Incidental Mutation 'R5065:Pcsk6'
| ID |
388290 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Pcsk6
|
| Ensembl Gene |
ENSMUSG00000030513 |
| Gene Name |
proprotein convertase subtilisin/kexin type 6 |
| Synonyms |
SPC4, PACE4, b2b2830Clo |
| MMRRC Submission |
042655-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly non essential
(E-score: 0.420)
|
| Stock # |
R5065 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
7 |
| Chromosomal Location |
65511884-65700134 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 65560047 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Aspartic acid to Glycine
at position 124
(D124G)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000095992
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000055576]
[ENSMUST00000098391]
[ENSMUST00000176199]
[ENSMUST00000176209]
|
| AlphaFold |
F6XJP7 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000055576
AA Change: D124G
PolyPhen 2
Score 0.746 (Sensitivity: 0.85; Specificity: 0.92)
|
| SMART Domains |
Protein: ENSMUSP00000053742
Gene: ENSMUSG00000030513
AA Change: D124G
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
54 |
N/A |
INTRINSIC |
|
Pfam:S8_pro-domain
|
65 |
141 |
3.1e-29 |
PFAM |
|
Pfam:Peptidase_S8
|
186 |
469 |
5.2e-49 |
PFAM |
|
Pfam:P_proprotein
|
529 |
619 |
9.7e-37 |
PFAM |
|
FU
|
682 |
729 |
5.87e-11 |
SMART |
|
EGF_like
|
688 |
737 |
5.03e1 |
SMART |
|
FU
|
733 |
780 |
4.35e-14 |
SMART |
|
EGF_like
|
738 |
771 |
3.57e1 |
SMART |
|
FU
|
784 |
828 |
2.08e-11 |
SMART |
|
EGF
|
789 |
819 |
2.48e1 |
SMART |
|
FU
|
832 |
877 |
9.4e-10 |
SMART |
|
EGF_like
|
837 |
868 |
6.28e1 |
SMART |
|
FU
|
885 |
933 |
8.58e-4 |
SMART |
|
EGF
|
890 |
920 |
1.69e1 |
SMART |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000098391
AA Change: D124G
PolyPhen 2
Score 0.843 (Sensitivity: 0.83; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000095992
Gene: ENSMUSG00000030513
AA Change: D124G
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
54 |
N/A |
INTRINSIC |
|
PDB:1KN6|A
|
62 |
129 |
2e-6 |
PDB |
|
low complexity region
|
131 |
144 |
N/A |
INTRINSIC |
|
Pfam:Peptidase_S8
|
190 |
478 |
1.1e-58 |
PFAM |
|
Pfam:P_proprotein
|
529 |
619 |
4.5e-37 |
PFAM |
|
FU
|
669 |
716 |
3.87e-11 |
SMART |
|
EGF_like
|
675 |
724 |
5.03e1 |
SMART |
|
FU
|
720 |
767 |
4.35e-14 |
SMART |
|
EGF_like
|
725 |
758 |
3.57e1 |
SMART |
|
FU
|
771 |
815 |
2.08e-11 |
SMART |
|
EGF
|
776 |
806 |
2.48e1 |
SMART |
|
FU
|
819 |
864 |
9.4e-10 |
SMART |
|
EGF_like
|
824 |
855 |
6.28e1 |
SMART |
|
FU
|
872 |
920 |
8.58e-4 |
SMART |
|
EGF
|
877 |
907 |
1.69e1 |
SMART |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000176199
AA Change: D2G
PolyPhen 2
Score 0.532 (Sensitivity: 0.88; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000135851
Gene: ENSMUSG00000030513
AA Change: D2G
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
9 |
22 |
N/A |
INTRINSIC |
|
Pfam:Peptidase_S8
|
68 |
160 |
1.3e-21 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000176209
AA Change: D37G
PolyPhen 2
Score 0.217 (Sensitivity: 0.91; Specificity: 0.88)
|
| SMART Domains |
Protein: ENSMUSP00000135033
Gene: ENSMUSG00000030513
AA Change: D37G
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
44 |
57 |
N/A |
INTRINSIC |
|
Pfam:Peptidase_S8
|
103 |
372 |
6.5e-50 |
PFAM |
|
Pfam:P_proprotein
|
368 |
458 |
6.2e-37 |
PFAM |
|
FU
|
521 |
568 |
5.87e-11 |
SMART |
|
EGF_like
|
527 |
576 |
5.03e1 |
SMART |
|
FU
|
572 |
619 |
4.35e-14 |
SMART |
|
EGF_like
|
577 |
610 |
3.57e1 |
SMART |
|
FU
|
623 |
667 |
2.08e-11 |
SMART |
|
EGF
|
628 |
658 |
2.48e1 |
SMART |
|
FU
|
671 |
716 |
9.4e-10 |
SMART |
|
EGF_like
|
676 |
707 |
6.28e1 |
SMART |
|
FU
|
724 |
772 |
8.58e-4 |
SMART |
|
EGF
|
729 |
759 |
1.69e1 |
SMART |
|
| Meta Mutation Damage Score |
0.1276 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.5%
- 10x: 96.8%
- 20x: 94.0%
|
| Validation Efficiency |
100% (36/36) |
| 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 the trans-Golgi network where a second autocatalytic event takes place and the catalytic activity is acquired. The encoded protease is constitutively secreted into the extracellular matrix and expressed in many tissues, including neuroendocrine, liver, gut, and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. Some of its substrates include transforming growth factor beta related proteins, proalbumin, and von Willebrand factor. This gene is thought to play a role in tumor progression and left-right patterning. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Feb 2014]
PHENOTYPE: Homozygous mutation of this gene results in partial lethality by E15.5. Embryos develop situs ambiguus with left pulmonary isomerism or craniofacial malformations including cyclopia, or both. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 31 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 2310009B15Rik |
T |
A |
1: 138,779,893 (GRCm39) |
N120Y |
probably damaging |
Het |
| A930011G23Rik |
G |
A |
5: 99,382,432 (GRCm39) |
T272M |
probably benign |
Het |
| Aldh9a1 |
A |
G |
1: 167,180,128 (GRCm39) |
E74G |
probably damaging |
Het |
| Asxl3 |
C |
G |
18: 22,658,356 (GRCm39) |
A2122G |
possibly damaging |
Het |
| Bcl2l10 |
A |
T |
9: 75,255,261 (GRCm39) |
E26V |
possibly damaging |
Het |
| Cspg4b |
T |
A |
13: 113,457,453 (GRCm39) |
H1166Q |
probably benign |
Het |
| Dennd2a |
C |
A |
6: 39,472,110 (GRCm39) |
|
probably null |
Het |
| Dock3 |
A |
G |
9: 106,832,883 (GRCm39) |
F129L |
probably damaging |
Het |
| Gm4847 |
A |
T |
1: 166,462,359 (GRCm39) |
I377N |
probably damaging |
Het |
| Gm8674 |
T |
C |
13: 50,056,613 (GRCm39) |
|
noncoding transcript |
Het |
| Hhipl2 |
A |
T |
1: 183,207,580 (GRCm39) |
H433L |
probably benign |
Het |
| Hsfy2 |
G |
A |
1: 56,675,626 (GRCm39) |
Q304* |
probably null |
Het |
| Ighg2c |
T |
C |
12: 113,251,708 (GRCm39) |
I140V |
unknown |
Het |
| Kmt2a |
T |
C |
9: 44,753,997 (GRCm39) |
|
probably benign |
Het |
| Map3k5 |
A |
G |
10: 19,958,213 (GRCm39) |
E671G |
probably damaging |
Het |
| Map6 |
A |
G |
7: 98,985,917 (GRCm39) |
D607G |
probably benign |
Het |
| Mroh4 |
C |
T |
15: 74,500,119 (GRCm39) |
|
probably null |
Het |
| Or10g6 |
A |
G |
9: 39,934,546 (GRCm39) |
I286V |
probably benign |
Het |
| Pkhd1l1 |
T |
A |
15: 44,445,689 (GRCm39) |
N3790K |
possibly damaging |
Het |
| Polr3b |
C |
A |
10: 84,468,402 (GRCm39) |
N129K |
probably benign |
Het |
| Ptpn23 |
A |
T |
9: 110,227,256 (GRCm39) |
L31Q |
possibly damaging |
Het |
| Sema3c |
A |
G |
5: 17,932,615 (GRCm39) |
N706S |
possibly damaging |
Het |
| Sipa1l2 |
T |
C |
8: 126,218,324 (GRCm39) |
I338V |
probably benign |
Het |
| Slc39a7 |
A |
G |
17: 34,250,033 (GRCm39) |
|
probably benign |
Het |
| Snd1 |
C |
A |
6: 28,888,239 (GRCm39) |
N891K |
probably damaging |
Het |
| Sntg1 |
A |
G |
1: 8,433,663 (GRCm39) |
|
probably benign |
Het |
| Stxbp5 |
A |
T |
10: 9,646,295 (GRCm39) |
L780Q |
probably damaging |
Het |
| Tacr1 |
G |
A |
6: 82,531,859 (GRCm39) |
V252M |
possibly damaging |
Het |
| Tdrp |
T |
C |
8: 14,003,791 (GRCm39) |
E182G |
probably damaging |
Het |
| Vmn1r58 |
A |
G |
7: 5,413,834 (GRCm39) |
I132T |
probably benign |
Het |
| Wap |
A |
T |
11: 6,586,840 (GRCm39) |
N86K |
probably damaging |
Het |
|
| Other mutations in Pcsk6 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00234:Pcsk6
|
APN |
7 |
65,577,568 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01609:Pcsk6
|
APN |
7 |
65,685,021 (GRCm39) |
splice site |
probably null |
|
|
IGL01986:Pcsk6
|
APN |
7 |
65,577,625 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02592:Pcsk6
|
APN |
7 |
65,618,776 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02720:Pcsk6
|
APN |
7 |
65,629,995 (GRCm39) |
nonsense |
probably null |
|
|
R0045:Pcsk6
|
UTSW |
7 |
65,612,676 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0045:Pcsk6
|
UTSW |
7 |
65,612,676 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0053:Pcsk6
|
UTSW |
7 |
65,633,451 (GRCm39) |
splice site |
probably benign |
|
|
R0053:Pcsk6
|
UTSW |
7 |
65,633,451 (GRCm39) |
splice site |
probably benign |
|
|
R0103:Pcsk6
|
UTSW |
7 |
65,578,845 (GRCm39) |
splice site |
probably benign |
|
|
R0103:Pcsk6
|
UTSW |
7 |
65,578,845 (GRCm39) |
splice site |
probably benign |
|
|
R0119:Pcsk6
|
UTSW |
7 |
65,688,791 (GRCm39) |
missense |
probably benign |
0.10 |
|
R0299:Pcsk6
|
UTSW |
7 |
65,688,791 (GRCm39) |
missense |
probably benign |
0.10 |
|
R0415:Pcsk6
|
UTSW |
7 |
65,683,622 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0496:Pcsk6
|
UTSW |
7 |
65,576,997 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0518:Pcsk6
|
UTSW |
7 |
65,629,915 (GRCm39) |
missense |
possibly damaging |
0.64 |
|
R0748:Pcsk6
|
UTSW |
7 |
65,688,716 (GRCm39) |
unclassified |
probably benign |
|
|
R1456:Pcsk6
|
UTSW |
7 |
65,693,283 (GRCm39) |
missense |
possibly damaging |
0.87 |
|
R1613:Pcsk6
|
UTSW |
7 |
65,560,059 (GRCm39) |
splice site |
probably benign |
|
|
R1680:Pcsk6
|
UTSW |
7 |
65,684,998 (GRCm39) |
missense |
probably benign |
0.14 |
|
R1682:Pcsk6
|
UTSW |
7 |
65,559,976 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1987:Pcsk6
|
UTSW |
7 |
65,577,035 (GRCm39) |
missense |
possibly damaging |
0.60 |
|
R4191:Pcsk6
|
UTSW |
7 |
65,675,056 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R4193:Pcsk6
|
UTSW |
7 |
65,675,056 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R4577:Pcsk6
|
UTSW |
7 |
65,609,014 (GRCm39) |
nonsense |
probably null |
|
|
R4592:Pcsk6
|
UTSW |
7 |
65,581,480 (GRCm39) |
missense |
possibly damaging |
0.54 |
|
R4687:Pcsk6
|
UTSW |
7 |
65,633,501 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4697:Pcsk6
|
UTSW |
7 |
65,608,989 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4778:Pcsk6
|
UTSW |
7 |
65,608,893 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5218:Pcsk6
|
UTSW |
7 |
65,675,036 (GRCm39) |
missense |
probably benign |
0.01 |
|
R5356:Pcsk6
|
UTSW |
7 |
65,620,340 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5427:Pcsk6
|
UTSW |
7 |
65,683,647 (GRCm39) |
missense |
probably benign |
0.01 |
|
R5589:Pcsk6
|
UTSW |
7 |
65,578,933 (GRCm39) |
critical splice donor site |
probably null |
|
|
R5637:Pcsk6
|
UTSW |
7 |
65,618,745 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5888:Pcsk6
|
UTSW |
7 |
65,693,372 (GRCm39) |
missense |
probably null |
|
|
R5958:Pcsk6
|
UTSW |
7 |
65,693,359 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5997:Pcsk6
|
UTSW |
7 |
65,609,041 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6191:Pcsk6
|
UTSW |
7 |
65,578,875 (GRCm39) |
missense |
probably benign |
0.19 |
|
R6274:Pcsk6
|
UTSW |
7 |
65,683,592 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6374:Pcsk6
|
UTSW |
7 |
65,629,903 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
R6393:Pcsk6
|
UTSW |
7 |
65,618,762 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6730:Pcsk6
|
UTSW |
7 |
65,629,996 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7205:Pcsk6
|
UTSW |
7 |
65,675,156 (GRCm39) |
critical splice donor site |
probably null |
|
|
R7493:Pcsk6
|
UTSW |
7 |
65,693,314 (GRCm39) |
missense |
possibly damaging |
0.53 |
|
R7570:Pcsk6
|
UTSW |
7 |
65,683,646 (GRCm39) |
missense |
probably benign |
0.03 |
|
R7731:Pcsk6
|
UTSW |
7 |
65,683,641 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7779:Pcsk6
|
UTSW |
7 |
65,675,152 (GRCm39) |
missense |
probably benign |
0.03 |
|
R8042:Pcsk6
|
UTSW |
7 |
65,577,683 (GRCm39) |
missense |
possibly damaging |
0.87 |
|
R8734:Pcsk6
|
UTSW |
7 |
65,581,481 (GRCm39) |
missense |
probably benign |
0.06 |
|
R8805:Pcsk6
|
UTSW |
7 |
65,578,891 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
R8987:Pcsk6
|
UTSW |
7 |
65,576,975 (GRCm39) |
nonsense |
probably null |
|
|
R9276:Pcsk6
|
UTSW |
7 |
65,559,950 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9492:Pcsk6
|
UTSW |
7 |
65,697,346 (GRCm39) |
missense |
probably benign |
0.02 |
|
R9747:Pcsk6
|
UTSW |
7 |
65,633,470 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Z1177:Pcsk6
|
UTSW |
7 |
65,683,559 (GRCm39) |
missense |
probably damaging |
0.99 |
|
Z1177:Pcsk6
|
UTSW |
7 |
65,608,861 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- ACTGACTGTGTGCCAAAAGC -3'
(R):5'- GAGAGCATTTAGTGGATGTGACATG -3'
Sequencing Primer
(F):5'- GCTCCTCTGGCAGCTGAATTG -3'
(R):5'- GATGTGACATGTTGCTCTATCTC -3'
|
| Posted On |
2016-06-06 |
Incidental Mutation