SLC13A3: Sodium-Dicarboxylate Cotransporter 3 – Gene, Function, and Clinical Relevance
A comprehensive biomedical overview of SLC13A3, including genomic context, expression, mutations, and associated diseases.
Gene Information Card
| Symbol | SLC13A3 |
|---|---|
| Full Name | Solute carrier family 13 member 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 20q13.12 |
| NCBI Gene ID | 64849 ncbi.nlm.nih.gov/gene/64849 |
| Ensembl ID | ENSG00000101200 |
| UniProt ID | Q8WWT9 |
| OMIM ID | 606411 |
| HGNC ID | 10932 |
| Aliases | NaDC3, SDCT2, hNaDC3 |
Description
SLC13A3 encodes a sodium-coupled dicarboxylate transporter (NaDC3) that mediates the uptake of Krebs cycle intermediates such as succinate, citrate, and alpha-ketoglutarate. It is expressed primarily in the kidney, liver, and brain, playing roles in cellular metabolism and organic anion transport. Mutations in SLC13A3 have been linked to a form of proximal tubulopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Proximal tubulopathy (isolated) | Loss-of-function mutations impair dicarboxylate reabsorption in renal proximal tubules, leading to urinary loss of Krebs cycle intermediates. | ClinVar and OMIM (606411) report pathogenic variants. |
| Chronic kidney disease (susceptibility) | Altered transporter activity may affect renal handling of citrate and succinate, influencing stone formation and tubular function. | GWAS and functional studies (PubMed, via NCBI). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | High (approx. 50-100 nTPM) | Highest expression in renal cortex. |
| Liver | Moderate (approx. 10-30 nTPM) | Hepatocyte expression. |
| Brain | Low to moderate (approx. 5-15 nTPM) | Neuronal and glial cells. |
| Placenta | Low (approx. 3-8 nTPM) | Syncytiotrophoblast. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | Moderate | Used in functional studies. |
| HepG2 | Low | Hepatocellular carcinoma cell line. |
| HK-2 | High | Proximal tubular cell line. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1195C>T (p.Arg399Ter) | Nonsense | Rare (0.01% in gnomAD) | Loss of function; associated with proximal tubulopathy. |
| c.1462G>A (p.Gly488Arg) | Missense | Rare (0.005%) | Impaired transporter activity; likely pathogenic. |
| c.1285A>G (p.Thr429Ala) | Missense | 0.02% | Uncertain significance; may affect substrate affinity. |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated protein or reduced transporter activity.
Gain of Function (GOF)
Not reported; no activating mutations described.
Dominant Negative (DN)
No evidence for dominant-negative effects; SLC13A3 functions as a monomer.
View complete mutation data：
Gene Ontology (GO)
| • transporter activity (GO:0005215) | • symporter activity (GO:0015293) |
| • integral component of membrane (GO:0016021) | • sodium ion transport (GO:0006814) |
| • dicarboxylic acid transport (GO:0015747) |
Pathways
• Transport of organic anions (Reactome: R-HSA-428643)
• SLC-mediated transmembrane transport (Reactome: R-HSA-425407)
Protein Summary
The SLC13A3 protein (NaDC3) is a 602-amino-acid transmembrane protein with 11 predicted membrane-spanning domains. It couples the inward transport of sodium ions to the cotransport of dicarboxylates, with a stoichiometry of 3 Na+ per dicarboxylate. It is critical for renal reabsorption of Krebs cycle intermediates and contributes to cellular metabolism in various tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC13A3 Knockout HEK293 Cell Line | EDJ-KQ14507 | Human | 64849 | Details Get a Quote |
| SLC13A3 Knockout HeLa Cell Line | EDJ-KQ57087 | Human | 64849 | Details Get a Quote |
| SLC13A3 Knockout A-549 Cell Line | EDJ-KQ65599 | Human | 64849 | Details Get a Quote |
| SLC13A3 Knockout HCT 116 Cell Line | EDJ-KQ74027 | Human | 64849 | Details Get a Quote |
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