Incidental Mutation 'R8805:Pcsk6'
ID 672001
Institutional Source Beutler Lab
Gene Symbol Pcsk6
Ensembl Gene ENSMUSG00000030513
Gene Name proprotein convertase subtilisin/kexin type 6
Synonyms SPC4, PACE4, b2b2830Clo
MMRRC Submission 068642-MU
Accession Numbers
Essential gene? Possibly non essential (E-score: 0.420) question?
Stock # R8805 (G1)
Quality Score 225.009
Status Validated
Chromosome 7
Chromosomal Location 65511884-65700134 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 65578891 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Asparagine at position 222 (Y222N)
Ref Sequence ENSEMBL: ENSMUSP00000095992 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000055576] [ENSMUST00000098391] [ENSMUST00000176199] [ENSMUST00000176209]
AlphaFold F6XJP7
Predicted Effect possibly damaging
Transcript: ENSMUST00000055576
AA Change: Y222N

PolyPhen 2 Score 0.670 (Sensitivity: 0.86; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000053742
Gene: ENSMUSG00000030513
AA Change: Y222N

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: Y222N

PolyPhen 2 Score 0.670 (Sensitivity: 0.86; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000095992
Gene: ENSMUSG00000030513
AA Change: Y222N

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 possibly damaging
Transcript: ENSMUST00000176199
AA Change: Y100N

PolyPhen 2 Score 0.619 (Sensitivity: 0.87; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000135851
Gene: ENSMUSG00000030513
AA Change: Y100N

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: Y135N

PolyPhen 2 Score 0.019 (Sensitivity: 0.95; Specificity: 0.80)
SMART Domains Protein: ENSMUSP00000135033
Gene: ENSMUSG00000030513
AA Change: Y135N

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: 100.0%
  • 3x: 100.0%
  • 10x: 99.8%
  • 20x: 99.3%
Validation Efficiency 96% (70/73)
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: 77 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700010I14Rik G A 17: 9,226,737 (GRCm39) W467* probably null Het
4921509C19Rik A T 2: 151,313,285 (GRCm39) probably benign Het
Actl6b G A 5: 137,552,918 (GRCm39) M82I probably benign Het
Bmp2 T A 2: 133,403,254 (GRCm39) D268E probably damaging Het
Cacng7 T A 7: 3,415,298 (GRCm39) L221H probably damaging Het
Ccser2 A G 14: 36,601,712 (GRCm39) V224A probably damaging Het
Cdc40 A G 10: 40,733,576 (GRCm39) F125L probably damaging Het
Cfap46 C T 7: 139,211,979 (GRCm39) A1669T unknown Het
Cfap58 A T 19: 47,941,535 (GRCm39) E301V probably damaging Het
Clcn2 C A 16: 20,532,168 (GRCm39) G96C probably damaging Het
Cotl1 T A 8: 120,536,944 (GRCm39) probably benign Het
Cps1 G A 1: 67,216,110 (GRCm39) A812T probably damaging Het
Cracd T C 5: 77,006,489 (GRCm39) V950A unknown Het
Crnkl1 T C 2: 145,773,350 (GRCm39) probably null Het
Cry1 A G 10: 84,992,969 (GRCm39) V83A probably benign Het
Cyp2a5 G T 7: 26,540,530 (GRCm39) R381L probably damaging Het
Cyp46a1 T C 12: 108,327,462 (GRCm39) F425L probably damaging Het
Dek A T 13: 47,252,930 (GRCm39) N158K unknown Het
Dgcr8 T A 16: 18,076,161 (GRCm39) Q674L probably damaging Het
Dlec1 C A 9: 118,941,650 (GRCm39) S345R probably benign Het
Dnah7b T A 1: 46,273,305 (GRCm39) C2478S possibly damaging Het
Dstyk T A 1: 132,361,963 (GRCm39) L131Q probably damaging Het
Fbxw7 T A 3: 84,862,227 (GRCm39) L186M Het
Fn1 T C 1: 71,644,239 (GRCm39) Q1684R probably benign Het
Fsip2 C A 2: 82,813,453 (GRCm39) H3257Q possibly damaging Het
Gm5773 T C 3: 93,681,042 (GRCm39) V238A probably damaging Het
Gm9611 T C 14: 42,116,657 (GRCm39) D131G Het
Gpatch8 T C 11: 102,371,018 (GRCm39) E840G unknown Het
Grm5 G A 7: 87,453,176 (GRCm39) R271Q probably damaging Het
Has3 A T 8: 107,601,135 (GRCm39) Y199F probably damaging Het
Hmcn2 A G 2: 31,315,393 (GRCm39) N3714S probably benign Het
Idh1 CA CAA 1: 65,204,347 (GRCm39) probably null Het
Il2 T A 3: 37,177,282 (GRCm39) T85S possibly damaging Het
Kank4 T C 4: 98,668,273 (GRCm39) H58R possibly damaging Het
Kcnk4 T A 19: 6,905,379 (GRCm39) I154F probably damaging Het
Krt1c T C 15: 101,724,379 (GRCm39) K295R possibly damaging Het
Lipm A T 19: 34,090,308 (GRCm39) D163V probably damaging Het
Lpl A G 8: 69,340,215 (GRCm39) N70S probably damaging Het
Mgme1 A G 2: 144,114,451 (GRCm39) probably benign Het
Mnd1 T A 3: 83,995,432 (GRCm39) E187D probably benign Het
Morn5 A G 2: 35,969,533 (GRCm39) D149G probably benign Het
Mrrf G A 2: 36,037,965 (GRCm39) V79I probably damaging Het
Msh4 T A 3: 153,563,270 (GRCm39) Q896L probably benign Het
Mtus2 A C 5: 148,015,303 (GRCm39) M699L possibly damaging Het
Mycbp T A 4: 123,803,880 (GRCm39) C130S unknown Het
Ntn5 A T 7: 45,333,899 (GRCm39) Y4F probably benign Het
Or7e174 T C 9: 20,012,580 (GRCm39) V175A probably benign Het
Osm A G 11: 4,189,839 (GRCm39) S208G probably benign Het
Pde6a A G 18: 61,390,104 (GRCm39) E486G probably benign Het
Pdzk1 T A 3: 96,758,910 (GRCm39) L105Q possibly damaging Het
Prkd1 C G 12: 50,435,155 (GRCm39) S524T probably benign Het
Prkd1 T A 12: 50,435,156 (GRCm39) S524C probably damaging Het
Rab4b T C 7: 26,874,148 (GRCm39) I90V Het
Rc3h1 T C 1: 160,795,222 (GRCm39) V1083A probably benign Het
Rfx7 C T 9: 72,524,316 (GRCm39) T502I probably benign Het
Rtn4rl2 T C 2: 84,702,558 (GRCm39) Y332C probably damaging Het
Senp2 A G 16: 21,846,789 (GRCm39) T265A probably benign Het
Slc38a3 T C 9: 107,532,345 (GRCm39) M396V probably benign Het
Sord G A 2: 122,094,607 (GRCm39) V332I probably benign Het
Sprr1b GTGGCAGGGCTCAGGAGCCTTGGGGTGGCAGGGCTCAGGAGCCTTGGGATGGCAGGGCTCAGGAGCCTTGGGGTGGCAGGGCTCAGGA GTGGCAGGGCTCAGGAGCCTTGGGGTGGCAGGGCTCAGGA 3: 92,344,653 (GRCm39) probably benign Het
Star G A 8: 26,299,577 (GRCm39) R53H probably benign Het
Stard4 T G 18: 33,336,749 (GRCm39) I189L possibly damaging Het
Stk38 G T 17: 29,219,094 (GRCm39) T7K probably benign Het
Stxbp5 T A 10: 9,713,859 (GRCm39) K227* probably null Het
Taf4b C T 18: 14,946,485 (GRCm39) P436L possibly damaging Het
Tgm3 T A 2: 129,889,702 (GRCm39) V632E probably damaging Het
Tmem158 A G 9: 123,089,309 (GRCm39) F101S probably damaging Het
Trmt10b T C 4: 45,301,281 (GRCm39) S77P probably benign Het
Ttn A T 2: 76,720,307 (GRCm39) L6973* probably null Het
Tubal3 T C 13: 3,983,293 (GRCm39) F358L probably damaging Het
Tut4 T C 4: 108,406,575 (GRCm39) V1381A possibly damaging Het
Vmn1r214 C T 13: 23,219,273 (GRCm39) L256F possibly damaging Het
Vmn2r86 A G 10: 130,282,396 (GRCm39) V740A probably benign Het
Yipf1 A T 4: 107,193,355 (GRCm39) E80D probably benign Het
Zdhhc2 G T 8: 40,898,846 (GRCm39) probably null Het
Zfp655 C T 5: 145,181,290 (GRCm39) H383Y probably damaging Het
Zfp981 C T 4: 146,622,410 (GRCm39) T445I 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
R1987:Pcsk6 UTSW 7 65,577,035 (GRCm39) missense possibly damaging 0.60
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
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'- TAGGATGGTAGTTACAGTCAGAGTG -3'
(R):5'- AACAATGTTTTGCCCCATTTCTGG -3'

Sequencing Primer
(F):5'- AGTTACAGTCAGAGTGATCCTGG -3'
(R):5'- TAACTCCATGGAAGCCATCTGTG -3'
Posted On 2021-04-30