Incidental Mutation 'R6567:Pcsk1'
ID 522780
Institutional Source Beutler Lab
Gene Symbol Pcsk1
Ensembl Gene ENSMUSG00000021587
Gene Name proprotein convertase subtilisin/kexin type 1
Synonyms PC3, Nec1, Phpp-1, Nec-1, SPC3, prohormone convertase 1/3, PC1
MMRRC Submission 044691-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R6567 (G1)
Quality Score 225.009
Status Validated
Chromosome 13
Chromosomal Location 75237945-75282980 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 75278189 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Asparagine at position 584 (I584N)
Ref Sequence ENSEMBL: ENSMUSP00000022075 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000022075]
AlphaFold P63239
PDB Structure Solution Structure of the Mouse Prohormone Convertase 1 Pro-Domain [SOLUTION NMR]
PC1/3 DCSG sorting domain structure in DPC [SOLUTION NMR]
PC1/3 DCSG sorting domain in CHAPS [SOLUTION NMR]
Predicted Effect probably damaging
Transcript: ENSMUST00000022075
AA Change: I584N

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000022075
Gene: ENSMUSG00000021587
AA Change: I584N

DomainStartEndE-ValueType
signal peptide 1 27 N/A INTRINSIC
Pfam:S8_pro-domain 34 110 6.4e-26 PFAM
Pfam:Peptidase_S8 158 442 2.2e-49 PFAM
Pfam:P_proprotein 504 591 6.1e-30 PFAM
low complexity region 679 694 N/A INTRINSIC
Pfam:Proho_convert 713 751 4.3e-26 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000222727
Meta Mutation Damage Score 0.8736 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.4%
  • 20x: 98.0%
Validation Efficiency 100% (32/32)
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. The 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. Mutations in this gene have been associated with susceptibility to obesity and proprotein convertase 1/3 deficiency. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene [provided by RefSeq, Jan 2014]
PHENOTYPE: Homozygotes for a null allele show pre- and postnatal death, low weight, diarrhea, hypoglycemia, low insulin and GHRH levels, and lack mature glucagon and ACTH levels. Homozygotes for another null allele die prior to implantation. ENU mutants show obesity, polyphagia and higher metabolic efficiency. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 31 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
9930111J21Rik1 T C 11: 48,838,950 (GRCm39) T546A probably benign Het
Ahnak G T 19: 8,986,170 (GRCm39) V2485L probably benign Het
C2cd5 T C 6: 142,976,974 (GRCm39) I722M possibly damaging Het
Clca4b A G 3: 144,638,100 (GRCm39) I54T possibly damaging Het
Dennd2c C T 3: 103,039,335 (GRCm39) A161V probably benign Het
Dmxl1 T C 18: 49,992,246 (GRCm39) Y331H probably damaging Het
Dnaaf11 C T 15: 66,310,228 (GRCm39) V347I probably benign Het
Dnajc2 G A 5: 21,971,676 (GRCm39) R247W probably damaging Het
Dock3 T C 9: 106,773,946 (GRCm39) T380A probably benign Het
Evc2 T C 5: 37,576,508 (GRCm39) V1044A probably benign Het
Ints2 T C 11: 86,117,487 (GRCm39) H745R probably benign Het
Kcnh1 T A 1: 191,959,412 (GRCm39) M322K probably benign Het
Mmp19 A G 10: 128,632,275 (GRCm39) T191A probably benign Het
Mms19 A G 19: 41,938,206 (GRCm39) probably null Het
Mtcl3 G T 10: 29,023,279 (GRCm39) V209F probably benign Het
Ncapd3 T C 9: 26,978,300 (GRCm39) I833T possibly damaging Het
Nif3l1 T A 1: 58,494,789 (GRCm39) C253S probably benign Het
Or52e2 A T 7: 102,804,135 (GRCm39) I273K possibly damaging Het
Pate5 T A 9: 35,750,411 (GRCm39) Y87F probably benign Het
Pms2 T C 5: 143,865,786 (GRCm39) V50A probably damaging Het
Rptor A G 11: 119,786,838 (GRCm39) I1268V probably benign Het
Scap C T 9: 110,212,630 (GRCm39) R1021W probably damaging Het
Sos1 A T 17: 80,740,932 (GRCm39) Y618N probably damaging Het
Tesk2 C T 4: 116,649,361 (GRCm39) A157V probably damaging Het
Tm6sf2 C A 8: 70,528,174 (GRCm39) H108N probably damaging Het
Trank1 T C 9: 111,176,589 (GRCm39) V287A probably benign Het
Tsks A T 7: 44,603,305 (GRCm39) Q369L probably damaging Het
Vmn2r58 T C 7: 41,514,673 (GRCm39) T99A probably benign Het
Wbp11 C T 6: 136,797,537 (GRCm39) S294N probably benign Het
Zfp608 T C 18: 55,030,628 (GRCm39) Y1104C probably damaging Het
Zfp759 T A 13: 67,287,150 (GRCm39) S234T probably benign Het
Other mutations in Pcsk1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00324:Pcsk1 APN 13 75,280,206 (GRCm39) missense probably benign
IGL01554:Pcsk1 APN 13 75,280,426 (GRCm39) missense probably benign
IGL01960:Pcsk1 APN 13 75,241,286 (GRCm39) missense possibly damaging 0.82
IGL02026:Pcsk1 APN 13 75,260,772 (GRCm39) missense probably benign 0.16
IGL02047:Pcsk1 APN 13 75,246,108 (GRCm39) missense probably benign 0.33
IGL02264:Pcsk1 APN 13 75,254,078 (GRCm39) missense probably damaging 1.00
IGL02441:Pcsk1 APN 13 75,280,282 (GRCm39) missense probably benign 0.16
IGL02795:Pcsk1 APN 13 75,260,739 (GRCm39) missense probably damaging 1.00
IGL02829:Pcsk1 APN 13 75,274,955 (GRCm39) missense probably damaging 1.00
IGL03116:Pcsk1 APN 13 75,280,335 (GRCm39) missense probably damaging 0.99
IGL03156:Pcsk1 APN 13 75,280,070 (GRCm39) missense probably benign
clipper UTSW 13 75,278,189 (GRCm39) missense probably damaging 1.00
spareribs UTSW 13 75,263,374 (GRCm39) missense possibly damaging 0.88
swivel UTSW 13 75,274,103 (GRCm39) missense probably damaging 1.00
Tweeze UTSW 13 75,274,958 (GRCm39) missense probably benign 0.00
PIT4453001:Pcsk1 UTSW 13 75,260,769 (GRCm39) missense probably damaging 1.00
R0771:Pcsk1 UTSW 13 75,280,281 (GRCm39) missense probably benign 0.31
R0894:Pcsk1 UTSW 13 75,246,096 (GRCm39) missense probably damaging 1.00
R1014:Pcsk1 UTSW 13 75,280,353 (GRCm39) missense probably damaging 1.00
R1035:Pcsk1 UTSW 13 75,280,238 (GRCm39) missense probably benign
R1199:Pcsk1 UTSW 13 75,244,532 (GRCm39) splice site probably benign
R1517:Pcsk1 UTSW 13 75,246,166 (GRCm39) nonsense probably null
R1625:Pcsk1 UTSW 13 75,274,971 (GRCm39) missense probably benign 0.11
R1691:Pcsk1 UTSW 13 75,280,344 (GRCm39) missense possibly damaging 0.65
R1717:Pcsk1 UTSW 13 75,258,947 (GRCm39) missense probably damaging 0.99
R2168:Pcsk1 UTSW 13 75,260,653 (GRCm39) intron probably benign
R2252:Pcsk1 UTSW 13 75,274,845 (GRCm39) missense probably benign 0.00
R2400:Pcsk1 UTSW 13 75,238,245 (GRCm39) missense probably benign 0.00
R4110:Pcsk1 UTSW 13 75,244,488 (GRCm39) missense probably damaging 0.99
R4358:Pcsk1 UTSW 13 75,260,838 (GRCm39) missense possibly damaging 0.58
R4359:Pcsk1 UTSW 13 75,260,838 (GRCm39) missense possibly damaging 0.58
R4657:Pcsk1 UTSW 13 75,280,354 (GRCm39) missense probably damaging 1.00
R5195:Pcsk1 UTSW 13 75,274,974 (GRCm39) missense probably damaging 1.00
R5669:Pcsk1 UTSW 13 75,278,221 (GRCm39) missense probably benign 0.01
R5671:Pcsk1 UTSW 13 75,246,026 (GRCm39) missense possibly damaging 0.63
R5745:Pcsk1 UTSW 13 75,280,079 (GRCm39) missense probably benign 0.03
R6107:Pcsk1 UTSW 13 75,275,967 (GRCm39) missense probably benign 0.09
R6200:Pcsk1 UTSW 13 75,263,374 (GRCm39) missense possibly damaging 0.88
R6326:Pcsk1 UTSW 13 75,280,298 (GRCm39) missense possibly damaging 0.89
R6537:Pcsk1 UTSW 13 75,280,358 (GRCm39) missense probably damaging 1.00
R6541:Pcsk1 UTSW 13 75,274,103 (GRCm39) missense probably damaging 1.00
R6723:Pcsk1 UTSW 13 75,241,188 (GRCm39) splice site probably null
R7258:Pcsk1 UTSW 13 75,241,305 (GRCm39) missense probably damaging 1.00
R7357:Pcsk1 UTSW 13 75,274,079 (GRCm39) missense probably damaging 0.96
R7487:Pcsk1 UTSW 13 75,259,002 (GRCm39) missense probably benign 0.01
R7519:Pcsk1 UTSW 13 75,258,984 (GRCm39) missense probably damaging 0.99
R7647:Pcsk1 UTSW 13 75,280,329 (GRCm39) missense possibly damaging 0.73
R7787:Pcsk1 UTSW 13 75,280,277 (GRCm39) missense possibly damaging 0.88
R7944:Pcsk1 UTSW 13 75,280,211 (GRCm39) missense probably benign
R7945:Pcsk1 UTSW 13 75,280,211 (GRCm39) missense probably benign
R7961:Pcsk1 UTSW 13 75,274,958 (GRCm39) missense probably benign 0.00
R8009:Pcsk1 UTSW 13 75,274,958 (GRCm39) missense probably benign 0.00
R8022:Pcsk1 UTSW 13 75,247,412 (GRCm39) missense possibly damaging 0.77
R8171:Pcsk1 UTSW 13 75,238,210 (GRCm39) nonsense probably null
R8489:Pcsk1 UTSW 13 75,274,121 (GRCm39) missense probably damaging 1.00
R9310:Pcsk1 UTSW 13 75,238,191 (GRCm39) missense probably benign
R9404:Pcsk1 UTSW 13 75,280,342 (GRCm39) missense probably benign 0.11
R9544:Pcsk1 UTSW 13 75,259,039 (GRCm39) missense probably damaging 0.99
R9588:Pcsk1 UTSW 13 75,259,039 (GRCm39) missense probably damaging 0.99
R9706:Pcsk1 UTSW 13 75,247,473 (GRCm39) critical splice donor site probably null
Z1176:Pcsk1 UTSW 13 75,246,161 (GRCm39) missense probably damaging 1.00
Z1177:Pcsk1 UTSW 13 75,273,983 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- CTTGGTTGTGAGGCAATAAGTCAG -3'
(R):5'- TGCCTACTGAGGTCTAAAAGAGAAC -3'

Sequencing Primer
(F):5'- TGTGAGGCAATAAGTCAGTTTTTC -3'
(R):5'- CTGAGGTCTAAAAGAGAACATGGTAC -3'
Posted On 2018-06-06