Incidental Mutation 'R5440:Pcsk2'
ID 428571
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 043005-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.205) question?
Stock # R5440 (G1)
Quality Score 225
Status Not validated
Chromosome 2
Chromosomal Location 143388076-143658205 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 143388463 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Glutamic Acid at position 18 (V18E)
Ref Sequence ENSEMBL: ENSMUSP00000028905 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000028905]
AlphaFold P21661
Predicted Effect probably benign
Transcript: ENSMUST00000028905
AA Change: V18E

PolyPhen 2 Score 0.221 (Sensitivity: 0.91; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000028905
Gene: ENSMUSG00000027419
AA Change: V18E

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: ENSMUST00000124751
Predicted Effect noncoding transcript
Transcript: ENSMUST00000126735
Predicted Effect noncoding transcript
Transcript: ENSMUST00000156780
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.3%
  • 20x: 95.3%
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: 42 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Apc G T 18: 34,354,213 (GRCm39) probably benign Het
Apol11b T A 15: 77,519,793 (GRCm39) K96* probably null Het
Arhgap35 C T 7: 16,296,849 (GRCm39) G739S probably damaging Het
Atp6v0a4 A C 6: 38,069,752 (GRCm39) F47V probably damaging Het
Bcl9 G A 3: 97,117,881 (GRCm39) P271L probably benign Het
Cd109 T C 9: 78,587,446 (GRCm39) probably null Het
Col12a1 T A 9: 79,521,645 (GRCm39) I2771F probably benign Het
Col6a1 A G 10: 76,559,288 (GRCm39) V116A probably damaging Het
Cpsf2 C G 12: 101,963,138 (GRCm39) L401V probably benign Het
Cwf19l2 G A 9: 3,475,549 (GRCm39) E829K probably damaging Het
D7Ertd443e G A 7: 133,951,004 (GRCm39) T223I probably damaging Het
Dtx4 G A 19: 12,469,681 (GRCm39) R149C probably damaging Het
Fam186b C T 15: 99,171,734 (GRCm39) A838T possibly damaging Het
Fzd4 G T 7: 89,057,326 (GRCm39) E458* probably null Het
Gm17669 C T 18: 67,695,526 (GRCm39) P24S possibly damaging Het
Grin2b C T 6: 135,713,304 (GRCm39) G859D probably damaging Het
Gucy2e T C 11: 69,114,472 (GRCm39) Y1019C probably damaging Het
Gzme T A 14: 56,355,910 (GRCm39) N134I possibly damaging Het
Havcr1 A T 11: 46,643,197 (GRCm39) Y39F probably damaging Het
Hint3 A T 10: 30,494,347 (GRCm39) M1K probably null Het
Hspa4l A G 3: 40,736,008 (GRCm39) K543R probably damaging Het
Ifna9 A G 4: 88,510,048 (GRCm39) probably null Het
Itgb4 C T 11: 115,874,983 (GRCm39) R447W probably benign Het
Lipo2 A G 19: 33,698,258 (GRCm39) I373T probably benign Het
Myo5c T A 9: 75,165,407 (GRCm39) I405N possibly damaging Het
Or10a49 T C 7: 108,467,833 (GRCm39) H176R probably damaging Het
P2rx1 A G 11: 72,899,329 (GRCm39) M108V probably benign Het
Pigr A T 1: 130,777,359 (GRCm39) probably null Het
Pkp1 A T 1: 135,810,230 (GRCm39) C447S probably benign Het
Prom1 T A 5: 44,215,988 (GRCm39) I96F probably benign Het
Prpf4b T C 13: 35,068,076 (GRCm39) probably benign Het
Ropn1 C A 16: 34,491,542 (GRCm39) D102E probably benign Het
Slc35e2 C T 4: 155,694,483 (GRCm39) P10L probably benign Het
Sphk1 T G 11: 116,425,714 (GRCm39) V17G possibly damaging Het
Syngr1 A G 15: 79,982,219 (GRCm39) N2S probably benign Het
Syt9 T G 7: 107,101,330 (GRCm39) S359A possibly damaging Het
Terb1 T C 8: 105,215,131 (GRCm39) I282V probably damaging Het
Ttn T A 2: 76,585,168 (GRCm39) I22042F probably damaging Het
Ttn A T 2: 76,739,600 (GRCm39) D3646E probably benign Het
Ube2d1 A G 10: 71,091,682 (GRCm39) W141R probably damaging Het
Vmn2r41 T A 7: 8,141,362 (GRCm39) I701F probably damaging Het
Zfp770 T C 2: 114,026,596 (GRCm39) D491G probably benign 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
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
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'- AGATTTGCTGTTTGCCAAGCTTC -3'
(R):5'- TGTCCCTCCTCTGGAAACAAC -3'

Sequencing Primer
(F):5'- GCTGTTTGCCAAGCTTCTTTTCTG -3'
(R):5'- CTCCTCTGGAAACAACATGTGAAATG -3'
Posted On 2016-09-01