DIO1 Gene Variant rs2235544 and Thyroid Hormone Conversion

Last reviewed: May 12, 2026 Last updated: May 12, 2026

Written by: Jay Hastings , CEO of PlexusDx

Jay Hastings is the CEO of PlexusDx, a precision health company focused on genetic testing, blood biomarker insights, and personalized wellness recommendations. He has more than 20 years of experience across healthcare innovation, genomics, laboratory operations, healthcare investing, and strategic finance. His work has included scaling healthcare startups, leading CLIA lab integrations, and helping expand consumer access to precision health tools.

Medically reviewed by: Jayden Lee, PharmD, EMBA

Jayden Lee, PharmD, EMBA, is the PlexusDx Medical Science Liaison with a PharmD and MBA specializing in pharmacogenomics and clinical product development, with a proven ability to bridge the gap between genomic research and practical patient outcomes. Dr. Lee has more than 10 years of professional experience in clinical pharmacy, academia, and research.

This article is part of the PlexusDx Education Hub — your resource for evidence-based guidance on Hormones & Genetics. Browse all Hormones & Genetics education

Your thyroid gland releases mostly thyroxine (T4), a relatively inactive hormone. The active hormone that drives metabolism, triiodothyronine (T3), is made largely by converting T4 in tissues throughout the body. The enzyme deiodinase type 1, encoded by the DIO1 gene, is a key part of that conversion. The DIO1 variant rs2235544 has been studied for its effect on the balance of thyroid hormones in the blood — a good example of how a single gene can shape hormone biology without causing overt thyroid disease.

How the thyroid actually works

The thyroid axis is a two-step system. The gland secretes T4, and then deiodinase enzymes remove an iodine atom to produce active T3 or, alternatively, inactive reverse T3 (rT3). This peripheral conversion is where much of your usable thyroid hormone is generated, which means the genes encoding deiodinase enzymes influence how effectively T4 becomes the active hormone your cells use.

Three deiodinase enzymes exist, and DIO1 is especially active in the liver and kidney, contributing to circulating T3 and helping clear rT3.

DIO1 and the rs2235544 variant

The DIO1 gene provides instructions for deiodinase type 1. Research, including work published in clinical endocrinology journals, has associated the rs2235544 variant with differences in deiodinase activity. Depending on which allele a person carries, studies have observed shifts in the ratio of free T3 to free T4 and in reverse T3 levels — signals that the enzyme is working at a slightly different pace.

Importantly, these are variations within the normal population, not a thyroid disorder. Most people carrying either genotype have thyroid function well within normal ranges; the variant nudges the balance rather than breaking the system.

DIO2 and the wider conversion pathway

DIO1 does not act alone. The DIO2 gene encodes deiodinase type 2, which is important for T3 production inside tissues like the brain and muscle. A well-known DIO2 variant, Thr92Ala, has been studied for its potential influence on how people feel on thyroid hormone. Looking at DIO1 and DIO2 together gives a fuller picture of the peripheral conversion pathway than any single gene can on its own.

Why the conversion pathway matters

Because so much active thyroid hormone is made outside the gland, standard thyroid blood tests do not always capture the whole story. Two people with identical T4 levels can convert it differently based on their deiodinase genetics, nutrition (the enzymes depend on selenium), and overall health. This is why some individuals with normal lab values still explore how efficiently their bodies activate thyroid hormone — always in partnership with a clinician who can interpret the full panel.

Understanding your hormone pathways

The PlexusDx Precision Peptide Genetic Test analyzes 14 pathways, 49 peptides, 150+ genetic insights across pathways that include hormone regulation and metabolism. Reporting a variant like DIO1 rs2235544 is educational context about your predispositions — it does not diagnose a thyroid condition, does not predict thyroid disease, and is not a treatment plan. Thyroid symptoms, lab interpretation, and any medication decisions belong with a qualified healthcare provider.

Evidence-based thyroid care is provider-led: appropriate blood testing (TSH, free T4, and free T3 when indicated), attention to nutrients like iodine and selenium, and individualized clinical judgment. Genetic insight simply helps you understand the conversion machinery behind those numbers.

Frequently Asked Questions

What does the DIO1 gene do?

The DIO1 gene encodes deiodinase type 1, an enzyme that converts thyroxine (T4) into the active thyroid hormone triiodothyronine (T3) and helps clear inactive reverse T3. It is especially active in the liver and kidney, making it an important part of how your body activates thyroid hormone.

How does the rs2235544 variant affect thyroid function?

Studies have associated the DIO1 rs2235544 variant with subtle differences in deiodinase activity, shifting the balance of free T3, free T4, and reverse T3. These are variations within the normal population rather than a disorder, so most carriers have thyroid function within normal ranges.

Can this variant cause hypothyroidism?

No. rs2235544 is a common variant that fine-tunes thyroid hormone conversion, not a cause of thyroid disease. Hypothyroidism is diagnosed through blood tests and clinical evaluation. Genetic insight into DIO1 offers pathway context only and should be discussed with a healthcare provider.

Does nutrition affect thyroid hormone conversion?

Yes. Deiodinase enzymes, including the one DIO1 encodes, are selenium-dependent, and overall health influences conversion efficiency. Adequate selenium and iodine support normal thyroid metabolism, but supplementation and any thyroid concern should be guided by a clinician who can interpret your full lab panel.

Want to see how your hormone and metabolism pathways are set up? Take the Precision Peptide Genetic Test to understand your genetic pathway context, then bring that insight to a conversation with your provider.

This article is part of the PlexusDx Education Hub. Browse all Hormones & Genetics education

The Precision Peptide Genetic Test analyzes how your genes influence peptide-related biological pathways. It does not recommend, prescribe, diagnose, or determine which peptides or treatments you should use. Consult a qualified healthcare provider before making decisions about your health or beginning any peptide protocol.

Medical and Editorial Standards

Medical review process: This article was reviewed for medical accuracy, scientific clarity, evidence alignment, and appropriate discussion of genetics, medications, supplements, biomarkers, and health-related claims.

Sources and evidence: PlexusDx educational content is developed using peer-reviewed research, clinical literature, reputable medical references, and, where applicable, public health or regulatory guidance. References are included at the end of the article when scientific, medical, or health-related claims are discussed.

Commercial transparency: PlexusDx offers genetic testing, blood biomarker testing, personalized supplement recommendations, and related precision wellness services. Product mentions are intended to help readers understand available options and should not be interpreted as medical advice.

Important disclaimer: PlexusDx educational content is for informational purposes only and should not be used as a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before making decisions about medications, supplements, genetic testing, lab testing, or health-related care.