The actinin family of actin cross-linking proteins – a genetic perspective

Cell & Bioscience

Table 1 Human actinin mutations and associated diseases or phenotypes

Protein	Mutation	Domain	Disease/Phenotype	Reference
Actinin-1	Asp22Asn	ABD	CMTP	[35]
	Gln32Lys	ABD, CH1	CMTP	[37]
	Arg46Gln	ABD, CH1	CMTP	[36, 37]
	Arg46Trp	ABD, CH1	CMTP	[35]
	Val105Ile	ABD, CH1	CMTP	[37]
	Glu225Lys	ABD, CH2	CMTP	[37]
	Gly251Arg	ABD/Neck	CMTP	[35]
	Thr737Asn	Rod/CaM	CMTP	[35]
	Arg738Trp	Rod/CaM	CMTP	[37]
	*Arg752Gln	CaM, EF12	CMTP	[37]
	Gly764Ser	CaM, EF12	CMTP	[35]
	Glu769Lys	CaM, EF12	CMTP	[35]
Actinin-2	Gln9Arg	ABD	DCM	[41]
	Gly111Val	ABD, CH1	HCM	[42]
	Ala119Thr	ABD, CH1	HCM, DCM, IVF, LVNC, SUD	[45, 44]
	Met228Thr	ABD, CH2	HCM + Atrial Arrhythmias	[46]
	Thr495Met	Rod, SLR2	HCM	[44, 42]
	Glu583Ala	Rod, SLR3	HCM	[44]
	Glu628Gly	Rod, SLR3	HCM	[44]
	*Arg759Thr	CaM, EF12	HCM	[42]
Actinin-3	Arg577X	Rod, SLR3	Altered muscle metabolism	[50]
Actinin-4	Trp59Arg	ABD, CH1	FSGS	[77]
	Ile149del	ABD, CH1	FSGS	[77]
	Lys255Glu	ABD, CH2	FSGS	[76]
	Thr259Ile	ABD, CH2	FSGS	[76]
	Ser262Pro	ABD, CH2	FSGS	[76]

Mutations in the four human actinin proteins that are associated with diseases or phenotypic traits are listed.
The protein domain and subdomain (e.g. ABD, CH1) in which each mutation occurs is indicated in the third column. A forward slash (e.g. Rod/CaM) indicates a mutation within a region linking the two domains indicated. The asterisk indicates that these are equivalent Arg residues in a sequence alignment of actinin-1 and −2. A multiple sequence alignment highlighting the postions of disease-causing mutations is provided as additional information [Additional file 1].
Abbreviations: IVF Idiopathic ventricular fibrillation, LVNC Left ventricular non-compaction, SUD Sudden unexplained death, CMTP Congenital macrothrombocytopenia, HCM Hypertrophic cardiomyopathy, DCM Dilated cardiomyopathy, FSGS Focal segmental glomerulosclerosis

ISSN: 2045-3701