. Author manuscript; available in PMC: 2015 Aug 1.

Published in final edited form as: Hum Mutat. 2014 Aug;35(8):915–926. doi: 10.1002/humu.22583

Table 1.

GNE variants associated with GNE myopathy

Amino Acid Substitution¹		Nucleotide Substitution²	GNE exon³	GNE protein domain⁴	Severity Prediction⁵	Ethnicity⁶	References
hGNE1 NP_005467.1	hGNE2 NP_001121699.1	mRNA Variant 1 NM_001128227.2		GNE protein domain⁴	Severity Prediction⁵	Ethnicity⁶	References
E2G	p.E33G	c.98A>G	3	ep	Severe	European	[Saechao et al., 2010]
R8*	p.R39*	c.115C>T	3	ep	Severe	Caucasian, Chinese, Japanese	[Saechao et al., 2010; Lu et al., 2011; Mori-Yoshimura et al., 2012]
R11W	p.R42W	c.124C>T	3	ep	Severe	Indian	[Huizing et al., 2004]
C13S	p.C44S	c.131G>C	3	ep	Medium	Chinese, Japanese, Korean	[Kim et al., 2006; Lu et al., 2011; Park et al., 2012; Tomimitsu et al., 2004]
A26P	p.A57P	c.169G>C	3	ep	Mild	Caucasian	[Weihl et al., 2011]
P27L	p.P58L	c.173C>T	3	ep	Medium	Japanese, Indian	[Mori-Yoshimura et al., 2012; Nalini et al., 2013]
P27S	p.P58S	c.172C>T	3	ep	Medium	Italian	[Broccolini et al., 2004]
I28M	p.I59M	c.177C>G	3	ep	Medium	Japanese	[Cho et al., 2013]
M29T	p.M60T	c.179T>C	3	ep	Medium	Korean, Japanese	[Kim et al., 2006; Cho et al., 2013]
M29R	p.M60R	c.179T>G	3	ep	Severe	Japanese	[Cho et al., 2013]
E35K	p.E66K	c.196G>A	3	ep	Medium	Chinese	[Li et al., 2011; Lu et al., 2011]
P36L	p.P67L	c.200C>T	3	ep	Severe	Italian	[Eisenberg et al., 2003]
E40K	p.E71K	c.211G>A	3	ep	Medium	Japanese	[Cho et al., 2013]
frameshift	frameshift	ins10 bp?	3	ep	Severe	Japanese	[Nishino et al., 2002]
I51M	p.I82M	c.246A>G	3	ep	Medium	Chinese	[Li et al., 2011; Lu et al., 2011]
exon 3 del	exon 3 del	?	3	ep	Severe	Japanese	[Cho et al., 2013]
M60V	p.M91V	c.271A>G	4	ep	Mild	Portuguese	novel
R71W	p.R102W	c.304A>T	4	ep	Severe	Caucasian	[Saechao et al., 2010]
G89R	p.G120R	c.358G>C	4	ep	Severe	Thai, Japanese	[Liewluck et al., 2006; Cho et al., 2013]
G89S	p.G120S	c.358G>A	4	ep	Medium	Japanese	[Mori-Yoshimura et al., 2012; Cho et al., 2013]
R101C	p.R132C	c.394C>T	4	ep	Severe	Korean	[Park et al., 2012]
R101H	p.R132H	c.395G>A	4	ep	Medium	Japanese	[Cho et al., 2013]
I106T	p.I137T	c.410T>C	4	ep	Medium	Chinese	[Lu et al., 2011]
I128Ifs*6	p.I159Ifs*6	c.476insT	4	ep-NES	Severe	Japanese	[Mori-Yoshimura et al., 2012; Cho et al., 2013]
R129Q	p.R160Q	c.479G>A	4	ep-NES	Medium	Japanese	[Mori-Yoshimura et al., 2012]
R129*	p.R160*	c.478C>T	4	ep-NES	Severe	Indian	novel
H132Q	p.H163Q	c.489C>G	4	ep-NES	Medium	Japanese	[Nishino et al., 2002; Tomimitsu et al., 2002]
G135V	p.G166V	c.497G>T	4	ep-NES	Severe	English, Irish, USA	[Sparks et al., 2005]
G136R	p.G167R	c.501G>A	4	ep-NES	Severe	Japanese	[Cho et al., 2013]
I142T	p.I173T	c.518T>C	4	ep	Severe	Caucasian	[Saechao et al., 2010]
I150V	p.I181V	c.541A>G	4	ep	Medium	European	[No et al., 2013]
Y156H	p.Y187H	c.559T>C	4	ep	Medium	Indian	novel
H157fs	p.H188fs	?	4	ep	Severe	Korean	[Sim et al., 2013]
R162C	p.R193C	c.515C>T	4	ep	Severe	Italian, Indian	[Del Bo et al., 2003; Nalini et al., 2013]
M171V	p.M202V	c.604A>G	4	ep	Severe	Italian	[Broccolini et al., 2002]
D176V	p.D207V	c.620A>T	4	ep	Medium	Chinese, Japanese, Korean	[Nishino et al., 2002; Tomimitsu et al., 2002, 2004; Motozaki et al., 2007; Li et al., 2011; Park et al., 2012]
R177C	p.R208C	c.622C>T	4	ep	Severe	Japanese	[Nishino et al., 2002; Cho et al., 2013]
I178N	p.I209N	c.626T>A	4	ep	Severe	Japanese	[Cho et al., 2013]
I178M	p.I209M	c.627C>G	4	ep	Medium	Japanese	[Cho et al., 2013]
L179F	p.L210F	c.628C>T	4	ep	Medium	Italian	[Grandis et al., 2010]
Y186C	p.Y217C	c.650A>G	4	ep	Severe	Pakistani	[No et al., 2013]
D187G	p.D218G	c.653A>G	4	ep	Severe	Japanese	[Mori-Yoshimura et al., 2012; Cho et al., 2013]
N194Tfs*4	p.N225Tfs*4	c.674delA	4	ep	Severe	Japanese	[Cho et al., 2013]
I200F	p.I231F	c.691A>T	4	ep	Medium	USA	[Eisenberg et al., 2003]
R202L	p.R233L	c.698G>T	4	ep	Medium	Greek	[Huizing et al., 2004]
W204*	p.W235*	c.705G>A	4	ep	Severe	Caucasian	[Saechao et al., 2010]
G206S	p.G237S	c.709G>A	4	ep	Medium	Italian	[Broccolini et al., 2004]
splicing	splicing	c.710-4A>G	in 4	ep	Splicing?	Japanese	[Cho et al., 2013]
G206Vfs*3	p.G237Vfs*3	c.710delG	5	ep	Severe	Italian	[Broccolini et al., 2004]
D208N	p.D239N	c.715G>A	5	ep	Mild	Korean	[Sim et al., 2013]
D213V	p.D244V	c.731A>T	5	ep	Medium	Indian	novel
V216A	p.V247A	c.740T>C	5	ep	Severe	USA, German, Dutch	[ Vasconcelos et al., 2002; Huizing et al., 2004]
Q219K	p.Q250K	c.748C>A	5	ep	Medium	Japanese	[Cho et al., 2013]
D225N	p.D256N	c.766G>A	5	ep	Medium	Bahamas	[Eisenberg et al., 2001]
F233S	p.F264S	c.791T>C	5	ep	Medium	Japanese	[Mori-Yoshimura et al., 2012]
I241S	p.I272S	c.815T>G	5	ep	Medium	Chinese, Taiwanese	[Ro et al., 2005; Chu et al., 2007; Li et al., 2011; Lu et al., 2011]
R246W	p.R277W	c.829C>T	5	ep	Severe	Caucasian, Chinese, Japanese, Italian, USA	[Darvish et al., 2002; Ro et al., 2005; Sparks et al., 2005; Saechao et al., 2010; Stober et al., 2010; Li et al., 2011; Cho et al., 2013]
R246Q	p.R277Q	c.830G>A	5	ep	Mild	Bahamas, Italian, Taiwanese, Japanese	[Eisenberg et al., 2001; Broccolini et al., 2004; Chu et al., 2007; Saechao et al., 2010; Chai et al., 2011]
splicing	splicing	c.862+4A>G	in 5	ep	Splicing	Japanese	[Nishino et al., 2002; Cho et al., 2013]
M261V	p.M292V	c.874A>G	6	ep-AR	Mild	Korean	[Park et al., 2012]
M261I	p.M292I	c.876G>?	6	ep-AR	Mild	Korean	[Sim et al., 2013]
M265T	p.M296T	c.887T>C	6	ep-AR	Medium	European	[No et al., 2013]
I270N	p.I301N	c.902T>A	6	ep-AR	Medium	Japanese	[Cho et al., 2013]
I270T	p.I301T	c.902T>C	6	ep-AR	Medium	Japanese	[Cho et al., 2013]
R277C	p.R308C	c.922C>T	6	ep-AR	Medium	French, Japanese	[Behin et al., 2008; Cho et al., 2013]
R277G	p.R308G	c.922C>G	6	ep-AR	Medium	Japanese	[Cho et al., 2013]
P283S	p.P314S	c.940C>T	6	ep-AR	Medium	Japanese	[Tomimitsu et al., 2004]
H293R	p.H324R	c.971A>G	6	ep-AR	Medium	Indian	[Kannan et al., 2012]
G295D	p.G326D	c.977G>A	6	ep-AR	Medium	Japanese	[Mori-Yoshimura et al., 2012]
G295R	p.G326R	c.976G>C	6	ep-AR	Medium	Japanese	[Cho et al., 2013]
M297T	p.M328T	c.983T>C	6	ep-AR	Medium	Indian	novel
I298T	p.I329T	c.986T>C	6	ep-AR	Severe	Asian, Chinese, Indian	[Saechao et al., 2010; Lu et al., 2011]
N300K	p.N331K	c.993C>A	6	ep-AR	Severe	Italian	[Tasca et al., 2012]
C303V	p.C334V	c.1000_1001TG>GT	6	ep-AR	Medium	Japanese	[Tomimitsu et al., 2002]
C303*	p.C334*	c.1002T>A	6	ep-AR	Severe	Indian	[Eisenberg et al., 2001]
G304R	p.G335R	c.1003G>A	6	ep	Severe	Indian	[Nalini et al., 2013]
R306Q	p.R337Q	c.1010G>A	6	ep	Medium	Japanese	[Nishino et al., 2002]
A310P	p.A341P	c.1021G>C	6	ep	Severe	Chinese	[Ro et al., 2005; Stober et al., 2010]
V315M	p.V346M	c.1036G>A	6	ep	Medium	European	[No et al., 2013]
N317D	p.N348D	c.1042A>G	6	ep	Severe	European	[No et al., 2013]
R321C	p.R352C	c.1054C>T	6	ep	Severe	Japanese	[Mori-Yoshimura et al., 2012]
splicing	splicing	c.1076-1delG	in 6	ep	Splicing?	Japanese	[Cho et al., 2013]
V331A	p.V362A	c.1085T>C	7	ep	Severe	Japanese	[Nishino et al., 2002]
H333R	p.H364R	c.1091A>G	7	ep	Medium	Caucasian	[Weihl et al., 2011]
R335W	p.R366W	c.1096C>T	7	ep	Severe	Caucasian	[Fisher et al., 2006; Saechao et al., 2010]
L347del; H348N	p.L378del; p.H379N	c.1132_1134 del;c.1135C>A	7	ep	Severe	Caucasian	[Fisher et al., 2006]
L347P	p.L378P	c.1133T>C	7	ep	Severe	Japanese	[Cho et al., 2013]
splicing	splicing	c.1163+2dupT	in 7	ep	Splicing	European, Italian	[Broccolini et al., 2004; No et al., 2013]
Y361*	p.Y392*	c.1176T>G	8	ep	Severe	Caucasian	[Weihl et al., 2011]
V367I	p.V398I	c.1192G>A	8	ep	Medium	Iranian	[Krause et al., 2003]
I377Tfs*15	p.I408Tfs*15	c.1223delT	8	ep	Severe	Italian	[Broccolini et al., 2004]
D378Y	p.D409Y	c.1225G>T	8	UF	Severe	European, Irish, Japanese, USA	[Nishino et al., 2002; Eisenberg et al., 2003; No et al., 2013]
L379H	p.L410H	c.1229T>A	8	UF	Severe	Tunisian	[Amouri et al., 2005]
P390S	p.P421S	c.1261C>T	8	UF	Medium	Korean	[Sim et al., 2013]
R420*	p.R451*	c.1351C>T	8	kin	Severe	Japanese, Indian	[Tomimitsu et al., 2004; Nalini et al., 2013]
V421A	p.V452A	c.1355T>C	8	kin	Medium	Japanese	[Tomimitsu et al., 2004; Cai et al., 2013]
K432Rfs*16	p.K463Rfs*16	c.1388delA	9	kin	Severe	Indian	[Voermans et al., 2010]
Y434C	p.Y465C	c.1394A>G	9	kin	Medium	Korean	[Sim et al., 2013]
Q436*	p.Q467*	c.1399C>T	9	kin	Severe	Taiwanese	[Saechao et al., 2010]
C453F	p.C484F	c.1451G>T	9	kin	Severe	Japanese	[Cho et al., 2013]
A460V	p.A491V	c.1472C>T	9	kin	Medium	Japanese	[Kayashima et al., 2002]
.L463P	p.L494P	c.1481T>C	9	ep	Severe	Korean	[Sim et al., 2013]
G469R	p.G500R	c.1498G>A	9	kin	Severe	Japanese	[Cho et al., 2013]
splicing	splicing	c.1504+5G>A	in 9	kin	Splicing	Japanese	[Cho et al., 2013]
splicing	splicing	c.1505-4G>A	in 9	kin	Splicing?	Japanese	[Cho et al., 2013]
I472T	p.I503T	c.1508T>C	10	kin	Severe	Japanese	[Nishino et al., 2002; Yabe et al., 2003]
W495*	p.W526*	c.1577G>A	10	kin	Severe	Caucasian	[No et al., 2013]
L508S	p.L539S	c.1616T>C	10	kin	Severe	Chinese	[Li et al., 2011; Lu et al., 2011]
H509Y	p.H540Y	c.1618C>T	10	kin	Medium	Chinese	[Lu et al., 2011]
P511H	p.P542H	c.1625C>A	10	kin	Severe	Japanese	[Motozaki et al., 2007]
P511L	p.P542L	c.1625C>T	10	kin	Severe	Thai	[Liewluck et al., 2006]
W513*	p.W544*	c.1632G>A	10	kin	Severe	Chinese, Taiwanese, Indian	[Ro et al., 2005; Li et al., 2011; Nalini et al., 2013]
V514del	p.V545del	c.1634_1637del	10	kin	Severe	Japanese	[Cho et al., 2013]
N519S	p.N550S	c.1649A>G	10	kin	Medium	Italian	[Broccolini et al., 2004]
A524V	p.A555V	c.1664C>T	10	kin	Severe	French, Mexican, Thai, Japanese	[Darvish et al., 2002; Liewluck et al., 2006; Behin et al., 2008; Cho et al., 2013]
F528C	p.F559C	c.1676T>G	10	kin	Severe	German	[Eisenberg et al., 2003]
G545Efs*11	p.G576Efs*11	c.1727delG	11	kin	Severe	Korean	[Park et al., 2012]
L556S	p.L587S	c.1760T>C	11	kin	Severe	Caucasian	[Saechao et al., 2010]
I557T	p.I588T	c.1763T>C	11	kin	Medium	Italian, Japanese	[Eisenberg et al., 2003; Tomimitsu et al., 2004]
G559R	p.G590R	c.1768G>C	11	kin	Severe	Japanese, Greek	[Huizing et al., 2004; Cho et al., 2013;]
G559A	p.G590A	c.1769G>C	11	kin	Severe	Turkish	novel
G568S	p.G599S	c.1795G>A	11	kin	Severe	Japanese	[Mori-Yoshimura et al., 2012]
G568V	p.G599V	c.1796G>T	11	kin	Severe	Indian	[Nalini et al., 2013]
V572del	p.V603del	c.1806_1808del	11	kin	Severe	Japanese	[Cho et al., 2013]
V572L	p.V603L	c.1807G>C	11	kin	Medium	Asian, Chinese, Japanese, Korean	[Kayashima et al., 2002; Tomimitsu et al., 2002; Kim et al., 2006; Li et al., 2011; Park et al., 2012]
G576E	p.G607E	c.1820G>A	11	kin	Severe	USA	[Eisenberg et al., 2001]
C579Y	p.C610Y	c.1829G>A	11	kin	Severe	Japanese	[Cho et al., 2013]
C581R	p.C612R	c.1834T>C	11	kin	Severe	Pakistani	novel
C586*	p.C617*	c.1850delG	11	kin	Severe	Japanese	[Mori-Yoshimura et al., 2012]
I587T	p.I618T	c.1853T>C	11	kin	Medium	Algerian, Chinese, Italian, Cajun, Japanese, Roma Gypsies	[Tomimitsu et al., 2002; Kalaydjieva et al., 2005; Behin et al., 2008; Grandis et al., 2010; Li et al., 2011; Cho et al., 2013]
I587N	p.I618N	c.1853T>A	11	kin	Medium	Japanese	[Cho et al., 2013]
A591T	p.A622T	c.1864G>A	11	kin	Severe	Chinese, Korean	[Kim et al., 2006; Lu et al., 2011]
A600E	p.A631E	c.1892C>A	11	kin	Severe	Japanese	[Mori-Yoshimura et al., 2012; Cho et al., 2013]
A600T	p.A631T	c.1891G>A	11	kin	Medium	Italian	[Broccolini et al., 2004]
L603F	p.L634F	c.1900C>T	11	kin	Medium	Japanese	[Mori-Yoshimura et al., 2012]
splicing	splicing	c.1909+5G>A	in 11	kin	Splicing	Indian	[Boyden et al., 2011]
S615*	p.S646*	c.1937C>G	12	kin	Severe	Caucasian	[Saechao et al., 2010]
A630Lfs*12	p.A661Lfs*12	c.1980delA	12	kin	Severe	Japanese	[Cho et al., 2013]
A630T	p.A661T	c.1981G>A	12	kin	Medium	Japanese	[Nishino et al., 2002; Cho et al., 2013]
A631T	p.A662T	c.1984G>A	12	kin	Severe	Caucasian, Senegalese, USA	[Eisenberg et al., 2001; Behin et al., 2008; No et al., 2013]
A631V	p.A662V	c.1985C>T	12	kin	Severe	Caucasian, Korean, Chinese, German, Irish, S. African, USA, Japanese	[Nishino et al., 2002; Tomimitsu et al., 2002; Vasconcelos et al., 2002; Eisenberg et al., 2003; Saechao et al., 2010; Li et al., 2011; Weihl et al., 2011; Park et al., 2012]
N635K	p.N666K	c.1998T>A	12	kin	Severe	Japanese	[Cho et al., 2013]
N635K	p.N666K	c.1998T>G	12	kin	Severe	Japanese	[Cai et al., 2013]
A648V	p.A679V	c.2036C>T	13	kin	Medium	German	novel
I656N	p.I687N	c.2060T>A	13	kin	Severe	Thai	[Liewluck et al., 2006]
G669R	p.G700R	c.2098G>A	13	kin	Severe	Japanese	[Cho et al., 2013]
G669R	p.G700R	c.2098G>C	13	kin	Severe	Asian, Indian, Portuguese	[No et al., 2013]
Y675H	p.Y706H	c.2116T>C	13	kin	Medium	Caucasian	[Darvish et al., 2002; Saechao et al., 2010]
V679G	p.V710G	c.2129T>G	13	kin	Severe	French	[Behin et al., 2008]
V696M	p.V727M	c.2179G>A	13	kin	Medium	Algerian, Asian, Chinese, Middle-Eastern, Indian, Pakistani, Thai, Portuguese	[Eisenberg et al., 2001; Huizing et al., 2004; Liewluck et al., 2006; Behin et al., 2008; Saechao et al., 2010; Voermans et al., 2010; Boyden et al., 2011; Lu et al., 2011; No et al., 2013]
S699L	p.S730L	c.2189C>T	13	kin	Severe	Middle-Eastern	[No et al., 2013]
G708S	p.G739S	c.2215G>A	13	kin	Severe	Japanese	[Tomimitsu et al., 2004; Cho et al., 2013]
M712T	p.M743T	c.2228T>C	13	kin	Severe	Egyptian-Muslim, Persian Jewish, Japanese	[Eisenberg et al., 2001; Broccolini et al., 2002; Darvish et al., 2002; Noguchi et al., 2004; Tomimitsu et al., 2004; Amouri et al., 2005; Cho et al., 2013]
large deletion	large deletion	del ex2-ex10 (>35.7kb)	2–10	ep + kin	Severe	Italian	[Del Bo et al., 2003]

Bold print: cDNA or protein truncating variants; Italic print + dark gray highlight: ‘Mild’ variants; ?: exact nomenclature could not be extracted from the reference. The DNA numbering system is based on cDNA sequence. Nucleotide numbering uses +1 as the A of the ATG translation initiation codon in the reference sequence, with the initiation codon as codon 1.

Amino acid substitutions are provided in the previously used hGNE1 (NP_005467.1) and in the preferred new hGNE2 (NP_001121699.1) nomenclature [Huizing et al. 2014b]. For some variants, updated nomenclature is provided extracted from the reference.

Nucleotide variants are provided in the mRNA variant 1 nomenclature (NM_001128227.2; longest mRNA spliceform; encoding hGNE2 protein).

Exon numbering according to genomic sequence (NC_000009.12) and as indicated in Figure 1. in = intron.

⁴

See text for details about GNE protein domains; ep = UDP-GlcNAc 2-epimerase domain; ep-NES = nuclear export signal; ep-AR: allosteric region; UF = unknown function; kin = ManNAc kinase domain; UF epimerase.

⁵

Combined pathogenicity scores, see Supp. Table S1. Intronic variants with predicted splicing effects are listed as “splicing’, and without such effects as “splicing?”, see Supp. Table S2.

⁶

Extracted from literature reference.