Incidental Mutation 'R5369:Pcsk5'
ID 429584
Institutional Source Beutler Lab
Gene Symbol Pcsk5
Ensembl Gene ENSMUSG00000024713
Gene Name proprotein convertase subtilisin/kexin type 5
Synonyms PC5A, PC5/6A, PC6, b2b1549Clo, b2b585Clo, SPC6
MMRRC Submission 042946-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R5369 (G1)
Quality Score 225
Status Validated
Chromosome 19
Chromosomal Location 17409683-17814996 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 17558619 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Alanine at position 596 (V596A)
Ref Sequence ENSEMBL: ENSMUSP00000050272 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000025618] [ENSMUST00000050715]
AlphaFold Q04592
Predicted Effect probably damaging
Transcript: ENSMUST00000025618
AA Change: V596A

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000025618
Gene: ENSMUSG00000024713
AA Change: V596A

DomainStartEndE-ValueType
low complexity region 17 29 N/A INTRINSIC
Pfam:S8_pro-domain 40 116 4.6e-27 PFAM
Pfam:Peptidase_S8 164 447 2.1e-46 PFAM
Pfam:P_proprotein 507 597 2.1e-33 PFAM
FU 632 682 4.92e-13 SMART
FU 685 732 4.84e-12 SMART
EGF_like 690 723 3.29e1 SMART
FU 736 779 1.29e-7 SMART
FU 781 826 5.74e-14 SMART
FU 834 881 2.23e-11 SMART
EGF_like 839 870 3.43e1 SMART
FU 884 929 1.84e-12 SMART
FU 931 981 1.47e-11 SMART
FU 984 1030 1e-4 SMART
EGF_like 989 1020 2.92e1 SMART
FU 1034 1079 5.04e-10 SMART
FU 1081 1123 3.08e-5 SMART
FU 1127 1168 4.88e-8 SMART
FU 1206 1248 2.7e-10 SMART
EGF_like 1211 1239 5.91e1 SMART
FU 1252 1299 1.48e-7 SMART
EGF 1264 1305 1.69e1 SMART
FU 1301 1345 2.31e-9 SMART
FU 1347 1390 8.98e-7 SMART
EGF_like 1352 1381 7.23e1 SMART
FU 1392 1438 1.04e-11 SMART
FU 1442 1487 6.8e-7 SMART
EGF 1447 1476 2.16e1 SMART
FU 1491 1536 3.37e-11 SMART
FU 1540 1585 9.32e-14 SMART
EGF_like 1545 1576 2.8e1 SMART
FU 1589 1636 1.39e-12 SMART
FU 1640 1685 6.49e-13 SMART
EGF_like 1645 1676 6.67e1 SMART
FU 1691 1738 7.01e-9 SMART
transmembrane domain 1770 1789 N/A INTRINSIC
low complexity region 1827 1840 N/A INTRINSIC
low complexity region 1858 1876 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000050715
AA Change: V596A

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000050272
Gene: ENSMUSG00000024713
AA Change: V596A

DomainStartEndE-ValueType
low complexity region 17 29 N/A INTRINSIC
PDB:1KN6|A 35 116 6e-11 PDB
Pfam:Peptidase_S8 168 456 2.9e-59 PFAM
Pfam:P_proprotein 507 597 1.5e-34 PFAM
FU 632 682 4.92e-13 SMART
FU 685 732 4.84e-12 SMART
EGF_like 690 723 3.29e1 SMART
FU 736 779 1.29e-7 SMART
FU 781 826 5.74e-14 SMART
FU 834 884 1.4e-8 SMART
EGF_like 839 870 3.43e1 SMART
Meta Mutation Damage Score 0.0979 question?
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.7%
  • 10x: 97.4%
  • 20x: 95.6%
Validation Efficiency 99% (77/78)
MGI Phenotype FUNCTION: This gene encodes a subtilisin-like proprotein convertase that mediates posttranslational endoproteolytic processing of various proprotein substrates traversing the secretory pathway. The encoded protein is an inactive zymogen that undergoes autoproteolytic processing in the endoplasmic reticulum and the Golgi network to generate an active enzyme. Mice lacking the encoded protein die at an early embryonic stage. Conditional inactivation this gene in the epiblast but not in the extraembryonic tissue bypasses embryonic lethality but results in death at birth. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2015]
PHENOTYPE: Mice homozygous for a null mutation in this gene display embryonic lethality between E4.5-E7.5. Mice homozygous for ENU-induced mutations exhibit heterotaxia with congenital heart defects and immotile respiratory cilia. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 74 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
A2ml1 T C 6: 128,545,796 (GRCm39) T444A probably damaging Het
A330070K13Rik G A 5: 130,407,932 (GRCm39) probably benign Het
Abcb8 C T 5: 24,605,137 (GRCm39) R108C possibly damaging Het
Acbd5 T A 2: 23,002,522 (GRCm39) L508Q probably damaging Het
Asb15 T C 6: 24,562,563 (GRCm39) V175A probably benign Het
B3galnt2 T C 13: 14,169,010 (GRCm39) probably null Het
BC024139 A C 15: 76,004,422 (GRCm39) S711R probably benign Het
Bod1l A G 5: 41,984,526 (GRCm39) I508T probably damaging Het
Btnl6 T A 17: 34,726,959 (GRCm39) R524* probably null Het
C3 C A 17: 57,528,159 (GRCm39) D687Y probably benign Het
Ccbe1 G A 18: 66,194,485 (GRCm39) A367V probably benign Het
Ccr1 A T 9: 123,764,326 (GRCm39) M68K probably damaging Het
Cd27 T A 6: 125,211,327 (GRCm39) probably benign Het
Celf2 C A 2: 7,085,892 (GRCm39) probably benign Het
Cfap54 T C 10: 92,897,119 (GRCm39) probably benign Het
Cfap97 A G 8: 46,622,687 (GRCm39) K26E probably damaging Het
Clcn4 T A 7: 7,299,032 (GRCm39) I48F probably benign Het
Cnot7 A T 8: 40,947,061 (GRCm39) N238K probably benign Het
Colec12 A G 18: 9,866,750 (GRCm39) I654V unknown Het
Dip2a A G 10: 76,128,194 (GRCm39) I22T probably damaging Het
Eif4g3 C T 4: 137,910,645 (GRCm39) T1375M possibly damaging Het
Eml5 C T 12: 98,825,042 (GRCm39) G725D probably damaging Het
F12 T C 13: 55,566,304 (GRCm39) E496G probably benign Het
Fam227a A T 15: 79,499,637 (GRCm39) S573T probably benign Het
Fnip1 T C 11: 54,393,415 (GRCm39) V593A probably benign Het
Focad T A 4: 88,039,610 (GRCm39) probably benign Het
Frem1 A G 4: 82,919,976 (GRCm39) I460T possibly damaging Het
Galnt10 T G 11: 57,656,573 (GRCm39) probably null Het
Gm5592 A T 7: 40,867,635 (GRCm39) probably benign Het
Gm6185 A T 1: 161,037,330 (GRCm39) noncoding transcript Het
Gm7935 A T 15: 73,952,963 (GRCm39) noncoding transcript Het
Grb14 C T 2: 64,747,653 (GRCm39) V369I probably benign Het
Gstm5 G A 3: 107,805,782 (GRCm39) A198T probably damaging Het
Herc2 T A 7: 55,832,448 (GRCm39) V3048D probably damaging Het
Htra4 T G 8: 25,523,585 (GRCm39) I327L possibly damaging Het
Ifi209 T C 1: 173,464,873 (GRCm39) M1T probably null Het
Ints6 T C 14: 62,981,384 (GRCm39) T135A probably damaging Het
Itpr1 T A 6: 108,496,385 (GRCm39) I2604N probably damaging Het
Krt6a T A 15: 101,600,993 (GRCm39) M268L probably benign Het
Lrp1b G T 2: 40,894,625 (GRCm39) S2201* probably null Het
Lrp2 T C 2: 69,289,904 (GRCm39) N3645S probably benign Het
Lrrc15 A T 16: 30,091,722 (GRCm39) I539N possibly damaging Het
Map3k6 T C 4: 132,974,992 (GRCm39) I675T probably damaging Het
Map3k9 T A 12: 81,768,826 (GRCm39) E1074V probably damaging Het
Med13l T A 5: 118,862,075 (GRCm39) S339R probably benign Het
Mrps18a T C 17: 46,436,552 (GRCm39) probably benign Het
Mtcl2 T C 2: 156,882,654 (GRCm39) E466G probably damaging Het
Nat8f2 G T 6: 85,844,854 (GRCm39) Y169* probably null Het
Nlrp1b A G 11: 71,072,625 (GRCm39) I406T probably benign Het
Npc1l1 A G 11: 6,167,705 (GRCm39) probably null Het
Or10z1 A G 1: 174,078,007 (GRCm39) V162A probably damaging Het
Or5ac20 A T 16: 59,104,743 (GRCm39) M39K probably damaging Het
Ostf1 C T 19: 18,558,689 (GRCm39) G198E probably benign Het
Pde4c T C 8: 71,202,754 (GRCm39) *647Q probably null Het
Pkm A T 9: 59,577,917 (GRCm39) I245F probably damaging Het
Prss3b T A 6: 41,009,940 (GRCm39) R131S probably benign Het
Ptprj T C 2: 90,299,985 (GRCm39) H179R probably benign Het
Rapgef2 A T 3: 78,976,739 (GRCm39) S1356T probably benign Het
Rbm45 T A 2: 76,200,594 (GRCm39) L41Q probably damaging Het
Rsf1 ATGGCG ATGGCGACGGTGGCG 7: 97,229,111 (GRCm39) probably benign Het
Scara5 CG C 14: 65,997,111 (GRCm39) probably null Het
Scel A T 14: 103,823,929 (GRCm39) I386F probably benign Het
Serpinb5 A T 1: 106,809,487 (GRCm39) N298Y possibly damaging Het
Sirt3 A T 7: 140,449,406 (GRCm39) L180Q probably damaging Het
Slc24a2 C T 4: 86,909,625 (GRCm39) V698I probably damaging Het
Slc43a3 A T 2: 84,788,067 (GRCm39) H483L probably damaging Het
Snrnp35 A G 5: 124,628,262 (GRCm39) D25G probably benign Het
Snrnp40 T C 4: 130,256,439 (GRCm39) S55P probably damaging Het
Snx9 T A 17: 5,970,855 (GRCm39) C399S probably damaging Het
Ttbk2 T C 2: 120,655,743 (GRCm39) probably benign Het
Vmn1r1 A G 1: 181,985,341 (GRCm39) V108A possibly damaging Het
Vmn1r201 T A 13: 22,659,672 (GRCm39) N295K probably benign Het
Zfp292 G A 4: 34,807,491 (GRCm39) P1851L possibly damaging Het
Zfp472 A T 17: 33,196,717 (GRCm39) D264V probably damaging Het
Other mutations in Pcsk5
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00418:Pcsk5 APN 19 17,488,785 (GRCm39) missense possibly damaging 0.49
IGL00423:Pcsk5 APN 19 17,619,923 (GRCm39) missense probably benign 0.23
IGL01315:Pcsk5 APN 19 17,429,322 (GRCm39) missense probably damaging 1.00
IGL01372:Pcsk5 APN 19 17,595,108 (GRCm39) missense probably damaging 1.00
IGL01738:Pcsk5 APN 19 17,411,144 (GRCm39) splice site probably benign
IGL01874:Pcsk5 APN 19 17,573,041 (GRCm39) missense probably damaging 0.96
IGL02070:Pcsk5 APN 19 17,416,406 (GRCm39) missense probably benign 0.25
IGL02311:Pcsk5 APN 19 17,410,784 (GRCm39) nonsense probably null
IGL02436:Pcsk5 APN 19 17,542,072 (GRCm39) critical splice donor site probably null
IGL02498:Pcsk5 APN 19 17,488,920 (GRCm39) missense probably damaging 0.99
IGL02504:Pcsk5 APN 19 17,455,236 (GRCm39) critical splice donor site probably null
IGL02664:Pcsk5 APN 19 17,434,134 (GRCm39) missense probably damaging 1.00
IGL02735:Pcsk5 APN 19 17,652,832 (GRCm39) missense probably damaging 1.00
IGL02941:Pcsk5 APN 19 17,424,865 (GRCm39) missense probably damaging 1.00
PIT4377001:Pcsk5 UTSW 19 17,416,466 (GRCm39) missense probably damaging 1.00
R0007:Pcsk5 UTSW 19 17,632,225 (GRCm39) missense probably damaging 1.00
R0007:Pcsk5 UTSW 19 17,632,225 (GRCm39) missense probably damaging 1.00
R0032:Pcsk5 UTSW 19 17,542,179 (GRCm39) missense possibly damaging 0.81
R0032:Pcsk5 UTSW 19 17,542,179 (GRCm39) missense possibly damaging 0.81
R0373:Pcsk5 UTSW 19 17,632,213 (GRCm39) missense probably damaging 1.00
R0784:Pcsk5 UTSW 19 17,692,133 (GRCm39) missense probably benign 0.06
R0843:Pcsk5 UTSW 19 17,632,182 (GRCm39) missense probably damaging 1.00
R1014:Pcsk5 UTSW 19 17,542,194 (GRCm39) missense probably damaging 1.00
R1221:Pcsk5 UTSW 19 17,814,512 (GRCm39) missense possibly damaging 0.85
R1435:Pcsk5 UTSW 19 17,541,246 (GRCm39) nonsense probably null
R1471:Pcsk5 UTSW 19 17,545,688 (GRCm39) missense probably damaging 1.00
R1564:Pcsk5 UTSW 19 17,632,120 (GRCm39) missense probably damaging 1.00
R1597:Pcsk5 UTSW 19 17,413,964 (GRCm39) missense probably benign 0.00
R1614:Pcsk5 UTSW 19 17,492,620 (GRCm39) missense probably damaging 1.00
R1661:Pcsk5 UTSW 19 17,424,938 (GRCm39) missense probably damaging 0.98
R1671:Pcsk5 UTSW 19 17,432,232 (GRCm39) missense probably damaging 1.00
R1703:Pcsk5 UTSW 19 17,729,458 (GRCm39) missense probably benign 0.15
R1793:Pcsk5 UTSW 19 17,432,114 (GRCm39) missense possibly damaging 0.83
R1855:Pcsk5 UTSW 19 17,492,556 (GRCm39) missense possibly damaging 0.93
R1909:Pcsk5 UTSW 19 17,410,825 (GRCm39) missense probably benign 0.00
R1959:Pcsk5 UTSW 19 17,410,782 (GRCm39) missense unknown
R2006:Pcsk5 UTSW 19 17,455,280 (GRCm39) missense probably benign 0.32
R2045:Pcsk5 UTSW 19 17,558,508 (GRCm39) missense possibly damaging 0.48
R2061:Pcsk5 UTSW 19 17,432,236 (GRCm39) missense probably benign 0.03
R2110:Pcsk5 UTSW 19 17,450,423 (GRCm39) missense probably damaging 1.00
R2402:Pcsk5 UTSW 19 17,452,198 (GRCm39) nonsense probably null
R2496:Pcsk5 UTSW 19 17,443,522 (GRCm39) nonsense probably null
R4115:Pcsk5 UTSW 19 17,410,783 (GRCm39) missense unknown
R4504:Pcsk5 UTSW 19 17,429,319 (GRCm39) missense probably damaging 1.00
R4616:Pcsk5 UTSW 19 17,538,114 (GRCm39) missense probably benign 0.00
R4683:Pcsk5 UTSW 19 17,450,405 (GRCm39) missense probably damaging 1.00
R4717:Pcsk5 UTSW 19 17,502,631 (GRCm39) missense probably damaging 1.00
R4761:Pcsk5 UTSW 19 17,814,512 (GRCm39) missense possibly damaging 0.85
R4789:Pcsk5 UTSW 19 17,410,963 (GRCm39) missense probably benign 0.09
R4880:Pcsk5 UTSW 19 17,425,054 (GRCm39) missense probably damaging 1.00
R5100:Pcsk5 UTSW 19 17,492,499 (GRCm39) critical splice donor site probably null
R5114:Pcsk5 UTSW 19 17,652,949 (GRCm39) missense probably damaging 1.00
R5116:Pcsk5 UTSW 19 17,440,798 (GRCm39) missense possibly damaging 0.87
R5193:Pcsk5 UTSW 19 17,542,174 (GRCm39) missense possibly damaging 0.79
R5279:Pcsk5 UTSW 19 17,573,022 (GRCm39) splice site probably null
R5334:Pcsk5 UTSW 19 17,439,215 (GRCm39) missense probably benign 0.00
R5451:Pcsk5 UTSW 19 17,440,720 (GRCm39) missense possibly damaging 0.91
R5547:Pcsk5 UTSW 19 17,729,488 (GRCm39) missense probably benign 0.08
R5630:Pcsk5 UTSW 19 17,553,195 (GRCm39) missense probably benign 0.04
R5805:Pcsk5 UTSW 19 17,434,193 (GRCm39) missense probably benign 0.01
R6063:Pcsk5 UTSW 19 17,432,045 (GRCm39) critical splice donor site probably null
R6130:Pcsk5 UTSW 19 17,488,920 (GRCm39) missense probably damaging 0.99
R6153:Pcsk5 UTSW 19 17,488,856 (GRCm39) missense probably damaging 0.98
R6163:Pcsk5 UTSW 19 17,450,405 (GRCm39) missense probably damaging 1.00
R6164:Pcsk5 UTSW 19 17,814,317 (GRCm39) critical splice donor site probably null
R6228:Pcsk5 UTSW 19 17,558,631 (GRCm39) missense possibly damaging 0.91
R6426:Pcsk5 UTSW 19 17,595,093 (GRCm39) missense probably damaging 1.00
R6601:Pcsk5 UTSW 19 17,488,744 (GRCm39) missense probably benign 0.00
R6648:Pcsk5 UTSW 19 17,553,185 (GRCm39) missense probably damaging 0.99
R6789:Pcsk5 UTSW 19 17,434,150 (GRCm39) missense possibly damaging 0.93
R6807:Pcsk5 UTSW 19 17,549,986 (GRCm39) splice site probably null
R6837:Pcsk5 UTSW 19 17,416,448 (GRCm39) missense probably benign 0.01
R6998:Pcsk5 UTSW 19 17,450,476 (GRCm39) missense probably benign 0.20
R7051:Pcsk5 UTSW 19 17,411,095 (GRCm39) missense probably benign 0.00
R7164:Pcsk5 UTSW 19 17,429,349 (GRCm39) missense probably damaging 1.00
R7173:Pcsk5 UTSW 19 17,455,241 (GRCm39) missense possibly damaging 0.85
R7348:Pcsk5 UTSW 19 17,434,182 (GRCm39) nonsense probably null
R7360:Pcsk5 UTSW 19 17,492,577 (GRCm39) missense probably benign 0.00
R7407:Pcsk5 UTSW 19 17,652,880 (GRCm39) missense probably damaging 1.00
R7447:Pcsk5 UTSW 19 17,487,600 (GRCm39) missense probably benign 0.31
R7521:Pcsk5 UTSW 19 17,432,196 (GRCm39) missense probably benign 0.29
R7525:Pcsk5 UTSW 19 17,619,954 (GRCm39) missense probably damaging 1.00
R7560:Pcsk5 UTSW 19 17,814,336 (GRCm39) missense probably benign 0.01
R7566:Pcsk5 UTSW 19 17,549,821 (GRCm39) missense probably benign
R7631:Pcsk5 UTSW 19 17,542,144 (GRCm39) missense probably damaging 1.00
R7654:Pcsk5 UTSW 19 17,434,168 (GRCm39) missense possibly damaging 0.46
R7677:Pcsk5 UTSW 19 17,558,593 (GRCm39) missense possibly damaging 0.59
R7711:Pcsk5 UTSW 19 17,416,444 (GRCm39) missense possibly damaging 0.82
R7903:Pcsk5 UTSW 19 17,549,847 (GRCm39) missense probably damaging 0.98
R7938:Pcsk5 UTSW 19 17,443,549 (GRCm39) critical splice acceptor site probably null
R8025:Pcsk5 UTSW 19 17,538,415 (GRCm39) intron probably benign
R8032:Pcsk5 UTSW 19 17,692,151 (GRCm39) missense probably damaging 0.98
R8064:Pcsk5 UTSW 19 17,692,225 (GRCm39) missense probably damaging 1.00
R8115:Pcsk5 UTSW 19 17,487,530 (GRCm39) critical splice donor site probably null
R8193:Pcsk5 UTSW 19 17,563,415 (GRCm39) missense possibly damaging 0.64
R8408:Pcsk5 UTSW 19 17,410,809 (GRCm39) missense probably benign 0.00
R8466:Pcsk5 UTSW 19 17,549,864 (GRCm39) nonsense probably null
R8739:Pcsk5 UTSW 19 17,432,138 (GRCm39) missense probably benign 0.00
R8753:Pcsk5 UTSW 19 17,446,408 (GRCm39) missense probably benign 0.00
R8797:Pcsk5 UTSW 19 17,443,472 (GRCm39) missense probably benign 0.00
R8944:Pcsk5 UTSW 19 17,452,275 (GRCm39) missense probably damaging 0.96
R9041:Pcsk5 UTSW 19 17,538,132 (GRCm39) nonsense probably null
R9135:Pcsk5 UTSW 19 17,563,472 (GRCm39) missense
R9288:Pcsk5 UTSW 19 17,814,345 (GRCm39) missense probably benign 0.10
R9406:Pcsk5 UTSW 19 17,771,097 (GRCm39) missense probably benign 0.14
R9581:Pcsk5 UTSW 19 17,432,196 (GRCm39) missense probably benign
R9592:Pcsk5 UTSW 19 17,652,899 (GRCm39) nonsense probably null
R9659:Pcsk5 UTSW 19 17,455,245 (GRCm39) missense probably benign 0.00
R9788:Pcsk5 UTSW 19 17,455,245 (GRCm39) missense probably benign 0.00
X0023:Pcsk5 UTSW 19 17,452,236 (GRCm39) missense possibly damaging 0.66
X0063:Pcsk5 UTSW 19 17,424,968 (GRCm39) missense probably damaging 1.00
Z1088:Pcsk5 UTSW 19 17,440,738 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- TACTTTACATGCCAGGAATATGCC -3'
(R):5'- TCCTATTGTGGGCGCTCAAG -3'

Sequencing Primer
(F):5'- CCAGGAATATGCCCAAGCTTTTG -3'
(R):5'- TATGGCCTGTGAACTGGGAAATCC -3'
Posted On 2016-09-06