Incidental Mutation 'IGL02795:Pcsk1'
ID359948
Institutional Source Australian Phenomics Network (link to record)
Gene Symbol Pcsk1
Ensembl Gene ENSMUSG00000021587
Gene Nameproprotein convertase subtilisin/kexin type 1
SynonymsPC3, PC1, Nec-1, SPC3, prohormone convertase 1/3, Nec1, Phpp-1
Accession Numbers
Is this an essential gene? Essential (E-score: 1.000) question?
Stock #IGL02795
Quality Score
Status
Chromosome13
Chromosomal Location75089826-75134861 bp(+) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) G to T at 75112620 bp
ZygosityHeterozygous
Amino Acid Change Glycine to Cysteine at position 321 (G321C)
Ref Sequence ENSEMBL: ENSMUSP00000022075 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000022075]
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: G321C

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000022075
Gene: ENSMUSG00000021587
AA Change: G321C

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
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: 56 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca12 A G 1: 71,288,748 L1391P probably damaging Het
Abcc3 G A 11: 94,361,642 probably benign Het
Acvr1 A G 2: 58,462,952 I332T probably damaging Het
Atp8a2 C T 14: 60,033,742 V247M probably damaging Het
Btn1a1 T C 13: 23,460,616 probably null Het
Btnl9 A T 11: 49,174,867 probably benign Het
Dbx1 T A 7: 49,636,577 I47F probably benign Het
Dnaja3 A G 16: 4,690,073 probably benign Het
Dnmt1 T C 9: 20,927,111 S220G probably benign Het
Dock9 A T 14: 121,639,978 M451K probably benign Het
Eml3 A G 19: 8,933,778 Y257C probably benign Het
Fbxw19 C A 9: 109,495,818 M10I possibly damaging Het
Flg2 C T 3: 93,203,613 R983W unknown Het
Galnt5 C A 2: 58,027,871 P707H probably damaging Het
Gba2 G T 4: 43,578,331 P6Q probably damaging Het
Gm13199 A G 2: 5,862,673 probably benign Het
Gpr45 C T 1: 43,032,493 R99C possibly damaging Het
Hecw1 G A 13: 14,322,517 S302L probably damaging Het
Hrg T C 16: 22,957,553 probably benign Het
Kdelc2 A G 9: 53,392,105 D99G probably damaging Het
Lama1 A G 17: 67,738,894 probably null Het
Lgr4 T C 2: 110,008,210 probably benign Het
Lrrc9 C T 12: 72,478,768 T830M probably damaging Het
Mdga2 T C 12: 66,689,432 T341A probably benign Het
Mms19 C T 19: 41,952,406 probably null Het
Nectin1 A G 9: 43,803,552 S362G probably benign Het
Nlrc3 G T 16: 3,965,285 H87N probably damaging Het
Oit1 T A 14: 8,355,497 M113L probably benign Het
Olfr1018 T A 2: 85,823,512 C180* probably null Het
Olfr142 A G 2: 90,252,562 L142P probably damaging Het
Olfr183 G T 16: 59,000,277 L197F possibly damaging Het
Olfr23 G A 11: 73,940,929 V228I probably benign Het
Olfr243 T A 7: 103,716,883 F96L probably benign Het
Prrc2c G T 1: 162,714,299 P374T probably benign Het
Rusc1 A T 3: 89,091,950 L175Q probably damaging Het
Ryr2 T C 13: 11,595,190 N4250S probably benign Het
Scara5 A C 14: 65,730,680 N134T possibly damaging Het
Sema4d T C 13: 51,703,411 K595R probably benign Het
Serpinb6a A C 13: 33,931,593 L15R probably damaging Het
Setdb1 A T 3: 95,327,373 N1006K probably damaging Het
Slc18a2 G A 19: 59,274,490 probably benign Het
Slc22a30 C T 19: 8,400,895 C139Y probably damaging Het
Slc25a27 T A 17: 43,647,112 Y269F probably damaging Het
Slc9c1 A T 16: 45,575,419 D611V probably benign Het
Spag6 G T 2: 18,733,083 V255F probably benign Het
St5 T C 7: 109,556,364 Y393C probably damaging Het
Svep1 C A 4: 58,123,223 G698W probably damaging Het
Syne2 T C 12: 75,966,549 L2839P probably damaging Het
Tfb2m T C 1: 179,545,959 E58G possibly damaging Het
Trim24 A T 6: 37,919,389 E260D probably damaging Het
Ugt2b1 T A 5: 86,917,701 D493V probably damaging Het
Vmn1r27 A G 6: 58,215,302 V189A possibly damaging Het
Vmn2r91 A G 17: 18,085,277 Q74R probably benign Het
Vps25 A G 11: 101,256,090 Y64C probably damaging Het
Xirp2 G A 2: 67,509,136 G574S probably damaging Het
Ythdc2 A G 18: 44,837,438 E273G possibly damaging Het
Other mutations in Pcsk1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00324:Pcsk1 APN 13 75132087 missense probably benign
IGL01554:Pcsk1 APN 13 75132307 missense probably benign
IGL01960:Pcsk1 APN 13 75093167 missense possibly damaging 0.82
IGL02026:Pcsk1 APN 13 75112653 missense probably benign 0.16
IGL02047:Pcsk1 APN 13 75097989 missense probably benign 0.33
IGL02264:Pcsk1 APN 13 75105959 missense probably damaging 1.00
IGL02441:Pcsk1 APN 13 75132163 missense probably benign 0.16
IGL02829:Pcsk1 APN 13 75126836 missense probably damaging 1.00
IGL03116:Pcsk1 APN 13 75132216 missense probably damaging 0.99
IGL03156:Pcsk1 APN 13 75131951 missense probably benign
clipper UTSW 13 75130070 missense probably damaging 1.00
spareribs UTSW 13 75115255 missense possibly damaging 0.88
swivel UTSW 13 75125984 missense probably damaging 1.00
PIT4453001:Pcsk1 UTSW 13 75112650 missense probably damaging 1.00
R0771:Pcsk1 UTSW 13 75132162 missense probably benign 0.31
R0894:Pcsk1 UTSW 13 75097977 missense probably damaging 1.00
R1014:Pcsk1 UTSW 13 75132234 missense probably damaging 1.00
R1035:Pcsk1 UTSW 13 75132119 missense probably benign
R1199:Pcsk1 UTSW 13 75096413 splice site probably benign
R1517:Pcsk1 UTSW 13 75098047 nonsense probably null
R1625:Pcsk1 UTSW 13 75126852 missense probably benign 0.11
R1691:Pcsk1 UTSW 13 75132225 missense possibly damaging 0.65
R1717:Pcsk1 UTSW 13 75110828 missense probably damaging 0.99
R2168:Pcsk1 UTSW 13 75112534 intron probably benign
R2252:Pcsk1 UTSW 13 75126726 missense probably benign 0.00
R2400:Pcsk1 UTSW 13 75090126 missense probably benign 0.00
R4110:Pcsk1 UTSW 13 75096369 missense probably damaging 0.99
R4358:Pcsk1 UTSW 13 75112719 missense possibly damaging 0.58
R4359:Pcsk1 UTSW 13 75112719 missense possibly damaging 0.58
R4657:Pcsk1 UTSW 13 75132235 missense probably damaging 1.00
R5195:Pcsk1 UTSW 13 75126855 missense probably damaging 1.00
R5669:Pcsk1 UTSW 13 75130102 missense probably benign 0.01
R5671:Pcsk1 UTSW 13 75097907 missense possibly damaging 0.63
R5745:Pcsk1 UTSW 13 75131960 missense probably benign 0.03
R6107:Pcsk1 UTSW 13 75127848 missense probably benign 0.09
R6200:Pcsk1 UTSW 13 75115255 missense possibly damaging 0.88
R6326:Pcsk1 UTSW 13 75132179 missense possibly damaging 0.89
R6537:Pcsk1 UTSW 13 75132239 missense probably damaging 1.00
R6541:Pcsk1 UTSW 13 75125984 missense probably damaging 1.00
R6567:Pcsk1 UTSW 13 75130070 missense probably damaging 1.00
R6723:Pcsk1 UTSW 13 75093069 splice site probably null
R7258:Pcsk1 UTSW 13 75093186 missense probably damaging 1.00
R7357:Pcsk1 UTSW 13 75125960 missense probably damaging 0.96
R7487:Pcsk1 UTSW 13 75110883 missense probably benign 0.01
R7519:Pcsk1 UTSW 13 75110865 missense probably damaging 0.99
R7647:Pcsk1 UTSW 13 75132210 missense possibly damaging 0.73
R7787:Pcsk1 UTSW 13 75132158 missense possibly damaging 0.88
R8009:Pcsk1 UTSW 13 75126839 missense probably benign 0.00
R8022:Pcsk1 UTSW 13 75099293 missense possibly damaging 0.77
Z1176:Pcsk1 UTSW 13 75098042 missense probably damaging 1.00
Z1177:Pcsk1 UTSW 13 75125864 missense probably damaging 1.00
Posted On2015-12-18