Incidental Mutation 'IGL00324:Pcsk1'
ID 4284
Institutional Source Australian Phenomics Network (link to record)
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
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # IGL00324
Quality Score
Status
Chromosome 13
Chromosomal Location 75237945-75282980 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 75280206 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Lysine to Arginine at position 677 (K677R)
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 benign
Transcript: ENSMUST00000022075
AA Change: K677R

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000022075
Gene: ENSMUSG00000021587
AA Change: K677R

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
Coding Region Coverage
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. 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: 30 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcd3 T C 3: 121,570,642 (GRCm39) probably benign Het
Cdk12 T A 11: 98,136,214 (GRCm39) L1156Q unknown Het
Ctsl T C 13: 64,515,982 (GRCm39) Y66C probably damaging Het
Esd C T 14: 74,973,467 (GRCm39) H21Y probably damaging Het
Fcrlb A C 1: 170,736,393 (GRCm39) Y128D possibly damaging Het
Gm17027 A T 14: 41,981,267 (GRCm39) N196K unknown Het
Gm4553 T C 7: 141,718,964 (GRCm39) S155G unknown Het
Hpcal1 A G 12: 17,841,146 (GRCm39) S175G probably benign Het
Itgam A T 7: 127,684,833 (GRCm39) D401V probably damaging Het
Kank1 A G 19: 25,389,122 (GRCm39) T932A probably benign Het
Lmod1 A G 1: 135,292,216 (GRCm39) K357R probably benign Het
Muc4 A G 16: 32,599,186 (GRCm39) I3271V probably benign Het
Nlrc5 A G 8: 95,248,107 (GRCm39) K1692E probably damaging Het
Ocln A G 13: 100,671,521 (GRCm39) W279R probably damaging Het
Or4p20 T C 2: 88,254,130 (GRCm39) I80V probably benign Het
Pitrm1 T A 13: 6,618,702 (GRCm39) L586Q probably damaging Het
Plppr3 G A 10: 79,702,503 (GRCm39) S217L probably damaging Het
Pnldc1 A T 17: 13,124,645 (GRCm39) probably benign Het
Pramel12 T A 4: 143,143,237 (GRCm39) M1K probably null Het
Pramel13 A G 4: 144,121,310 (GRCm39) L238P possibly damaging Het
Sema6b C T 17: 56,437,048 (GRCm39) D204N probably damaging Het
Slc12a5 A G 2: 164,839,041 (GRCm39) N1063S probably damaging Het
Tg T C 15: 66,565,273 (GRCm39) V1205A probably benign Het
Tmem260 T C 14: 48,724,336 (GRCm39) F205L probably benign Het
Trappc11 A T 8: 47,956,337 (GRCm39) probably benign Het
Tsen34 A G 7: 3,703,530 (GRCm39) *296W probably null Het
Ubr2 A G 17: 47,296,986 (GRCm39) probably benign Het
Vmn2r23 T A 6: 123,706,684 (GRCm39) W505R possibly damaging Het
Wbp11 A G 6: 136,798,668 (GRCm39) probably benign Het
Znfx1 A T 2: 166,878,649 (GRCm39) M1909K possibly damaging Het
Other mutations in Pcsk1
AlleleSourceChrCoordTypePredicted EffectPPH Score
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
R6567:Pcsk1 UTSW 13 75,278,189 (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
Posted On 2012-04-20