SLC16A2: Monocarboxylate Transporter 8 (MCT8) – Thyroid Hormone Transporter
SLC16A2 encodes MCT8, a critical thyroid hormone transporter; mutations cause Allan-Herndon-Dudley syndrome and are implicated in neurodevelopmental disorders.
Gene Information Card
| Symbol | SLC16A2 |
|---|---|
| Full Name | Solute Carrier Family 16 Member 2 |
| Gene Type | Protein coding |
| Chromosomal Location | Xq13.2 |
| NCBI Gene ID | 6567 ncbi.nlm.nih.gov/gene/6567 |
| Ensembl ID | ENSG00000147100 |
| UniProt ID | P36021 |
| OMIM ID | 300095 |
| HGNC ID | 10923 |
| Aliases | MCT8, MCT 8, XPCT, DXS128E, MCT7, SLC16A2 |
Description
SLC16A2 (Solute Carrier Family 16 Member 2) encodes the monocarboxylate transporter 8 (MCT8), a transmembrane protein that facilitates the cellular uptake and efflux of thyroid hormones, particularly T3 (triiodothyronine) and T4 (thyroxine). MCT8 is essential for thyroid hormone transport across the blood-brain barrier and into neurons. Loss-of-function mutations in SLC16A2 cause Allan-Herndon-Dudley syndrome (AHDS), an X-linked disorder characterized by severe intellectual disability, hypotonia, and abnormal thyroid hormone levels. The gene is expressed in multiple tissues, including brain, liver, kidney, and heart.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Allan-Herndon-Dudley syndrome (AHDS) | Loss-of-function mutations impair thyroid hormone transport into neurons, leading to severe neurodevelopmental delay, hypotonia, and elevated serum T3 with low/normal T4. | ClinVar, OMIM |
| X-linked intellectual disability | MCT8 deficiency disrupts thyroid hormone signaling in the developing brain, causing cognitive impairment. | OMIM, PubMed |
| Thyroid hormone resistance (peripheral) | Impaired cellular uptake of T3/T4 due to MCT8 dysfunction results in abnormal serum thyroid profiles. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Liver | 8.3 | Medium |
| Kidney | 6.1 | Medium |
| Heart | 5.4 | Medium |
| Skeletal Muscle | 3.2 | Low |
| Lung | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.0 | High expression; used in thyroid hormone transport studies |
| HepG2 (hepatocellular carcinoma) | 9.8 | Medium expression |
| HEK293 (embryonic kidney) | 7.5 | Medium expression |
| A549 (lung carcinoma) | 2.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.632G>A (p.Arg211His) | Missense | <0.01% | Loss of function; impaired T3 transport; associated with AHDS |
| c.1003C>T (p.Arg335*) | Nonsense | <0.01% | Truncation; complete loss of MCT8 function; severe AHDS phenotype |
| c.1340delC (p.Pro447Leufs*12) | Frameshift | <0.01% | Premature stop; loss of transporter activity |
| c.2T>C (p.Met1?) | Start loss | <0.01% | No protein production; severe AHDS |
Mutation functional classification
Loss of Function (LOF)
Most SLC16A2 mutations are loss-of-function, reducing or abolishing thyroid hormone transport. This leads to Allan-Herndon-Dudley syndrome with severe neurodevelopmental deficits.
Gain of Function (GOF)
No gain-of-function mutations have been reported in SLC16A2.
Dominant Negative (DN)
No dominant-negative effects described; SLC16A2 is X-linked and hemizygous in males, so dominant-negative mechanisms are not applicable.
View complete mutation data：
Gene Ontology (GO)
| • monocarboxylic acid transmembrane transporter activity (GO:0008028) | • thyroid hormone transmembrane transporter activity (GO:0015349) |
| • thyroid hormone transport (GO:0015889) | • integral component of membrane (GO:0016021) |
| • transmembrane transport (GO:0055085) |
Pathways
• Thyroid hormone synthesis and transport (Reactome: R-HSA-209776)
• Transport of small molecules (Reactome: R-HSA-382551)
• SLC-mediated transmembrane transport (Reactome: R-HSA-425407)
Protein Summary
MCT8 (monocarboxylate transporter 8) is a 613-amino acid transmembrane protein with 12 predicted alpha-helical domains. It specifically mediates the sodium-independent, high-affinity transport of thyroid hormones (T3 and T4) across cell membranes. MCT8 is critical for thyroid hormone entry into neurons and across the blood-brain barrier. The protein is localized to the plasma membrane and endosomes. Defects in MCT8 lead to intracellular thyroid hormone deficiency in the brain, despite elevated serum T3 levels, causing severe neurological impairment.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC16A2 Knockout HEK293 Cell Line | EDJ-KQ5791 | Human | 6567 | Details Get a Quote |
| SLC16A2 Knockout A-549 Cell Line | EDJ-KQ29207 | Human | 6567 | Details Get a Quote |
| SLC16A2 Knockout HeLa Cell Line | EDJ-KQ54511 | Human | 6567 | Details Get a Quote |
| SLC16A2 Knockout HCT 116 Cell Line | EDJ-KQ71466 | Human | 6567 | Details Get a Quote |
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