Details Of Published TSH Receptor Mutation

Thr 632 Ala

c.1894A>G

Constitutively Activating TSH Receptor Mutation

Type
gain
Manifestation
somatic
Exon
10
Molecular Characteristics:
default 
Clinical Features:
*based on 7 hot nodules investigated by Tonacchera et al. 2000, Vanvooren et al. 2002, Gozu et al. 2006, Trülzsch et al. 2001, Mon et al 2018, Sancak et al. 2011 
Treatment:
default
Functional Characteristics:
cAMP
(basal)
cAMP
(TSH)
IP
(basal)
IP
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.3-4.2
1.5
n.d.
n.d.
0.4-0.5
7
2,7
Legend:
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.
Reference 1:
Trülzsch et al.
J. Mol. Med. 78: 684-691
Detection of thyroid-stimulating hormone receptor and Gsalpha mutations: in 75 toxic thyroid nodules by denaturing gradient gel electrophoresis.
2001
Reference 2:
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.
2002
Reference 3:
Tonacchera et al.
J Clin Endocrinol Metab. 85: 2270-4
Activating thyrotropin receptor mutations are present in nonadenomatous hyperfunctioning nodules of toxic or autonomous multinodular goiter.
2000
Reference 4:
Gozu et al.
Eur J Endocrinol. 155: 535-45
Similar prevalence of somatic TSH receptor and Gsalpha mutations in toxic thyroid nodules in geographical regions with different iodine supply in Turkey.
2006
Reference 5:
Vanvooren et al.
Eur J Endocrinol. 147: 287-91
Oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in the Japanese population.
2002
Reference 6:
Sancak et al.
Horm Metab Res. 43:562-8
High Prevalence of TSHR/Gsalpha Mutation-negative Clonal Hot Thyroid Nodules (HNs) in a Turkish Cohort
2011
Reference 7:
Urizar et al.
J Biol Chem 280:17135-17141
An activation switch in the rhodopsin family of G protein-coupled receptors: the thyrotropin receptor.
2005
Reference 8:
Mon et al.
Diagnostic Cytopathology
Cancer risk and clinicopathological characteristics of thyroid nodules harboring thyroid-stimulating hormone receptor gene mutations
2018