THRB Gene (Thyroid Hormone Receptor Beta): Function, Mutations, and Associated Diseases
Comprehensive biomedical resource on the THRB gene, including genomic information, protein function, expression profiles, disease associations, and mutation data from authoritative databases.
Gene Information Card
| Symbol | THRB |
|---|---|
| Full Name | Thyroid Hormone Receptor Beta |
| Gene Type | Protein coding |
| Chromosomal Location | 3p24.2 |
| NCBI Gene ID | 7068 ncbi.nlm.nih.gov/gene/7068 |
| Ensembl ID | ENSG00000151090 |
| UniProt ID | P10828 |
| OMIM ID | 190160 |
| HGNC ID | 11799 |
| Aliases | THR1, ERBA2, NR1A2, MGC126109, MGC126110, c-erbA-2, thyroid hormone receptor, beta |
Description
The THRB gene encodes thyroid hormone receptor beta (TRβ), a nuclear hormone receptor that acts as a ligand-activated transcription factor. It binds to thyroid hormone (T3) and regulates the expression of genes involved in metabolism, development, and cellular differentiation. TRβ is critical for the feedback regulation of thyroid-stimulating hormone (TSH) in the pituitary, liver function, and auditory and visual development. Mutations in THRB cause Resistance to Thyroid Hormone (RTH), a syndrome characterized by elevated circulating thyroid hormones with inappropriately normal or elevated TSH. Additionally, somatic mutations and altered expression of THRB are implicated in various cancers, including thyroid cancer and hepatocellular carcinoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Resistance to Thyroid Hormone (RTH) | Heterozygous or homozygous mutations in THRB lead to reduced receptor affinity for T3 or impaired transcriptional activity, causing tissue-specific resistance to thyroid hormone action. This disrupts the hypothalamic-pituitary-thyroid axis feedback, leading to elevated T3/T4 levels with unsuppressed TSH. | OMIM #188570; ClinVar; Multiple publications (e.g., Refetoff et al., 1967; Weiss et al., 1998) |
| Thyroid Carcinoma (Follicular and Papillary) | Somatic mutations and loss of heterozygosity at the THRB locus are found in thyroid cancers. Loss of TRβ function can promote tumorigenesis through dysregulation of cell cycle and apoptosis pathways, acting as a tumor suppressor. | COSMIC; NCBI Gene; PubMed (e.g., Puzianowska-Kuznicka et al., 2002) |
| Hepatocellular Carcinoma (HCC) | Reduced expression or mutation of THRB is observed in HCC. TRβ can modulate cell proliferation and invasion; its loss contributes to hepatocarcinogenesis, potentially through altered signaling pathways like PI3K/AKT. | COSMIC; PubMed (e.g., Lin et al., 1999; Chen et al., 2008) |
| Pituitary Tumors (TSH-secreting) | Somatic mutations in THRB have been identified in a subset of TSH-secreting pituitary adenomas, leading to reduced negative feedback by thyroid hormone and uncontrolled TSH secretion. | COSMIC; PubMed (e.g., Ando et al., 2001) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High | High |
| Kidney | Medium | Medium |
| Heart | Medium | Medium |
| Skeletal Muscle | Medium | Medium |
| Brain (Cerebellum, Pituitary) | Medium | Medium |
| Lung | Low | Low |
| Testis | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (Liver) | High | Hepatocellular carcinoma cell line; high expression of THRB. |
| A549 (Lung) | Low | Lung carcinoma; low expression. |
| MCF7 (Breast) | Medium | Breast adenocarcinoma; moderate expression. |
| K562 (Leukemia) | Low | Chronic myelogenous leukemia; low expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg338Trp (R338W) | Missense | Common in RTH; ~10% of RTH families | Reduced T3 binding affinity and transcriptional activity; dominant negative effect. |
| p.Arg438His (R438H) | Missense | Reported in RTH | Impaired ligand binding and coactivator interaction. |
| p.Pro453Ala (P453A) | Missense | Reported in RTH | Alters receptor conformation and reduces T3 binding. |
| p.Arg320Cys (R320C) | Missense | Reported in RTH | Disrupts DNA binding domain function. |
| p.Val458Ala (V458A) | Missense | Somatic in thyroid carcinoma | Impaired transcriptional regulation; potential oncogenic role. |
| c.94C>T (p.Gln32Ter) | Nonsense | Rare in RTH | Premature truncation, loss of function. |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations or frameshifts leading to truncated proteins lacking the ligand-binding or DNA-binding domains result in complete loss of receptor function. These are rare and often associated with severe RTH when homozygous.
Gain of Function (GOF)
Gain-of-function mutations in THRB are not well-documented in the literature. Most pathogenic mutations lead to loss of function or dominant negative activity.
Dominant Negative (DN)
The majority of THRB mutations causing RTH are missense mutations in the ligand-binding domain that produce a receptor with reduced or absent T3 binding and transcriptional activity. These mutant receptors can dimerize with wild-type receptors (TRα or TRβ) and interfere with their function, exhibiting a dominant negative effect, which explains the autosomal dominant inheritance pattern of RTH.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • Nuclear receptor activity | • Ligand-activated transcription factor activity |
| • Zinc ion binding | • Steroid hormone receptor activity |
| • Transcription coregulator binding | • Protein homodimerization activity |
| • Protein heterodimerization activity | • Chromatin binding |
Pathways
• Thyroid hormone signaling pathway
• Nuclear receptor transcription pathway
• Gene expression (Transcription)
• Regulation of lipid metabolism by PPARalpha
• Developmental Biology
Protein Summary
The thyroid hormone receptor beta (TRβ) is a 461-amino acid nuclear receptor that mediates the biological actions of thyroid hormones (T3 and T4). It contains an N-terminal activation function 1 (AF-1) domain, a central DNA-binding domain (DBD) with two zinc finger motifs, and a C-terminal ligand-binding domain (LBD) that also harbors a dimerization interface and activation function 2 (AF-2). TRβ binds to thyroid hormone response elements (TREs) in the promoter regions of target genes as a homodimer or heterodimer with retinoid X receptor (RXR). In the absence of ligand, TRβ recruits corepressor complexes to repress gene transcription. Upon T3 binding, it undergoes a conformational change, releasing corepressors and recruiting coactivators to activate transcription. TRβ is essential for the feedback regulation of TSH in the pituitary, and plays critical roles in liver metabolism, bone development, and auditory function. Alternative splicing produces multiple isoforms (TRβ1, TRβ2, TRβ3, TRβ4) with distinct tissue-specific expression and functions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| THRB Knockout HEK293 Cell Line | EDJ-KQ2592 | Human | 7068 | Details Get a Quote |
| THRB Knockout HCT 116 Cell Line | EDJ-KQ21921 | Human | 7068 | Details Get a Quote |
| THRB Knockout A-549 Cell Line | EDJ-KQ23286 | Human | 7068 | Details Get a Quote |
| THRB Knockout HeLa Cell Line | EDJ-KQ54657 | Human | 7068 | Details Get a Quote |
