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TSHR

From SNPedia
is agene
is mentioned by
Full namethyroid stimulating hormone receptor
EntrezGene7253
PheGenI7253
VariationViewer7253
ClinVarTSHR
GeneCardsTSHR
dbSNP7253
DiseasesTSHR
SADR7253
HugeNav7253
wikipediaTSHR
googleTSHR
gopubmedTSHR
EVSTSHR
HEFalMpTSHR
MyGene2TSHR
23andMeTSHR
UniProtP16473
EnsemblENSG00000165409
OMIM603372
# SNPs52
 Max MagnitudeChromosome positionSummary
rs1064794318081,068,278
rs1085307573081,091,094
rs121012551.480,984,708
rs1210126180,984,885
rs121908859081,143,914
rs121908860081,143,925
rs121908861081,143,949
rs121908862081,092,563
rs121908863081,092,547
rs121908864081,143,416
rs121908865081,087,962
rs121908866081,143,695
rs121908867081,143,028
rs121908868081,143,286
rs121908869080,955,802
rs121908870081,143,633
rs121908871081,143,228
rs121908872081,143,715
rs121908873081,139,828
rs121908874081,143,584
rs121908875081,144,073
rs121908876081,143,572
rs121908877081,143,945
rs121908878081,139,828
rs121908879081,096,641
rs121908880081,143,973
rs121908881081,143,488
rs121908882081,142,986
rs121908883081,143,349
rs121908884081,143,856
rs121908885081,143,458
rs1711139481,056,784
rs1711153081,132,568
rs1792471.380,966,202
rs189261858081,143,407
rs199059581,106,042
rs1991517181,144,239
rs201889708081,143,400
rs2075173081,088,273
rs223961080,955,913
rs226845880,996,551
rs226847581,105,966
rs2288493081,145,262
rs28937584081,143,955
rs3783938081,128,036
rs61747482080,955,786
rs7144481081,144,598
rs760874290081,091,070
rs772490052081,143,581
rs786204790081,092,610
... further results


TSHR is the "thyroid stimulating hormone receptor" gene, one of many genes involved in the function of the thyroid gland and thyroid hormone balance. Some TSHR SNPs have also been found significant for bone density and insulin resistance.

[PMID 17903292OA-icon.png] A 2017 article "Genetics of Thyroid-Stimulating Hormone Receptor—Relevance for Autoimmune Thyroid Disease" explained that "Production of thyroid-stimulating hormone receptor (TSHR) antibodies represents the hallmark of Graves' disease (GD) pathogenesis." "The TSHR gene, located on chromosome 14q31, consists of 10 exons and encodes for a G protein-coupled receptor that plays a central role in the regulation of thyroid development, growth, and function." The authors listed various SNPs of the TSHR gene that are associated with GD in the literature, highlighting rs179247, rs2284720, rs12101255, rs12101261, and rs2268458. The article presented theories of the role of TSHR intron 1 variants in gene function and thyroid autoimmunity.


[PMID 17903292OA-icon.png] A 2012 article "Delineating the autoimmune mechanisms in Graves’ disease" responded to the oversimplified view that Graves' disease involves TSHR antibodies in a single pathway that necessarily leads to hyperthyroidism and orbitopathy. They outlined how three types of TSHR antibodies (stimulating, blocking and neutral) function differently in various phenotypes of GD patients, who vary from hyperthyroid to hypothyroid. TSHR blocking antibodies may prevent TSHR from binding to the receptor to such an extent that they may induce hypothyroidism. They also explored several immune mechanisms by which thyroid gland cell death (apoptosis) occurs, resulting in hypothyroidism. Therefore, GD involves genetic risk via multiple gene polymorphisms that interact with epigenetics and environmental factors.

[PMID 22147956OA-icon.png] A 2011 article "Genetics of thyroid function and disease" reviewed past research. Genome-wide association studies have not shown SNPs in TSHR such as rs1991517 to be associated with TSH concentrations at a high level of significance, but together with two other SNPs in other genes, (PDE8B rs4704397 and CAPZB rs10917469, the three SNPs may account for "4.5% of the variation in TSH concentrations." TSHR gene SNPs have not been associated with T3 and T4 thyroid hormone levels, while deiodinase genes such as DIO1 rs2235544 have been associated with them. The authors also cited articles claiming that the often-studied TSHR polymorphism of rs1991517 was relevant to bone density and insulin resistance.

[PMID 22313426OA-icon.png] A 2007 study "Consecutive mutational events in a TSHR allele of Arab families with resistance to thyroid stimulating hormone" outlined that TSH resistance (RTSH) "is a syndrome of reduced sensitivity to TSH, characterized by elevated serum TSH levels, absence of goiter, and normal or low levels of thyroid hormones. "Inactivating TSHR gene mutations are the most common causes for RTSH." In cases of polymorphism, "Homozygotes or compound heterozygotes may have compensated hypothyroidism (only mild elevation of serum TSH concentration), or frank hypothyroidism that may be mild, moderate, or severe. Some heterozygotes may also manifest only an elevated level of serum TSH." RTSH was considered to be a rare condition, but one past study discovered RTSH in 9.4% of Japanese patients found to have high TSH at birth, and estimate 0.6% in the general Japanese population, and another previous study found RTSH in 22.9% in a population of young subjects with nonautoimmune subclinical hypothyroidism.