Details Of Published TSH Receptor Mutation
Thr 632 Ala
c.1894A>GConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
carcinoma
Exon
10
Molecular Characteristics:
default
Clinical Features:
follicular carcinoma with clinical phenotype of "hot nodule"
*based on 6 hot nodules investigated by Tonacchera et al. 2000, Vanvooren et al. 2002, Gozu et al. 2006, Trulzsch et al. 2001, Sancak et al. 2011
and on 1 hot thyroid carcinoma investigated by Spambalg et al. 1996
*based on 6 hot nodules investigated by Tonacchera et al. 2000, Vanvooren et al. 2002, Gozu et al. 2006, Trulzsch et al. 2001, Sancak et al. 2011
and on 1 hot thyroid carcinoma investigated by Spambalg et al. 1996
Treatment:
default
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
3.3-4.2
1.5
n.d.
n.d.
nd
0.4-0.5
1
1,3
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:
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 2:
Spambalg et al.
J. Clin. Endocrinol. Metab. 81: 3898-3901
Structural studies of the thyrotropin receptor and Gs alpha in human thyroid cancers: low prevalence of mutations predicts infrequent involvement in malignant transformation.
1996
Reference 3:
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