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.

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 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
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