Structure and activation of the TSH receptor transmembrane domain

Autoimmunity Highlights

Table 7 TSH receptor-inactivating/silencing mutations reported in the literature

Mutation	BW number	Type^a	Activity	References
V424I	1.42	Silencing	cAMP 0.3-fold WT	[86]
D460A	2.50	Silencing	cAMP 0.28-fold WT	[16]
D460N	2.50	Silencing	cAMP 0.18-fold WT	[16]
L467V	2.57	Silencing	cAMP 0.1-fold WT	[86]
W488R	ECL1	Inactivating	TSH binding abolished	[87]
V502A	3.33	Silencing	cAMP 0.0-fold WT	[86]
M527T	ICL2	Inactivating	TSH induced max. cAMP 30% WT	[87]
Y582A	5.39	Silencing	cAMP 0.2-fold WT	[86]
Y582F	5.39	Silencing	cAMP 0.4-fold WT	[86]
A593P	5.50	Silencing	cAMP 0.19-fold WT	[15]
A593V	5.50	Silencing	cAMP 0.33-fold WT	[15]
F594I	5.51	Silencing	cAMP 0.13-fold WT	[15]
R625A	6.36	Silencing	cAMP 0.11-fold WT	[16]
F634I	6.45	Silencing	cAMP 0.13-fold WT	[15]
A638V	6.49	Inactivating	TSH induced EC₅₀ 7.85-fold WT	[15]
F642I	6.53	Inactivating	TSH induced EC₅₀ 8.21-fold WT	[15]
Y643A	6.54	Silencing	cAMP 0.2-fold WT	[86]
A644V	6.55	Inactivating	TSH induced EC₅₀ 8.88-fold WT	[15]
L665V	7.40	Silencing	cAMP 0.3-fold WT	[86]

Mutations causing decrease of constitutive activity above 0.5-fold of WT are not included
BW Ballesteros–Weinstein numbering, WT wild type
^aMutation causing decrease of the receptor constitutive activity is defined as silencing. Mutation causing decrease of hormone-induced cyclic AMP activity is defined as inactivating

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