Structural Medicine      The Serpin Database
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Serpin Mutations

A list of pathological human and recombinant stable serpin mutations.

Click on region in first column to view (highlighted in red) the secondary structure where the mutation appears.

(NB This list is continually under construction. Please address any queries to Tim Dafforn at td214@cam.ac.uk)
 

Secondary structure Template  Serpin Name Mutation Consequence Disease Ref. 
Signal peptide -28 Antithrombin Dublin Val -3>Glu Loss of N-terminal dipeptide; decreased heparin cofactor activity; normal heparin affinity; ?Thrombosis 93
Signal peptide -19 Antitrypsin Z Wrexham Ser -19> Leu Glu 342> Lys Poor expression; deficiency (See antitrypsin Z) Emphysema 94
N-terminus Image VRML -19 Antithrombin Rouen-III Ile 7>Asn New glycosylation site; decreased heparin affinity Thrombosis 63
N-terminus Image VRML -2 Antithrombin Rouen-IV Arg 24>Cys Loss of positive charge; decreased heparin affinity; normal antigenic levels Thrombosis 54
N-terminus Image VRML 2 Antitrypsin - Asp 21>Ala Normal polymorphism None -
N-terminus Image VRML 16 Antithrombin Basel Pro 41>Leu Disruption of heparin site; decreased heparin affinity; normal antigenic levels Thrombosis 559
A-helix Image VRML 22 Antithrombin Toyama Arg 47>Cys Loss of positive charge; Decreased heparin affinity; normal antigenic levels Thrombosis 55
A-helix Image VRML 22 Antithrombin Rouen-I Arg 47>His Loss of positive charge; decreased heparin affinity; normal antigenic levels Thrombosis  56
A-helix Image VRML 22 Antithrombin Rouen-II Arg 47>Ser Loss of positive charge; decreased heparin affinity; normal antigenic levels Thrombosis 57
A-helix Image VRML 27 TBG San Diego Ser 23>Thr Deficiency, decreases T4 binding ? ?
A-helix Image VRML 30 PAI-1 Recombinant Ala 12>Val ? ? ?
A-helix Image VRML 30,32 Antithrombin - Asn 55 del  
Arg 57>Cys		 Disruption of hA; deficiency Thrombosis 95
A-helix Image VRML 31 PAI-1 Recombinant Ser 13>Lys ? ? ?
A-helix Image VRML 32 PAI-1 Recombinant Asp 14>Thr ? ? ?
A-helix Image VRML 33 Antithrombin Budapest-6 Phe 58>Leu Loss of conserved Phe; disturbed packing at buried site; Thrombosis 96
A-helix Image VRML 34 Antitrypsin Karlsruhe Ala 34> Thr Normal Polymorphism None 96
A-helix Image VRML 38 Antithrombin - Tyr 63>Cys ? ? ?
A-helix Image VRML 38 Antithrombin - Tyr 63>Ser Loss of conserved aromatic residue; disturbed packing at buried site; deficiency Thrombosis 97
A-helix Image VRML 39 Antitrypsin I - Arg 39>Cys Loss of salt bridge to hG; slightly decreased inhibitory activity; mild deficiency Emphysema  42
A-helix Image VRML 40 Antithrombin - Leu 66>Pro ? ? ?
A-helix Image VRML 41 Antitrypsin M Procida Leu 41>Pro Distortion of hA; decreased inhibitory activity; deffciency Emphysema 68
A-helix Image VRML 45 Antitrypsin Bonn Ser 45>Thr Normal polymorphism None 68
s6B Image VRML 51 Antitrypsin M Palermo Phe 51 del Deficiency ? ?
s6B Image VRML 52 Antitrypsin M  Malton Phe 52 del Shutter domain; disturbed packing of hB beneath sheet A; polymers in liver cells; deficiency Emphysema, Liver disease 42
s6B Image VRML 52 Antitrypsin M Nichinan Phe 52 del Shutter domain; disturbed packing of hB beneath sheet A; polymers in liver cells; deficiency Emphysema, Liver disease 98
s6B Image VRML 52 C1-inhibitor - Phe 147>Ser Shutter domain ;deficiency Angioedema ?
s6B-hB 53 Antitrypsin  Siiyama Ser 53>Phe Shutter domain; polymers in liver cells and plasma; deficiency Emphysema, Liver disease 41, 44
hB Image VRML 54 PAI-1 Recombinant Pro 36>Ser ;Thr Stable ? ?
hB Image VRML 54 Antithrombin - Pro 80>Thr Shutter domain; loss of conserved Pro initiating hB; disturbed packing at buried site; deficiency Thrombosis  99
hB Image VRML 54 C1-inhibitor - Pro 149>Leu Shutter domain; deficiency Angioedema ?
hB Image VRML 55 Antichymotrypsin Bochum-1 Leu 55>Pro Shutter domain; distortion of hB, decreased inhibitory activity; deficiency Emphysema 70
hB Image VRML 59 Antitrypsin Recombinant Thr 59 >Ala Increased stability ? ?
hB Image VRML 60 Antitrypsin M6 Passau Ala 60>Thr Normal Polymorphism None ?
hB Image VRML 63 PAI-1 Recombinant Met 45>Lys Stable ? ?
hB Image VRML 67 PAI-1 Recombinant Thr 49>Ala Stable ? ?
hB Image VRML 67 Antitrypsin M Mineral Springs Gly 67>Glu Loss of conserved Gly; disturbed packing; degraded in liver cells; decreased inhibitory activity; deficiency Emphysema 74
hB Image VRML 68 Antitrypsin Recombinant Thr 68>Ala Increased stability ? ?
hB Image VRML 68 Antitrypsin Lisbon Thr 68>Ile Null ? ?
hB Image VRML 69 Antithrombin Morioka Cys 95>Arg Deficiency Thrombosis ?
hB Image VRML 70 Antitrypsin Recombinant Ala 70>Gly ? ? ?
hC Image VRML 73 PAI-1 Recombinant Gln 55>Leu ? ? ?
hC Image VRML 73 Antithrombin Budapest-3  Leu 99>Phe Disturbed packing beneath heparin site; decreased heparin affinity; normal antigenic levels Thrombosis 60
hC Image VRML 73 Antithrombin Southport Leu 99>Val Disturbed packing beneath heparin site; decreased heparin activity Thrombosis  61
hC Image VRML 74 Antithrombin - Gln 101>Lys Null - ?
hC Image VRML 75 Antithrombin - Gln 101>Lys Deficiency  Thrombosis ?
hD Image VRML 88 Antitrypsin M5 Berlin Pro 88>Thr Normal Polymorphism None ?
hD Image VRML 89 Antithrombin Nagasaki Ser 116>Pro Disruption of heparin site; decreased heparin affinity; normal antigenic levels Thrombosis 62
hD Image VRML 91 Antithrombin Vienna Gln 118>Pro Disruption of heparin site; decreased heparin affinity Thrombosis 61
hD Image VRML 92 Antitrypsin Ludwigshafen Ile 92>Asn Disturbed packing at buried site; deficiency  Emphysema 75
hD Image VRML 93 Antithrombin - His 120>Tyr Disturbed packing at buried site; loss of salt bridge to Y166; deficiency Thrombosis 99
hD Image VRML 99 Antithrombin - Leu 126>Pro Disruption of D helix Not expressed Thrombosis ?
hD Image VRML 100 Thyroxine binding globin Gary Ile 96>Asn New glycosylation site; no hormone binding; unstable; deficiency None 74
hD Image VRML 101 Antithrombin - Cys 128>Tyr High molecular weight complex? ? ?
hD Image VRML 102 Heparin cofactor II - Arg 189>His Loss of positive charge; decreased dermatan sulphate binding ?Thrombosis 64
hD Image VRML 102 Corticosteroid binding globulin Leuven Leu 93>His Impaired hormone binding mechanism; normal antigenic levels None 90, 91, 92
hD Image VRML 102 Antithrombin Geneva Arg 129>Gln Loss of positive charge; decreased heparin affinity; normal antigenic levels Thrombosis 58
hD Image VRML 105 PAI-1 Recombinant Gly 84>Arg ? ? ?
s2A Image VRML 112 PAI-1 Recombinant Ile 91>Leu Stable ? ?
s2A Image VRML 114 PAI-1 Recombinant Thr 93>Ser Stable ? ?
s2A Image VRML 114 Angiotensinogen - Thr 174>Met - ?Hypertension 84
s2A Image VRML 115 342 Antitrypsin Null (Z) Newport Gly 115>Ser  
Glu 342>Lys 		 Deficiency (See antitrypsin Z) Emphysema 94
s2A Image VRML 117 Thyroxine binding globin Montreal Ala 113>Pro Decreased binding of T4; Deficiency ? ?
hE Image VRML 130 Antithrombin ? Tyr 158>Cys ? ? ?
hE Image VRML 134 Antithrombin - Ser 162>Asn Buried sidechain; General structural peturbation - -
hE Image VRML 138 Antithrombin - Tyr 166>Cys Loss of conserved aromatic residue; disturbed packing at buried site; loss of salt bridge to H120; deficiency Thrombosis 95
s1A Image VRML 144 PAI-1 Recombinant Glu 123>Arg ? ? ?
s1A Image VRML 148 Antitrypsin M2 Obernburz Gly 148>Trp Normal Polymorphism None ?
hF Image VRML 153 Antithrombin - Ser 182>Tyr Disturbed packing; deficiency Thrombosis 97
hF Image VRML 156 Antitrypsin Frankfurt Gln 156>Glu Normal Polymorphism None
hF Image VRML 158 Antithrombin Rouen-V Asn 187>Asp Loss of salt bridge to CO of I202; polymers and L-form; decreased heparin affinity; decreased inhibitory activity;  Thrombosis 39
hF Image VRML 158 Antithrombin Glasgow-III Asn 187>Lys Loss of salt bridge to CO of I202; decreased inhibitory activity; normal antigenic levels Thrombosis 39
hF Image VRML 162 Antithrombin ? Ser 191>Pro ? ? ?
hF Image VRML 162 PAI-1 Recombinant Lys 141>Gln ? ? ?
hF Image VRML 167 Antithrombin ? Gly 196>Ala Type 1? ? ?
hF-s3A 168 C1-inhibitor Ta Lys 251 del New glycosylation site; no interaction with protease Angioedema 77
hF-s3A 171 PAI-1 Recombinant Asn 150>His Stable ? ?
hF-s3A 174 Angiotensinogen - Met 235>Thr Increased plasma levels ?Hypertension ?Preeclampsia 84
hF-s3A 175 PAI-1 Recombinant Lys 154>Thr Stable -
s3A Image VRML 188 Antithrombin ? Tyr 158> Cys ? ? ?
s3A Image VRML 194 Antithrombin ? ? ? ? ?
s3A Image VRML 195 Thyroxine binding globin A Ala 191>Thr Mutation near binding cleft; impaired hormone binding; unstable; deficiency None 88
s4C Image VRML 204 Antitrypsin - Glu 204>Lys Normal Polymorphism none ?
s4C 206 Antithrombin Truro Glu 237>Lys Increased positive charge; increased heparin affinity; decreased inhibitory activity; deficiency Thrombosis  96
s3C Image VRML 213 Antitrypsin M1 - Ala 213>Val Normal polymorphism None -
s3C Image VRML 220 Antithrombin - Met 251>Ile Loss of conserved Met; surface exposed; ?interference with thrombin docking; decreased inhibitory activity; deficiency Thrombosis 99
s3C Image VRML 221 Antitrypsin St Louis Met 221>Thr Normal polymorphism. None ?
s3C Image VRML 223 Antitrypsin F - Arg 223>Cys ? ? ?
s3C-s2B  228  Antichymotrypsin  Bonn-I Pro 229>Ala Disruption of turn; aggregation in liver cells; decreased inhibitory activity; deficiency Emphysema Liver disease 70
s3C-s2B 229 PAI-1 Recombinant Glu 212>Val ? ? ?
s2B Image VRML 240 Antithrombin - Leu 270>Pro Distortion of beta-strand; deficiency Thrombosis ?
s3B Image VRML 247 PAI-1 Recombinant Thr 232>Ser ? ? ?
s3B Image VRML 250 PAI-1 Recombinant Met 235>Leu ? ? ?
s3B Image VRML 251 PAI-1 Recombinant Phe 236>Ile ? ? ?
s3B Image VRML 253 Antichymotrypsin Haslar Ile 284>Asn Disturbed packing at hydrophobic site; decreased inhibitory activity; deficiency Thrombosis 96
s3B-hG 256 Antitrypsin P  Lowell Asp 256>Val Loss of salt bridge to H231; degraded in liver cells; deficiency  Emphysema 101/
hG Image VRML 264 Antitrypsin S - Glu 264>Val Loss of conserved salt bridge to K387; increased turnover; decreased inhibitory activity; mild deficiency Emphysema 67
hG Image VRML 266 PAI-1 Recombinant Ile 253>Thr ? ? ?
hH Image VRML 270 Antithrombin - Glu 302>Lys Decreased heparin cofactor activity; normal heparin affinity;normal antigenic levels ?mechanism Thrombosis DJ Perry unpublished 
s2C Image VRML 284 PAI-1 Recombinant Arg 271>Cys Stable ? ?
hI-s5A 312 Thyroxine binding globin Chicago Tyr 309>Phe Heat resistant? ? ?
hI-s5A 317  Antithrombin - Ser 349>Pro Disruption of turn; deficiency Thrombosis 102
hI-s5A 320  C1-inhibitor - Gly 407>Arg Loss of conserved Gly; disturbed packing; deficiency Angioedema  48
s5A Image VRML 330 PAI-1 Recombinant Ala 318>Ser Stable, reversion to conserved Ser ? ?
s5A Image VRML 330 Antitrypsin Munich Ser 330>Phe Normal Polymorphism None -
s5A Image VRML 331 PAI-1 Recombinant Gln 319>Leu Stable ? ?
s5A Image VRML 333 Antithrombin Seoul Phe 368>Ser ? ? ?
s5A Image VRML 334 Thyroxine binding protein Quebec His 331>Tyr Decreased thyroxine binding, deficiency ? ?
s5A Image VRML 336 PAI-1 Recombinant Val 324>Ala Stable, reversion to conserved Ala ? ?
s5A Image VRML 336 Antitrypsin W Bethesda Ala 336>Thr Disturbed packing against sheet B; degraded in liver cells; deficiency Emphysema 76
s5A Image VRML 339 PAI-1 Recombinant Glu? 327>Val Stable ? ?
s5A Image VRML 341 Antitrypsin Donauwoerth Asp 341>Asn Normal polymorphism none ?
s5A Image VRML 342(P17) Antitrypsin Z - Glu 342>Lys Loss of salt bridge to K290; polymers in liver cells; decreased inhibitory activity; deficiency Emphysema ;Liver disease 38
s5A Image VRML 343(P16) PAI-1 Recombinant Ser 331>Gly Stable ? ?
Hinge 345(P14) C1-inhibitor We Val 432>Glu Disturbed loop insertion in sheet A; no inhibitory activity protease substrate Angioedema 29
Hinge 345(P13) PAI-1 Recombinant Thr 333>Ser ? ? ?
Hinge 346 PAI-1 Recombinant Val 334>Gly Stable Reversion to conserved Glu ?
Hinge 347(P12) Antithrombin  Hamilton Ala 382>Thr Disturbed loop insertion in sheetA; decreased inhibitory activity; protease substrate; normal antigenic levels Thrombosis  24
Hinge 349(P10)  Antithrombin Cambridge-II Ala 384>Se Disturbed loop insertion in sheet A; decreased inhibitory activity;normal antigenic levels Thrombosis 11
Hinge 349(P10) Antithrombin Cambridge-I Ala 384>Pro Disturbed loop insertion in sheet A; decreased inhibitory activity; protease substrate; normal antigenic levels Thrombosis 25
Hinge 349(P10) C1-inhibitor - Ala 436>Val Disturbed loop insertion in sheet A; no inhibitory activity Angioedema 26
Hinge 349(P10) C1-inhibitor Mo Ala 436>Thr Disturbed loop insertion in sheet A; polymers; no inhibitory activity Angioedema  27
Hinge 346-350 Antiplasmin Enschede Ala insertion 353-357 Altered loop conformation; decreased inhibitory activity; plasmin substrate Bleeding 103
RCL Image VRML 351(P8) PAI-1 Recombinant Thr 339>Ser ? ? ?
RCL Image VRML 352(P7) Antithrombin - Ala 387>Val Deficiency ?mechanism  Thrombosis  104
RCL Image VRML 355(P4) PAI-1 Recombinant Val 343>Ala ? ? ?
RCL Image VRML 357(P2) Antithrombin Stockholm Gly 392>Asp No inhibitory activity Thrombosis  51
RCL Image VRML 358(P1) Antitrypsin  Pittsburgh  Met 358>Arg Altered inhibitor specificity  Bleeding 51
RCL Image VRML 358(P1) Antithrombin Northwick Park  Arg 393>Cys No inhibitory activity; increased heparin affinity; disulphide link to albumin; normal antigenic levels Thrombosis 49
RCL Image VRML 358(P1) Antithrombin Glasgow Arg 393>His No inhibitory activity; increased heparin affinity; normal antigenic levels Thrombosis 49
RCL Image VRML 358(P1) Antithrombin Pescara Arg 393>Pro No inhibitory activity; increased heparin affinity;normal antigenic levels Thrombosis 50
RCL Image VRML 358(P1) C1-inhibitor At Arg 444>His No inhibitory activity Angioedema 106
RCL Image VRML 358(P1) C1-inhibitor Da Arg 444>Cys No inhibitory activity Angioedema 107
RCL Image VRML 358(P1) C1-inhibitor - Arg 444>Ser No inhibitory activity Angioedema 108
RCL Image VRML 358(P1) C1-inhibitor - Arg 444>Leu  No inhibitory activity Angioedema 109
RCL Image VRML 359(P1') Antithrombin Denver Ser 394>Leu Decreased inhibitory activity; Normal antigenic levels Thrombosis 110
s1C Image VRML 362(P4') Antitrypsin Offenbach Pro 262>Thr Normal polymorphism None ?
s1C Image VRML 363(P5') Antitrypsin ? Glu 263>Lys Normal polymorphism ? ?
s1C Image VRML 364(P6') Antithrombin Rosny Phe 402>Cys Disturbed packing at buried site; decreased inhibitory activity; decreased heparin affinity; deficiency Thrombosis 36
s1C Image VRML 264(P6') Antithrombin  Maisons Lafitte  Phe 402>Leu Disturbed packing at buried site; decreased inhibitory activity; decreased heparin affinity; deficiency Thrombosis  36
s1C Image VRML 364(P6') Antithrombin Torino  Phe 402>Ser Disturbed packing at buried site; decreased inhibitory activity;decreased heparin affinity;deficiency Thrombosis 36
s1C Image VRML 366(P8') PAI-1 Recombinant Met 354>Ile Stable ? ?
s1C Image VRML 366(P8') Antithrombin Oslo Ala 404>Thr Disturbed packing at buried site; decreased inhibitory activity; decreased heparin affinity; Thrombosis 111
s1C Image VRML 366(P8') C1-inhibitor  - Val 451>Met Disturbed packing at buried site; deficiency; polymerises; no inhibitory activity Angioedema  33
s1C-s4B  367(P9') Antithrombi La Rochelle Asn 405>Lys Disturbed flexibility at distal hinge; decreased inhibitory activity; decreased heparin affinity; deficiency Thrombosis  36
s1C-s4B  367(P9') C1-inhibitor - Gln 452>Glu  Probable polymorphism ?Normal function - 33
s1C-s4B  368(P10') Antithrombin Kyoto Arg 406>Met Disturbed flexibility at distal hinge; decreased inhibitory activity; deficiency Thrombosis 112
s1C-s4B 368(P10') Antithrombin ? Arg 406>Gly TypeII PE ? ?
s1C-s4B 369(P11') Antithrombin Budapest-5 Pro 407>Thr Loss of conserved Pro; disturbed flexibility at distal hinge; decreased inhibitory activity; decreased heparin activity; normal antigenic levels. Thrombosis 36
s1C-s4B  369(P11') Antithrombin Utah Pro 407>Leu Loss of conserved Pro; disturbed flexibility at distal hinge; decreased inhibitory activity; decreased heparin affinity; deficiency Thrombosis 115
s1C-s4B 369(P11') Antitrypsin M Heerlen Pro 369>Leu  Loss of conserved Pro; disturbed flexibility at distal hinge; deficiency Emphysema 71,72
s1C-s4B 370(P12') C1-inhibitor  - Phe 455> Ser Loss of conserved Phe; polymerises, defective intracellular transport deficiency Angioedema  19,33
s4B Image VRML 374 C1-inhibitor - Leu 459>Arg  Loss of conserved hydrophobic residue; disturbed packing; not secreted Angioedema  33
s4B Image VRML 374  C1-inhibitor - Leu 459>Pro Loss of conserved hydrophobic residue; disturbed packing; accumulation in ER; deficiency Angioedema 33
s4B Image VRML 374 Antitrypsin Recombinant Met 374> Ile Stable? - -
s4B Image VRML 376 Antitrypsin M3 - Glu 376>Asp Normal polymorphism Nonr -
s4B Image VRML 377 Antithrombin - Val 415>Asp Higher heparin dependency; Reduced Factor XIa activity - -
s5B Image VRML 381 Antitrypsin - Ser 381>Ala Stable - -
s5B Image VRML 382 C1-inhibitor - Pro 467>Arg Disruption of strand ; Not secreted Angioedema 33
s5B Image VRML 383 Antithrombin - Ile 421>Thr Disturbed packing at buried site; deficiency Thrombosis 97
s5B Image VRML 384 PAI-1 Recombinant Phe 372 > Leu, Ile Stable - -
s5B Image VRML 385 Antichymotrypsin - Met 389>Val - Occlusive cerebrovascular disease -
s5B Image VRML 386  Antithrombin - Gly 424>Arg Loss of conserved glycine; disturbed packing at buried site;deficiency Thrombosis 114
s5B Image VRML 387 Antithrombin  - Arg 425>Thr  Loss of conserved salt bridge to E296; deficiency Thrombosis  DM Keeling unpublished
s5B Image VRML 387 Antytrypsin ? Lys 387>Arg Stable ? ?
s5B Image VRML 389 Antithrombin - Ala 427>Asp Disturbed packing; deficiency Thrombosis  105
C-terminus  391 Antithrombin Budapest Pro 429>Leu Disruption of turn; decreased inhibitory activity; normal/ decreased heparin affinity; deficiency Thrombosis 73
C-terminus  391 C1-inhibitor - Pro 476>Ser Disruption of turn; polymerises, defective intracellular transport deficiency Angioedema 33
C-terminus  392 Antithrombin - Cys 430> Phe Disruption of disulphide bond to C247; deficiency Thrombosis 97