Incidental Mutation 'R1987:Pcsk6'
ID 222664
Institutional Source Beutler Lab
Gene Symbol Pcsk6
Ensembl Gene ENSMUSG00000030513
Gene Name proprotein convertase subtilisin/kexin type 6
Synonyms SPC4, PACE4, b2b2830Clo
MMRRC Submission 039999-MU
Accession Numbers
Essential gene? Possibly non essential (E-score: 0.420) question?
Stock # R1987 (G1)
Quality Score 225
Status Not validated
Chromosome 7
Chromosomal Location 65511884-65700134 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 65577035 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Methionine to Leucine at position 158 (M158L)
Ref Sequence ENSEMBL: ENSMUSP00000095992 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000055576] [ENSMUST00000098391] [ENSMUST00000176199] [ENSMUST00000176209]
AlphaFold F6XJP7
Predicted Effect probably benign
Transcript: ENSMUST00000055576
AA Change: M158L

PolyPhen 2 Score 0.448 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000053742
Gene: ENSMUSG00000030513
AA Change: M158L

DomainStartEndE-ValueType
signal peptide 1 54 N/A INTRINSIC
Pfam:S8_pro-domain 65 141 3.1e-29 PFAM
Pfam:Peptidase_S8 186 469 5.2e-49 PFAM
Pfam:P_proprotein 529 619 9.7e-37 PFAM
FU 682 729 5.87e-11 SMART
EGF_like 688 737 5.03e1 SMART
FU 733 780 4.35e-14 SMART
EGF_like 738 771 3.57e1 SMART
FU 784 828 2.08e-11 SMART
EGF 789 819 2.48e1 SMART
FU 832 877 9.4e-10 SMART
EGF_like 837 868 6.28e1 SMART
FU 885 933 8.58e-4 SMART
EGF 890 920 1.69e1 SMART
Predicted Effect possibly damaging
Transcript: ENSMUST00000098391
AA Change: M158L

PolyPhen 2 Score 0.598 (Sensitivity: 0.87; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000095992
Gene: ENSMUSG00000030513
AA Change: M158L

DomainStartEndE-ValueType
signal peptide 1 54 N/A INTRINSIC
PDB:1KN6|A 62 129 2e-6 PDB
low complexity region 131 144 N/A INTRINSIC
Pfam:Peptidase_S8 190 478 1.1e-58 PFAM
Pfam:P_proprotein 529 619 4.5e-37 PFAM
FU 669 716 3.87e-11 SMART
EGF_like 675 724 5.03e1 SMART
FU 720 767 4.35e-14 SMART
EGF_like 725 758 3.57e1 SMART
FU 771 815 2.08e-11 SMART
EGF 776 806 2.48e1 SMART
FU 819 864 9.4e-10 SMART
EGF_like 824 855 6.28e1 SMART
FU 872 920 8.58e-4 SMART
EGF 877 907 1.69e1 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000176199
AA Change: M36L

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)
SMART Domains Protein: ENSMUSP00000135851
Gene: ENSMUSG00000030513
AA Change: M36L

DomainStartEndE-ValueType
low complexity region 9 22 N/A INTRINSIC
Pfam:Peptidase_S8 68 160 1.3e-21 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000176209
AA Change: M71L

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)
SMART Domains Protein: ENSMUSP00000135033
Gene: ENSMUSG00000030513
AA Change: M71L

DomainStartEndE-ValueType
low complexity region 44 57 N/A INTRINSIC
Pfam:Peptidase_S8 103 372 6.5e-50 PFAM
Pfam:P_proprotein 368 458 6.2e-37 PFAM
FU 521 568 5.87e-11 SMART
EGF_like 527 576 5.03e1 SMART
FU 572 619 4.35e-14 SMART
EGF_like 577 610 3.57e1 SMART
FU 623 667 2.08e-11 SMART
EGF 628 658 2.48e1 SMART
FU 671 716 9.4e-10 SMART
EGF_like 676 707 6.28e1 SMART
FU 724 772 8.58e-4 SMART
EGF 729 759 1.69e1 SMART
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.4%
  • 10x: 96.4%
  • 20x: 92.6%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER and sorts to the trans-Golgi network where a second autocatalytic event takes place and the catalytic activity is acquired. The encoded protease is constitutively secreted into the extracellular matrix and expressed in many tissues, including neuroendocrine, liver, gut, and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. Some of its substrates include transforming growth factor beta related proteins, proalbumin, and von Willebrand factor. This gene is thought to play a role in tumor progression and left-right patterning. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Feb 2014]
PHENOTYPE: Homozygous mutation of this gene results in partial lethality by E15.5. Embryos develop situs ambiguus with left pulmonary isomerism or craniofacial malformations including cyclopia, or both. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 79 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Ahnak A T 19: 8,992,615 (GRCm39) D4633V probably damaging Het
Akap6 T C 12: 53,187,578 (GRCm39) F1664S possibly damaging Het
Arhgef28 T C 13: 98,103,604 (GRCm39) M803V probably benign Het
Bltp1 T A 3: 37,008,134 (GRCm39) probably null Het
Bltp2 A T 11: 78,158,993 (GRCm39) Q433L probably damaging Het
Ccdc73 T A 2: 104,761,390 (GRCm39) L130* probably null Het
Ccdc73 A G 2: 104,829,504 (GRCm39) E1059G probably damaging Het
Ccer2 A C 7: 28,456,708 (GRCm39) S151R possibly damaging Het
Cep128 T A 12: 91,197,603 (GRCm39) H406L probably benign Het
Cep135 A G 5: 76,745,275 (GRCm39) D229G probably benign Het
Cpvl T A 6: 53,931,596 (GRCm39) D103V probably benign Het
Crppa T A 12: 36,571,995 (GRCm39) L301Q probably damaging Het
Cstdc6 C A 16: 36,142,194 (GRCm39) G61C probably damaging Het
Disp3 G A 4: 148,343,210 (GRCm39) A567V probably damaging Het
Dnah5 T C 15: 28,343,737 (GRCm39) I2379T probably damaging Het
Dnah6 T C 6: 73,072,027 (GRCm39) Y2433C probably damaging Het
Dock3 A G 9: 106,985,620 (GRCm39) I85T probably benign Het
Dock9 A C 14: 121,829,242 (GRCm39) S1380A probably benign Het
Erbin T C 13: 104,022,711 (GRCm39) T43A probably benign Het
Fastkd3 T C 13: 68,733,360 (GRCm39) V502A possibly damaging Het
Fn1 T C 1: 71,690,784 (GRCm39) H59R probably damaging Het
Fsd2 A G 7: 81,209,407 (GRCm39) V145A possibly damaging Het
Fzr1 A G 10: 81,206,153 (GRCm39) V178A probably damaging Het
Gnpnat1 T C 14: 45,618,455 (GRCm39) R116G probably damaging Het
Grm7 T A 6: 110,891,472 (GRCm39) V235E probably damaging Het
Hdac4 A C 1: 91,862,367 (GRCm39) N1002K probably damaging Het
Hey1 C T 3: 8,729,957 (GRCm39) A167T probably benign Het
Hrnr A G 3: 93,239,911 (GRCm39) N3383S unknown Het
Ints2 A T 11: 86,108,626 (GRCm39) V907D probably benign Het
Jchain T A 5: 88,669,326 (GRCm39) Q109L probably damaging Het
Klhdc7a A T 4: 139,693,335 (GRCm39) Y537* probably null Het
Klra1 C T 6: 130,354,742 (GRCm39) S92N probably benign Het
Krt31 C T 11: 99,940,406 (GRCm39) G150S probably benign Het
Lrrc71 G A 3: 87,649,950 (GRCm39) T326M probably benign Het
Lrrn4 T C 2: 132,712,363 (GRCm39) T487A probably benign Het
Map4k5 T G 12: 69,889,686 (GRCm39) R198S probably damaging Het
Men1 G A 19: 6,388,867 (GRCm39) C354Y probably damaging Het
Ms4a18 A T 19: 10,991,019 (GRCm39) V25E probably damaging Het
Mutyh T A 4: 116,676,565 (GRCm39) S512R possibly damaging Het
Myh10 G T 11: 68,705,322 (GRCm39) A1947S possibly damaging Het
Nfasc T C 1: 132,538,624 (GRCm39) D427G probably damaging Het
Nlrp9c A G 7: 26,077,481 (GRCm39) M767T probably benign Het
Nrbp1 T C 5: 31,402,735 (GRCm39) L185P probably damaging Het
Pcdh9 G A 14: 94,125,741 (GRCm39) P143L probably damaging Het
Pkd1 G T 17: 24,795,566 (GRCm39) probably null Het
Plk4 A T 3: 40,760,252 (GRCm39) S383C possibly damaging Het
Plxna2 T C 1: 194,326,297 (GRCm39) L77P probably damaging Het
Pnpla6 A T 8: 3,592,370 (GRCm39) T1209S probably benign Het
Prdm2 A G 4: 142,859,079 (GRCm39) S1404P possibly damaging Het
Preb T C 5: 31,116,157 (GRCm39) D150G probably damaging Het
Prrt2 A G 7: 126,617,902 (GRCm39) V59A probably benign Het
Prss40 T C 1: 34,597,095 (GRCm39) N151S possibly damaging Het
Ptprt G T 2: 161,400,818 (GRCm39) A1053D probably damaging Het
Ptprt A G 2: 161,608,241 (GRCm39) V685A possibly damaging Het
Rfx4 C T 10: 84,731,952 (GRCm39) S549F possibly damaging Het
Rnaset2b T A 17: 7,263,876 (GRCm39) V87E probably benign Het
Rnf213 G A 11: 119,331,933 (GRCm39) E2381K probably damaging Het
Sectm1a A T 11: 120,960,506 (GRCm39) I103N probably damaging Het
Selp T A 1: 163,970,327 (GRCm39) L597Q probably damaging Het
Sema6a T C 18: 47,433,209 (GRCm39) D74G probably damaging Het
Serpinb9b T C 13: 33,213,542 (GRCm39) V33A probably benign Het
Setd1b A T 5: 123,285,769 (GRCm39) T272S unknown Het
Sgf29 G C 7: 126,248,649 (GRCm39) probably null Het
Slc4a10 C A 2: 62,098,548 (GRCm39) Q561K probably damaging Het
Slc4a5 T C 6: 83,250,214 (GRCm39) I649T possibly damaging Het
Slc5a7 A G 17: 54,600,863 (GRCm39) Y91H probably damaging Het
Styxl1 T C 5: 135,785,976 (GRCm39) Y23C probably damaging Het
Tbc1d24 A G 17: 24,425,846 (GRCm39) V490A possibly damaging Het
Tbpl2 A T 2: 23,984,744 (GRCm39) F133L probably benign Het
Tnfrsf22 T C 7: 143,192,126 (GRCm39) probably benign Het
Top2b A G 14: 16,398,916 (GRCm38) E512G probably damaging Het
Trgc3 C A 13: 19,445,164 (GRCm39) F37L probably damaging Het
Ttc17 T A 2: 94,194,690 (GRCm39) H561L probably benign Het
Ttll4 G T 1: 74,724,527 (GRCm39) V566L possibly damaging Het
Ubqlnl A G 7: 103,797,692 (GRCm39) Y602H probably benign Het
Vmn1r231 T A 17: 21,110,212 (GRCm39) E234D probably damaging Het
Wbp11 A G 6: 136,797,583 (GRCm39) S279P probably damaging Het
Wdr6 A G 9: 108,453,733 (GRCm39) L50P probably damaging Het
Zfp715 A C 7: 42,948,073 (GRCm39) I629S possibly damaging Het
Other mutations in Pcsk6
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00234:Pcsk6 APN 7 65,577,568 (GRCm39) missense probably damaging 1.00
IGL01609:Pcsk6 APN 7 65,685,021 (GRCm39) splice site probably null
IGL01986:Pcsk6 APN 7 65,577,625 (GRCm39) missense probably damaging 1.00
IGL02592:Pcsk6 APN 7 65,618,776 (GRCm39) missense probably damaging 1.00
IGL02720:Pcsk6 APN 7 65,629,995 (GRCm39) nonsense probably null
R0045:Pcsk6 UTSW 7 65,612,676 (GRCm39) missense probably damaging 1.00
R0045:Pcsk6 UTSW 7 65,612,676 (GRCm39) missense probably damaging 1.00
R0053:Pcsk6 UTSW 7 65,633,451 (GRCm39) splice site probably benign
R0053:Pcsk6 UTSW 7 65,633,451 (GRCm39) splice site probably benign
R0103:Pcsk6 UTSW 7 65,578,845 (GRCm39) splice site probably benign
R0103:Pcsk6 UTSW 7 65,578,845 (GRCm39) splice site probably benign
R0119:Pcsk6 UTSW 7 65,688,791 (GRCm39) missense probably benign 0.10
R0299:Pcsk6 UTSW 7 65,688,791 (GRCm39) missense probably benign 0.10
R0415:Pcsk6 UTSW 7 65,683,622 (GRCm39) missense probably damaging 1.00
R0496:Pcsk6 UTSW 7 65,576,997 (GRCm39) missense probably benign 0.00
R0518:Pcsk6 UTSW 7 65,629,915 (GRCm39) missense possibly damaging 0.64
R0748:Pcsk6 UTSW 7 65,688,716 (GRCm39) unclassified probably benign
R1456:Pcsk6 UTSW 7 65,693,283 (GRCm39) missense possibly damaging 0.87
R1613:Pcsk6 UTSW 7 65,560,059 (GRCm39) splice site probably benign
R1680:Pcsk6 UTSW 7 65,684,998 (GRCm39) missense probably benign 0.14
R1682:Pcsk6 UTSW 7 65,559,976 (GRCm39) missense probably damaging 1.00
R4191:Pcsk6 UTSW 7 65,675,056 (GRCm39) missense probably damaging 0.98
R4193:Pcsk6 UTSW 7 65,675,056 (GRCm39) missense probably damaging 0.98
R4577:Pcsk6 UTSW 7 65,609,014 (GRCm39) nonsense probably null
R4592:Pcsk6 UTSW 7 65,581,480 (GRCm39) missense possibly damaging 0.54
R4687:Pcsk6 UTSW 7 65,633,501 (GRCm39) missense probably damaging 1.00
R4697:Pcsk6 UTSW 7 65,608,989 (GRCm39) missense probably damaging 1.00
R4778:Pcsk6 UTSW 7 65,608,893 (GRCm39) missense probably damaging 1.00
R5065:Pcsk6 UTSW 7 65,560,047 (GRCm39) missense possibly damaging 0.84
R5218:Pcsk6 UTSW 7 65,675,036 (GRCm39) missense probably benign 0.01
R5356:Pcsk6 UTSW 7 65,620,340 (GRCm39) missense probably damaging 1.00
R5427:Pcsk6 UTSW 7 65,683,647 (GRCm39) missense probably benign 0.01
R5589:Pcsk6 UTSW 7 65,578,933 (GRCm39) critical splice donor site probably null
R5637:Pcsk6 UTSW 7 65,618,745 (GRCm39) missense probably damaging 1.00
R5888:Pcsk6 UTSW 7 65,693,372 (GRCm39) missense probably null
R5958:Pcsk6 UTSW 7 65,693,359 (GRCm39) missense probably damaging 1.00
R5997:Pcsk6 UTSW 7 65,609,041 (GRCm39) missense probably damaging 1.00
R6191:Pcsk6 UTSW 7 65,578,875 (GRCm39) missense probably benign 0.19
R6274:Pcsk6 UTSW 7 65,683,592 (GRCm39) missense probably damaging 1.00
R6374:Pcsk6 UTSW 7 65,629,903 (GRCm39) missense possibly damaging 0.80
R6393:Pcsk6 UTSW 7 65,618,762 (GRCm39) missense probably damaging 1.00
R6730:Pcsk6 UTSW 7 65,629,996 (GRCm39) missense probably damaging 1.00
R7205:Pcsk6 UTSW 7 65,675,156 (GRCm39) critical splice donor site probably null
R7493:Pcsk6 UTSW 7 65,693,314 (GRCm39) missense possibly damaging 0.53
R7570:Pcsk6 UTSW 7 65,683,646 (GRCm39) missense probably benign 0.03
R7731:Pcsk6 UTSW 7 65,683,641 (GRCm39) missense probably benign 0.00
R7779:Pcsk6 UTSW 7 65,675,152 (GRCm39) missense probably benign 0.03
R8042:Pcsk6 UTSW 7 65,577,683 (GRCm39) missense possibly damaging 0.87
R8734:Pcsk6 UTSW 7 65,581,481 (GRCm39) missense probably benign 0.06
R8805:Pcsk6 UTSW 7 65,578,891 (GRCm39) missense possibly damaging 0.67
R8987:Pcsk6 UTSW 7 65,576,975 (GRCm39) nonsense probably null
R9276:Pcsk6 UTSW 7 65,559,950 (GRCm39) missense probably damaging 1.00
R9492:Pcsk6 UTSW 7 65,697,346 (GRCm39) missense probably benign 0.02
R9747:Pcsk6 UTSW 7 65,633,470 (GRCm39) missense probably damaging 1.00
Z1177:Pcsk6 UTSW 7 65,683,559 (GRCm39) missense probably damaging 0.99
Z1177:Pcsk6 UTSW 7 65,608,861 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- TGTTGCTGCTAGATTACCGATAG -3'
(R):5'- TCTCACACAGGCCTTCAAGTAG -3'

Sequencing Primer
(F):5'- GGTTCCTGGGCTTAAACTCAG -3'
(R):5'- CCTTCAAGTAGAGCAGAGGTTCTC -3'
Posted On 2014-08-25