|Institutional Source||Beutler Lab|
|Gene Name||proprotein convertase subtilisin/kexin type 1|
|Synonyms||PC3, PC1, Nec-1, SPC3, prohormone convertase 1/3, Nec1, Phpp-1|
|Is this an essential gene?||Essential (E-score: 1.000)|
|Stock #||R1717 (G1)|
|Chromosomal Location||75089826-75134861 bp(+) (GRCm38)|
|Type of Mutation||missense|
|DNA Base Change (assembly)||G to C at 75110828 bp|
|Amino Acid Change||Methionine to Isoleucine at position 240 (M240I)|
|Ref Sequence||ENSEMBL: ENSMUSP00000022075 (fasta)|
|Gene Model||predicted gene model for transcript(s): [ENSMUST00000022075]|
|Predicted Effect||probably damaging
AA Change: M240I
PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)
AA Change: M240I
|Predicted Effect||noncoding transcript
AA Change: M3I
|Meta Mutation Damage Score||0.108|
|Coding Region Coverage||
|Validation Efficiency||98% (81/83)|
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||
|Other mutations in Pcsk1||
(F):5'- TTCACAGAAACAGGATTTCGTCCCC -3'
(R):5'- GGAATGTAAGCACCATCCTTCCTGG -3'
(F):5'- GGTGCTATTAGGAACCACCTC -3'
(R):5'- AGGACATTTTGACTCCATAGCC -3'