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SLC16A2

solute carrier family 16 member 2

The SLC16A2 gene provides instructions for a protein critical in transporting thyroid hormone into nerve cells, essential for proper nervous system development. The SLC16A2 gene, also known as MCT8, encodes a protein that facilitates the transport of the thyroid hormone triiodothyronine (T3) into nerve cells.

Chromosome Xq13.2 X-linked HGNC:10923 Tier C
SLC16A2 Xq13.2 p arm q arm X

SLC16A2 is located on the long (q) arm of chromosome X, at band Xq13.2. Arm ratio per GRCh38 - banding schematic.

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Clinical tests that include this

Carrier Screening panel
SLC16A2 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The SLC16A2 gene, which stands for "solute carrier family 16 member 2", plays a crucial role in human development, particularly in the nervous system. It encodes a protein that acts as a transporter for thyroid hormones, primarily triiodothyronine (T3), across cell membranes. Proper function of this gene is essential for normal brain development and overall metabolic regulation.

What the gene does

The SLC16A2 gene provides instructions for creating a protein known as monocarboxylate transporter 8 (MCT8). This protein's primary function is to transport the thyroid hormone triiodothyronine (T3) into nerve cells within the developing brain. Once inside, T3 interacts with nuclear receptors to regulate gene expression, which is critical for the maturation of nerve cells, their movement to correct locations (cell migration), and the formation of dendrites, which are specialised outgrowths that receive signals. T3 is also thought to contribute to the development of synapses, the junctions where nerve cells communicate. Beyond the nervous system, T3, along with other thyroid hormones, helps regulate the development of various organs and controls metabolic rates throughout the body.

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Chromosome location

The SLC16A2 gene is located on the X chromosome at position Xq13.2. This genomic location means the gene is situated on the long arm of the X chromosome.

Protein structure

The SLC16A2 protein is composed of 539 amino acids. Its structure includes two notable disordered regions: one spanning amino acids 1-92 at the N-terminus and another from amino acids 508-539 at the C-terminus. These disordered regions may play roles in protein-protein interactions or regulatory functions.

Key variants

Variants within the SLC16A2 gene can involve various genetic changes, including insertions, deletions, or single amino acid substitutions. These genetic alterations can impact the structure and function of the SLC16A2 protein, potentially leading to its reduced ability to transport thyroid hormones effectively. Understanding these variants is crucial for identifying individuals at risk for associated conditions.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for SLC16A2.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1399+1G>A
single nucleotide variant
 - Pathogenic ★★☆☆ Spastic paraplegia
c.154C>T
single nucleotide variant
 p.Gln52Ter Pathogenic ★★☆☆ Spastic paraplegia
c.25G>T
single nucleotide variant
 p.Glu9Ter Pathogenic ★★☆☆ Allan-Herndon-Dudley syndrome
c.359_360del
Microsatellite
 p.Ser120fs Pathogenic ★★☆☆ Spastic paraplegia
c.407dup
Duplication
 p.Asn136fs Pathogenic/Likely pathogenic ★★☆☆ Allan-Herndon-Dudley syndrome
c.46C>T
single nucleotide variant
 p.Gln16Ter Pathogenic ★★☆☆ Spastic paraplegia
c.511C>T
single nucleotide variant
 p.Arg171Ter Pathogenic ★★☆☆ Spastic paraplegia
c.576-1G>A
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Spastic paraplegia
c.653_660del
Deletion
 p.Val218fs Pathogenic/Likely pathogenic ★★☆☆ Allan-Herndon-Dudley syndrome
c.97dup
Duplication
 p.Ser33fs Pathogenic/Likely pathogenic ★★☆☆ Allan-Herndon-Dudley syndrome

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the SLC16A2 gene are primarily associated with Allan-Herndon-Dudley syndrome, an X-linked intellectual disability. This condition is characterised by severe neurological impairment due to impaired thyroid hormone transport into the brain. The inheritance pattern for Allan-Herndon-Dudley syndrome is X-linked recessive.

Inheritance pattern

Conditions caused by pathogenic SLC16A2 variants typically follow x-linked inheritance.

♀ Carrier mother 1 altered X ♂ Unaffected father Typical Y Carrier daughter Unaffected daughter Affected son Unaffected son Affected Carrier Unaffected Circles = females · Squares = males

X-linked recessive: sons of a carrier mother have a 50% chance of being affected. Daughters have a 50% chance of being carriers.

Carrier frequency by population How common is heterozygous SLC16A2 carrier status across ancestry groups?

UK clinical status

The SLC16A2 gene is recognised within the NHS Genomic Medicine Service due to its association with several conditions. It is listed on multiple green-rated PanelApp panels, including Congenital hypothyroidism (R145), Dystonia, chorea or related movement disorder, childhood onset (R57), Early onset or syndromic epilepsy, Foetal anomalies (R21), Hereditary spastic paraplegia, Hereditary spastic paraplegia, childhood onset (R61), Hyperthyroidism (R182), Inherited white matter disorders, Intellectual disability, and White matter disorders and cerebral calcification - childhood onset. It is also part of the DDG2P (Developmental Disorders Genotype-Phenotype Database) panel.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Congenital hypothyroidism · R145 NHS GMS → Dystonia, chorea or related movement disorder, childhood onset · R57 NHS GMS → Fetal anomalies · R21 NHS GMS → Hereditary spastic paraplegia, childhood onset · R61 NHS GMS → Hyperthyroidism · R182 NHS GMS → DDG2P NHS GMS → Early onset or syndromic epilepsy NHS GMS → Intellectual disability NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the main function of the SLC16A2 gene?

The SLC16A2 gene provides instructions for a protein that transports the thyroid hormone triiodothyronine (T3) into nerve cells. This transport is vital for proper brain development and overall metabolic regulation.

Which condition is primarily associated with SLC16A2 variants?

Pathogenic variants in the SLC16A2 gene are primarily associated with Allan-Herndon-Dudley syndrome, an X-linked disorder characterised by severe intellectual disability and neurological impairment.

How is Allan-Herndon-Dudley syndrome inherited?

Allan-Herndon-Dudley syndrome follows an X-linked recessive inheritance pattern, meaning it is caused by a gene variant on the X chromosome and primarily affects males.

References

  1. Herzovich V, Vaiani E, Marino R. Unexpected peripheral markers of thyroid function in a patient with a novel mutation of the MCT8 thyroid hormone transporter gene. Hormone research. 2007. PMID: 16974106
  2. Jansen J, Friesema EC, Kester MH. Functional analysis of monocarboxylate transporter 8 mutations identified in patients with X-linked psychomotor retardation and elevated serum triiodothyronine. The Journal of clinical endocrinology and metabolism. 2007. PMID: 17356046
  3. Maranduba CM, Friesema EC, Kok F. Decreased cellular uptake and metabolism in Allan-Herndon-Dudley syndrome (AHDS) due to a novel mutation in the MCT8 thyroid hormone transporter. Journal of medical genetics. 2006. PMID: 15980113
  4. Dumitrescu AM, Liao XH, Weiss RE. Tissue-specific thyroid hormone deprivation and excess in monocarboxylate transporter (mct) 8-deficient mice. Endocrinology. 2006. PMID: 16709608
  5. Friesema EC, Kuiper GG, Jansen J. Thyroid hormone transport by the human monocarboxylate transporter 8 and its rate-limiting role in intracellular metabolism. Molecular endocrinology (Baltimore, Md.). 2006. PMID: 16887882
  6. Friesema EC, Jansen J, Heuer H. Mechanisms of disease: psychomotor retardation and high T3 levels caused by mutations in monocarboxylate transporter 8. Nature clinical practice. Endocrinology & metabolism. 2006. PMID: 16957765
  7. Schwartz CE, May MM, Carpenter NJ. Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene. American journal of human genetics. 2005. PMID: 15889350
  8. Jansen J, Friesema EC, Milici C. Thyroid hormone transporters in health and disease. Thyroid : official journal of the American Thyroid Association. 2005. PMID: 16131319
  9. Kakinuma H, Itoh M, Takahashi H. A novel mutation in the monocarboxylate transporter 8 gene in a boy with putamen lesions and low free T4 levels in cerebrospinal fluid. The Journal of pediatrics. 2005. PMID: 16227048
  10. Holden KR, Zuñiga OF, May MM. X-linked MCT8 gene mutations: characterization of the pediatric neurologic phenotype. Journal of child neurology. 2005. PMID: 16417886
  11. Friesema EC, Grueters A, Biebermann H. Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation. Lancet (London, England). 2004. PMID: 15488219
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 11 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .