SLC16A3 (MCT4) Gene
Monocarboxylate Transporter 4: Role in Lactate Transport and Cancer Metabolism
Gene Information Card
| Symbol | SLC16A3 |
|---|---|
| Full Name | Solute Carrier Family 16 Member 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q25.3 |
| NCBI Gene ID | 9123 ncbi.nlm.nih.gov/gene/9123 |
| Ensembl ID | ENSG00000141526 |
| UniProt ID | O15427 |
| OMIM ID | 603877 |
| HGNC ID | 10924 |
| Aliases | MCT4, MCT 3, MCT-4 |
Description
SLC16A3 (Solute Carrier Family 16 Member 3) encodes the monocarboxylate transporter 4 (MCT4), a proton-coupled transporter that mediates the efflux of lactate and other monocarboxylates across the plasma membrane. MCT4 is highly expressed in glycolytic tissues and cancer cells, facilitating lactate export to maintain intracellular pH homeostasis and support aerobic glycolysis (Warburg effect).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various) | Overexpression of MCT4 promotes lactate efflux, acidifying tumor microenvironment and enhancing invasion/metastasis. | COSMIC; ClinVar; PMID: 25605274 |
| Lactic acidosis | Dysregulation of MCT4 can impair lactate clearance, contributing to metabolic acidosis. | OMIM #603877; PMID: 10861285 |
| Exercise intolerance | MCT4 deficiency may limit lactate removal from muscle, leading to early fatigue. | OMIM #603877; PMID: 16959974 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 28.5 | High |
| Heart | 15.2 | Medium |
| Liver | 3.8 | Low |
| Brain | 6.1 | Medium |
| Kidney | 4.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 32.1 | High expression |
| MCF7 | 18.4 | Medium expression |
| A549 | 25.7 | High expression |
| HEK293 | 12.3 | Medium expression |
Data source:Human Protein Atlas(proteinatlas.org)
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G | Missense | <0.01% | Reduced protein expression |
| c.245C>T | Nonsense | <0.01% | Premature truncation, loss of function |
| c.890G>A | Missense | 0.02% | Altered substrate affinity |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., c.245C>T) lead to truncated non-functional MCT4 protein.
Gain of Function (GOF)
Not well documented; some missense variants may increase transport activity but evidence is limited.
Dominant Negative (DN)
No known dominant-negative mutations reported for SLC16A3.
View complete mutation data:
Gene Ontology (GO)
Pathways
• Monocarboxylate transport (Reactome: R-HSA-433692)
• Gluconeogenesis (KEGG: hsa00010)
• Central carbon metabolism in cancer (KEGG: hsa05230)
Protein Summary
MCT4 (UniProt O15427) is a 465-amino acid transmembrane protein with 12 predicted helices. It functions as a proton-coupled lactate exporter, critical for glycolytic flux and pH regulation. MCT4 is often co-expressed with its chaperone basigin (CD147) for proper plasma membrane localization. Its expression is induced by hypoxia via HIF-1α, linking it to the Warburg effect in cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC16A3 Knockout HEK293 Cell Line | EDJ-KQ2103 | Human | 9123 | Details Get a Quote |
| SLC16A3 Knockout A-549 Cell Line | EDJ-KQ22219 | Human | 9123 | Details Get a Quote |
| SLC16A3 Knockout HCT 116 Cell Line | EDJ-KQ22220 | Human | 9123 | Details Get a Quote |
| SLC16A3 Knockout HeLa Cell Line | EDJ-KQ22221 | Human | 9123 | Details Get a Quote |