SLC12A8
protein-codingsolute carrier family 12 member 8, the group of MicroRNA protein coding host genes|Solute carrier family 12
Gene summary
This gene is thought to be a candidate for psoriasis susceptibility. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Sep 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~130.2 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 SLC12A8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024628.6. 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 | 130 | 8 | 138 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 137 | 8 | 0 | 145 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_078904.4 | 13 | MANE Select | |
| Ensembl | ENSP00000418783.1 | 13 | MANE Select | |
| RefSeq | NP_001182412.2 | 13 | Standard | |
| Ensembl | ENSP00000377112.4 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| slc12a8 | Danio rerio | Structure: otolith Quality: malformed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cell volume homeostasis
- chloride ion homeostasis
- potassium ion homeostasis
- chloride transmembrane transport
- potassium ion import across plasma membrane
Molecular Function
- potassium:chloride symporter activity
Cellular Component
- cell
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000393469
- Coding exons
- 13
- Length
- 196542
- Individuals with no LoFs
- 124566
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 286
- Defined
- 124854
- p
- 0.00115
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.306 | 429 | 412 | 1.04 | 0.0000231 | 4605 |
| Missense (PolyPhen) | 175 | 175.53 | 0.99696 | 1973 | ||
| Synonymous | -0.242 | 187 | 183 | 1.02 | 0.0000116 | 1500 |
| Loss of Function | 0.518 | 30 | 33.2 | 0.903 | 0.00000158 | 362 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0060 | 0.0058 | notable |
| Latino/Admixed American | 0.0012 | 0.0012 | notable |
| Ashkenazi Jewish | 0.0030 | 0.0030 | notable |
| East Asian | 0.00045 | 0.00044 | rare |
| Finnish | 0.00028 | 0.00028 | rare |
| European (Non-Finnish) | 0.00081 | 0.00080 | rare |
| South Asian | 0.00049 | 0.00049 | rare |
| Other | 0.0010 | 0.00099 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cation/chloride cotransporter that may play a role in the control of keratinocyte proliferation. {ECO:0000269|PubMed:11863360}.;
Intolerance Scores
- LoFtool
- 0.185
- RVIS EVS
- 0.67
- RVIS percentile EVS
- 84.75
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.119
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |