Incidental Mutation 'R8820:Pcsk2'
| ID |
672969 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Pcsk2
|
| Ensembl Gene |
ENSMUSG00000027419 |
| Gene Name |
proprotein convertase subtilisin/kexin type 2 |
| Synonyms |
Nec-2, PC2, Phpp-2, SPC2, Nec2, 6330411F23Rik, prohormone convertase 2 |
| MMRRC Submission |
068653-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably non essential
(E-score: 0.205)
|
| Stock # |
R8820 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
2 |
| Chromosomal Location |
143388076-143658205 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to A
at 143642990 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Histidine to Glutamine
at position 422
(H422Q)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000028905
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000028905]
|
| AlphaFold |
P21661 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000028905
AA Change: H422Q
PolyPhen 2
Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)
|
| SMART Domains |
Protein: ENSMUSP00000028905
Gene: ENSMUSG00000027419
AA Change: H422Q
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
24 |
N/A |
INTRINSIC |
|
Pfam:S8_pro-domain
|
32 |
108 |
2.9e-21 |
PFAM |
|
Pfam:Peptidase_S8
|
157 |
444 |
5e-44 |
PFAM |
|
Pfam:P_proprotein
|
503 |
590 |
4.3e-28 |
PFAM |
|
low complexity region
|
617 |
630 |
N/A |
INTRINSIC |
|
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 100.0%
- 10x: 99.8%
- 20x: 99.4%
|
| Validation Efficiency |
100% (58/58) |
| 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 protein undergoes an initial autocatalytic processing event and interacts with a neuroendocrine secretory protein in the ER, exits the ER and sorts to secretory granules, where it is cleaved and catalytically activated during intracellular transport. The encoded 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. Single nucleotide polymorphisms in this gene may increase susceptibility to myocardial infarction and type 2 diabetes. This gene may also play a role in tumor development and progression. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2014]
PHENOTYPE: Mice homozygous for disruptions of this gene display abnormalities in the maturation of peptide hormones leading to reduced female fertility, increased blood pressure on a high salt diet, and abnormal glucose metabolism. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 56 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abca17 |
A |
G |
17: 24,547,576 (GRCm39) |
L266P |
probably damaging |
Het |
| Abcb1a |
A |
T |
5: 8,773,204 (GRCm39) |
T811S |
possibly damaging |
Het |
| Als2cl |
T |
C |
9: 110,714,855 (GRCm39) |
F125L |
probably benign |
Het |
| Arhgap33 |
T |
C |
7: 30,228,165 (GRCm39) |
I406V |
probably benign |
Het |
| Cdyl |
T |
C |
13: 36,042,174 (GRCm39) |
I404T |
probably damaging |
Het |
| Cemip2 |
G |
A |
19: 21,784,818 (GRCm39) |
V434M |
probably damaging |
Het |
| Clasrp |
C |
T |
7: 19,320,362 (GRCm39) |
R432H |
unknown |
Het |
| Clk2 |
T |
A |
3: 89,082,730 (GRCm39) |
M392K |
probably damaging |
Het |
| Cps1 |
T |
A |
1: 67,267,439 (GRCm39) |
N1402K |
possibly damaging |
Het |
| Cyp2u1 |
T |
C |
3: 131,092,016 (GRCm39) |
H168R |
probably damaging |
Het |
| Dapl1 |
T |
C |
2: 59,335,056 (GRCm39) |
L70P |
probably damaging |
Het |
| Ddr2 |
T |
A |
1: 169,805,483 (GRCm39) |
K836* |
probably null |
Het |
| Dsel |
A |
G |
1: 111,787,994 (GRCm39) |
L847P |
probably benign |
Het |
| Fbxw17 |
A |
T |
13: 50,587,351 (GRCm39) |
K437M |
possibly damaging |
Het |
| Fktn |
T |
C |
4: 53,735,001 (GRCm39) |
V174A |
possibly damaging |
Het |
| Frem1 |
C |
A |
4: 82,821,754 (GRCm39) |
S2118I |
probably damaging |
Het |
| Fzd8 |
G |
A |
18: 9,213,247 (GRCm39) |
V110M |
unknown |
Het |
| Gabrb3 |
T |
C |
7: 57,442,329 (GRCm39) |
S212P |
probably damaging |
Het |
| Gimap9 |
A |
G |
6: 48,654,821 (GRCm39) |
D136G |
probably benign |
Het |
| Gldc |
C |
G |
19: 30,078,212 (GRCm39) |
M928I |
probably benign |
Het |
| Hmmr |
G |
A |
11: 40,612,499 (GRCm39) |
S206F |
probably damaging |
Het |
| Ift46 |
C |
T |
9: 44,701,819 (GRCm39) |
T283I |
probably damaging |
Het |
| Il36b |
C |
T |
2: 24,049,892 (GRCm39) |
Q168* |
probably null |
Het |
| Ldb2 |
G |
A |
5: 44,956,757 (GRCm39) |
Q27* |
probably null |
Het |
| Lmcd1 |
T |
A |
6: 112,306,770 (GRCm39) |
I314N |
probably damaging |
Het |
| Lypd9 |
T |
G |
11: 58,337,129 (GRCm39) |
S115R |
probably damaging |
Het |
| Mctp2 |
C |
A |
7: 71,879,081 (GRCm39) |
V259L |
probably benign |
Het |
| Midn |
T |
G |
10: 79,990,234 (GRCm39) |
S302A |
probably damaging |
Het |
| Ncor2 |
A |
G |
5: 125,106,291 (GRCm39) |
V797A |
|
Het |
| Npm2 |
A |
G |
14: 70,885,768 (GRCm39) |
S146P |
probably damaging |
Het |
| Npr1 |
G |
A |
3: 90,372,201 (GRCm39) |
R204C |
probably damaging |
Het |
| Or1j10 |
T |
C |
2: 36,267,006 (GRCm39) |
S73P |
probably damaging |
Het |
| Or1n1b |
C |
A |
2: 36,780,622 (GRCm39) |
M79I |
probably benign |
Het |
| Or52n3 |
T |
A |
7: 104,530,862 (GRCm39) |
V316D |
possibly damaging |
Het |
| Or6e1 |
C |
T |
14: 54,520,070 (GRCm39) |
G94D |
probably benign |
Het |
| Orc2 |
T |
C |
1: 58,515,639 (GRCm39) |
N290D |
probably benign |
Het |
| Paip2b |
A |
C |
6: 83,791,738 (GRCm39) |
M48R |
probably damaging |
Het |
| Pcdhb15 |
T |
A |
18: 37,606,971 (GRCm39) |
S68T |
probably benign |
Het |
| Pcnx1 |
T |
A |
12: 82,020,022 (GRCm39) |
H715Q |
|
Het |
| Pdzph1 |
G |
C |
17: 59,187,715 (GRCm39) |
Y1168* |
probably null |
Het |
| Peli2 |
G |
A |
14: 48,490,130 (GRCm39) |
E201K |
possibly damaging |
Het |
| Prelp |
T |
C |
1: 133,842,878 (GRCm39) |
N89S |
probably damaging |
Het |
| Proz |
T |
A |
8: 13,113,253 (GRCm39) |
F25I |
probably damaging |
Het |
| Rapgef3 |
T |
C |
15: 97,646,538 (GRCm39) |
N799S |
probably benign |
Het |
| Relch |
T |
A |
1: 105,654,179 (GRCm39) |
F873L |
possibly damaging |
Het |
| Ryr3 |
G |
A |
2: 112,466,137 (GRCm39) |
R4795W |
probably damaging |
Het |
| Ryr3 |
A |
G |
2: 112,690,069 (GRCm39) |
V1180A |
probably benign |
Het |
| Scn11a |
T |
C |
9: 119,645,586 (GRCm39) |
I123V |
probably benign |
Het |
| Sema4b |
G |
C |
7: 79,870,248 (GRCm39) |
E475D |
probably damaging |
Het |
| Serinc2 |
C |
A |
4: 130,149,172 (GRCm39) |
M343I |
probably damaging |
Het |
| Serinc5 |
G |
T |
13: 92,844,544 (GRCm39) |
V429F |
probably benign |
Het |
| Smyd2 |
T |
A |
1: 189,632,018 (GRCm39) |
K115N |
probably benign |
Het |
| Tenm3 |
T |
G |
8: 48,763,759 (GRCm39) |
D765A |
probably damaging |
Het |
| Unc13d |
AATGCCTCCCATGCC |
AATGCCTCCCATGCCTCCCATGCC |
11: 115,958,998 (GRCm39) |
|
probably benign |
Het |
| Ythdc2 |
C |
T |
18: 44,967,531 (GRCm39) |
R176* |
probably null |
Het |
| Zfp27 |
T |
C |
7: 29,594,013 (GRCm39) |
K651E |
probably benign |
Het |
|
| Other mutations in Pcsk2 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00503:Pcsk2
|
APN |
2 |
143,635,159 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01609:Pcsk2
|
APN |
2 |
143,643,078 (GRCm39) |
missense |
possibly damaging |
0.88 |
|
IGL01690:Pcsk2
|
APN |
2 |
143,529,490 (GRCm39) |
missense |
probably benign |
|
|
IGL01833:Pcsk2
|
APN |
2 |
143,529,500 (GRCm39) |
missense |
possibly damaging |
0.62 |
|
IGL01962:Pcsk2
|
APN |
2 |
143,655,552 (GRCm39) |
nonsense |
probably null |
|
|
IGL02219:Pcsk2
|
APN |
2 |
143,635,045 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02572:Pcsk2
|
APN |
2 |
143,532,262 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02752:Pcsk2
|
APN |
2 |
143,615,865 (GRCm39) |
missense |
probably benign |
0.09 |
|
P0035:Pcsk2
|
UTSW |
2 |
143,637,871 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0092:Pcsk2
|
UTSW |
2 |
143,642,944 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1424:Pcsk2
|
UTSW |
2 |
143,415,348 (GRCm39) |
splice site |
probably benign |
|
|
R1470:Pcsk2
|
UTSW |
2 |
143,388,438 (GRCm39) |
nonsense |
probably null |
|
|
R1470:Pcsk2
|
UTSW |
2 |
143,388,438 (GRCm39) |
nonsense |
probably null |
|
|
R1832:Pcsk2
|
UTSW |
2 |
143,635,189 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1993:Pcsk2
|
UTSW |
2 |
143,529,539 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4615:Pcsk2
|
UTSW |
2 |
143,637,889 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4783:Pcsk2
|
UTSW |
2 |
143,529,599 (GRCm39) |
critical splice donor site |
probably null |
|
|
R4796:Pcsk2
|
UTSW |
2 |
143,655,345 (GRCm39) |
missense |
probably benign |
0.16 |
|
R4827:Pcsk2
|
UTSW |
2 |
143,643,099 (GRCm39) |
nonsense |
probably null |
|
|
R5357:Pcsk2
|
UTSW |
2 |
143,415,384 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5413:Pcsk2
|
UTSW |
2 |
143,538,620 (GRCm39) |
splice site |
probably null |
|
|
R5440:Pcsk2
|
UTSW |
2 |
143,388,463 (GRCm39) |
missense |
probably benign |
0.22 |
|
R5546:Pcsk2
|
UTSW |
2 |
143,388,480 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5605:Pcsk2
|
UTSW |
2 |
143,591,165 (GRCm39) |
intron |
probably benign |
|
|
R5821:Pcsk2
|
UTSW |
2 |
143,591,035 (GRCm39) |
splice site |
probably null |
|
|
R5905:Pcsk2
|
UTSW |
2 |
143,591,060 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R6120:Pcsk2
|
UTSW |
2 |
143,643,031 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6135:Pcsk2
|
UTSW |
2 |
143,415,460 (GRCm39) |
missense |
possibly damaging |
0.63 |
|
R6657:Pcsk2
|
UTSW |
2 |
143,532,286 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6925:Pcsk2
|
UTSW |
2 |
143,655,667 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7223:Pcsk2
|
UTSW |
2 |
143,532,253 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R7289:Pcsk2
|
UTSW |
2 |
143,532,343 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8043:Pcsk2
|
UTSW |
2 |
143,655,450 (GRCm39) |
nonsense |
probably null |
|
|
R8803:Pcsk2
|
UTSW |
2 |
143,637,870 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8819:Pcsk2
|
UTSW |
2 |
143,642,990 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R9131:Pcsk2
|
UTSW |
2 |
143,655,583 (GRCm39) |
missense |
possibly damaging |
0.56 |
|
R9643:Pcsk2
|
UTSW |
2 |
143,655,501 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9753:Pcsk2
|
UTSW |
2 |
143,635,150 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- TAACACACAAATGCCTTCCTTGAG -3'
(R):5'- AAGAAGTTCTGCCCCTACTTACTC -3'
Sequencing Primer
(F):5'- GCCTTCCTTGAGTTAAAAGTTCACAG -3'
(R):5'- ACTTACTCAGGGTTCTGCACAGAG -3'
|
| Posted On |
2021-04-30 |
Incidental Mutation