Table 1.

Loss-of-function GPCR mutations associated with diverse human diseases.

Receptor	Disease	Clinical features	References
GPR54	Idiopathic hypogonadotropic hypogonadism	Attenuated secretion of GnRH, sexual development disruption	[215]
PROKR2	Kallmann syndrome	Impaired development of the olfactory system and reproductive axis	[271]
FSHR	Oligospermia and subfertility Ovarian dysgenesis	Small testes with impaired spermatogenesis in males Absence of follicular maturation in females	[272]
TSHR	Euthyroid hyperthyrotropinemia Congenital hypothyroidism	TSH resistance with normal biological effects of TH TSH resistance with reduced biological effects of TH	[234, 273]
CaSR	Familial hypocalciuric hypercalcemia	Lifelong moderate elevation of serum calcium concentration and inappropriately normal PTH levels	[274, 275]
	Neonatal severe hyperparathyroidism	Neonatal marked elevation of serum calcium and PTH levels
AVPR2	Nephrogenic diabetes insipidus	Polyuria, polydipsia, hypernatremia, low urine osmolality, and AVP resistance	[236]
MC1R	Pigmentation defect	Red hair color phenotype: red hair, fair skin, poor ability to tan, and increased risk of melanoma	[276]
MC2R	Familial glucocorticoid deficiency	Low or undetectable cortisol levels and elevated ACTH levels	[277]
MC4R	Obesity	Hyperphagia, increased fat and lean mass, and increased bone mass	[278]
PTHR1	Blomstrand chondrodysplasia	Advanced endochondral bone maturation associated with breast development and tooth impaction	[279, 280]
Rhodopsin	Retinitis pigmentosa	Loss of vision, insensitivity in dim light	[16]