Details Of Published TSH Receptor Mutation
Asp 633 Tyr
c1897G>TConstitutively Activating TSH Receptor Mutation
Type
gain
Manifestation
somatic
Exon
10
Molecular Characteristics:
default
Clinical Features:
based on 18 hot nodules investigated by Porcellini et al. 1994, Parma et al. 1997, Russo et al. 1996, Nogueira et al. 1999, Gozu et al. 2005, and 2006, Mon et al. 2018, Stephenson et al. 2020, Trulzsch et al. 2001 and Palos-Paz et al. 2008, Kohn et al. 2009, Schwab et al. 2009,
and on 1 activating sporadic germline mutation investigated by Bircan et al. 2008
and on 1 hot thyroid carcinoma investigated by Führer et al. 2003
and on 1 activating sporadic germline mutation investigated by Bircan et al. 2008
and on 1 hot thyroid carcinoma investigated by Führer et al. 2003
Treatment:
default
Functional Characteristics:
cAMP
(basal)
(basal)
cAMP
(TSH)
(TSH)
IP
(basal)
(basal)
IP
(TSH)
(TSH)
TSH-Binding
Cell Surface Expression
Prevalence
LRA
Ref
4.1
0.9
1.3
0.8
-
n.d.
18
16.4±6.4
6,10
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:
Parma et al.
J. Clin. Endocrinol. Metab. 82: 2695-2701
Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas
1997
Reference 2:
Porcellini et al.
J. Clin. Endocrinol. Metab. 79: 657-661
Novel mutations of thyrotropin receptor gene in thyroid hyperfunctioning adenomas. Rapid identification by fine needle aspiration biopsy
1994
Reference 3:
Russo et al.
J. Clin. Endocrinol. Metab. 80: 1347-1351
Genetic alterations in thyroid hyperfunctioning adenomas
1995
Reference 4:
Nogueira et al.
Thyroid 9: 1063-1068
Thyrotropin receptor mutations in hyperfunctioning thyroid adenomas from Brazil
1999
Reference 5:
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 6:
Kosugi et al.
FEBS Lett 356: 291-294
Constitutive activation of cyclic AMP but not phosphatidylinositol signaling caused by four mutations in the 6th transmembrane helix of the human thyrotropin receptor.
1994
Reference 7:
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 8:
Palos-Paz et al.
Eur J Endocrinol. 159: 623-31
Prevalence of mutations in TSHR, GNAS, PRKAR1A and RAS genes in a large series of toxic thyroid adenomas from Galicia, an iodine-deficient area in NW Spain.
2008
Reference 9:
Gozu et al.
Endocr J. 52: 577-85
Mutations in the thyrotropin receptor signal transduction pathway in the hyperfunctioning thyroid nodules from multinodular goiters: a study in the Turkish population.
2005
Reference 10:
Lüblinghoff et al.
J Endocrinol Invest 33:228-233
Lack of consistent association of thyrotropin receptor mutations in vitro activity with the clinical course of patients with sporadic non-autoimmune hyperthyroidism.
2010
Reference 11:
Kohn et al.
Thyroid
A somatic gain-of-function mutation in the thyrotropin receptor gene producing a toxic adenoma in an infant
2009
Reference 12:
Stephenson et al.
Thyroid
Sensitive Sequencing Analysis Suggests Thyrotropin
Receptor and Guanine Nucleotide-Binding Protein G Subunit
Alpha as Sole Driver Mutations in Hot Thyroid Nodules
2020
Reference 13:
Mon et al.
Diagnostic Cytopathology
Cancer risk and clinicopathological characteristics of thyroid nodules harboring thyroid-stimulating hormone receptor gene mutations
2018