Incidental Mutation 'R2252:Pcsk1'
| ID |
241769 |
| Institutional Source |
Beutler Lab
|
| 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 |
| MMRRC Submission |
040252-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R2252 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
13 |
| Chromosomal Location |
75237945-75282980 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to A
at 75274845 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Alanine to Aspartic acid
at position 478
(A478D)
|
| 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 benign
Transcript: ENSMUST00000022075
AA Change: A478D
PolyPhen 2
Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
|
| SMART Domains |
Protein: ENSMUSP00000022075
Gene: ENSMUSG00000021587
AA Change: A478D
| Domain | Start | End | E-Value | Type |
|---|
|
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 |
- 1x: 99.1%
- 3x: 98.6%
- 10x: 97.3%
- 20x: 95.1%
|
| 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
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 1700129C05Rik |
G |
A |
14: 59,380,061 (GRCm39) |
S79F |
probably damaging |
Het |
| Acaca |
G |
T |
11: 84,262,358 (GRCm39) |
V1987L |
probably damaging |
Het |
| B3gnt3 |
A |
T |
8: 72,145,462 (GRCm39) |
M302K |
probably damaging |
Het |
| BC048507 |
T |
C |
13: 68,011,626 (GRCm39) |
M1T |
probably null |
Het |
| Bckdk |
C |
A |
7: 127,504,590 (GRCm39) |
R105S |
probably damaging |
Het |
| Casp3 |
G |
T |
8: 47,090,990 (GRCm39) |
W214L |
probably damaging |
Het |
| Cd180 |
A |
T |
13: 102,842,906 (GRCm39) |
K651* |
probably null |
Het |
| Cdh15 |
T |
A |
8: 123,584,161 (GRCm39) |
D87E |
probably damaging |
Het |
| Cldn24 |
G |
T |
8: 48,275,363 (GRCm39) |
R62S |
probably benign |
Het |
| Cnot1 |
A |
G |
8: 96,489,814 (GRCm39) |
V463A |
probably benign |
Het |
| Cspg4 |
C |
T |
9: 56,805,330 (GRCm39) |
T2047I |
probably damaging |
Het |
| Cul2 |
A |
T |
18: 3,399,876 (GRCm39) |
L3F |
probably damaging |
Het |
| Cwc27 |
A |
T |
13: 104,768,237 (GRCm39) |
H419Q |
probably damaging |
Het |
| Dgkg |
A |
T |
16: 22,441,010 (GRCm39) |
M1K |
probably null |
Het |
| Dock5 |
A |
T |
14: 68,022,261 (GRCm39) |
L1171H |
probably damaging |
Het |
| Drc1 |
G |
T |
5: 30,500,075 (GRCm39) |
V103F |
probably benign |
Het |
| Ep400 |
A |
T |
5: 110,866,957 (GRCm39) |
N1062K |
unknown |
Het |
| Faap20 |
A |
C |
4: 155,335,010 (GRCm39) |
E37A |
possibly damaging |
Het |
| Foxa2 |
A |
G |
2: 147,886,086 (GRCm39) |
F243S |
probably damaging |
Het |
| Gzf1 |
T |
C |
2: 148,525,856 (GRCm39) |
M109T |
probably damaging |
Het |
| Itch |
T |
A |
2: 155,054,259 (GRCm39) |
M701K |
probably benign |
Het |
| Kpna1 |
T |
C |
16: 35,841,939 (GRCm39) |
Y280H |
possibly damaging |
Het |
| L1td1 |
A |
G |
4: 98,625,874 (GRCm39) |
|
probably null |
Het |
| Lrrc37a |
T |
C |
11: 103,392,293 (GRCm39) |
Q1044R |
probably benign |
Het |
| Lrrc52 |
A |
T |
1: 167,293,937 (GRCm39) |
I116N |
probably damaging |
Het |
| Mbd5 |
A |
G |
2: 49,147,698 (GRCm39) |
E636G |
probably damaging |
Het |
| Mrpl40 |
T |
C |
16: 18,694,125 (GRCm39) |
H29R |
probably benign |
Het |
| Nrip1 |
T |
C |
16: 76,088,173 (GRCm39) |
Y1128C |
probably damaging |
Het |
| Or10d3 |
G |
T |
9: 39,461,273 (GRCm39) |
A298D |
probably damaging |
Het |
| Or4g16 |
A |
G |
2: 111,136,655 (GRCm39) |
Y35C |
probably damaging |
Het |
| Or5ak20 |
A |
G |
2: 85,184,202 (GRCm39) |
S23P |
possibly damaging |
Het |
| Or8c8 |
A |
G |
9: 38,165,126 (GRCm39) |
I135V |
probably benign |
Het |
| Pard3 |
A |
T |
8: 128,337,080 (GRCm39) |
E1232V |
probably damaging |
Het |
| Pcif1 |
A |
G |
2: 164,732,799 (GRCm39) |
E628G |
probably benign |
Het |
| Pkd1l2 |
T |
C |
8: 117,784,177 (GRCm39) |
Y700C |
probably damaging |
Het |
| Pknox2 |
T |
C |
9: 36,821,816 (GRCm39) |
N270D |
probably benign |
Het |
| Plcb2 |
T |
C |
2: 118,554,246 (GRCm39) |
N69S |
probably benign |
Het |
| Reep1 |
T |
A |
6: 71,733,426 (GRCm39) |
|
probably null |
Het |
| Sash1 |
A |
T |
10: 8,605,741 (GRCm39) |
M883K |
probably benign |
Het |
| Secisbp2l |
C |
T |
2: 125,582,657 (GRCm39) |
G933D |
possibly damaging |
Het |
| Septin4 |
A |
G |
11: 87,480,637 (GRCm39) |
N405D |
possibly damaging |
Het |
| Serpinb3b |
T |
C |
1: 107,083,208 (GRCm39) |
I231M |
possibly damaging |
Het |
| Serping1 |
A |
G |
2: 84,600,195 (GRCm39) |
S322P |
probably damaging |
Het |
| Slc7a2 |
T |
C |
8: 41,358,658 (GRCm39) |
Y334H |
probably benign |
Het |
| Spink5 |
G |
T |
18: 44,153,891 (GRCm39) |
E1013* |
probably null |
Het |
| Thoc3 |
A |
T |
13: 54,615,646 (GRCm39) |
N139K |
probably benign |
Het |
| Tns2 |
C |
T |
15: 102,017,369 (GRCm39) |
R281C |
probably damaging |
Het |
| Tubb2b |
T |
A |
13: 34,314,198 (GRCm39) |
I7F |
possibly damaging |
Het |
| Upf2 |
A |
G |
2: 5,966,271 (GRCm39) |
D297G |
unknown |
Het |
| Vmn2r18 |
T |
C |
5: 151,508,441 (GRCm39) |
I228V |
possibly damaging |
Het |
| Vmn2r98 |
A |
C |
17: 19,300,698 (GRCm39) |
S567R |
probably benign |
Het |
| Vwa5a |
T |
C |
9: 38,639,376 (GRCm39) |
I369T |
probably damaging |
Het |
| Yjefn3 |
A |
C |
8: 70,342,095 (GRCm39) |
F42V |
probably damaging |
Het |
| Zfp472 |
A |
T |
17: 33,195,257 (GRCm39) |
R69* |
probably null |
Het |
| Zfp536 |
T |
C |
7: 37,178,814 (GRCm39) |
S200G |
probably benign |
Het |
| Zfp970 |
T |
A |
2: 177,166,614 (GRCm39) |
|
probably null |
Het |
|
| Other mutations in Pcsk1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH 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 |
|
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 |
|
|
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 |
|
| Predicted Primers |
PCR Primer
(F):5'- TTGATATCCTTGTCATGGACCAC -3'
(R):5'- GAGTGGTTGTTGAAGTTTACCAAC -3'
Sequencing Primer
(F):5'- GGACCACTTTTGTTGAATTGAAGAC -3'
(R):5'- TGTTGAAGTTTACCAACAGCAG -3'
|
| Posted On |
2014-10-16 |
Incidental Mutation