Incidental Mutation 'R9526:Pcsk4'
ID 719251
Institutional Source Beutler Lab
Gene Symbol Pcsk4
Ensembl Gene ENSMUSG00000020131
Gene Name proprotein convertase subtilisin/kexin type 4
Synonyms PC4, SPC5
MMRRC Submission
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R9526 (G1)
Quality Score 225.009
Status Not validated
Chromosome 10
Chromosomal Location 80157117-80165332 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 80161800 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Aspartic acid to Glycine at position 164 (D164G)
Ref Sequence ENSEMBL: ENSMUSP00000020340 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000020340] [ENSMUST00000040081] [ENSMUST00000105354] [ENSMUST00000105355] [ENSMUST00000105357] [ENSMUST00000105358] [ENSMUST00000128653] [ENSMUST00000135071] [ENSMUST00000186864]
AlphaFold P29121
Predicted Effect probably damaging
Transcript: ENSMUST00000020340
AA Change: D164G

PolyPhen 2 Score 0.963 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000020340
Gene: ENSMUSG00000020131
AA Change: D164G

DomainStartEndE-ValueType
signal peptide 1 26 N/A INTRINSIC
Pfam:S8_pro-domain 34 110 1.2e-24 PFAM
Pfam:Peptidase_S8 146 429 3.1e-50 PFAM
Pfam:P_proprotein 488 574 5e-25 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000040081
SMART Domains Protein: ENSMUSP00000043722
Gene: ENSMUSG00000035504

DomainStartEndE-ValueType
Pfam:TB2_DP1_HVA22 50 118 8e-28 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000105354
SMART Domains Protein: ENSMUSP00000100991
Gene: ENSMUSG00000035504

DomainStartEndE-ValueType
Pfam:TB2_DP1_HVA22 50 144 5e-36 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000105355
SMART Domains Protein: ENSMUSP00000100992
Gene: ENSMUSG00000035504

DomainStartEndE-ValueType
Pfam:TB2_DP1_HVA22 50 144 3.4e-36 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000105357
SMART Domains Protein: ENSMUSP00000100994
Gene: ENSMUSG00000035504

DomainStartEndE-ValueType
low complexity region 22 61 N/A INTRINSIC
low complexity region 108 129 N/A INTRINSIC
low complexity region 297 319 N/A INTRINSIC
low complexity region 340 352 N/A INTRINSIC
low complexity region 411 428 N/A INTRINSIC
SCOP:d1gkub1 434 465 1e-3 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000105358
SMART Domains Protein: ENSMUSP00000100995
Gene: ENSMUSG00000035504

DomainStartEndE-ValueType
low complexity region 22 61 N/A INTRINSIC
low complexity region 108 129 N/A INTRINSIC
low complexity region 324 346 N/A INTRINSIC
low complexity region 367 379 N/A INTRINSIC
low complexity region 438 455 N/A INTRINSIC
SCOP:d1gkub1 461 492 8e-4 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000128653
AA Change: D164G

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000137809
Gene: ENSMUSG00000020131
AA Change: D164G

DomainStartEndE-ValueType
signal peptide 1 26 N/A INTRINSIC
SCOP:d1kn6a_ 31 102 8e-29 SMART
Pfam:Peptidase_S8 150 242 6.4e-18 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000135071
AA Change: D147G

PolyPhen 2 Score 0.867 (Sensitivity: 0.83; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000137719
Gene: ENSMUSG00000020131
AA Change: D147G

DomainStartEndE-ValueType
SCOP:d1kn6a_ 14 85 3e-27 SMART
Pfam:Peptidase_S8 133 187 1.7e-7 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000186864
SMART Domains Protein: ENSMUSP00000140840
Gene: ENSMUSG00000035504

DomainStartEndE-ValueType
Pfam:TB2_DP1_HVA22 50 144 5e-36 PFAM
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.6%
  • 20x: 98.8%
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 encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER and sorts to subcellular compartments where a second autocatalytic even takes place and the catalytic activity is acquired. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. The protease is expressed only in the testis, placenta, and ovary. It plays a critical role in fertilization, fetoplacental growth, and embryonic development and processes multiple prohormones including pro-pituitary adenylate cyclase-activating protein and pro-insulin-like growth factor II. [provided by RefSeq, Jan 2014]
PHENOTYPE: Inactivation of this locus results in significantly reduced male fertility, putatively due to impaired fertilization. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 103 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Actn1 A G 12: 80,230,393 (GRCm39) L287S probably damaging Het
Adgrf1 A T 17: 43,616,237 (GRCm39) Q292L possibly damaging Het
Arhgap32 A G 9: 32,172,026 (GRCm39) D1602G probably benign Het
Atrnl1 C T 19: 57,617,551 (GRCm39) P109S probably damaging Het
Camsap1 G A 2: 25,843,962 (GRCm39) H230Y probably benign Het
Capns1 C T 7: 29,891,612 (GRCm39) C144Y probably damaging Het
Ccdc17 G A 4: 116,455,994 (GRCm39) V341I possibly damaging Het
Cd36 T C 5: 18,002,033 (GRCm39) T323A probably damaging Het
Cdc14a CGCTGCTGCTGCTGCTGCTG CGCTGCTGCTGCTGCTG 3: 116,087,509 (GRCm39) probably benign Het
Ckap2l G A 2: 129,111,161 (GRCm39) Q679* probably null Het
Clec4g T A 8: 3,768,565 (GRCm39) N93I probably benign Het
Cntnap2 T A 6: 45,992,165 (GRCm39) L364Q probably damaging Het
Cul9 A G 17: 46,841,026 (GRCm39) M748T probably benign Het
Dnah11 A T 12: 118,150,711 (GRCm39) I349N probably damaging Het
Dnajc14 T A 10: 128,642,260 (GRCm39) Y61N probably benign Het
Dock6 A T 9: 21,713,802 (GRCm39) Y1909* probably null Het
Dock8 T A 19: 25,165,739 (GRCm39) D1874E probably benign Het
Dpm1 A G 2: 168,072,210 (GRCm39) S22P probably benign Het
Dysf T C 6: 84,128,885 (GRCm39) L1385P probably damaging Het
Egf T C 3: 129,491,421 (GRCm39) T859A probably benign Het
Eif2b1 A T 5: 124,711,867 (GRCm39) S162T probably benign Het
Emilin1 T C 5: 31,075,484 (GRCm39) L575P probably damaging Het
Erp27 T A 6: 136,886,550 (GRCm39) Q161L probably benign Het
Fbxw10 C A 11: 62,765,945 (GRCm39) D738E possibly damaging Het
Fcgbp T G 7: 27,790,937 (GRCm39) C733G probably damaging Het
Fgb T A 3: 82,957,122 (GRCm39) probably benign Het
Gata3os A T 2: 9,887,634 (GRCm39) T12S unknown Het
Got1l1 G T 8: 27,688,503 (GRCm39) Q283K probably benign Het
Grk2 G A 19: 4,340,871 (GRCm39) R226C probably damaging Het
Hoxa10 T C 6: 52,211,334 (GRCm39) D194G probably benign Het
Ipcef1 G A 10: 6,840,620 (GRCm39) T363I probably damaging Het
Itga10 C A 3: 96,564,273 (GRCm39) T922N probably damaging Het
Itgad T C 7: 127,777,552 (GRCm39) I144T probably benign Het
Kat6b C A 14: 21,567,564 (GRCm39) Q208K possibly damaging Het
Kidins220 T G 12: 25,088,383 (GRCm39) L1042R probably damaging Het
Kmt2c T C 5: 25,486,355 (GRCm39) S4733G probably damaging Het
Lrig3 A G 10: 125,850,736 (GRCm39) I1101V probably benign Het
Lrp1 T A 10: 127,431,229 (GRCm39) N311I probably damaging Het
Man2a1 A T 17: 64,958,310 (GRCm39) K275I probably benign Het
Map3k10 T A 7: 27,364,434 (GRCm39) N318I probably damaging Het
Map3k8 G A 18: 4,333,869 (GRCm39) R408W probably damaging Het
Mast1 A G 8: 85,647,805 (GRCm39) M523T probably damaging Het
Mast4 T C 13: 102,873,593 (GRCm39) H1925R probably benign Het
Med12l C T 3: 58,984,207 (GRCm39) S461L probably damaging Het
Mfap1a T C 2: 121,333,237 (GRCm39) K65E probably damaging Het
Mical1 T C 10: 41,358,602 (GRCm39) S507P probably benign Het
Miga2 T C 2: 30,268,400 (GRCm39) V433A unknown Het
Mpdz T C 4: 81,274,653 (GRCm39) T848A probably benign Het
Mycn A G 12: 12,989,778 (GRCm39) V206A probably benign Het
Ndst1 G A 18: 60,838,220 (GRCm39) Q342* probably null Het
Nectin1 A G 9: 43,702,369 (GRCm39) M39V probably benign Het
Nectin4 A T 1: 171,210,209 (GRCm39) R234* probably null Het
Ngb C G 12: 87,145,317 (GRCm39) V113L possibly damaging Het
Nphp3 T A 9: 103,913,337 (GRCm39) Y990N probably damaging Het
Nrdc T C 4: 108,915,833 (GRCm39) probably null Het
Or10a2 A T 7: 106,673,739 (GRCm39) K235* probably null Het
Or1e23 T A 11: 73,407,351 (GRCm39) I225F probably damaging Het
Or5p60 T A 7: 107,723,801 (GRCm39) Y223F probably benign Het
Osbpl6 A G 2: 76,415,603 (GRCm39) Y655C probably damaging Het
Pcdhgb4 A G 18: 37,855,882 (GRCm39) Q759R probably benign Het
Pde4d T A 13: 110,071,915 (GRCm39) I303N probably damaging Het
Pdf T A 8: 107,774,972 (GRCm39) M87L probably benign Het
Pigb A G 9: 72,941,840 (GRCm39) S140P probably damaging Het
Plch1 T A 3: 63,758,549 (GRCm39) probably benign Het
Plxna1 G T 6: 89,319,633 (GRCm39) D557E probably benign Het
Polr2e C T 10: 79,872,792 (GRCm39) V149M probably benign Het
Polr3a A T 14: 24,503,313 (GRCm39) C1174S probably benign Het
Prb1c T A 6: 132,338,891 (GRCm39) N109I unknown Het
Psmd2 T A 16: 20,474,369 (GRCm39) S308R probably benign Het
Ptger1 T A 8: 84,396,002 (GRCm39) V353E probably damaging Het
Ptprc A G 1: 137,996,111 (GRCm39) M940T probably benign Het
Pus7l T C 15: 94,425,781 (GRCm39) N540S probably damaging Het
Rap1gds1 T A 3: 138,756,317 (GRCm39) I13L probably benign Het
Rasl10b A T 11: 83,303,590 (GRCm39) N49I probably damaging Het
Rftn1 A T 17: 50,301,237 (GRCm39) N537K probably benign Het
Rnase4 A G 14: 51,342,645 (GRCm39) Y123C probably damaging Het
Rnf181 A C 6: 72,338,302 (GRCm39) N26K probably benign Het
Rnf31 G A 14: 55,836,269 (GRCm39) probably null Het
Rpusd3 C G 6: 113,393,200 (GRCm39) C304S unknown Het
Rsf1 CGGC CGGCGGCGGGGGC 7: 97,229,139 (GRCm39) probably benign Het
Ryr3 C A 2: 112,664,270 (GRCm39) V1694L probably benign Het
Sanbr T C 11: 23,559,098 (GRCm39) Y372C probably damaging Het
Sephs2 T C 7: 126,872,346 (GRCm39) D249G probably damaging Het
Serpina10 A G 12: 103,583,217 (GRCm39) I409T probably damaging Het
Serpina5 C T 12: 104,069,403 (GRCm39) A205V probably damaging Het
Sfr1 T A 19: 47,723,453 (GRCm39) V319E probably damaging Het
Skil T A 3: 31,171,639 (GRCm39) Y542N probably benign Het
Slc15a5 T C 6: 138,049,954 (GRCm39) T154A probably benign Het
Slc27a2 T A 2: 126,429,846 (GRCm39) L618Q probably damaging Het
Slc6a6 A T 6: 91,726,808 (GRCm39) Y483F probably benign Het
Sprr1b T C 3: 92,344,443 (GRCm39) I144M probably benign Het
Stat5a T A 11: 100,771,161 (GRCm39) V580E Het
Tnk1 C T 11: 69,746,011 (GRCm39) D305N probably damaging Het
Tox2 A G 2: 163,164,930 (GRCm39) *523W probably null Het
Trav12-2 A G 14: 53,854,085 (GRCm39) N20D probably benign Het
Trav16 T A 14: 53,981,046 (GRCm39) N78K probably damaging Het
Trf C T 9: 103,104,130 (GRCm39) A78T probably damaging Het
Ttn A G 2: 76,711,543 (GRCm39) probably benign Het
Vmn2r67 T A 7: 84,785,834 (GRCm39) M724L probably benign Het
Vmn2r94 A T 17: 18,477,261 (GRCm39) F383L probably benign Het
Vwa2 T C 19: 56,895,208 (GRCm39) S461P probably benign Het
Zfp991 G A 4: 147,264,327 (GRCm39) G568E probably damaging Het
Zfpl1 A G 19: 6,134,440 (GRCm39) F15S probably damaging Het
Other mutations in Pcsk4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00161:Pcsk4 APN 10 80,158,657 (GRCm39) missense probably damaging 1.00
IGL02818:Pcsk4 APN 10 80,158,626 (GRCm39) missense probably damaging 0.98
IGL03115:Pcsk4 APN 10 80,164,883 (GRCm39) missense probably damaging 1.00
IGL03354:Pcsk4 APN 10 80,161,893 (GRCm39) missense probably damaging 0.99
R0538:Pcsk4 UTSW 10 80,161,168 (GRCm39) missense probably damaging 1.00
R0760:Pcsk4 UTSW 10 80,161,775 (GRCm39) unclassified probably benign
R1462:Pcsk4 UTSW 10 80,161,815 (GRCm39) missense probably damaging 1.00
R1462:Pcsk4 UTSW 10 80,161,815 (GRCm39) missense probably damaging 1.00
R1554:Pcsk4 UTSW 10 80,157,785 (GRCm39) missense probably benign 0.01
R1728:Pcsk4 UTSW 10 80,159,404 (GRCm39) missense probably damaging 0.99
R1784:Pcsk4 UTSW 10 80,159,404 (GRCm39) missense probably damaging 0.99
R1886:Pcsk4 UTSW 10 80,164,794 (GRCm39) missense probably benign 0.32
R1981:Pcsk4 UTSW 10 80,161,613 (GRCm39) missense probably damaging 1.00
R2090:Pcsk4 UTSW 10 80,161,655 (GRCm39) missense probably benign 0.02
R2125:Pcsk4 UTSW 10 80,159,713 (GRCm39) missense probably benign 0.32
R2283:Pcsk4 UTSW 10 80,158,584 (GRCm39) missense probably damaging 1.00
R4183:Pcsk4 UTSW 10 80,160,845 (GRCm39) missense probably benign 0.12
R4283:Pcsk4 UTSW 10 80,165,287 (GRCm39) unclassified probably benign
R4798:Pcsk4 UTSW 10 80,158,938 (GRCm39) missense probably damaging 1.00
R4857:Pcsk4 UTSW 10 80,160,873 (GRCm39) missense probably damaging 1.00
R4990:Pcsk4 UTSW 10 80,161,215 (GRCm39) missense possibly damaging 0.74
R4991:Pcsk4 UTSW 10 80,161,215 (GRCm39) missense possibly damaging 0.74
R5020:Pcsk4 UTSW 10 80,161,869 (GRCm39) missense probably benign 0.00
R5123:Pcsk4 UTSW 10 80,157,979 (GRCm39) missense probably null 0.56
R5354:Pcsk4 UTSW 10 80,159,523 (GRCm39) missense probably damaging 0.98
R6077:Pcsk4 UTSW 10 80,162,073 (GRCm39) missense probably damaging 0.99
R6102:Pcsk4 UTSW 10 80,161,651 (GRCm39) nonsense probably null
R6250:Pcsk4 UTSW 10 80,161,426 (GRCm39) missense probably benign 0.04
R6378:Pcsk4 UTSW 10 80,164,809 (GRCm39) missense probably benign 0.34
R6729:Pcsk4 UTSW 10 80,160,935 (GRCm39) missense probably damaging 0.99
R7308:Pcsk4 UTSW 10 80,159,007 (GRCm39) missense probably benign 0.41
R7595:Pcsk4 UTSW 10 80,157,935 (GRCm39) missense possibly damaging 0.84
R8004:Pcsk4 UTSW 10 80,158,674 (GRCm39) missense probably damaging 1.00
R8675:Pcsk4 UTSW 10 80,158,896 (GRCm39) missense probably damaging 1.00
R8777:Pcsk4 UTSW 10 80,159,557 (GRCm39) missense probably benign 0.29
R8777-TAIL:Pcsk4 UTSW 10 80,159,557 (GRCm39) missense probably benign 0.29
R9030:Pcsk4 UTSW 10 80,164,858 (GRCm39) missense probably damaging 1.00
R9262:Pcsk4 UTSW 10 80,160,864 (GRCm39) missense probably damaging 1.00
R9278:Pcsk4 UTSW 10 80,161,224 (GRCm39) missense probably damaging 1.00
R9546:Pcsk4 UTSW 10 80,157,741 (GRCm39) missense possibly damaging 0.59
R9733:Pcsk4 UTSW 10 80,158,034 (GRCm39) missense probably damaging 0.99
Z1176:Pcsk4 UTSW 10 80,158,560 (GRCm39) missense possibly damaging 0.94
Predicted Primers PCR Primer
(F):5'- TAGCTCACCGGTTCTCATCG -3'
(R):5'- TACATGGTGAGCACTTGGG -3'

Sequencing Primer
(F):5'- CACCGGTTCTCATCGTTGGG -3'
(R):5'- AGCACTTGGGCTGGGTG -3'
Posted On 2022-07-18