Incidental Mutation 'R0413:Pcsk9'
ID 36773
Institutional Source Beutler Lab
Gene Symbol Pcsk9
Ensembl Gene ENSMUSG00000044254
Gene Name proprotein convertase subtilisin/kexin type 9
Synonyms Narc1
MMRRC Submission 038615-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R0413 (G1)
Quality Score 194
Status Validated
Chromosome 4
Chromosomal Location 106299531-106321522 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to T at 106311538 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Asparagine at position 231 (T231N)
Ref Sequence ENSEMBL: ENSMUSP00000055757 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000049507]
AlphaFold Q80W65
Predicted Effect probably damaging
Transcript: ENSMUST00000049507
AA Change: T231N

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000055757
Gene: ENSMUSG00000044254
AA Change: T231N

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 0.8967 question?
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.6%
  • 10x: 97.0%
  • 20x: 94.9%
Validation Efficiency 99% (99/100)
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: 97 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcb11 A G 2: 69,158,355 (GRCm39) probably benign Het
Adh1 C T 3: 137,986,193 (GRCm39) T60I probably benign Het
Agtpbp1 T A 13: 59,661,966 (GRCm39) I282F probably damaging Het
Arih2 G T 9: 108,493,916 (GRCm39) Q166K probably damaging Het
Cacna1s A G 1: 136,025,947 (GRCm39) T1031A probably benign Het
Ccdc102a C A 8: 95,629,914 (GRCm39) E542D probably benign Het
Cdk1 T C 10: 69,180,929 (GRCm39) I94V probably benign Het
Cep290 C T 10: 100,359,176 (GRCm39) Q969* probably null Het
Cilp2 A G 8: 70,335,643 (GRCm39) S452P probably benign Het
Col12a1 T C 9: 79,606,642 (GRCm39) T594A probably damaging Het
Cpox A G 16: 58,491,232 (GRCm39) T148A possibly damaging Het
Csf3r A G 4: 125,933,460 (GRCm39) probably benign Het
Csmd1 A T 8: 16,760,530 (GRCm39) C202S probably damaging Het
Dlgap4 T C 2: 156,604,746 (GRCm39) S261P probably damaging Het
Dnah9 T A 11: 65,998,961 (GRCm39) Y1029F probably damaging Het
Dok5 T C 2: 170,671,880 (GRCm39) probably benign Het
Dusp11 A T 6: 85,929,352 (GRCm39) probably benign Het
Edar T C 10: 58,465,262 (GRCm39) N34D probably benign Het
Efcab7 C T 4: 99,766,943 (GRCm39) T56I probably damaging Het
Entpd1 G A 19: 40,699,729 (GRCm39) V47I probably benign Het
Ephx4 A G 5: 107,551,601 (GRCm39) N62S probably benign Het
Etaa1 A T 11: 17,896,350 (GRCm39) L589* probably null Het
Fam135b T A 15: 71,335,670 (GRCm39) N508I probably benign Het
Fam193a T C 5: 34,623,552 (GRCm39) V27A possibly damaging Het
Fmnl1 A G 11: 103,084,889 (GRCm39) probably benign Het
Fstl1 A C 16: 37,641,516 (GRCm39) probably null Het
Gbp4 G A 5: 105,268,972 (GRCm39) R394C possibly damaging Het
Gemin4 T C 11: 76,102,148 (GRCm39) Y871C probably benign Het
Get1 T G 16: 95,954,217 (GRCm39) S105R probably benign Het
Gm7247 T C 14: 51,760,929 (GRCm39) V166A probably benign Het
Gpcpd1 A T 2: 132,406,543 (GRCm39) probably benign Het
Gpnmb A G 6: 49,019,737 (GRCm39) D36G probably benign Het
Ido2 C T 8: 25,048,159 (GRCm39) probably null Het
Igfn1 G A 1: 135,895,334 (GRCm39) T1744I probably benign Het
Inf2 T G 12: 112,568,110 (GRCm39) F221V probably damaging Het
Itga10 T A 3: 96,556,375 (GRCm39) I170N probably damaging Het
Lrp6 A T 6: 134,484,587 (GRCm39) D345E probably damaging Het
Macf1 A T 4: 123,366,062 (GRCm39) S2900T probably benign Het
Med13 C A 11: 86,190,033 (GRCm39) probably benign Het
Morc3 T C 16: 93,667,362 (GRCm39) V507A probably damaging Het
Myadm AC ACC 7: 3,345,276 (GRCm39) probably null Het
Myl6 C T 10: 128,328,091 (GRCm39) probably benign Het
Mylk T C 16: 34,742,314 (GRCm39) V942A probably benign Het
Myorg G T 4: 41,498,585 (GRCm39) H348Q probably benign Het
Ncdn G T 4: 126,644,327 (GRCm39) T165K possibly damaging Het
Ncf1 T C 5: 134,251,656 (GRCm39) probably benign Het
Neb T C 2: 52,180,751 (GRCm39) probably benign Het
Nid1 T A 13: 13,656,681 (GRCm39) I604N probably benign Het
Nsrp1 T C 11: 76,936,997 (GRCm39) R400G probably benign Het
Nup43 T G 10: 7,546,791 (GRCm39) I137S probably benign Het
Nynrin A G 14: 56,109,648 (GRCm39) N1585S possibly damaging Het
Obscn T A 11: 58,893,823 (GRCm39) Y6748F probably benign Het
Omg A G 11: 79,393,661 (GRCm39) S66P possibly damaging Het
Or13a27 A T 7: 139,925,108 (GRCm39) S265T possibly damaging Het
Or2y1d T C 11: 49,322,212 (GRCm39) V303A possibly damaging Het
Or4c15 A G 2: 88,759,906 (GRCm39) V251A probably benign Het
Or51b6b A T 7: 103,309,957 (GRCm39) F167I possibly damaging Het
Or52z1 A G 7: 103,437,362 (GRCm39) Y41H probably damaging Het
Or5ak22 T C 2: 85,230,019 (GRCm39) N286S probably damaging Het
Or8g27 A G 9: 39,129,566 (GRCm39) I304M probably benign Het
Or8k24 G A 2: 86,216,058 (GRCm39) R235C probably benign Het
Ormdl1 C T 1: 53,347,978 (GRCm39) probably benign Het
Ovch2 T A 7: 107,381,243 (GRCm39) I552L probably benign Het
Pcare T G 17: 72,059,212 (GRCm39) D155A probably benign Het
Pgpep1 T C 8: 71,110,100 (GRCm39) N22S probably damaging Het
Plb1 T C 5: 32,512,706 (GRCm39) F1355L probably damaging Het
Plcg1 G T 2: 160,603,349 (GRCm39) L1173F probably damaging Het
Plch2 A T 4: 155,091,373 (GRCm39) probably null Het
Ppp1r3g T A 13: 36,153,331 (GRCm39) F250L probably damaging Het
Prkcg A G 7: 3,368,095 (GRCm39) I381V probably benign Het
Pum2 C T 12: 8,763,464 (GRCm39) A207V probably benign Het
Rabac1 T C 7: 24,669,607 (GRCm39) E166G probably damaging Het
Rad21l G A 2: 151,493,851 (GRCm39) S450L probably benign Het
Rangap1 ACACTCA ACA 15: 81,600,876 (GRCm39) probably null Het
Reg3b G T 6: 78,348,824 (GRCm39) C40F probably damaging Het
Rfx2 A G 17: 57,091,418 (GRCm39) probably benign Het
Rrp15 G A 1: 186,481,346 (GRCm39) probably benign Het
Schip1 G T 3: 68,401,946 (GRCm39) G36C probably damaging Het
Sec61a2 A T 2: 5,881,165 (GRCm39) probably benign Het
Sema5a A G 15: 32,669,590 (GRCm39) K705E probably damaging Het
Setx A G 2: 29,029,290 (GRCm39) Y186C probably damaging Het
Slc22a23 T C 13: 34,367,115 (GRCm39) E631G probably damaging Het
Slc5a5 T C 8: 71,344,319 (GRCm39) T134A possibly damaging Het
Stx7 T C 10: 24,057,492 (GRCm39) S173P probably damaging Het
Sybu T C 15: 44,536,668 (GRCm39) T353A probably damaging Het
Syde2 T A 3: 145,712,887 (GRCm39) N1008K probably damaging Het
Tiam1 T C 16: 89,606,253 (GRCm39) probably benign Het
Timm10b G A 7: 105,327,537 (GRCm39) E61K probably benign Het
Tm2d1 A G 4: 98,253,810 (GRCm39) I121T probably damaging Het
Trim75 T C 8: 65,435,892 (GRCm39) E186G probably benign Het
Tti1 T C 2: 157,837,396 (GRCm39) K895E probably benign Het
Vmn1r43 A G 6: 89,846,830 (GRCm39) S219P probably damaging Het
Vmn2r73 A T 7: 85,521,087 (GRCm39) S294T possibly damaging Het
Vmn2r94 A T 17: 18,464,080 (GRCm39) F737I probably damaging Het
Vsx2 A T 12: 84,616,777 (GRCm39) T21S probably benign Het
Zfp462 G T 4: 55,010,534 (GRCm39) R833S probably damaging Het
Zfpl1 G A 19: 6,132,482 (GRCm39) P143L 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
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
R5249:Pcsk9 UTSW 4 106,320,950 (GRCm39) missense probably benign 0.01
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'- AAACTGTGCGTGACAGAGACTGCC -3'
(R):5'- AACCCAGGAACTGTTCTCCTCACTC -3'

Sequencing Primer
(F):5'- TGCCTGACAGTGAGACCTTG -3'
(R):5'- GTATCTCTTAGATACCAGCATCCAGG -3'
Posted On 2013-05-09