DIO2, a.k.a. "Iodothyronine Deiodinase 2" or "Type II Iodothyronine Deiodinase," is one of three genes responsible for thyroid hormone metabolism and catabolism throughout the body. The other two deiodinase genes are DIO1 and DIO3. Deiodinase type 2 encodes proteins that convert the prohormone thyroxine (T4) to the bioactive thyroid hormone (T3) by means of deiodination.
According to GeneCards, "This gene is widely expressed, including in thyroid, placenta, pituitary and brain. It is thought to be responsible for the 'local' production of T3, and thus important in influencing thyroid hormone action in these tissues. It has also been reported to be highly expressed in thyroids of patients with Graves disease, and in follicular adenomas. The intrathyroidal T4 to T3 conversion by this enzyme may contribute significantly to the relative increase in thyroidal T3 production in these patients."
Polymorphisms in the rs225014 and rs12885300 SNPs of the DIO2 gene have been associated with risk for various conditions in the literature: osteoarthritis, psychological disorders, reduced thyroid hormone metabolism, Type 2 diabetes, and various other conditions.
[PMID 18815314] Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. This 2008 article abstract stated "The activating deiodinase (D2) and the inactivating deiodinase (D3) can locally increase or decrease thyroid hormone signaling in a tissue- and temporal-specific fashion, independent of changes in thyroid hormone serum concentrations. This mechanism is particularly relevant because deiodinase expression can be modulated by a wide variety of endogenous signaling molecules such as sonic hedgehog, nuclear factor-kappaB, growth factors, bile acids, hypoxia-inducible factor-1alpha, as well as a growing number of xenobiotic substances. In light of these findings, it seems clear that deiodinases play a much broader role than once thought, with great ramifications for the control of thyroid hormone signaling during vertebrate development and metamorphosis, as well as injury response, tissue repair, hypothalamic function, and energy homeostasis in adults." (Abstract)
[PMID 25040645] A 2014 article called "Defending plasma T3 is a biological priority" explained the mechanism and importance of the enzyme Deiodinase type 2 (D2) in protecting appropriate levels of T3 in blood plasma. Normally D2) is involved in the majority of human T3 production, approx. 20 µg/day, with less production mediated by D1 (5 µg/day). However, Type 2 deiodinase is organ and tissue-specific. High D2-activity is found "in the brain, pituitary gland, brown adipose tissue (BAT) and heart." D2 less active in tissues such as "skin, skeletal muscle, skeleton, vascular smooth muscle and testis." However, this does not mean that D2 is less important for skin, bones, etc. Compared to the D1 deiodinase, which remains in the cell for about 30 minutes, "D2 remains in the target cell for a longer period time, approximately 8 h." Thus, D2 powerfully triggers actions in the cells where it is produced. Then D2 is expelled from the cell and enters blood circulation, contributing to the maintenance of appropriate plasma levels of T3. An imbalance in deiodinase-specific metabolism, further mediated by increased activity of deiodinase type 3 which catabolizes thyroid hormones, may contribute to significant T3 plasma depletion. The article stated that in patients with a normal, active thyroid gland, plasma T3 depletion may be corrected, but this may not be possible in patients with primary hypothyroidism due to damaged, or surgically removed thyroid glands.
[PMID 21715540] The Type 2 Deiodinase ORFa-Gly3Asp Polymorphism (rs12885300) Influences the Set Point of the Hypothalamus-Pituitary-Thyroid Axis in Patients Treated for Differentiated Thyroid Carcinoma. (Published 2012.) Concluded that "that the negative feedback of FT4 on TSH is weaker in patients homozygous for the D2-rs12885300 T allele than in wild-type and heterozygous subjects." (Abstract). Included discussion of the three DIO genes in relation to thyroid hormone metabolism and catabolism. It was hypothesized that the HPT axis was altered in part due to thyroid cancer treatment involving large TSH-suppressing doses of L-T4, which could down-regulate genes for D1 and D2 and upregulate the gene for D3.