Table 2.
Allele 11 | Allele 21 | Domain2 | Cell system | GNE-ep3 | GNE-kin3 | References | ||
---|---|---|---|---|---|---|---|---|
hGNE1 | hGNE2 | hGNE1 | hGNE2 | |||||
GNE myopathy patient cells | ||||||||
G135V | p.G166V | R246W | p.R277W | ep-NES/ep | fibroblasts | 38 % | 72% | [Sparks et al., 2005] |
V367I | p.V398I | V367I | p.V398I | ep/ep | myoblasts | 40 % | ND | [Salama et al., 2005] |
D176V | p.D207V | D176V | p.D207V | ep/ep | lymphoblasts | <10% | ND | [Nishino et al., 2002] |
D176V | p.D207V | V331A | p.V362A | ep/ep | lymphoblasts | <10% | ND | [Nishino et al., 2002] |
R11W | p.R42W | F537I | p.F568I | ep/kin | myoblasts | 43 % | ND | [Salama et al., 2005] |
D176V | p.D207V | I472T | p.I503T | ep/kin | lymphoblasts | <10% | ND | [Nishino et al., 2002] |
D176V | p.D207V | V572L | p.V603L | ep/kin | lymphoblasts | <10% | ND | [Nishino et al., 2002] |
D176V | p.D207V | A630T | p.A661T | ep/kin | lymphoblasts | <10% | ND | [Nishino et al., 2002] |
V216A | p.V247A | A631V | p.A662V | ep/kin | fibroblasts | 48 % | 63% | [Sparks et al., 2005] |
V572L | p.V603L | V572L | p.V603L | kin/kin | lymphoblasts | <10% | ND | [Nishino et al., 2002] |
M712T | p.M743T | M712T | p.M743T | kin/kin | fibroblasts | 83 % | 55% | [Sparks et al., 2005] |
M712T | p.M743T | M712T | p.M743T | kin/kin | myoblasts | 75 %4 | ND | [Salama et al., 2005] |
M712T | p.M743T | M712T | p.M743T | kin/kin | lymphoblasts | 65 %5 | ND | [Hinderlich et al., 2004] |
In vitro recombinant enzyme - cell expression systems | ||||||||
R11W | p.R42W | - | - | ep | Sf9 cells | 15 % | 40 % | [Penner et al., 2006] |
C13S | p.C44S | - | - | ep | COS cells | 20% | 100% | [Noguchi et al., 2004] |
H132Q | p.H163Q | - | - | ep-NES | COS cells | 5 % | 50 % | [Noguchi et al., 2004] |
D176V | p.D207V | - | - | ep | COS cells | 18 % | 87 % | [Noguchi et al., 2004] |
R177C | p.R208C | - | - | ep | COS cells | 10 % | 78 % | [Noguchi et al., 2004] |
I200F | p.I231F | - | - | ep | Sf9 cells | 90 % | 75 % | [Penner et al., 2006] |
C303V | p.C334V | - | - | ep-AR | Sf9 cells | 80 % | 60 % | [Penner et al., 2006] |
C303* | p.C334* | - | - | ep-AR | Sf9 cells | 0 % | 0 % | [Penner et al., 2006] |
V331A | p.V362A | - | - | ep | COS cells | 16 % | 114 % | [Noguchi et al., 2004] |
D378Y | p.D409Y | - | - | ep | Sf9 cells | 30 % | 45 % | [Penner et al., 2006] |
D378Y | p.D409Y | - | - | ep | COS cells | 10% | 100% | [Noguchi et al., 2004] |
I472T | p.I503T | - | - | kin | COS cells | 48 % | 5 % | [Noguchi et al., 2004] |
N519S | p.N550S | - | - | kin | Sf9 cells | 40 % | 20 % | [Penner et al., 2006] |
A524V | p.A555V | - | - | kin | COS cells | 5% | 30 % | [Noguchi et al., 2004] |
F528C | p.F559C | - | - | kin | Sf9 cells | 70 % | 35 % | [Penner et al., 2006] |
F537I | p.F568I | - | - | kin | Sf9 cells | 45 % | 60 % | [Penner et al., 2006] |
V572L | p.V603L | - | - | kin | COS cells | 68 % | 8 % | [Noguchi et al., 2004] |
G576E | p.G607E | - | - | kin | Sf9 cells | 15 % | 15 % | [Penner et al., 2006] |
I587T | p.I618T | - | - | kin | Sf9 cells | 55 % | 35 % | [Penner et al., 2006] |
A630T | p.A661T | - | - | kin | COS cells | 80 % | 40 % | [Noguchi et al., 2004] |
A631T | p.A662T | - | - | kin | Sf9 cells | 80 % | 75 % | [Penner et al., 2006] |
A631V | p.A662V | - | - | kin | Sf9 cells | 70 % | 65 % | [Penner et al., 2006] |
A631V | p.A662V | - | - | kin | COS cells | 75 % | 5 % | [Noguchi et al., 2004] |
G708S | p.G739S | - | - | kin | COS cells | 48 % | 5 % | [Noguchi et al., 2004] |
M712T | p.M743T | - | - | kin | Sf9 cells | 100% | 70% | [Hinderlich et al., 2004] |
Cell free system | ||||||||
G135V | p.G166V | - | - | ep-NES | cell free | 0.6 % | 7 % | [Sparks et al., 2005] |
V216A | p.V247A | - | - | ep | cell free | 2 % | 19 % | [Sparks et al., 2005] |
R246W | p.R277W | - | - | ep | cell free | 0.5 % | 17 % | [Sparks et al., 2005] |
A631T | p.A662V | - | - | kin | cell free | 3 % | 12 % | [Sparks et al., 2005] |
M712T | p.M743T | - | - | kin | cell free | 3 % | 8 % | [Sparks et al., 2005] |
Amino acid substitutions are provided in the previously used hGNE1 (NP_005467.1; encoded by mRNA NM_005476.5) and in the preferred new hGNE2 (NP_001121699.1; encoded by mRNA NM_001128227.2) nomenclature [Huizing et al. 2014b]. The 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.
Domains correspond to GNE protein domains of Table 1 and Fig. 1. ep = UDP-GlcNAc 2-epimerase domain; ep-NES = nuclear export signal; ep-AR: allosteric region; kin = ManNAc kinase domain.
All enzyme activities are expressed as percentage of wild type activity.
Combined average activity of myoblast cell lines from 9 patients homozygous for M712T (hGNE1 nomenclature).
Combined average of lymphoblast cell lines from 6 patients homozygous for M712T (hGNE1 nomenclature).