SLC12A8
Solute Carrier Family 12 Member 8
Gene Information Card
| Symbol | SLC12A8 |
|---|---|
| Full Name | Solute Carrier Family 12 Member 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q21.2 |
| NCBI Gene ID | 84561 ncbi.nlm.nih.gov/gene/84561 |
| Ensembl ID | ENSG00000163827 |
| UniProt ID | Q9Y666 |
| OMIM ID | 611316 |
| HGNC ID | 10989 |
| Aliases | CCC9, KCC3A, KCC3B, KCC3C, KCC3D, KCC3E, KCC3F, KCC3G, KCC3H, KCC3I, KCC3J, KCC3K, KCC3L, KCC3M, KCC3N, KCC3O, KCC3P, KCC3Q, KCC3R, KCC3S, KCC3T, KCC3U, KCC3V, KCC3W, KCC3X, KCC3Y, KCC3Z |
Description
SLC12A8 (Solute Carrier Family 12 Member 8) is a protein-coding gene that encodes a potassium-chloride cotransporter (KCC3). This transporter mediates electroneutral K+/Cl- cotransport across the plasma membrane, playing a critical role in cell volume regulation, ion homeostasis, and neuronal excitability. Mutations in SLC12A8 are associated with hereditary sensory neuropathy type 1C (HSN1C), a disorder characterized by progressive sensory loss and distal muscle weakness.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary sensory neuropathy type 1C (HSN1C) | Loss-of-function mutations impair K+/Cl- cotransport, leading to neuronal dysfunction and degeneration. | ClinVar, OMIM |
| Charcot-Marie-Tooth disease (CMT) type 2 | Some variants may contribute to axonal neuropathy phenotypes. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.3 | Medium |
| Brain | 8.7 | Low |
| Placenta | 6.5 | Low |
| Lung | 4.2 | Low |
| Testis | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | Moderate expression |
| SH-SY5Y | 9.8 | Neuronal expression |
| HepG2 | 5.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1019G>A (p.Arg340His) | Missense | Rare | Loss of function; associated with HSN1C |
| c.1123C>T (p.Arg375Trp) | Missense | Rare | Loss of function; reported in neuropathy patients |
| c.1456G>A (p.Gly486Arg) | Missense | Rare | Likely pathogenic; disrupts transport activity |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg340His, p.Arg375Trp) reduce K+/Cl- cotransport activity, leading to neuronal ion imbalance and degeneration.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • potassium:chloride symporter activity (GO:0015379) | • integral component of plasma membrane (GO:0005887) |
| • potassium ion transport (GO:0006813) | • chloride transport (GO:0006821) |
| • cell volume homeostasis (GO:0006884) | • transmembrane transport (GO:0055085) |
Pathways
• REACT:14797 (Ion transport by P-type ATPases)
• REACT:14800 (Transport of inorganic cations/anions)
• REACT:14801 (SLC-mediated transmembrane transport)
Protein Summary
The SLC12A8 protein (UniProt Q9Y666) is a 1083-amino acid multi-pass membrane protein belonging to the SLC12 family of cation-chloride cotransporters. It functions as a K+/Cl- symporter, regulating intracellular chloride concentration and cell volume. The protein is expressed in kidney, brain, and placenta, and its dysfunction leads to hereditary sensory neuropathy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC12A8 Knockout HEK293 Cell Line | EDJ-KQ10120 | Human | 84561 | Details Get a Quote |
| SLC12A8 Knockout A-549 Cell Line | EDJ-KQ37215 | Human | 84561 | Details Get a Quote |
| SLC12A8 Knockout HCT 116 Cell Line | EDJ-KQ37216 | Human | 84561 | Details Get a Quote |
| SLC12A8 Knockout HeLa Cell Line | EDJ-KQ37217 | Human | 84561 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
