 | 589 | ||
| Synonymous | -0.700 | 67 | 60.1 | 1.11 | 0.00000292 | 711 |
| Loss of Function | 3.41 | 3 | 19.1 | 0.157 | 0.00000111 | 222 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000177 | 0.0000176 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
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