Hyperthyroidism
Gene: THRBEnsemblGeneIds (GRCh38): ENSG00000151090
EnsemblGeneIds (GRCh37): ENSG00000151090
OMIM: 190160, Gene2Phenotype
THRB is in 7 panels
1 review
Anna Le Fevre (Victorian Clinical Genetics Services)
Monoallelic variants in THRB can cause a dominant negative effect due to an altered thyroid hormone receptor (THR) β inhibiting the function of the wild-type THRβ. This can lead to elevated thyroid hormone signaling through THRα receptors.
Diagnosis of this familial euthyroid hyperthyroxinemia is important to avoid unnecessary medical or surgical treatment and may impact on pregnancy management.
Different variants can have varying effects on THRβ function and THRβ expression varies among organs, which is thought to make the genotype and phenotype relationship unclear. There is overlap between the previously subcategorised peripheral, isolated pituitary and generalised phenotypes.
Biallelic variants cause a more severe phenotype including hearing impairment (consider adding THRB to hearing loss panel). A speculated mechanism in this condition is dominant-negative effect of mutant THRβ on wild-type THRα.Created: 26 Sep 2020, 2:23 a.m. | Last Modified: 26 Sep 2020, 2:44 a.m.
Panel Version: 0.4
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes
#188570 THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL DOMINANT; #274300 THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL RECESSIVE; #145650 THYROID HORMONE RESISTANCE, SELECTIVE PITUITARY
Publications
Mode of pathogenicity
Other
Details
- Mode of Inheritance
- BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
- Sources
-
- Expert Review Green
- Genomics England PanelApp
- Phenotypes
-
- Thyroid hormone resistance, MIM# 188570
- Thyroid hormone resistance, autosomal recessive, MIM# 274300
- Thyroid hormone resistance, selective pituitary, MIM# 145650
- OMIM
- 190160
- Clinvar variants
- Variants in THRB
- Penetrance
- None
- Publications
- Mode of Pathogenicity
- Other
- Panels with this gene
History Filter Activity
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Gene: thrb has been classified as Green List (High Evidence).
Set Phenotypes
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Phenotypes for gene: THRB were changed from Thyroid Hormone Resistance, Selective Pituitary; 145650; THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL RECESSIVE; thyroid hormone unresponsiveness, generalized RTH, RTH beta; THYROID HORMONE UNRESPONSIVENESS; REFETOFF SYNDROME; Refetoff syndrome; THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL DOMINANT; PRTH; Thyroid hormone resistance, selective pituitary, 145650; GRTH; THYROID HORMONE RESISTANCE, SELECTIVE PITUITARY; Resistance to thyroid hormone (RTH); Thyroid hormone resistance, 188570; Thyroid hormone resistance, autosomal recessive, 274300; Thyroid Hormone Resistance (monoallelic); HYPERTHYROIDISM, FAMILIAL, DUE TO INAPPROPRIATE THYROTROPIN SECRETION; THYROID HORMONE UNRESPONSIVENESS HYPERTHYROXINEMIA, FAMILIAL EUTHYROID, SECONDARY TO PITUITARY AND PERIPHERAL RESISTANCE TO THYROID HORMONES to Thyroid hormone resistance, MIM# 188570; Thyroid hormone resistance, autosomal recessive, MIM# 274300; Thyroid hormone resistance, selective pituitary, MIM# 145650
Set publications
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Publications for gene: THRB were set to 24847459
Set mode of pathogenicity
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Mode of pathogenicity for gene: THRB was changed from to Other
Set mode of inheritance
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Mode of inheritance for gene: THRB was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)gene: THRB was added gene: THRB was added to Hyperthyroidism. Sources: Genomics England PanelApp,Expert Review Green Mode of inheritance for gene: THRB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: THRB were set to 24847459 Phenotypes for gene: THRB were set to Thyroid Hormone Resistance, Selective Pituitary; 145650; THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL RECESSIVE; thyroid hormone unresponsiveness, generalized RTH, RTH beta; THYROID HORMONE UNRESPONSIVENESS; REFETOFF SYNDROME; Refetoff syndrome; THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL DOMINANT; PRTH; Thyroid hormone resistance, selective pituitary, 145650; GRTH; THYROID HORMONE RESISTANCE, SELECTIVE PITUITARY; Resistance to thyroid hormone (RTH); Thyroid hormone resistance, 188570; Thyroid hormone resistance, autosomal recessive, 274300; Thyroid Hormone Resistance (monoallelic); HYPERTHYROIDISM, FAMILIAL, DUE TO INAPPROPRIATE THYROTROPIN SECRETION; THYROID HORMONE UNRESPONSIVENESS HYPERTHYROXINEMIA, FAMILIAL EUTHYROID, SECONDARY TO PITUITARY AND PERIPHERAL RESISTANCE TO THYROID HORMONES