Incidental Mutation 'R4056:Pcsk9'
| ID |
314236 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Pcsk9
|
| Ensembl Gene |
ENSMUSG00000044254 |
| Gene Name |
proprotein convertase subtilisin/kexin type 9 |
| Synonyms |
Narc1 |
| MMRRC Submission |
041617-MU
|
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
R4056 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
4 |
| Chromosomal Location |
106299531-106321522 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to A
at 106301899 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Histidine to Leucine
at position 616
(H616L)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000055757
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000049507]
[ENSMUST00000094933]
[ENSMUST00000165709]
|
| AlphaFold |
Q80W65 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000049507
AA Change: H616L
PolyPhen 2
Score 0.023 (Sensitivity: 0.95; Specificity: 0.81)
|
| SMART Domains |
Protein: ENSMUSP00000055757
Gene: ENSMUSG00000044254
AA Change: H616L
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
12 |
27 |
N/A |
INTRINSIC |
|
Pfam:Peptidase_S8
|
180 |
438 |
3.1e-34 |
PFAM |
|
low complexity region
|
471 |
481 |
N/A |
INTRINSIC |
|
low complexity region
|
490 |
500 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000094933
|
| SMART Domains |
Protein: ENSMUSP00000092538
Gene: ENSMUSG00000028514
| Domain | Start | End | E-Value | Type |
|---|
|
Blast:UBA
|
5 |
43 |
2e-16 |
BLAST |
|
low complexity region
|
57 |
96 |
N/A |
INTRINSIC |
|
SCOP:d1gw5a_
|
348 |
882 |
6e-7 |
SMART |
|
low complexity region
|
1031 |
1059 |
N/A |
INTRINSIC |
|
low complexity region
|
1124 |
1150 |
N/A |
INTRINSIC |
|
low complexity region
|
1365 |
1378 |
N/A |
INTRINSIC |
|
Pfam:UCH
|
1685 |
2036 |
3.7e-54 |
PFAM |
|
Pfam:UCH_1
|
1686 |
1993 |
1.8e-27 |
PFAM |
|
low complexity region
|
2066 |
2081 |
N/A |
INTRINSIC |
|
low complexity region
|
2256 |
2267 |
N/A |
INTRINSIC |
|
low complexity region
|
2576 |
2592 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000165709
|
| SMART Domains |
Protein: ENSMUSP00000133095
Gene: ENSMUSG00000028514
| Domain | Start | End | E-Value | Type |
|---|
|
Blast:UBA
|
5 |
43 |
2e-16 |
BLAST |
|
low complexity region
|
57 |
96 |
N/A |
INTRINSIC |
|
SCOP:d1gw5a_
|
348 |
883 |
8e-7 |
SMART |
|
low complexity region
|
1032 |
1060 |
N/A |
INTRINSIC |
|
low complexity region
|
1125 |
1151 |
N/A |
INTRINSIC |
|
low complexity region
|
1366 |
1379 |
N/A |
INTRINSIC |
|
Pfam:UCH
|
1686 |
2037 |
2e-49 |
PFAM |
|
Pfam:UCH_1
|
1687 |
1994 |
4e-24 |
PFAM |
|
low complexity region
|
2067 |
2082 |
N/A |
INTRINSIC |
|
low complexity region
|
2257 |
2268 |
N/A |
INTRINSIC |
|
low complexity region
|
2577 |
2593 |
N/A |
INTRINSIC |
|
| Meta Mutation Damage Score |
0.0735 |
| Coding Region Coverage |
- 1x: 99.1%
- 3x: 98.5%
- 10x: 97.1%
- 20x: 94.6%
|
| Validation Efficiency |
100% (39/39) |
| 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 autocatalytic processing event with its prosegment in the ER and is constitutively secreted as an inactive protease into the extracellular matrix and trans-Golgi network. It is expressed in liver, intestine and kidney tissues and escorts specific receptors for lysosomal degradation. It plays a role in cholesterol and fatty acid metabolism. Mutations in this gene have been associated with autosomal dominant familial hypercholesterolemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]
PHENOTYPE: Homozygous null mice exhibit increased clearance of circulating cholesterol and decreased plasma cholesterol levels. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 38 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 5730455P16Rik |
T |
A |
11: 80,266,329 (GRCm39) |
|
probably benign |
Het |
| Abcf1 |
A |
G |
17: 36,270,807 (GRCm39) |
I510T |
possibly damaging |
Het |
| Adamts18 |
T |
A |
8: 114,464,212 (GRCm39) |
K749* |
probably null |
Het |
| Alms1 |
A |
G |
6: 85,564,785 (GRCm39) |
E53G |
unknown |
Het |
| Bmper |
A |
G |
9: 23,310,925 (GRCm39) |
H453R |
probably benign |
Het |
| Btg1 |
T |
A |
10: 96,454,216 (GRCm39) |
M1K |
probably null |
Het |
| Cfap91 |
A |
G |
16: 38,118,576 (GRCm39) |
V741A |
probably benign |
Het |
| Cntfr |
A |
G |
4: 41,658,900 (GRCm39) |
I277T |
probably damaging |
Het |
| Col6a4 |
C |
A |
9: 105,903,665 (GRCm39) |
R1642I |
probably damaging |
Het |
| Ctnna3 |
T |
C |
10: 64,838,347 (GRCm39) |
I808T |
probably damaging |
Het |
| Cyp1a1 |
T |
A |
9: 57,607,432 (GRCm39) |
V20D |
probably benign |
Het |
| Dnah17 |
T |
C |
11: 117,961,364 (GRCm39) |
T2554A |
probably benign |
Het |
| Fcgbp |
A |
T |
7: 27,803,541 (GRCm39) |
Q1715L |
probably benign |
Het |
| Gabarapl1 |
T |
C |
6: 129,515,593 (GRCm39) |
F77S |
probably damaging |
Het |
| Gvin3 |
G |
T |
7: 106,203,216 (GRCm39) |
D9E |
possibly damaging |
Het |
| Hpse2 |
T |
C |
19: 43,282,714 (GRCm39) |
K180E |
probably damaging |
Het |
| Hs3st2 |
T |
A |
7: 121,099,925 (GRCm39) |
L257Q |
probably damaging |
Het |
| Ighv1-18 |
T |
C |
12: 114,646,287 (GRCm39) |
T106A |
probably benign |
Het |
| Ints2 |
A |
C |
11: 86,133,778 (GRCm39) |
L424R |
probably damaging |
Het |
| Iqgap2 |
A |
G |
13: 95,886,541 (GRCm39) |
V114A |
probably damaging |
Het |
| Kalrn |
A |
T |
16: 34,134,579 (GRCm39) |
I401N |
probably damaging |
Het |
| Mast2 |
T |
A |
4: 116,194,698 (GRCm39) |
|
probably benign |
Het |
| Myo18a |
A |
G |
11: 77,702,839 (GRCm39) |
E5G |
possibly damaging |
Het |
| Nav3 |
A |
T |
10: 109,716,394 (GRCm39) |
|
probably null |
Het |
| Net1 |
G |
A |
13: 3,934,949 (GRCm39) |
T359I |
probably damaging |
Het |
| Plekha5 |
G |
T |
6: 140,534,958 (GRCm39) |
V597L |
possibly damaging |
Het |
| Plekhg3 |
T |
A |
12: 76,612,021 (GRCm39) |
I374N |
probably damaging |
Het |
| Pros1 |
A |
T |
16: 62,721,008 (GRCm39) |
R188* |
probably null |
Het |
| Rhbg |
C |
T |
3: 88,150,755 (GRCm39) |
V434I |
probably damaging |
Het |
| Rims1 |
A |
G |
1: 22,363,163 (GRCm39) |
|
probably benign |
Het |
| Rxfp2 |
T |
C |
5: 149,975,098 (GRCm39) |
|
probably null |
Het |
| Sbf2 |
T |
C |
7: 110,040,673 (GRCm39) |
I385V |
probably damaging |
Het |
| Slc22a23 |
A |
C |
13: 34,482,987 (GRCm39) |
Y181* |
probably null |
Het |
| Spata31 |
T |
A |
13: 65,069,469 (GRCm39) |
V539E |
probably benign |
Het |
| Trpv5 |
G |
A |
6: 41,636,639 (GRCm39) |
R436C |
probably damaging |
Het |
| Vmn1r13 |
G |
A |
6: 57,186,970 (GRCm39) |
C43Y |
probably benign |
Het |
| Wif1 |
G |
A |
10: 120,918,099 (GRCm39) |
V156I |
probably benign |
Het |
| Zfyve16 |
T |
C |
13: 92,641,057 (GRCm39) |
N1229S |
probably damaging |
Het |
|
| Other mutations in Pcsk9 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL02140:Pcsk9
|
APN |
4 |
106,311,843 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL02709:Pcsk9
|
APN |
4 |
106,304,886 (GRCm39) |
splice site |
probably benign |
|
|
IGL02804:Pcsk9
|
APN |
4 |
106,314,161 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02850:Pcsk9
|
APN |
4 |
106,316,062 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03009:Pcsk9
|
APN |
4 |
106,311,542 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03294:Pcsk9
|
APN |
4 |
106,303,967 (GRCm39) |
missense |
probably benign |
|
|
R0271:Pcsk9
|
UTSW |
4 |
106,306,246 (GRCm39) |
splice site |
probably benign |
|
|
R0321:Pcsk9
|
UTSW |
4 |
106,301,891 (GRCm39) |
missense |
probably benign |
|
|
R0413:Pcsk9
|
UTSW |
4 |
106,311,538 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0426:Pcsk9
|
UTSW |
4 |
106,307,274 (GRCm39) |
missense |
possibly damaging |
0.77 |
|
R0783:Pcsk9
|
UTSW |
4 |
106,307,314 (GRCm39) |
missense |
probably benign |
0.00 |
|
R2136:Pcsk9
|
UTSW |
4 |
106,303,967 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4438:Pcsk9
|
UTSW |
4 |
106,316,156 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4683:Pcsk9
|
UTSW |
4 |
106,316,092 (GRCm39) |
missense |
possibly damaging |
0.59 |
|
R4739:Pcsk9
|
UTSW |
4 |
106,304,353 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4801:Pcsk9
|
UTSW |
4 |
106,304,766 (GRCm39) |
missense |
probably benign |
0.43 |
|
R4802:Pcsk9
|
UTSW |
4 |
106,304,766 (GRCm39) |
missense |
probably benign |
0.43 |
|
R5249:Pcsk9
|
UTSW |
4 |
106,320,950 (GRCm39) |
missense |
probably benign |
0.01 |
|
R5307:Pcsk9
|
UTSW |
4 |
106,304,371 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5320:Pcsk9
|
UTSW |
4 |
106,320,988 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5653:Pcsk9
|
UTSW |
4 |
106,316,113 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5827:Pcsk9
|
UTSW |
4 |
106,306,144 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6010:Pcsk9
|
UTSW |
4 |
106,311,469 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
R6019:Pcsk9
|
UTSW |
4 |
106,314,073 (GRCm39) |
missense |
probably benign |
0.02 |
|
R6393:Pcsk9
|
UTSW |
4 |
106,304,793 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7472:Pcsk9
|
UTSW |
4 |
106,316,094 (GRCm39) |
missense |
probably benign |
0.08 |
|
R7614:Pcsk9
|
UTSW |
4 |
106,304,763 (GRCm39) |
missense |
probably benign |
0.34 |
|
R7807:Pcsk9
|
UTSW |
4 |
106,321,092 (GRCm39) |
missense |
possibly damaging |
0.73 |
|
R8036:Pcsk9
|
UTSW |
4 |
106,311,536 (GRCm39) |
missense |
possibly damaging |
0.88 |
|
R8735:Pcsk9
|
UTSW |
4 |
106,311,808 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9258:Pcsk9
|
UTSW |
4 |
106,316,047 (GRCm39) |
missense |
possibly damaging |
0.63 |
|
R9404:Pcsk9
|
UTSW |
4 |
106,311,723 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9684:Pcsk9
|
UTSW |
4 |
106,307,386 (GRCm39) |
missense |
probably benign |
0.29 |
|
Z1176:Pcsk9
|
UTSW |
4 |
106,316,138 (GRCm39) |
missense |
probably damaging |
0.96 |
|
| Predicted Primers |
PCR Primer
(F):5'- CCTTGTTTAACTGGACCAGAGTG -3'
(R):5'- CAGAGTCTGAGCTGCATGTTC -3'
Sequencing Primer
(F):5'- TGTTTAACTGGACCAGAGTGAAACC -3'
(R):5'- CATGTTCTCTGTTCTAGGCTGCAG -3'
|
| Posted On |
2015-04-30 |
Incidental Mutation