Incidental Mutation 'IGL03116:Pcsk1'
ID 419425
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 # IGL03116
Quality Score
Status
Chromosome 13
Chromosomal Location 75237945-75282980 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 75280335 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Leucine to Glutamine at position 720 (L720Q)
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: L720Q

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000022075
Gene: ENSMUSG00000021587
AA Change: L720Q

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: 41 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1810030O07Rik T C X: 12,535,892 (GRCm39) probably benign Het
9530068E07Rik A G 11: 52,294,331 (GRCm39) I199V probably benign Het
Aasdh A T 5: 77,049,936 (GRCm39) probably null Het
Aatk T C 11: 119,907,577 (GRCm39) I84V probably benign Het
Adcy1 A G 11: 7,100,071 (GRCm39) H727R probably benign Het
Aff2 T C X: 68,878,092 (GRCm39) V626A probably benign Het
Ano2 C A 6: 125,957,134 (GRCm39) Y634* probably null Het
Apob C A 12: 8,066,350 (GRCm39) Q4407K probably damaging Het
Asz1 T C 6: 18,076,642 (GRCm39) probably benign Het
Atp2b4 T G 1: 133,656,506 (GRCm39) T715P possibly damaging Het
Brip1 G T 11: 85,955,735 (GRCm39) S926* probably null Het
Cpd A T 11: 76,702,539 (GRCm39) Y610N probably damaging Het
Dennd4c T C 4: 86,707,057 (GRCm39) probably benign Het
Dido1 G A 2: 180,312,772 (GRCm39) T1041I probably damaging Het
Dpp8 A T 9: 64,973,749 (GRCm39) T658S probably damaging Het
Efcab3 T A 11: 104,612,359 (GRCm39) S661T probably benign Het
Fcer1a G A 1: 173,049,128 (GRCm39) Q172* probably null Het
Frem3 A G 8: 81,339,435 (GRCm39) E576G possibly damaging Het
Gcsam T C 16: 45,440,431 (GRCm39) F136S possibly damaging Het
Glmn T G 5: 107,698,949 (GRCm39) T430P probably damaging Het
Gm5934 T C X: 24,340,931 (GRCm39) N194S probably benign Het
Gpatch11 T A 17: 79,151,282 (GRCm39) L231* probably null Het
Hibadh A T 6: 52,525,917 (GRCm39) N244K probably damaging Het
Kank2 A G 9: 21,684,060 (GRCm39) V723A probably damaging Het
Kcnn2 A T 18: 45,788,273 (GRCm39) D192V probably damaging Het
Ksr2 G A 5: 117,846,022 (GRCm39) E630K probably benign Het
Lmod3 T C 6: 97,224,156 (GRCm39) H555R possibly damaging Het
Mycs A G X: 5,380,922 (GRCm39) F53L probably damaging Het
Ndufa10 G A 1: 92,392,109 (GRCm39) Q215* probably null Het
Ninl C T 2: 150,806,139 (GRCm39) A361T probably damaging Het
Pbsn A G X: 76,891,624 (GRCm39) C58R probably damaging Het
Prss12 T C 3: 123,299,925 (GRCm39) F679L probably benign Het
Sohlh1 C T 2: 25,735,660 (GRCm39) probably null Het
Sspo T C 6: 48,471,035 (GRCm39) F701L probably benign Het
Tdp1 T C 12: 99,921,290 (GRCm39) S609P probably benign Het
Tmtc4 T A 14: 123,165,044 (GRCm39) N605I probably benign Het
Tnc G A 4: 63,932,270 (GRCm39) P715S probably damaging Het
Ubn2 T C 6: 38,468,834 (GRCm39) S1181P probably damaging Het
Ubr4 T C 4: 139,206,892 (GRCm39) probably benign Het
Vmn1r46 T C 6: 89,953,898 (GRCm39) F249S probably benign Het
Zfp382 T C 7: 29,833,614 (GRCm39) S422P probably damaging 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
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 2016-08-02