SLC8B1
protein-codingsolute carrier family 8 member B1, the group of Solute carrier family 8
Gene summary
SLC24A6 belongs to a family of potassium-dependent sodium/calcium exchangers that maintain cellular calcium homeostasis through the electrogenic countertransport of 4 sodium ions for 1 calcium ion and 1 potassium ion (Cai and Lytton, 2004 [PubMed 14625281]).[supplied by OMIM, Mar 2008]
- SLC24A6
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~60.7 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 SLC8B1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001358345.2. 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 | 0 | |||||
| missense | 100 | 1 | 101 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 100 | 1 | 0 | 101 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001345274.1 | 15 | MANE Select | |
| Ensembl | ENSP00000506377.1 | 15 | MANE Select | |
| RefSeq | NP_001317395.1 | 14 | Standard | |
| RefSeq | NP_079235.2 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Sodium/Calcium exchangers
- Transport of inorganic cations/anions and amino acids/oligopeptides
- SLC-mediated transmembrane transport
- Transport of small molecules
- Mitochondrial calcium ion transport
Biological Process
- ion transport
- mitochondrial calcium ion transmembrane transport
- sodium ion transmembrane transport
- glucose homeostasis
- regulation of insulin secretion
Molecular Function
- calcium:sodium antiporter activity
- calcium:cation antiporter activity
- protein homodimerization activity
- calcium:sodium antiporter activity involved in regulation of cardiac muscle cell membrane potential
Cellular Component
- mitochondrial inner membrane
- plasma membrane
- mitochondrial crista
- integral component of mitochondrial membrane
- sarcolemma
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000552014
- Coding exons
- 15
- Length
- 60735
- Individuals with no LoFs
- 125500
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 247
- Defined
- 125748
- p
- 0.000987
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.318 | 326 | 343 | 0.952 | 0.0000208 | 3717 |
| Missense (PolyPhen) | 102 | 114.34 | 0.89209 | 1280 | ||
| Synonymous | -0.0153 | 152 | 152 | 1.00 | 0.00000940 | 1283 |
| Loss of Function | 0.539 | 26 | 29.1 | 0.892 | 0.00000152 | 300 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00020 | 0.00018 | rare |
| Latino/Admixed American | 0.00020 | 0.00020 | rare |
| Ashkenazi Jewish | 0.0083 | 0.0082 | notable |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.00059 | 0.00059 | rare |
| South Asian | 0.0023 | 0.0023 | notable |
| Other | 0.0016 | 0.0016 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mitochondrial sodium/calcium antiporter that mediates sodium-dependent calcium efflux from mitochondrion, by mediating the exchange of 3 sodium ions per 1 calcium ion (PubMed:20018762, PubMed:22829870, PubMed:23056385, PubMed:24898248, PubMed:28219928). Plays a central role in mitochondrial calcium homeostasis by mediating mitochondrial calcium extrusion: calcium efflux is essential for mitochondrial function and cell survival, notably in cardiomyocytes (By similarity). Regulates rates of glucose-dependent insulin secretion in pancreatic beta-cells during the first phase of insulin secretion: acts by mediating efflux of calcium from mitochondrion, thereby affecting cytoplasmic calcium responses (PubMed:23056385). Required for store-operated Ca(2+) entry (SOCE) and Ca(2+) release-activated Ca(2+) (CRAC) channel regulation: sodium transport by SLC8B1 leads to promote calcium-shuttling that modulates mitochondrial redox status, thereby regulating SOCE activity (PubMed:28219928). Involved in B-lymphocyte chemotaxis (By similarity). Able to transport Ca(2+) in exchange of either Li(+) or Na(+), explaining how Li(+) catalyzes Ca(2+) exchange (PubMed:15060069). In contrast to other members of the family its function is independent of K(+) (PubMed:15060069). {ECO:0000250|UniProtKB:Q925Q3, ECO:0000269|PubMed:15060069, ECO:0000269|PubMed:20018762, ECO:0000269|PubMed:22829870, ECO:0000269|PubMed:23056385, ECO:0000269|PubMed:24898248, ECO:0000269|PubMed:28219928}.;
Intolerance Scores
- RVIS EVS
- -1
- RVIS percentile EVS
- 8.54
Essentials
- Essential (CRISPR)
- N
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |