Table 2.

Review of Inherited Human Diseases Caused by Impaired GPCR Function

Characteristic	Receptor − Phenotypes: Loss-of-Function Mutation	Receptor + Phenotypes: Gain-of-Function Mutation	Gαs − Phenotypes: Loss-of-Function Mutation/Maternal Imprinting	Gαs + Phenotypes: Gain-of-Function Mutation +
LHCGR	Leydig cell hypoplasia (male)	Precocious puberty (male)	Unknown	Precocious puberty (McCune-Albright syndrome), male + female
	Hypergonadotrophic hypogonadism (male and female)	Leydig cell adenoma (male)
TSHR	Congenital hypothyroidism	Nonautoimmune hyperthyroidism	Hyperthyrotropinemia	Hyperthyroidism (McCune-Albright syndrome)
	Hyperthyrotropinemia	Thyroid adenoma	Hypothyroidism	Thyroid adenoma
PTH1R	Blomstrand chondrodysplasia	Jansen metaphyseal chondrodysplasia	Albright hereditary osteodystrophy	New: this report (F376V)
			Pseudohypoparathyroidism	Fibrous dysplasia (MAS)
V2R	X-linked nephrogenic diabetes insipidus	NSIAD	Unknown	New: NSIAD this report (F376V)

Human diseases caused by variants of GPCR or Gαs of either loss- or gain-of-function consequences, including the novel phenotypes caused by variant p.F376V studied in this report. Boldface indicates phenotypes of the patients in this study. Receptor +/Gαs + = gain-of-function variants; Receptor −/Receptor − = loss-of-function variants.

Abbreviation: MAS, McCune-Albright syndrome.