Incidental Mutation 'IGL02264:Pcsk1'
ID 286854
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 # IGL02264
Quality Score
Status
Chromosome 13
Chromosomal Location 75237945-75282980 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to A at 75254078 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Lysine at position 210 (T210K)
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: T210K

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000022075
Gene: ENSMUSG00000021587
AA Change: T210K

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 noncoding transcript
Transcript: ENSMUST00000135349
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: 31 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4921504E06Rik A G 2: 19,547,180 (GRCm39) probably null Het
Abhd17b T C 19: 21,655,796 (GRCm39) L26P probably damaging Het
Abtb1 A G 6: 88,813,517 (GRCm39) V407A probably benign Het
Adamts17 C A 7: 66,697,207 (GRCm39) probably null Het
Arhgap21 G T 2: 20,864,850 (GRCm39) probably null Het
Brwd1 T C 16: 95,820,656 (GRCm39) D1290G probably damaging Het
Btbd6 A G 12: 112,940,589 (GRCm39) T49A probably damaging Het
Carmil1 C T 13: 24,259,699 (GRCm39) V702I possibly damaging Het
Cts8 T A 13: 61,398,772 (GRCm39) I245F probably damaging Het
Dclre1a T A 19: 56,532,725 (GRCm39) N623I possibly damaging Het
Dnah9 A T 11: 65,971,314 (GRCm39) probably benign Het
Emc1 T C 4: 139,102,775 (GRCm39) F978S probably damaging Het
Fam185a G A 5: 21,685,392 (GRCm39) V363I possibly damaging Het
Iglc2 G T 16: 19,017,397 (GRCm39) S69R probably damaging Het
Ints5 T C 19: 8,873,076 (GRCm39) V345A probably benign Het
Kif21b T A 1: 136,087,495 (GRCm39) L937Q probably damaging Het
Lrba A G 3: 86,687,569 (GRCm39) R2825G probably damaging Het
Map1a A G 2: 121,137,794 (GRCm39) E2870G probably damaging Het
Or4c125 G T 2: 89,170,028 (GRCm39) T206K probably benign Het
Or4k41 A G 2: 111,280,207 (GRCm39) T241A probably benign Het
Or5aq7 C T 2: 86,937,785 (GRCm39) probably benign Het
Or8b48 C T 9: 38,492,809 (GRCm39) P79S probably damaging Het
Phaf1 C T 8: 105,961,178 (GRCm39) A71V possibly damaging Het
Slco5a1 A G 1: 12,942,219 (GRCm39) V809A probably benign Het
Synm T C 7: 67,384,144 (GRCm39) T1173A probably damaging Het
Tbc1d9b T C 11: 50,040,584 (GRCm39) I367T probably damaging Het
Tmem169 T A 1: 72,340,114 (GRCm39) Y181* probably null Het
Trp73 G T 4: 154,148,885 (GRCm39) F289L probably null Het
Ttll9 A G 2: 152,842,055 (GRCm39) Y303C probably damaging Het
Ubr4 G T 4: 139,182,939 (GRCm39) E3577* probably null Het
Zbtb3 T G 19: 8,780,729 (GRCm39) V114G 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
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 2015-04-16