Incidental Mutation 'R5249:Pcsk9'
ID 398755
Institutional Source Beutler Lab
Gene Symbol Pcsk9
Ensembl Gene ENSMUSG00000044254
Gene Name proprotein convertase subtilisin/kexin type 9
Synonyms Narc1
MMRRC Submission 042820-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R5249 (G1)
Quality Score 225
Status Validated
Chromosome 4
Chromosomal Location 106299531-106321522 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 106320950 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Aspartic acid to Glycine at position 53 (D53G)
Ref Sequence ENSEMBL: ENSMUSP00000055757 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000049507]
AlphaFold Q80W65
Predicted Effect probably benign
Transcript: ENSMUST00000049507
AA Change: D53G

PolyPhen 2 Score 0.009 (Sensitivity: 0.96; Specificity: 0.77)
SMART Domains Protein: ENSMUSP00000055757
Gene: ENSMUSG00000044254
AA Change: D53G

DomainStartEndE-ValueType
low complexity region 12 27 N/A INTRINSIC
Pfam:Peptidase_S8 180 438 3.1e-34 PFAM
low complexity region 471 481 N/A INTRINSIC
low complexity region 490 500 N/A INTRINSIC
Meta Mutation Damage Score 0.1376 question?
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.6%
  • 10x: 97.1%
  • 20x: 94.8%
Validation Efficiency 98% (93/95)
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 autocatalytic processing event with its prosegment in the ER and is constitutively secreted as an inactive protease into the extracellular matrix and trans-Golgi network. It is expressed in liver, intestine and kidney tissues and escorts specific receptors for lysosomal degradation. It plays a role in cholesterol and fatty acid metabolism. Mutations in this gene have been associated with autosomal dominant familial hypercholesterolemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]
PHENOTYPE: Homozygous null mice exhibit increased clearance of circulating cholesterol and decreased plasma cholesterol levels. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 89 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
A4gnt A G 9: 99,502,284 (GRCm39) H148R probably damaging Het
Acrbp A G 6: 125,037,885 (GRCm39) D394G probably damaging Het
Adam18 T C 8: 25,115,868 (GRCm39) T609A probably benign Het
Adam25 T A 8: 41,208,991 (GRCm39) N752K probably benign Het
Ano6 A C 15: 95,811,469 (GRCm39) S176R probably benign Het
Ano7 T C 1: 93,302,918 (GRCm39) S19P probably benign Het
Ap1b1 A G 11: 4,976,364 (GRCm39) E437G probably damaging Het
Arfgap2 T A 2: 91,095,982 (GRCm39) C46* probably null Het
Arhgef26 T A 3: 62,247,981 (GRCm39) L355Q probably damaging Het
B4galnt4 C T 7: 140,644,983 (GRCm39) T219I probably damaging Het
Bap1 C T 14: 30,979,243 (GRCm39) probably benign Het
Catip T G 1: 74,401,954 (GRCm39) L43R probably damaging Het
Ccdc177 G A 12: 80,805,282 (GRCm39) R331C unknown Het
Cep85l T C 10: 53,195,690 (GRCm39) probably null Het
Cfap206 T A 4: 34,714,502 (GRCm39) Q398L probably benign Het
Clec18a A G 8: 111,800,368 (GRCm39) C352R probably damaging Het
Clic6 A T 16: 92,336,339 (GRCm39) Y549F probably damaging Het
Cpne9 C T 6: 113,270,034 (GRCm39) probably benign Het
Cyb5r3 A C 15: 83,042,836 (GRCm39) probably benign Het
Dnah6 C T 6: 73,090,471 (GRCm39) R2293K probably damaging Het
Dnmbp C A 19: 43,890,879 (GRCm39) R296L probably damaging Het
Dtwd1 C A 2: 125,996,694 (GRCm39) Q60K probably benign Het
Esyt1 C A 10: 128,352,443 (GRCm39) V723L probably benign Het
Fbxo42 T C 4: 140,926,335 (GRCm39) L339P probably damaging Het
Furin A T 7: 80,043,169 (GRCm39) N347K probably damaging Het
Fzd7 T C 1: 59,522,522 (GRCm39) M135T probably damaging Het
Garin1b A G 6: 29,323,896 (GRCm39) D207G probably damaging Het
Hlf A G 11: 90,278,632 (GRCm39) M144T probably benign Het
Hyal5 C T 6: 24,876,648 (GRCm39) Q174* probably null Het
Kcnb1 T A 2: 166,947,103 (GRCm39) M582L possibly damaging Het
Kdm5d T C Y: 916,692 (GRCm39) Y391H probably damaging Het
Khdc4 T A 3: 88,604,032 (GRCm39) I283N probably damaging Het
Kif21b C T 1: 136,096,966 (GRCm39) T1297M probably damaging Het
Krt8 T G 15: 101,906,875 (GRCm39) N317T possibly damaging Het
Lctl G T 9: 64,045,196 (GRCm39) V372L probably benign Het
Lig1 C T 7: 13,042,432 (GRCm39) H822Y possibly damaging Het
Lrrc4b A G 7: 44,111,988 (GRCm39) D620G possibly damaging Het
Mboat4 C T 8: 34,582,275 (GRCm39) H10Y probably benign Het
Med1 A T 11: 98,048,066 (GRCm39) M910K probably benign Het
Mia2 A T 12: 59,154,911 (GRCm39) D209V probably damaging Het
Mpp4 C T 1: 59,184,017 (GRCm39) probably benign Het
Mrgprb1 A T 7: 48,097,225 (GRCm39) V229E possibly damaging Het
Mtor T A 4: 148,548,189 (GRCm39) C485S probably damaging Het
Mx1 T C 16: 97,258,628 (GRCm39) D23G probably damaging Het
Myrfl T C 10: 116,619,138 (GRCm39) D740G probably benign Het
Myt1l G A 12: 29,882,331 (GRCm39) G509R unknown Het
Nav2 G A 7: 49,185,661 (GRCm39) V874I probably damaging Het
Ntrk3 A T 7: 78,110,914 (GRCm39) N262K possibly damaging Het
Opa1 A T 16: 29,437,077 (GRCm39) D699V probably damaging Het
Or10u4 C T 10: 129,802,078 (GRCm39) A164T probably benign Het
Or8b51 A G 9: 38,569,374 (GRCm39) C105R possibly damaging Het
Otud7a A G 7: 63,407,181 (GRCm39) N495D possibly damaging Het
Pdcd5 A G 7: 35,346,421 (GRCm39) probably benign Het
Phf21a C T 2: 92,058,822 (GRCm39) P28L probably damaging Het
Pitpnm1 T A 19: 4,158,130 (GRCm39) D573E probably damaging Het
Ppp1r35 C T 5: 137,777,406 (GRCm39) probably benign Het
Ptprq T C 10: 107,535,496 (GRCm39) Q423R probably damaging Het
Pum1 A T 4: 130,490,125 (GRCm39) Y699F probably benign Het
Rabgef1 A G 5: 130,241,841 (GRCm39) D415G probably benign Het
Rapgef6 A G 11: 54,413,943 (GRCm39) E23G probably benign Het
Rpia G T 6: 70,760,563 (GRCm39) C121* probably null Het
Sanbr A G 11: 23,525,483 (GRCm39) *719Q probably null Het
Serpinb13 T A 1: 106,926,427 (GRCm39) W201R probably damaging Het
Sh3bp4 T C 1: 89,065,456 (GRCm39) C17R probably damaging Het
Sh3d21 A G 4: 126,055,858 (GRCm39) probably benign Het
Slamf6 A C 1: 171,764,249 (GRCm39) N214T probably damaging Het
Slc7a2 T C 8: 41,361,130 (GRCm39) Y365H possibly damaging Het
Sox18 T C 2: 181,312,971 (GRCm39) probably null Het
Spink7 A T 18: 62,725,507 (GRCm39) F79I possibly damaging Het
Srpk3 C T X: 72,818,555 (GRCm39) R82* probably null Het
Sspo A T 6: 48,470,244 (GRCm39) H4561L probably damaging Het
Tcaf1 T C 6: 42,653,793 (GRCm39) K700R probably benign Het
Tcf25 G T 8: 124,115,372 (GRCm39) R203L probably damaging Het
Tcp11 T C 17: 28,290,757 (GRCm39) I201V possibly damaging Het
Tex2 T C 11: 106,437,615 (GRCm39) D685G unknown Het
Themis G T 10: 28,637,195 (GRCm39) E100* probably null Het
Tmem52b G A 6: 129,491,221 (GRCm39) probably null Het
Tnr C T 1: 159,512,226 (GRCm39) probably benign Het
Tox3 T C 8: 90,975,444 (GRCm39) I396V probably benign Het
Tpm2 T A 4: 43,514,828 (GRCm39) E269V probably benign Het
Tulp1 C T 17: 28,581,651 (GRCm39) probably benign Het
Tymp GC GCC 15: 89,258,567 (GRCm39) probably null Het
Ube2j2 A C 4: 156,033,515 (GRCm39) K30Q possibly damaging Het
Usp19 T A 9: 108,369,807 (GRCm39) M1K probably null Het
Vmn2r52 C A 7: 9,910,197 (GRCm39) R6L probably benign Het
Zbed4 G A 15: 88,665,290 (GRCm39) V453M probably benign Het
Zfp319 T C 8: 96,055,099 (GRCm39) E368G probably benign Het
Zfp366 A C 13: 99,366,117 (GRCm39) E426A probably damaging Het
Zfp687 A T 3: 94,916,777 (GRCm39) I783N probably damaging Het
Other mutations in Pcsk9
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02140:Pcsk9 APN 4 106,311,843 (GRCm39) missense probably benign 0.00
IGL02709:Pcsk9 APN 4 106,304,886 (GRCm39) splice site probably benign
IGL02804:Pcsk9 APN 4 106,314,161 (GRCm39) missense probably damaging 1.00
IGL02850:Pcsk9 APN 4 106,316,062 (GRCm39) missense probably damaging 1.00
IGL03009:Pcsk9 APN 4 106,311,542 (GRCm39) missense probably damaging 1.00
IGL03294:Pcsk9 APN 4 106,303,967 (GRCm39) missense probably benign
R0271:Pcsk9 UTSW 4 106,306,246 (GRCm39) splice site probably benign
R0321:Pcsk9 UTSW 4 106,301,891 (GRCm39) missense probably benign
R0413:Pcsk9 UTSW 4 106,311,538 (GRCm39) missense probably damaging 1.00
R0426:Pcsk9 UTSW 4 106,307,274 (GRCm39) missense possibly damaging 0.77
R0783:Pcsk9 UTSW 4 106,307,314 (GRCm39) missense probably benign 0.00
R2136:Pcsk9 UTSW 4 106,303,967 (GRCm39) missense probably benign 0.00
R4056:Pcsk9 UTSW 4 106,301,899 (GRCm39) missense probably benign 0.02
R4438:Pcsk9 UTSW 4 106,316,156 (GRCm39) missense probably benign 0.00
R4683:Pcsk9 UTSW 4 106,316,092 (GRCm39) missense possibly damaging 0.59
R4739:Pcsk9 UTSW 4 106,304,353 (GRCm39) missense probably damaging 1.00
R4801:Pcsk9 UTSW 4 106,304,766 (GRCm39) missense probably benign 0.43
R4802:Pcsk9 UTSW 4 106,304,766 (GRCm39) missense probably benign 0.43
R5307:Pcsk9 UTSW 4 106,304,371 (GRCm39) missense probably damaging 1.00
R5320:Pcsk9 UTSW 4 106,320,988 (GRCm39) missense probably benign 0.00
R5653:Pcsk9 UTSW 4 106,316,113 (GRCm39) missense probably damaging 1.00
R5827:Pcsk9 UTSW 4 106,306,144 (GRCm39) missense probably damaging 1.00
R6010:Pcsk9 UTSW 4 106,311,469 (GRCm39) missense possibly damaging 0.92
R6019:Pcsk9 UTSW 4 106,314,073 (GRCm39) missense probably benign 0.02
R6393:Pcsk9 UTSW 4 106,304,793 (GRCm39) missense probably benign 0.00
R7472:Pcsk9 UTSW 4 106,316,094 (GRCm39) missense probably benign 0.08
R7614:Pcsk9 UTSW 4 106,304,763 (GRCm39) missense probably benign 0.34
R7807:Pcsk9 UTSW 4 106,321,092 (GRCm39) missense possibly damaging 0.73
R8036:Pcsk9 UTSW 4 106,311,536 (GRCm39) missense possibly damaging 0.88
R8735:Pcsk9 UTSW 4 106,311,808 (GRCm39) missense probably damaging 1.00
R9258:Pcsk9 UTSW 4 106,316,047 (GRCm39) missense possibly damaging 0.63
R9404:Pcsk9 UTSW 4 106,311,723 (GRCm39) missense probably damaging 1.00
R9684:Pcsk9 UTSW 4 106,307,386 (GRCm39) missense probably benign 0.29
Z1176:Pcsk9 UTSW 4 106,316,138 (GRCm39) missense probably damaging 0.96
Predicted Primers PCR Primer
(F):5'- GAGCACTAAGTCTTGCCCTC -3'
(R):5'- TTTCTGAGGCTAGAGGACTGAGC -3'

Sequencing Primer
(F):5'- ACTAAGTCTTGCCCTCGCCTC -3'
(R):5'- AGTCCTTGGCTCCCCAGAG -3'
Posted On 2016-07-06