SLC12A4
protein-codingsolute carrier family 12 member 4, the group of Solute carrier family 12
Gene summary
This gene encodes a member of the SLC12A transporter family. The encoded protein mediates the coupled movement of potassium and chloride ions across the plasma membrane. This gene is expressed ubiquitously. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jan 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~26.1 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 SLC12A4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005072.5. 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 | 7 | 1 | 8 | |||
| missense | 172 | 8 | 180 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 9 | 9 | ||||
| Total | 0 | 0 | 188 | 10 | 0 | 198 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005063.1 | 24 | MANE Select | |
| Ensembl | ENSP00000318557.3 | 24 | MANE Select | |
| RefSeq | NP_001139433.1 | 24 | Standard | |
| RefSeq | NP_001139434.1 | 23 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
- Cation-coupled Chloride cotransporters
- Transport of inorganic cations/anions and amino acids/oligopeptides
Biological Process
- ion transport
- cell volume homeostasis
- chemical synaptic transmission
- chloride ion homeostasis
- potassium ion homeostasis
Molecular Function
- potassium:chloride symporter activity
- protein kinase binding
Cellular Component
- lysosomal membrane
- plasma membrane
- integral component of plasma membrane
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000422611
- Coding exons
- 23
- Length
- 26128
- Individuals with no LoFs
- 125682
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 66
- Defined
- 125748
- p
- 0.000262
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.35 | 594 | 694 | 0.855 | 0.0000447 | 7000 |
| Missense (PolyPhen) | 272 | 331.63 | 0.82019 | 3369 | ||
| Synonymous | -0.989 | 318 | 296 | 1.07 | 0.0000202 | 2280 |
| Loss of Function | 3.48 | 27 | 54.8 | 0.493 | 0.00000282 | 566 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00050 | 0.00049 | rare |
| Latino/Admixed American | 0.00032 | 0.00032 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.000094 | 0.000092 | rare |
| European (Non-Finnish) | 0.00029 | 0.00029 | rare |
| South Asian | 0.00026 | 0.00026 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia (By similarity). Isoform 4 has no transport activity. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.272
Intolerance Scores
- LoFtool
- 0.0282
- RVIS EVS
- -1.92
- RVIS percentile EVS
- 1.93
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.572
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |