Table II.

Genes associated with FTLD and ALS.

Gene	Locus	Inheritance	Mutation type	Mutation frequency FTLD	Mutation frequency ALS	Molecular pathology	Comment
MAPT (94)	17q21	AD	Missense, splice site, deletion	5%–10%	–	Tau
PGRN (92,93)	17q21	AD	Nonsense, splice site, frameshift, deletion, met1, missense	5%–10%	–	TDP-43	FTLD-TDP type A
VCP (105)	9p13	AD	Missense	< 1%	< 1%	TDP-43	In combination with IBM and PDB; FTLD-TDP type D
CHMP2B (100)	3p11	AD	Nonsense	< 1%	–	UPS
TMEM106B (131)	7p21	Risk factor	/	/	/	TDP-43
C9orf72 (132–134)	9p21	AD	GGGGCC expansion	5%–10%?	5%–10%?	TDP-43, UPS	FTLD-TDP type B?
SOD1 (106)	21q22	AD and AR	Missense, frameshift nonsense	–	∼5%	SOD1
TARDBP (110,111)	1p36	AD	Missense, nonsense	< 1%	∼1%	TDP-43
FUS (65,66)	16q12	AD and AR	Missense, nonsense, splice site, frameshift	< 1%	∼1%	FUS	Also associated with juvenile ALS with BIBD
ATXN2 (112)	12q24	AD and risk factor	GAG expansion	–	∼1%	TDP-43	Intermediate expanded alleles cause ALS, longer alleles cause SCA2
ANG (115)	14q11	AD and risk factor	Missense	–	< 1%	TDP-43
OPTN (117)	10p13	AD and AR	Missense, exon-deletion nonsense	–	< 1%	TDP-43
VAPB (116)	20q13	AD	Missense	–	< 1%	?	Classic ALS, slow-progressive ALS, late onset SMA
UBQLN2 (118)	Xp11	AD	Missense	< 1%	< 1%	TDP-43

Sub-classification of FTLD-TDP is according to (135).

AD = autosomal dominant; AR = autosomal recessive; BIBD = basophilic inclusion body disease; IBM = inclusion body myositis; met1 = mutation of Met1 translation initiation codon; PDB = Paget's disease of the bone; SCA2 = spinocerebellar ataxia type 2; SMA = spinal muscular atrophy.