SLC25A27
protein-codingsolute carrier family 25 member 27, the group of Solute carrier family 25
Gene summary
Mitochondrial uncoupling proteins (UCP) are members of the larger family of mitochondrial anion carrier proteins (MACP). UCPs separate oxidative phosphorylation from ATP synthesis with energy dissipated as heat, also referred to as the mitochondrial proton leak. UCPs facilitate the transfer of anions from the inner to the outer mitochondrial membrane and the return transfer of protons from the outer to the inner mitochondrial membrane. They also reduce the mitochondrial membrane potential in mammalian cells. Tissue specificity occurs for the different UCPs and the exact methods of how UCPs transfer H+/OH- are not known. UCPs contain the three homologous protein domains of MACPs. Transcripts of this gene are only detected in brain tissue and are specifically modulated by various environmental conditions. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~25.3 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 SLC25A27 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004277.5. 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 | 36 | 36 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 36 | 0 | 1 | 37 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004268.3 | 9 | MANE Select | |
| Ensembl | ENSP00000360398.3 | 9 | MANE Select | |
| RefSeq | NP_001190980.1 | 9 | Standard | |
| RefSeq | NP_001190981.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Electron Transport Chain
- The citric acid (TCA) cycle and respiratory electron transport
- Metabolism
- The fatty acid cycling model
- The proton buffering model
Biological Process
- positive regulation of cell population proliferation
- response to cold
- negative regulation of mitochondrial membrane potential
- cellular triglyceride homeostasis
- negative regulation of apoptotic process
Molecular Function
- transmembrane transporter activity
Cellular Component
- mitochondrion
- mitochondrial inner membrane
- integral component of membrane
- mitochondrial membrane
- neuronal cell body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000371347
- Coding exons
- 9
- Length
- 25253
- Individuals with no LoFs
- 124759
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 36
- Defined
- 124795
- p
- 0.000144
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.34 | 127 | 177 | 0.717 | 0.00000874 | 2065 |
| Missense (PolyPhen) | 36 | 68.305 | 0.52705 | 807 | ||
| Synonymous | -1.13 | 74 | 62.6 | 1.18 | 0.00000316 | 633 |
| Loss of Function | 2.60 | 10 | 23.7 | 0.422 | 0.00000148 | 238 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00013 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00020 | 0.00019 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: UCP are mitochondrial transporter proteins that create proton leaks across the inner mitochondrial membrane, thus uncoupling oxidative phosphorylation from ATP synthesis. As a result, energy is dissipated in the form of heat. May play a role in thermoregulatory heat production and metabolism in brain.;
Recessive Scores
- pRec
- 0.147
Intolerance Scores
- LoFtool
- 0.495
- RVIS EVS
- 0.53
- RVIS percentile EVS
- 80.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.531
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |