TSHR (Thyroid Stimulating Hormone Receptor)
A G protein-coupled receptor critical for thyroid function and growth, with mutations linked to thyroid disorders and cancer.
Gene Information Card
| Symbol | TSHR |
|---|---|
| Full Name | Thyroid Stimulating Hormone Receptor |
| Gene Type | protein-coding |
| Chromosomal Location | 14q31.1 |
| NCBI Gene ID | 7253 ncbi.nlm.nih.gov/gene/7253 |
| Ensembl ID | ENSG00000165409 |
| UniProt ID | P16473 |
| OMIM ID | 603372 |
| HGNC ID | 12373 |
| Aliases | LGR3, MNG1, TSHR-I, TSHR-II |
Description
The TSHR gene encodes the thyroid stimulating hormone receptor, a G protein-coupled receptor primarily expressed on the surface of thyroid follicular cells. Binding of thyroid stimulating hormone (TSH) activates intracellular signaling pathways (mainly cAMP/PKA) that regulate thyroid hormone synthesis and secretion, as well as thyroid cell growth and differentiation. Mutations in TSHR can lead to constitutive activation (causing hyperthyroidism) or loss of function (causing hypothyroidism), and somatic mutations are frequently found in thyroid adenomas and carcinomas.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Graves disease | Autoantibodies activate TSHR, mimicking TSH and causing hyperthyroidism | ClinVar, OMIM |
| Familial nonautoimmune hyperthyroidism | Germline gain-of-function mutations in TSHR lead to constitutive receptor activation | OMIM, ClinVar |
| Congenital hypothyroidism | Loss-of-function mutations in TSHR impair TSH binding or signaling, reducing thyroid hormone production | ClinVar, OMIM |
| Thyroid adenoma | Somatic gain-of-function mutations in TSHR drive clonal expansion and nodule formation | COSMIC, NCBI |
| Thyroid carcinoma | Somatic TSHR mutations (e.g., in hot nodules) can contribute to follicular thyroid carcinoma | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Thyroid | 27.8 | High |
| Pituitary | 0.2 | Not detected |
| Adipose tissue | 0.1 | Not detected |
| Skin | 0.1 | Not detected |
| Testis | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Thyroid follicular cells | 27.8 | Primary cell type expressing TSHR |
| HEK293 | 0.0 | No endogenous expression |
| HeLa | 0.0 | No endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1833C>G (p.Ile611Met) | Missense | <1% | Gain-of-function; associated with hyperthyroidism |
| c.1856C>T (p.Pro639Ser) | Missense | <1% | Loss-of-function; associated with congenital hypothyroidism |
| c.1349G>A (p.Arg450His) | Missense | <1% | Gain-of-function; found in thyroid adenoma |
| c.1897C>T (p.Arg633Cys) | Missense | <1% | Loss-of-function; associated with TSH resistance |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair TSH binding, receptor trafficking, or G protein coupling, leading to reduced cAMP signaling and hypothyroidism.
Gain of Function (GOF)
Mutations that constitutively activate the receptor in the absence of TSH, causing hyperthyroidism and thyroid cell proliferation.
Dominant Negative (DN)
Rare; some loss-of-function mutations may exert dominant-negative effects by forming inactive dimers with wild-type receptors.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • thyroid stimulating hormone receptor activity |
| • signal transduction | • cAMP-mediated signaling |
| • cell surface receptor signaling pathway | • thyroid hormone generation |
Pathways
• Thyroid hormone synthesis (Reactome: R-HSA-209968)
• GPCR downstream signaling (Reactome: R-HSA-388396)
• cAMP/PKA signaling (KEGG: hsa04024)
Protein Summary
The thyroid stimulating hormone receptor (TSHR) is a 764-amino acid glycoprotein with a large extracellular N-terminal domain responsible for TSH binding, seven transmembrane helices, and a cytoplasmic C-terminal tail. It belongs to the rhodopsin-like G protein-coupled receptor family. Upon TSH binding, the receptor activates Gs alpha, stimulating adenylyl cyclase and increasing intracellular cAMP, which regulates thyroid hormone production and cell growth. TSHR is also a major autoantigen in Graves disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TSHR Knockout HEK293 Cell Line | EDJ-KQ1771 | Human | 7253 | Details Get a Quote |
| TSHR Knockout HeLa Cell Line | EDJ-KQ54698 | Human | 7253 | Details Get a Quote |
| TSHR Knockout A-549 Cell Line | EDJ-KQ63185 | Human | 7253 | Details Get a Quote |
| TSHR Knockout HCT 116 Cell Line | EDJ-KQ71657 | Human | 7253 | Details Get a Quote |
| TSHR Knockout MOLP-8 Cell Line | EDC07700 | Human | 7253 | Details Get a Quote |
| TSHR Overexpression HEK293 Stable Cell Line | EDJ-GQ117 | Human | 7253 | Details Get a Quote |
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