Opportunities for developing therapies for rare genetic diseases: focus on gain-of-function and allostery

Table 2 Top targetable genetic diseases due to loss-of-function mutations

Disease name	OMIM	Gene/Protein	Allosteric activators
Brugada syndrome 3	611875	CACANA1C	BayK 8644, FPL64176
Congenital amegakaryocytic thrombocytopenia	604498	MPL	PF
Frontal lobe nocturnal epilepsy 3	605375	CHRNB2	Desformylflustrabromine and others
Glycogen storage disease V	232600	PYGM	AMP and IMP
Glycogen storage disease VI	232700	PYGL	AMP and IMP
Hereditary pancreatitis	167800	CTRC	BisQ, Bis Q Benzyl
Homocystinuria due to cystathionine beta-sythease deficiency	236200	CBS	SAM
Hyperekplexia hereditary 1	149400	GLRA1	Ajulemic acid, Trifluoroacetate
Isolated growth hormone deficiency type III	307200	BTK	PIP3
Lung cancer susceptibility	612052	CHRNA3	rac-12 k, rac-14e
Muscle glycogen storage disease 0	611556	GYS1	Glc6P
Ovarian dysgenesis 1	233300	FSHR	Ajulemic acid, Trifluoroacetate
Pigmented nodular adrenocortical disease	610475	PDE11A	Estradiol
Thrombocysthemia 2	601977	MPL	PF

Corresponding disease names, OMIM identifiers, mutated genes and known allosteric activators are listed. Allosteric activators are queried from the Allosteric Database. The rest of potential candidates can be found in Additional file 1: Table S8

ISSN: 1750-1172