- | p.Cys55Phe | 55 | No | No | No | ER | Disulfide on C55-C358 locks initial β-strand on B-peptide (α/β) |
- | p.His72Leu | 72 | No | Yes | Yes | Lysosomal,Lysosomal | Active site, Zn++ coordination (α/β) |
- | p.Asp74Glu | 74 | No | Yes | Yes | Lysosomal | Active site, Zn++ coordination (α/β) |
- | p.Ala95Pro | 95 | No | Abnormal | Yes | ER | Loop over the active site; dimer interface (α/β) |
- | p.Tyr99His | 99 | No | Yes | Yes | Lysosomal | Dimer interface (α/β) |
- | p.Asp102Asn | 102 | No | Yes | Yes | Lysosomal | Folding of the α/β-domain |
- | p.Gly153Val | 153 | No | Yes | Yes, weak | Lysosomal | Destabilisation of the α/β-domain and interface to β3 |
- | p.Asp159Asn | 159 | No | Yes | Yes | Lysosomal | Turn between barrel strand and helix (α/β) |
- | p.Pro197Arg | 197 | No | No | Yes | ER | Active site area (α/β) |
- | p.His200Leu | 200 | Some | Yes | Yes | Lysosomal | Active site area (α/β) |
- | p.His200Asn | 200 | Yes | Yes | Yes | Lysosomal | Active site area (α/β) |
- | p.Arg202Pro | 202 | Some | Yes | Yes | ER | Active site area (α/β) |
- | p.Arg229Trp | 229 | Yes | Yes | Yes | Lysosomal | Surface helix, interior (α/β) |
- | p.Pro248Leu | 248 | Yes | Yes,Yes | Yes | - | Exposed on surface, Tolerated |
- | p.Val256_Gly260del5 | 256 | No | No | Yes | ER | - |
- | p.Pro263Leu | 263 | No | Yes | Yes | Lysosomal | Two adjacent prolines preceding disulfide C268-C273 (α/β) |
- | p.Leu278Val | 278 | Yes | - | Yes | - | Buried in surface loop, Tolerated |
- | p.Pro282Ser | 282 | Yes | Yes | Yes | - | Exposed on surface, Tolerated |
- | p.Thr312Ile | 312 | Yes | Yes | Yes | - | Buried, Tolerated |
- | p.Ser318Leu | 318 | Yes | Yes, weak | Yes | Lysosomal | Surface, close to disulfide C268-C273 (α/β) |
- | p.Arg337Gln | 337 | Yes | Yes | Yes | - | Exposed on surface, Tolerated |
- | p.Gln339_Val342del4 | 339 | No | No | No | ER | - |
- | p.Leu352Pro | 352 | No | No | No | ER | Destabilisation of β-sheet below N-terminus (α/β) |
- | p.Thr355Pro | 355 | No | No | No | ER | Preceding α-helix and disulphide bond C55-C358 (α/β) |
- | p.Pro356Arg | 356 | No | No | No | ER | Initiation of α-helix and disulphide bond C55-C358 (α/β) |
- | p.Pro379Leu | 379 | No | Yes | Yes | Lysosomal | Preceding a loop to the active site area (a/ß) |
- | p.Gly390Cys | 390 | No | No | No | ER | Interface between a/ß and ß2 domain |
- | p.Glu402Lys | 402 | Yes | Yes | Yes | Lysosomal | Buried, Tolerated |
- | p.Asn413Ser | 413 | Yes | Yes | Yes | - | Exposed on surface, Tolerated |
- | p.Gly420Val | 420 | No | Abnormal | No | Lysosomal | Turn preceding the proteolytic site between B and C-peptides (3α) |
- | p.His445Tyr | 445 | No | No | Yes | ER | Active site area (3α) |
- | p.Gly451Cys | 451 | Yes | Yes, weak | Yes | Lysosomal | Active site area (3α) |
- | p.Ser453Tyr | 453 | No | Yes, weak | Yes | ER | Active site area (3α) |
- | p.Ser453Phe | 453 | No | No | Yes | ER | Active site area (3α) |
- | p.Val457Glu | 457 | Yes | Yes, weak | Yes | Lysosomal | Active site area, right behind Trp77 (3α) |
- | p.Ala481Ser | 481 | Yes | No | Yes | - | Exposed on surface, Tolerated |
- | p.Cys501Ser | 501 | Yes | Abnormal | Yes | Lysosomal | Disulfide C493-C501 supports conserved glycosylation at Asn497 |
- | p.Leu565Pro | 565 | Some | No | No | ER | Destabilisation of β-sheet (β1) |
- | p.Pro669Leu | 669 | Yes | Yes | Yes | - | Buried in surface structure, Tolerated |
- | p.Trp714Arg | 714 | No | No | No | ER | Interior of large β-domain (β2) |
- | p.Thr745Arg | 745 | No | Yes, weak | No | Lysosomal | Interior of large β-domain (β2) |
- | p.Arg750Trp | 750 | No | No | No | ER (lamp),ER (pdi) | Domain interface from β2 to α/β and β3) |
- | p.Gly800Trp | 800 | No | No | Yes | ER | β sheet double layer (β2) |
- | p.Gly800Arg | 800 | No | No | Yes | ER | β sheet double layer (β2) |
- | p.Leu809Pro | 809 | No | No | No | ER | Destabilisation of β-sheet (β2) |
- | p.His814_Arg815dup | 814 | No | Yes | Yes | ER | HR duplication on loop towards α/β (β2) |
- | p.Gly891Arg | 891 | No | No | No | ER | Hinge between β1 and β3 |
- | p.Leu892Pro | 892 | No | No | No | ER | Hinge between β1 and β3 |
- | p.Arg916His | 916 | No | No | No | ER | Domain interface between β3 and α/β (β3) |
- | p.Arg916Cys | 916 | No | No | No | ER | Domain interface between β3 and α/β (β3) |
- | p.Arg950Pro | 950 | No | Yes | No | Lysosomal | Surface residue, proline destabilises β-sheet (β3) |
- | p.Leu956Arg | 956 | No | No | No | ER | Domain interface between β3 and α/β (β3) |
- | p.Arg962His | 962 | Yes | No | Yes | Lysosomal | Interaction between β3 and the α/β-domain |
- | p.Phe1000Ser | 1000 | No | Yes, weak | No | ER | Core of ß3 |