Incidental Mutation 'R4615:Pcsk2'
ID 345001
Institutional Source Beutler Lab
Gene Symbol Pcsk2
Ensembl Gene ENSMUSG00000027419
Gene Name proprotein convertase subtilisin/kexin type 2
Synonyms Nec-2, PC2, Phpp-2, SPC2, Nec2, 6330411F23Rik, prohormone convertase 2
MMRRC Submission 041826-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.205) question?
Stock # R4615 (G1)
Quality Score 225
Status Not validated
Chromosome 2
Chromosomal Location 143388076-143658205 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to T at 143637889 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Cysteine to Phenylalanine at position 375 (C375F)
Ref Sequence ENSEMBL: ENSMUSP00000028905 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000028905]
AlphaFold P21661
Predicted Effect probably damaging
Transcript: ENSMUST00000028905
AA Change: C375F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000028905
Gene: ENSMUSG00000027419
AA Change: C375F

DomainStartEndE-ValueType
signal peptide 1 24 N/A INTRINSIC
Pfam:S8_pro-domain 32 108 2.9e-21 PFAM
Pfam:Peptidase_S8 157 444 5e-44 PFAM
Pfam:P_proprotein 503 590 4.3e-28 PFAM
low complexity region 617 630 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000156362
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.2%
  • 20x: 95.1%
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 protein undergoes an initial autocatalytic processing event and interacts with a neuroendocrine secretory protein in the ER, exits the ER and sorts to secretory granules, where it is cleaved and catalytically activated during intracellular transport. The encoded protease is packaged into and activated in dense core secretory granules and expressed in the neuroendocrine system and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It functions in the proteolytic activation of polypeptide hormones and neuropeptides precursors. Single nucleotide polymorphisms in this gene may increase susceptibility to myocardial infarction and type 2 diabetes. This gene may also play a role in tumor development and progression. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2014]
PHENOTYPE: Mice homozygous for disruptions of this gene display abnormalities in the maturation of peptide hormones leading to reduced female fertility, increased blood pressure on a high salt diet, and abnormal glucose metabolism. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 63 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca12 T C 1: 71,369,493 (GRCm39) I363V probably benign Het
Abcc9 C G 6: 142,634,833 (GRCm39) A144P possibly damaging Het
Adgrv1 C T 13: 81,642,688 (GRCm39) probably null Het
Adprhl1 A G 8: 13,292,250 (GRCm39) probably null Het
Angptl3 A T 4: 98,919,598 (GRCm39) E119D probably benign Het
Atp8b1 T C 18: 64,686,170 (GRCm39) N671S probably null Het
C9 A G 15: 6,520,944 (GRCm39) D51G probably damaging Het
Carmil2 A G 8: 106,421,706 (GRCm39) D1019G possibly damaging Het
Cdh8 A T 8: 100,006,254 (GRCm39) I111K probably damaging Het
Cep120 T C 18: 53,847,913 (GRCm39) R649G probably damaging Het
Clptm1l A T 13: 73,755,857 (GRCm39) K158* probably null Het
Cmtm1 CGGCACGTACTGAAGGTCGCTGACTGGATGGTGTGGCACGTACTGAAGGTCGCTGACTGGATGGTGTGGCACGTACTGAAGGTCGCTGACTGGATGGT CGGCACGTACTGAAGGTCGCTGACTGGATGGTGTGGCACGTACTGAAGGTCGCTGACTGGATGGT 8: 105,036,102 (GRCm39) probably benign Het
Cnga1 A C 5: 72,762,117 (GRCm39) L466V probably damaging Het
Cpsf1 T C 15: 76,481,137 (GRCm39) T1240A possibly damaging Het
Cubn A G 2: 13,433,560 (GRCm39) S1117P probably damaging Het
Cyp2b9 T A 7: 25,900,550 (GRCm39) L396Q probably damaging Het
Cyp8b1 A T 9: 121,745,164 (GRCm39) L56* probably null Het
Dcbld2 A G 16: 58,276,457 (GRCm39) T458A probably benign Het
Dio2 G T 12: 90,696,595 (GRCm39) P131Q probably damaging Het
Dlg5 T C 14: 24,208,236 (GRCm39) Y990C probably damaging Het
Dsc3 T C 18: 20,104,545 (GRCm39) D594G possibly damaging Het
Dsp A G 13: 38,375,608 (GRCm39) E1131G probably damaging Het
Fdx1 A T 9: 51,859,945 (GRCm39) Y21* probably null Het
Gal3st4 A G 5: 138,264,525 (GRCm39) V158A probably damaging Het
Gm10269 T A 18: 20,815,820 (GRCm39) E67D probably benign Het
Gm5773 A G 3: 93,681,339 (GRCm39) H337R probably benign Het
Gng2 C T 14: 19,941,395 (GRCm39) V16I possibly damaging Het
Gpr20 T C 15: 73,567,585 (GRCm39) N268S probably benign Het
Ighv1-82 T C 12: 115,916,280 (GRCm39) T77A probably benign Het
Itprid2 A G 2: 79,492,726 (GRCm39) E1091G probably damaging Het
Lama2 C A 10: 26,857,520 (GRCm39) V3110F probably damaging Het
Mplkipl1 C T 19: 61,164,364 (GRCm39) G24R unknown Het
Mtmr4 T C 11: 87,501,761 (GRCm39) L548S probably damaging Het
Ncapg A T 5: 45,844,741 (GRCm39) M579L probably benign Het
Oog3 A T 4: 143,884,899 (GRCm39) Y346N probably benign Het
Or10ak14 T C 4: 118,611,334 (GRCm39) T134A probably benign Het
Or14c39 T C 7: 86,343,936 (GRCm39) S91P probably damaging Het
Orm2 A G 4: 63,281,536 (GRCm39) D89G probably damaging Het
Pcdhb4 T A 18: 37,441,553 (GRCm39) S288T probably benign Het
Pdcd10 T C 3: 75,428,398 (GRCm39) I138M probably damaging Het
Pde8a T C 7: 80,970,485 (GRCm39) W536R probably damaging Het
Phkg2 C T 7: 127,176,792 (GRCm39) R61W probably damaging Het
Plcl1 A T 1: 55,737,293 (GRCm39) N878I probably benign Het
Prkdc A T 16: 15,480,938 (GRCm39) D353V probably damaging Het
Psme4 C T 11: 30,784,287 (GRCm39) T954I probably benign Het
Ran A G 5: 129,099,162 (GRCm39) I115V probably benign Het
Reln A G 5: 22,177,870 (GRCm39) L1867P possibly damaging Het
S100a1 A G 3: 90,418,562 (GRCm39) V84A possibly damaging Het
Sall2 G A 14: 52,550,207 (GRCm39) P994L probably benign Het
Shtn1 A T 19: 59,010,648 (GRCm39) I273N probably benign Het
Slc17a9 T C 2: 180,373,699 (GRCm39) I40T probably benign Het
Slc29a2 T C 19: 5,079,292 (GRCm39) V305A probably damaging Het
Taar2 T A 10: 23,817,263 (GRCm39) F268I probably benign Het
Taf3 G A 2: 9,956,901 (GRCm39) T422I probably damaging Het
Tgs1 T C 4: 3,585,156 (GRCm39) F99L probably damaging Het
Tox2 T C 2: 163,162,567 (GRCm39) L479P probably damaging Het
Ttn A G 2: 76,597,219 (GRCm39) I19898T probably damaging Het
Ulk1 G T 5: 110,936,912 (GRCm39) T3N probably damaging Het
Vars1 A T 17: 35,232,857 (GRCm39) K900N probably damaging Het
Vmn2r15 A G 5: 109,441,348 (GRCm39) V170A possibly damaging Het
Vmn2r53 A T 7: 12,316,229 (GRCm39) L530Q probably damaging Het
Zar1l G T 5: 150,441,528 (GRCm39) Q33K probably benign Het
Zdhhc16 T C 19: 41,932,122 (GRCm39) V358A possibly damaging Het
Other mutations in Pcsk2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00503:Pcsk2 APN 2 143,635,159 (GRCm39) missense probably damaging 1.00
IGL01609:Pcsk2 APN 2 143,643,078 (GRCm39) missense possibly damaging 0.88
IGL01690:Pcsk2 APN 2 143,529,490 (GRCm39) missense probably benign
IGL01833:Pcsk2 APN 2 143,529,500 (GRCm39) missense possibly damaging 0.62
IGL01962:Pcsk2 APN 2 143,655,552 (GRCm39) nonsense probably null
IGL02219:Pcsk2 APN 2 143,635,045 (GRCm39) missense probably damaging 1.00
IGL02572:Pcsk2 APN 2 143,532,262 (GRCm39) missense probably damaging 1.00
IGL02752:Pcsk2 APN 2 143,615,865 (GRCm39) missense probably benign 0.09
P0035:Pcsk2 UTSW 2 143,637,871 (GRCm39) missense probably damaging 1.00
R0092:Pcsk2 UTSW 2 143,642,944 (GRCm39) missense probably damaging 1.00
R1424:Pcsk2 UTSW 2 143,415,348 (GRCm39) splice site probably benign
R1470:Pcsk2 UTSW 2 143,388,438 (GRCm39) nonsense probably null
R1470:Pcsk2 UTSW 2 143,388,438 (GRCm39) nonsense probably null
R1832:Pcsk2 UTSW 2 143,635,189 (GRCm39) missense probably damaging 1.00
R1993:Pcsk2 UTSW 2 143,529,539 (GRCm39) missense probably benign 0.00
R4783:Pcsk2 UTSW 2 143,529,599 (GRCm39) critical splice donor site probably null
R4796:Pcsk2 UTSW 2 143,655,345 (GRCm39) missense probably benign 0.16
R4827:Pcsk2 UTSW 2 143,643,099 (GRCm39) nonsense probably null
R5357:Pcsk2 UTSW 2 143,415,384 (GRCm39) missense probably benign 0.00
R5413:Pcsk2 UTSW 2 143,538,620 (GRCm39) splice site probably null
R5440:Pcsk2 UTSW 2 143,388,463 (GRCm39) missense probably benign 0.22
R5546:Pcsk2 UTSW 2 143,388,480 (GRCm39) missense probably benign 0.00
R5605:Pcsk2 UTSW 2 143,591,165 (GRCm39) intron probably benign
R5821:Pcsk2 UTSW 2 143,591,035 (GRCm39) splice site probably null
R5905:Pcsk2 UTSW 2 143,591,060 (GRCm39) missense probably damaging 0.98
R6120:Pcsk2 UTSW 2 143,643,031 (GRCm39) missense probably damaging 1.00
R6135:Pcsk2 UTSW 2 143,415,460 (GRCm39) missense possibly damaging 0.63
R6657:Pcsk2 UTSW 2 143,532,286 (GRCm39) missense probably damaging 1.00
R6925:Pcsk2 UTSW 2 143,655,667 (GRCm39) missense probably damaging 1.00
R7223:Pcsk2 UTSW 2 143,532,253 (GRCm39) missense possibly damaging 0.95
R7289:Pcsk2 UTSW 2 143,532,343 (GRCm39) missense probably damaging 1.00
R8043:Pcsk2 UTSW 2 143,655,450 (GRCm39) nonsense probably null
R8803:Pcsk2 UTSW 2 143,637,870 (GRCm39) missense probably damaging 0.99
R8819:Pcsk2 UTSW 2 143,642,990 (GRCm39) missense probably damaging 0.99
R8820:Pcsk2 UTSW 2 143,642,990 (GRCm39) missense probably damaging 0.99
R9131:Pcsk2 UTSW 2 143,655,583 (GRCm39) missense possibly damaging 0.56
R9643:Pcsk2 UTSW 2 143,655,501 (GRCm39) missense probably damaging 1.00
R9753:Pcsk2 UTSW 2 143,635,150 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- TCCAAAAGCCAAGCTCAGTG -3'
(R):5'- GACTTTCTAGGTGCTCATATCCATG -3'

Sequencing Primer
(F):5'- GTGCAACCCAAATCACCATTG -3'
(R):5'- TCTCTGTGGACACCTGGCATG -3'
Posted On 2015-09-25