Details Of Published TSH Receptor Mutation
Tyr 601 Asnc.1801T>A
Constitutively Activating TSH Receptor Mutation
based on 2 hot nodules investigated by Arseven et al. 2000, Stephenson et al. 2020, and Georgopoulos et al. 2003
Cell Surface Expression
cAMP (basal): basal in vitro cAMP production of mutant over wild-type TSHR
cAMP (TSH): maximal in vitro cAMP production of mutant over wild-type TSHR
IP (basal): basal in vitro IP production of mutant over wild-type TSHR
IP (TSH): maximal in vitro IP production of mutant over wild-type TSHR
TSH-binding: maximal TSH-binding compared to the wild-type TSHR
Cell surface expression: cell surface expression of mutant compared to WT-TSHR
LRA: linear regression analysis (LRA) of constitutive activity as a function of TSHR expression determined by 125I-bTSH binding or FACS analysis compared to the wild-type TSHR
Prevalence: Prevalence of (somatic and germline) activating mutations*
Ref: Reference for functional characterization
Child: Found in children.
Arseven et al.
Thyroid 10: 3-10
Substitutions of tyrosine 601 in the human thyrotropin receptor result in increase or loss of basal activation of the cyclic adenosine monophosphate pathway and disrupt coupling to Gq/11
Claeysen et al.
FEBS Lett 517: 195-200
A conserved Asn in TM7 of the thyrotropin receptor is a common requirement for activation by both mutations and its natural agonist.
Georgopoulos et al.
Eur J Endocrinol. 149: 287-92
Autonomously functioning thyroid nodules in a former iodine-deficient area commonly harbor gain-of-function mutations in the thyrotropin signaling pathway.
Jäschke et al.
Cell Mol Life Sci 65:4028-4038
Preferences of transmembrane helices for cooperative amplification of G(alpha)s and G (alpha)q signaling of the thyrotropin receptor.
Stephenson et al.
Sensitive Sequencing Analysis Suggests Thyrotropin Receptor and Guanine Nucleotide-Binding Protein G Subunit Alpha as Sole Driver Mutations in Hot Thyroid Nodules