rs225014

This is a variant in the DIO2 gene that changes a threonine to an alanine.

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GWAS Catalog Trait Associations (1)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

thyroxine level

Teumer A et al. “Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.” Nature Communications 9(1):4455 (2018)

Allele T

OR 0.05

p 5.0e-17

N 49,269

Large GWAS

European

Jacobs BM et al. “Genetic architecture of routinely acquired blood tests in a British South Asian cohort.” Nature Communications 15(1):8929 (2024)

Allele T

OR 0.05

p 1.0e-10

N 38,000

Large GWAS

South Asian

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ClinVar annotation

other

1 submitter

Levothyroxine response

View on ClinVar →

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Research that mentions this SNP (1)

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A genome‐wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22

AssociationN=53,938Hanneke J. M. Kerkhof et al.(2010)· Arthritis & Rheumatism

Genome-wide association study identifying 14,938 osteoarthritis cases and approximately 39,000 controls found that the C-allele of rs3815148 on chromosome 7q22 (near GPR22 gene) is associated with 1.14-fold increased risk of knee/hand OA (p=8×10⁻⁸) and 30% increased risk for knee OA progression. The same study identified rs10248619 and rs6088813 with secondary associations to OA.

Traits studied:Hand osteoarthritisHip osteoarthritisKnee osteoarthritisKnee osteoarthritis progressionOsteoarthritis

PubMed DOI Metascience Observatory

About DIO2

The protein encoded by this gene belongs to the iodothyronine deiodinase family. It catalyzes the conversion of prohormone thyroxine (3,5,3',5'-tetraiodothyronine, T4) to the bioactive thyroid hormone (3,5,3'-triiodothyronine, T3) by outer ring 5'-deiodination. This gene is widely expressed, including in thyroid 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. This protein is a selenoprotein containing the non-standard amino acid, selenocysteine (Sec), which is encoded by the UGA codon that normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Unlike the other two members (DIO1 and DIO3) of this enzyme family, the mRNA for this gene contains an additional in-frame UGA codon that has been reported (in human) to function either as a Sec or a stop codon, which can result in two isoforms with one or two Sec residues; however, only the upstream Sec (conserved with the single Sec residue found at the active site in DIO1 and DIO3) was shown to be essential for enzyme activity (PMID:10403186). Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2018]