Incidental Mutation 'R1981:Pcsk4'
| ID |
222357 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Pcsk4
|
| Ensembl Gene |
ENSMUSG00000020131 |
| Gene Name |
proprotein convertase subtilisin/kexin type 4 |
| Synonyms |
PC4, SPC5 |
| MMRRC Submission |
039993-MU
|
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
R1981 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
10 |
| Chromosomal Location |
80157117-80165332 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to A
at 80161613 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Glutamic Acid to Valine
at position 176
(E176V)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000137719
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000020340]
[ENSMUST00000040081]
[ENSMUST00000105354]
[ENSMUST00000105355]
[ENSMUST00000105357]
[ENSMUST00000105358]
[ENSMUST00000128653]
[ENSMUST00000135071]
[ENSMUST00000186864]
|
| AlphaFold |
P29121 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000020340
AA Change: E193V
PolyPhen 2
Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000020340
Gene: ENSMUSG00000020131
AA Change: E193V
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
26 |
N/A |
INTRINSIC |
|
Pfam:S8_pro-domain
|
34 |
110 |
1.2e-24 |
PFAM |
|
Pfam:Peptidase_S8
|
146 |
429 |
3.1e-50 |
PFAM |
|
Pfam:P_proprotein
|
488 |
574 |
5e-25 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000040081
|
| SMART Domains |
Protein: ENSMUSP00000043722
Gene: ENSMUSG00000035504
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:TB2_DP1_HVA22
|
50 |
118 |
8e-28 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000105354
|
| SMART Domains |
Protein: ENSMUSP00000100991
Gene: ENSMUSG00000035504
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:TB2_DP1_HVA22
|
50 |
144 |
5e-36 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000105355
|
| SMART Domains |
Protein: ENSMUSP00000100992
Gene: ENSMUSG00000035504
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:TB2_DP1_HVA22
|
50 |
144 |
3.4e-36 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000105357
|
| SMART Domains |
Protein: ENSMUSP00000100994
Gene: ENSMUSG00000035504
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
22 |
61 |
N/A |
INTRINSIC |
|
low complexity region
|
108 |
129 |
N/A |
INTRINSIC |
|
low complexity region
|
297 |
319 |
N/A |
INTRINSIC |
|
low complexity region
|
340 |
352 |
N/A |
INTRINSIC |
|
low complexity region
|
411 |
428 |
N/A |
INTRINSIC |
|
SCOP:d1gkub1
|
434 |
465 |
1e-3 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000105358
|
| SMART Domains |
Protein: ENSMUSP00000100995
Gene: ENSMUSG00000035504
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
22 |
61 |
N/A |
INTRINSIC |
|
low complexity region
|
108 |
129 |
N/A |
INTRINSIC |
|
low complexity region
|
324 |
346 |
N/A |
INTRINSIC |
|
low complexity region
|
367 |
379 |
N/A |
INTRINSIC |
|
low complexity region
|
438 |
455 |
N/A |
INTRINSIC |
|
SCOP:d1gkub1
|
461 |
492 |
8e-4 |
SMART |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000128653
AA Change: E193V
PolyPhen 2
Score 0.685 (Sensitivity: 0.86; Specificity: 0.92)
|
| SMART Domains |
Protein: ENSMUSP00000137809
Gene: ENSMUSG00000020131
AA Change: E193V
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
26 |
N/A |
INTRINSIC |
|
SCOP:d1kn6a_
|
31 |
102 |
8e-29 |
SMART |
|
Pfam:Peptidase_S8
|
150 |
242 |
6.4e-18 |
PFAM |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000135071
AA Change: E176V
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000137719
Gene: ENSMUSG00000020131
AA Change: E176V
| Domain | Start | End | E-Value | Type |
|---|
|
SCOP:d1kn6a_
|
14 |
85 |
3e-27 |
SMART |
|
Pfam:Peptidase_S8
|
133 |
187 |
1.7e-7 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000137177
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000147132
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000153167
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000130521
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000186864
|
| SMART Domains |
Protein: ENSMUSP00000140840
Gene: ENSMUSG00000035504
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:TB2_DP1_HVA22
|
50 |
144 |
5e-36 |
PFAM |
|
| Meta Mutation Damage Score |
0.1651 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.5%
- 10x: 96.9%
- 20x: 94.6%
|
| Validation Efficiency |
99% (80/81) |
| 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. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. The protease is expressed only in the testis, placenta, and ovary. It plays a critical role in fertilization, fetoplacental growth, and embryonic development and processes multiple prohormones including pro-pituitary adenylate cyclase-activating protein and pro-insulin-like growth factor II. [provided by RefSeq, Jan 2014]
PHENOTYPE: Inactivation of this locus results in significantly reduced male fertility, putatively due to impaired fertilization. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 80 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Anks1 |
T |
C |
17: 28,204,095 (GRCm39) |
V181A |
probably damaging |
Het |
| Aqp4 |
T |
C |
18: 15,526,608 (GRCm39) |
D291G |
probably damaging |
Het |
| Atad1 |
G |
T |
19: 32,673,210 (GRCm39) |
D224E |
probably benign |
Het |
| Atp1a3 |
T |
G |
7: 24,700,400 (GRCm39) |
E33A |
probably benign |
Het |
| Baz2b |
A |
G |
2: 59,754,024 (GRCm39) |
F1100L |
possibly damaging |
Het |
| Car7 |
C |
T |
8: 105,275,009 (GRCm39) |
|
probably benign |
Het |
| Casp8 |
C |
A |
1: 58,868,121 (GRCm39) |
|
probably null |
Het |
| Cdh23 |
A |
T |
10: 60,214,530 (GRCm39) |
L1495H |
probably damaging |
Het |
| Ceacam9 |
T |
G |
7: 16,459,232 (GRCm39) |
L177R |
probably benign |
Het |
| Col16a1 |
C |
G |
4: 129,959,236 (GRCm39) |
P346A |
unknown |
Het |
| Cyp2c29 |
A |
G |
19: 39,296,216 (GRCm39) |
|
probably null |
Het |
| Cyp3a13 |
T |
C |
5: 137,910,118 (GRCm39) |
S139G |
probably damaging |
Het |
| Dapk2 |
A |
G |
9: 66,176,180 (GRCm39) |
H327R |
probably benign |
Het |
| Ddx19b |
T |
C |
8: 111,735,975 (GRCm39) |
T357A |
possibly damaging |
Het |
| Dnah2 |
A |
G |
11: 69,365,151 (GRCm39) |
Y1944H |
probably damaging |
Het |
| Dnai2 |
T |
A |
11: 114,623,755 (GRCm39) |
V6E |
probably damaging |
Het |
| Eipr1 |
T |
C |
12: 28,913,024 (GRCm39) |
Y242H |
probably damaging |
Het |
| Fam149a |
T |
G |
8: 45,834,778 (GRCm39) |
D7A |
probably damaging |
Het |
| Fam217a |
T |
A |
13: 35,100,737 (GRCm39) |
D140V |
probably benign |
Het |
| Fat4 |
G |
A |
3: 39,045,813 (GRCm39) |
C3944Y |
probably damaging |
Het |
| Fezf2 |
G |
T |
14: 12,344,405 (GRCm38) |
P261T |
probably benign |
Het |
| Gcsam |
A |
T |
16: 45,440,337 (GRCm39) |
T127S |
probably damaging |
Het |
| Git2 |
C |
T |
5: 114,887,620 (GRCm39) |
|
probably benign |
Het |
| Gm1527 |
T |
C |
3: 28,969,984 (GRCm39) |
|
probably null |
Het |
| Gtf3c1 |
A |
G |
7: 125,243,444 (GRCm39) |
L1720P |
possibly damaging |
Het |
| H2-T9 |
T |
A |
17: 36,439,614 (GRCm39) |
D122V |
probably damaging |
Het |
| Hat1 |
A |
G |
2: 71,220,321 (GRCm39) |
T28A |
probably benign |
Het |
| Igf2r |
G |
A |
17: 12,952,790 (GRCm39) |
Q219* |
probably null |
Het |
| Impdh1 |
T |
A |
6: 29,206,450 (GRCm39) |
D129V |
possibly damaging |
Het |
| Kcnh8 |
GAGACCAACGAGCAGCTGATGCTTCAGA |
GAGA |
17: 53,032,934 (GRCm39) |
74 |
probably benign |
Het |
| Ltbp3 |
A |
G |
19: 5,808,107 (GRCm39) |
Q1250R |
probably benign |
Het |
| Mansc4 |
T |
A |
6: 146,977,173 (GRCm39) |
I148F |
probably benign |
Het |
| Mast2 |
T |
C |
4: 116,172,037 (GRCm39) |
Y569C |
probably damaging |
Het |
| Mcoln3 |
A |
T |
3: 145,846,345 (GRCm39) |
K552* |
probably null |
Het |
| Mctp2 |
T |
C |
7: 71,814,446 (GRCm39) |
Q601R |
probably benign |
Het |
| Mei1 |
A |
G |
15: 81,987,513 (GRCm39) |
N859S |
probably benign |
Het |
| Myo19 |
A |
T |
11: 84,782,996 (GRCm39) |
Q170L |
possibly damaging |
Het |
| Myo1h |
T |
C |
5: 114,491,898 (GRCm39) |
F676S |
probably damaging |
Het |
| Myo9a |
A |
G |
9: 59,801,429 (GRCm39) |
T1876A |
probably benign |
Het |
| Nav3 |
G |
T |
10: 109,554,951 (GRCm39) |
|
probably benign |
Het |
| Ndor1 |
T |
C |
2: 25,145,236 (GRCm39) |
Y43C |
probably damaging |
Het |
| Nlrp1a |
A |
G |
11: 70,989,764 (GRCm39) |
V1102A |
probably damaging |
Het |
| Nmnat3 |
T |
C |
9: 98,292,352 (GRCm39) |
I199T |
possibly damaging |
Het |
| Nsun7 |
T |
C |
5: 66,418,557 (GRCm39) |
S96P |
probably damaging |
Het |
| Ntng1 |
A |
G |
3: 109,842,326 (GRCm39) |
V149A |
possibly damaging |
Het |
| Oas3 |
T |
C |
5: 120,899,900 (GRCm39) |
|
probably benign |
Het |
| Or10v9 |
T |
G |
19: 11,832,371 (GRCm39) |
Q315H |
possibly damaging |
Het |
| Or4k47 |
T |
A |
2: 111,451,586 (GRCm39) |
I278F |
probably benign |
Het |
| Or5bw2 |
A |
G |
7: 6,573,557 (GRCm39) |
D189G |
probably benign |
Het |
| Or6z7 |
T |
C |
7: 6,483,931 (GRCm39) |
M75V |
probably benign |
Het |
| Or8b3 |
T |
C |
9: 38,315,031 (GRCm39) |
L287P |
probably damaging |
Het |
| Or8k53 |
A |
T |
2: 86,177,486 (GRCm39) |
I208N |
possibly damaging |
Het |
| Pax2 |
G |
A |
19: 44,806,904 (GRCm39) |
D301N |
probably damaging |
Het |
| Pkhd1 |
G |
A |
1: 20,187,284 (GRCm39) |
P3675S |
probably benign |
Het |
| Plekho2 |
A |
T |
9: 65,465,974 (GRCm39) |
L138Q |
probably damaging |
Het |
| Ppp4r3c1 |
A |
T |
X: 88,975,051 (GRCm39) |
V382E |
probably damaging |
Het |
| Prkcsh |
A |
G |
9: 21,924,164 (GRCm39) |
D458G |
probably damaging |
Het |
| Prr11 |
T |
A |
11: 86,994,116 (GRCm39) |
D100V |
probably damaging |
Het |
| Qars1 |
A |
G |
9: 108,392,227 (GRCm39) |
N136D |
probably damaging |
Het |
| Rbm15b |
A |
G |
9: 106,758,822 (GRCm39) |
|
probably benign |
Het |
| Rel |
C |
T |
11: 23,692,761 (GRCm39) |
G424D |
probably benign |
Het |
| Rsrc1 |
A |
G |
3: 67,257,338 (GRCm39) |
D250G |
probably benign |
Het |
| Samt3 |
A |
C |
X: 85,090,740 (GRCm39) |
M211L |
probably benign |
Het |
| Scn2a |
C |
A |
2: 65,520,514 (GRCm39) |
N503K |
probably damaging |
Het |
| Sh2d6 |
G |
A |
6: 72,494,527 (GRCm39) |
|
probably benign |
Het |
| Smg8 |
T |
C |
11: 86,976,157 (GRCm39) |
T475A |
probably benign |
Het |
| Ssxb10 |
A |
G |
X: 8,197,258 (GRCm39) |
D77G |
probably benign |
Het |
| Tbx20 |
T |
A |
9: 24,682,209 (GRCm39) |
K48N |
possibly damaging |
Het |
| Tead1 |
C |
A |
7: 112,490,952 (GRCm39) |
D231E |
probably benign |
Het |
| Ticam1 |
C |
T |
17: 56,578,555 (GRCm39) |
R180H |
probably damaging |
Het |
| Tjp1 |
A |
T |
7: 64,962,603 (GRCm39) |
F1111L |
probably damaging |
Het |
| Tlr11 |
T |
A |
14: 50,599,445 (GRCm39) |
I477K |
possibly damaging |
Het |
| Ttc13 |
A |
G |
8: 125,440,926 (GRCm39) |
|
probably null |
Het |
| Ttc17 |
T |
C |
2: 94,157,049 (GRCm39) |
N411S |
probably benign |
Het |
| Usp15 |
T |
A |
10: 122,960,946 (GRCm39) |
|
probably benign |
Het |
| Usp18 |
A |
G |
6: 121,229,476 (GRCm39) |
K32E |
probably benign |
Het |
| Vmn1r12 |
A |
T |
6: 57,136,646 (GRCm39) |
M248L |
probably benign |
Het |
| Zbtb14 |
C |
A |
17: 69,695,497 (GRCm39) |
F398L |
probably damaging |
Het |
| Zfp930 |
T |
A |
8: 69,680,824 (GRCm39) |
L172H |
probably damaging |
Het |
| Zfp976 |
G |
A |
7: 42,263,046 (GRCm39) |
H264Y |
probably damaging |
Het |
|
| Other mutations in Pcsk4 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00161:Pcsk4
|
APN |
10 |
80,158,657 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02818:Pcsk4
|
APN |
10 |
80,158,626 (GRCm39) |
missense |
probably damaging |
0.98 |
|
IGL03115:Pcsk4
|
APN |
10 |
80,164,883 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03354:Pcsk4
|
APN |
10 |
80,161,893 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R0538:Pcsk4
|
UTSW |
10 |
80,161,168 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0760:Pcsk4
|
UTSW |
10 |
80,161,775 (GRCm39) |
unclassified |
probably benign |
|
|
R1462:Pcsk4
|
UTSW |
10 |
80,161,815 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1462:Pcsk4
|
UTSW |
10 |
80,161,815 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1554:Pcsk4
|
UTSW |
10 |
80,157,785 (GRCm39) |
missense |
probably benign |
0.01 |
|
R1728:Pcsk4
|
UTSW |
10 |
80,159,404 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1784:Pcsk4
|
UTSW |
10 |
80,159,404 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1886:Pcsk4
|
UTSW |
10 |
80,164,794 (GRCm39) |
missense |
probably benign |
0.32 |
|
R2090:Pcsk4
|
UTSW |
10 |
80,161,655 (GRCm39) |
missense |
probably benign |
0.02 |
|
R2125:Pcsk4
|
UTSW |
10 |
80,159,713 (GRCm39) |
missense |
probably benign |
0.32 |
|
R2283:Pcsk4
|
UTSW |
10 |
80,158,584 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4183:Pcsk4
|
UTSW |
10 |
80,160,845 (GRCm39) |
missense |
probably benign |
0.12 |
|
R4283:Pcsk4
|
UTSW |
10 |
80,165,287 (GRCm39) |
unclassified |
probably benign |
|
|
R4798:Pcsk4
|
UTSW |
10 |
80,158,938 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4857:Pcsk4
|
UTSW |
10 |
80,160,873 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4990:Pcsk4
|
UTSW |
10 |
80,161,215 (GRCm39) |
missense |
possibly damaging |
0.74 |
|
R4991:Pcsk4
|
UTSW |
10 |
80,161,215 (GRCm39) |
missense |
possibly damaging |
0.74 |
|
R5020:Pcsk4
|
UTSW |
10 |
80,161,869 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5123:Pcsk4
|
UTSW |
10 |
80,157,979 (GRCm39) |
missense |
probably null |
0.56 |
|
R5354:Pcsk4
|
UTSW |
10 |
80,159,523 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R6077:Pcsk4
|
UTSW |
10 |
80,162,073 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R6102:Pcsk4
|
UTSW |
10 |
80,161,651 (GRCm39) |
nonsense |
probably null |
|
|
R6250:Pcsk4
|
UTSW |
10 |
80,161,426 (GRCm39) |
missense |
probably benign |
0.04 |
|
R6378:Pcsk4
|
UTSW |
10 |
80,164,809 (GRCm39) |
missense |
probably benign |
0.34 |
|
R6729:Pcsk4
|
UTSW |
10 |
80,160,935 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7308:Pcsk4
|
UTSW |
10 |
80,159,007 (GRCm39) |
missense |
probably benign |
0.41 |
|
R7595:Pcsk4
|
UTSW |
10 |
80,157,935 (GRCm39) |
missense |
possibly damaging |
0.84 |
|
R8004:Pcsk4
|
UTSW |
10 |
80,158,674 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8675:Pcsk4
|
UTSW |
10 |
80,158,896 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8777:Pcsk4
|
UTSW |
10 |
80,159,557 (GRCm39) |
missense |
probably benign |
0.29 |
|
R8777-TAIL:Pcsk4
|
UTSW |
10 |
80,159,557 (GRCm39) |
missense |
probably benign |
0.29 |
|
R9030:Pcsk4
|
UTSW |
10 |
80,164,858 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9262:Pcsk4
|
UTSW |
10 |
80,160,864 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9278:Pcsk4
|
UTSW |
10 |
80,161,224 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9526:Pcsk4
|
UTSW |
10 |
80,161,800 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R9546:Pcsk4
|
UTSW |
10 |
80,157,741 (GRCm39) |
missense |
possibly damaging |
0.59 |
|
R9733:Pcsk4
|
UTSW |
10 |
80,158,034 (GRCm39) |
missense |
probably damaging |
0.99 |
|
Z1176:Pcsk4
|
UTSW |
10 |
80,158,560 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
| Predicted Primers |
PCR Primer
(F):5'- TCTAGCATTGAAGGCCACAC -3'
(R):5'- TGGCATTGAGAAAGACCACCC -3'
Sequencing Primer
(F):5'- CCGGCACCACAGAAACCG -3'
(R):5'- CCGGACCTCTGGGCTAATTATG -3'
|
| Posted On |
2014-08-25 |
Incidental Mutation