MCUB
protein-codingmitochondrial calcium uniporter dominant negative subunit beta
Gene summary
Enables calcium channel inhibitor activity. Involved in negative regulation of calcium import into the mitochondrion. Located in mitochondrial inner membrane. Part of uniplex complex. [provided by Alliance of Genome Resources, Jun 2026]
- CCDC109B
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~128.5 kbGenCC 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 MCUB variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017918.5. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 3 | 3 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 7 | 0 | 0 | 7 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060388.2 | 8 | MANE Select | |
| Ensembl | ENSP00000378145.4 | 8 | MANE Select | |
| Ensembl | ENSP00000537506.1 | 7 | Standard | |
| Ensembl | ENSP00000537506.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Transport of small molecules
- Mitochondrial calcium ion transport
- Processing of SMDT1
Biological Process
- mitochondrial calcium ion transmembrane transport
- calcium import into the mitochondrion
- mitochondrial calcium ion homeostasis
Molecular Function
- ion channel activity
- calcium channel inhibitor activity
Cellular Component
- mitochondrion
- mitochondrial inner membrane
- intrinsic component of membrane
- integral component of mitochondrial inner membrane
- calcium channel complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000394650
- Coding exons
- 8
- Length
- 128514
- Individuals with no LoFs
- 125703
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 45
- Defined
- 125748
- p
- 0.000179
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.193 | 147 | 154 | 0.956 | 0.00000760 | 2190 |
| Missense (PolyPhen) | 36 | 37.408 | 0.96237 | 488 | ||
| Synonymous | 0.301 | 53 | 55.9 | 0.949 | 0.00000283 | 621 |
| Loss of Function | 0.542 | 13 | 15.3 | 0.850 | 7.09e-7 | 211 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00016 | 0.00016 | rare |
| South Asian | 0.00036 | 0.00036 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Negatively regulates the activity of MCU, the mitochondrial inner membrane calcium uniporter, and thereby modulates calcium uptake into the mitochondrion. Does not form functional calcium channels by itself. Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates cell bioenergetics, cytoplasmic calcium signals and activation of cell death pathways. {ECO:0000250|UniProtKB:Q810S1}.;
Recessive Scores
- pRec
- 0.0874
Intolerance Scores
- RVIS EVS
- 0.4
- RVIS percentile EVS
- 76.15
Essentials
- Essential (gene trap)
- N