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

Table 1 Top targetable diseases due to gain-of-function mutations

Type	Diseases	OMIM	Gene/Protein
Over-activation	Hereditary motor and sensory neuropathy type IIC	606071	TRPV4
	Postsynaptic slow-channel congenital myasthenic syndrome	601462	CHRNA1, CHRND, CHRNE, CHRNB1
	PRPS1 superactivity	300661	PRPS1
	Parkinson disease-8	607060	LRRK2
	Tubular aggregate myopathy	160565	STIM1
	Achondroplasia	100800	FGFR3
Gene duplication	Lubs X-linked mental retardation syndrome	300260	MECP2
Gene duplication	Parkinson disease-4	605543	SNCA
CAG repeat	Spinocerebellar ataxia 1,2,3,6,7,17	183086, 183090, 109150, 183086, 164500, 607136	ATXN1,2,3, CACNA1A,ATXN7, TBP
	Huntington	6066438	HTT
	Spinal and bulbar muscular atrophy X-linked	313700	AR
Non-CAG trinucletide repeat	Friederich Ataxia 1	229300	FXN
	Myotonic Dystrophy 1	160900	DMPK
	Oculopharyngeal muscular dystrophy	164300	PABPN1
	Spinocerebellar ataxia 8	608768	ATXN8

Corresponding disease names, OMIM identifiers, and mutated genes are listed. Diseases are grouped by the molecular mechanism as indicated in the type column. The rest of potential candidates can be found in Additional file 1: Table S7

ISSN: 1750-1172