SLC16A2 (Solute Carrier Family 16 Member 2), also known as MCT8, encodes a thyroid hormone transporter that is essential for thyroid hormone uptake into brain cells. Mutations in this gene cause a severe X-linked neurodevelopmental disorder known as Allan-Herndon-Dudley syndrome (AHDS).
| Attribute |
Value |
| Gene Symbol |
SLC16A2 (MCT8) |
| Full Name |
Solute Carrier Family 16 Member 2 (Monocarboxylate Transporter 8) |
| Chromosomal Location |
Xq13.2 |
| NCBI Gene ID |
6568 |
| Ensembl ID |
ENSG00000147100 |
| UniProt ID |
P36012 |
| Associated Diseases |
Allan-Herndon-Dudley syndrome (AHDS), thyroid hormone resistance |
MCT8 is a thyroid hormone transporter that facilitates the cellular uptake of thyroid hormones, particularly:
- T3 (triiodothyronine) — the active form
- T4 (thyroxine) — the prohormone
- Reverse T3 (rT3) — the inactive form
MCT8 is expressed in:
- Blood-brain barrier — endothelial cells for thyroid hormone entry into the brain
- Neurons — for cellular uptake
- Astrocytes — for thyroid hormone metabolism
- Choroid plexus — for CSF hormone exchange
MCT8 operates as a sodium-independent transporter with high affinity for thyroid hormones. It is essential because:
- Thyroid hormones cannot cross the cell membrane by passive diffusion efficiently
- MCT8 provides the primary mechanism for neuronal uptake
- Mutations cause severe neurological deficits despite normal circulating hormone levels
MCT8 is highly expressed in:
- Cerebral cortex (neurons and astrocytes)
- Hippocampus
- Cerebellum (Purkinje cells)
- Basal ganglia
- Hypothalamus
- Choroid plexus
X-linked disorder caused by SLC16A2 mutations characterized by:
Neurological Features:
- Severe intellectual disability
- Developmental delay
- Hypotonia (in infancy) progressing to spastic quadriplegia
- Ataxia
- Seizures
- Movement disorders (dystonia, choreoathetosis)
Additional Features:
- Thyroid dysfunction (elevated T3, normal/low T4)
- Delayed myelination
- Absent speech or severe speech impairment
- Characteristic facial features
Pathophysiology:
- Impaired thyroid hormone transport into neurons
- Reduced T3 uptake during critical developmental periods
- Abnormal neuronal migration and differentiation
- Impaired myelination
- Reduced transporter function
- May contribute to neurological disorders
- Variable phenotypes
Current Approaches:
- Thyroid hormone analog therapy (e.g., TRIAC)
- Gene therapy research
- Symptomatic management
Emerging Treatments:
- Thyroid hormone receptor agonists
- AAV-based gene delivery
- Small molecule transporters
- Allan-Herndon-Dudley syndrome: clinical and MCT8 gene mutations
- MCT8 deficiency: understanding thyroid hormone transport into the brain
- Thyroid hormone transporters in neurological development
- Gene therapy for MCT8 deficiency