Incidental Mutation 'R4827:Pcsk2'
ID 372481
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 042443-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.205) question?
Stock # R4827 (G1)
Quality Score 225
Status Validated
Chromosome 2
Chromosomal Location 143388076-143658205 bp(+) (GRCm39)
Type of Mutation nonsense
DNA Base Change (assembly) A to T at 143643099 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Lysine to Stop codon at position 459 (K459*)
Ref Sequence ENSEMBL: ENSMUSP00000028905 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000028905]
AlphaFold P21661
Predicted Effect probably null
Transcript: ENSMUST00000028905
AA Change: K459*
SMART Domains Protein: ENSMUSP00000028905
Gene: ENSMUSG00000027419
AA Change: K459*

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
Meta Mutation Damage Score 0.9754 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.5%
  • 10x: 96.8%
  • 20x: 94.0%
Validation Efficiency 96% (67/70)
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: 67 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adck1 A G 12: 88,413,489 (GRCm39) R274G probably benign Het
Agbl5 T G 5: 31,053,158 (GRCm39) S83R probably damaging Het
Ankib1 A G 5: 3,751,907 (GRCm39) I711T probably damaging Het
Arnt T A 3: 95,397,224 (GRCm39) probably null Het
Atad2 C G 15: 57,971,744 (GRCm39) V702L probably benign Het
B4galnt4 A G 7: 140,648,392 (GRCm39) E636G probably benign Het
Btbd2 A G 10: 80,482,223 (GRCm39) I244T probably damaging Het
Cenpc1 A T 5: 86,182,290 (GRCm39) N531K possibly damaging Het
Ces3b T A 8: 105,813,527 (GRCm39) M266K probably benign Het
Cfap54 A T 10: 92,737,937 (GRCm39) probably benign Het
Coq8a A G 1: 179,994,903 (GRCm39) V590A possibly damaging Het
Drc7 A G 8: 95,798,267 (GRCm39) Y504C probably damaging Het
Elovl4 T C 9: 83,688,091 (GRCm39) M1V probably null Het
Exd1 C T 2: 119,350,807 (GRCm39) A485T probably benign Het
Fads2 A G 19: 10,059,958 (GRCm39) F239L probably benign Het
Gcc2 A T 10: 58,121,953 (GRCm39) probably null Het
Ggact C T 14: 123,128,987 (GRCm39) R76H probably benign Het
Gm17535 T A 9: 3,035,786 (GRCm39) L218H probably benign Het
Gm3739 A T 14: 18,506,218 (GRCm39) F13I probably damaging Het
Gng2 T C 14: 19,925,898 (GRCm39) K65E possibly damaging Het
Gnmt A G 17: 47,038,245 (GRCm39) Y94H possibly damaging Het
Gzme C A 14: 56,356,755 (GRCm39) R69M probably null Het
Hdc G A 2: 126,436,233 (GRCm39) P546L probably benign Het
Ibtk C A 9: 85,610,607 (GRCm39) V326F probably benign Het
Inpp5b G T 4: 124,637,643 (GRCm39) probably benign Het
Kcnh7 A T 2: 62,546,564 (GRCm39) C1006S probably benign Het
Kcnk18 A T 19: 59,208,362 (GRCm39) N66I probably damaging Het
Lpar6 T A 14: 73,476,190 (GRCm39) N50K probably damaging Het
Lrba G T 3: 86,267,457 (GRCm39) D1716Y possibly damaging Het
Ltf T A 9: 110,856,445 (GRCm39) probably benign Het
Map3k6 A G 4: 132,976,160 (GRCm39) T794A possibly damaging Het
Mcm8 A G 2: 132,665,174 (GRCm39) T217A probably damaging Het
Meaf6 A G 4: 124,996,713 (GRCm39) E141G probably damaging Het
Mmp13 A G 9: 7,278,880 (GRCm39) T324A possibly damaging Het
Mplkipl1 C T 19: 61,164,364 (GRCm39) G24R unknown Het
Msl2 T G 9: 100,979,350 (GRCm39) F575V probably benign Het
Ncoa4-ps C T 12: 119,225,529 (GRCm39) noncoding transcript Het
Nlrp2 A T 7: 5,331,950 (GRCm39) W149R possibly damaging Het
Ntng1 C A 3: 110,042,727 (GRCm39) C33F probably damaging Het
Nxn A G 11: 76,152,418 (GRCm39) Y359H probably benign Het
Olfml2a A C 2: 38,850,033 (GRCm39) D583A probably damaging Het
Or12j5 A C 7: 140,083,583 (GRCm39) L263R probably damaging Het
Or1e32 A T 11: 73,705,547 (GRCm39) Y120* probably null Het
Or2t48 A G 11: 58,420,422 (GRCm39) I130T probably damaging Het
Or4b1b A T 2: 90,112,547 (GRCm39) I124N probably damaging Het
Or51ac3 A T 7: 103,213,752 (GRCm39) S245T probably damaging Het
Pcdha4 T C 18: 37,086,251 (GRCm39) S145P probably damaging Het
Pirb C T 7: 3,720,602 (GRCm39) G299S probably benign Het
Plch2 A G 4: 155,075,570 (GRCm39) F653S probably damaging Het
Plpp3 T C 4: 105,088,167 (GRCm39) I296T probably benign Het
Polr2b A G 5: 77,490,398 (GRCm39) E846G probably benign Het
Ptpro A T 6: 137,419,708 (GRCm39) N157Y probably damaging Het
Ralgapa1 A G 12: 55,723,222 (GRCm39) L1815P probably damaging Het
Sap18 A G 14: 58,036,020 (GRCm39) N69D probably damaging Het
Sncg C A 14: 34,095,284 (GRCm39) V74F probably damaging Het
Spata31e2 T C 1: 26,724,923 (GRCm39) K86E possibly damaging Het
Spmip4 A C 6: 50,572,836 (GRCm39) S26A possibly damaging Het
Tmem186 A T 16: 8,453,681 (GRCm39) Y193* probably null Het
Trrap A G 5: 144,737,758 (GRCm39) S1045G probably benign Het
Tti2 T G 8: 31,640,998 (GRCm39) S41A probably benign Het
Unc13c T C 9: 73,838,568 (GRCm39) E761G probably damaging Het
Vamp2 T A 11: 68,980,637 (GRCm39) D68E probably benign Het
Vmn1r200 A T 13: 22,579,265 (GRCm39) M14L probably benign Het
Vps35 T A 8: 86,000,186 (GRCm39) D480V possibly damaging Het
Zfp462 T C 4: 55,012,213 (GRCm39) L1393P probably damaging Het
Zfp512 G A 5: 31,630,158 (GRCm39) M274I probably benign Het
Znfx1 C G 2: 166,886,151 (GRCm39) G803A 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
R4615:Pcsk2 UTSW 2 143,637,889 (GRCm39) missense probably damaging 1.00
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
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'- TAACCAGCCTGGATCTGACC -3'
(R):5'- ACATCTGTGTTCTGGGTCATGC -3'

Sequencing Primer
(F):5'- TCTGACCTGGAGAGACATGC -3'
(R):5'- ACAGCTGTGCATCTCTATAGC -3'
Posted On 2016-03-01