Incidental Mutation 'P0014:Pkp2'
ID |
7576 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Pkp2
|
Ensembl Gene |
ENSMUSG00000041957 |
Gene Name |
plakophilin 2 |
Synonyms |
Pkp2l, 1200008D14Rik, 1200012P04Rik |
MMRRC Submission |
038267-MU
|
Accession Numbers |
|
Essential gene? |
Essential
(E-score: 1.000)
|
Stock # |
P0014 (G1)
|
Quality Score |
|
Status
|
Validated
|
Chromosome |
16 |
Chromosomal Location |
16031209-16090576 bp(+) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
C to T
at 16058386 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Proline to Leucine
at position 356
(P356L)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000036890
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000039408]
[ENSMUST00000161342]
|
AlphaFold |
Q9CQ73 |
Predicted Effect |
probably benign
Transcript: ENSMUST00000039408
AA Change: P356L
PolyPhen 2
Score 0.080 (Sensitivity: 0.93; Specificity: 0.85)
|
SMART Domains |
Protein: ENSMUSP00000036890 Gene: ENSMUSG00000041957 AA Change: P356L
Domain | Start | End | E-Value | Type |
low complexity region
|
258 |
271 |
N/A |
INTRINSIC |
ARM
|
342 |
382 |
7.5e-9 |
SMART |
ARM
|
384 |
425 |
5.14e-7 |
SMART |
Blast:ARM
|
426 |
481 |
2e-29 |
BLAST |
ARM
|
484 |
530 |
8.76e-1 |
SMART |
ARM
|
631 |
672 |
2.98e-3 |
SMART |
Blast:ARM
|
677 |
718 |
2e-11 |
BLAST |
Blast:ARM
|
720 |
763 |
5e-17 |
BLAST |
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000161342
|
SMART Domains |
Protein: ENSMUSP00000125219 Gene: ENSMUSG00000041957
Domain | Start | End | E-Value | Type |
low complexity region
|
258 |
271 |
N/A |
INTRINSIC |
Pfam:Arm
|
342 |
382 |
3.5e-10 |
PFAM |
Pfam:Arm
|
384 |
425 |
4.7e-9 |
PFAM |
Blast:ARM
|
426 |
477 |
5e-27 |
BLAST |
|
Meta Mutation Damage Score |
0.0898 |
Coding Region Coverage |
- 1x: 85.4%
- 3x: 80.7%
- 10x: 66.7%
- 20x: 50.4%
|
Validation Efficiency |
95% (100/105) |
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 arm-repeat (armadillo) and plakophilin gene families. Plakophilin proteins contain numerous armadillo repeats, localize to cell desmosomes and nuclei, and participate in linking cadherins to intermediate filaments in the cytoskeleton. This gene product may regulate the signaling activity of beta-catenin. Two alternately spliced transcripts encoding two protein isoforms have been identified. A processed pseudogene with high similarity to this locus has been mapped to chromosome 12p13. [provided by RefSeq, Jul 2008] PHENOTYPE: Homozygous null mice display embryonic lethality with impaired heart formation, hemopericardium, and hemoperitoneum. [provided by MGI curators]
|
Allele List at MGI |
All alleles(6) : Targeted(2) Gene trapped(4)
|
Other mutations in this stock |
Total: 19 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
Abcb4 |
A |
G |
5: 9,000,083 (GRCm39) |
Y1017C |
probably benign |
Het |
Acly |
T |
C |
11: 100,375,430 (GRCm39) |
I787V |
probably benign |
Het |
Aldob |
T |
C |
4: 49,538,153 (GRCm39) |
Q325R |
probably benign |
Het |
Armh4 |
C |
T |
14: 49,989,116 (GRCm39) |
E618K |
probably damaging |
Het |
Capns2 |
A |
G |
8: 93,628,842 (GRCm39) |
T244A |
probably damaging |
Het |
Clec16a |
C |
T |
16: 10,378,020 (GRCm39) |
|
probably benign |
Het |
Creb3 |
A |
G |
4: 43,563,265 (GRCm39) |
T121A |
possibly damaging |
Het |
Ddah1 |
A |
G |
3: 145,558,913 (GRCm39) |
D160G |
probably benign |
Het |
Dhx57 |
A |
T |
17: 80,582,620 (GRCm39) |
H328Q |
probably benign |
Het |
Dmxl2 |
A |
C |
9: 54,309,048 (GRCm39) |
L1901R |
probably damaging |
Het |
Dnah5 |
T |
A |
15: 28,403,619 (GRCm39) |
L3448Q |
probably damaging |
Het |
Gcdh |
A |
G |
8: 85,615,154 (GRCm39) |
|
probably null |
Het |
Lrrc8c |
T |
C |
5: 105,755,110 (GRCm39) |
V295A |
probably benign |
Het |
Nek1 |
A |
T |
8: 61,524,781 (GRCm39) |
|
probably benign |
Het |
Sipa1l3 |
T |
C |
7: 29,082,640 (GRCm39) |
T752A |
probably damaging |
Het |
Slc38a2 |
C |
A |
15: 96,588,042 (GRCm39) |
W494L |
probably damaging |
Het |
Ttn |
T |
C |
2: 76,628,814 (GRCm39) |
D12734G |
probably damaging |
Het |
Uggt2 |
A |
G |
14: 119,281,950 (GRCm39) |
S742P |
probably damaging |
Het |
Vwa3b |
C |
T |
1: 37,212,995 (GRCm39) |
|
probably benign |
Het |
|
Other mutations in Pkp2 |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
R0131:Pkp2
|
UTSW |
16 |
16,058,577 (GRCm39) |
splice site |
probably benign |
|
R0581:Pkp2
|
UTSW |
16 |
16,087,647 (GRCm39) |
splice site |
probably benign |
|
R0722:Pkp2
|
UTSW |
16 |
16,064,892 (GRCm39) |
missense |
probably benign |
|
R0882:Pkp2
|
UTSW |
16 |
16,087,575 (GRCm39) |
missense |
probably damaging |
1.00 |
R0942:Pkp2
|
UTSW |
16 |
16,043,894 (GRCm39) |
missense |
probably benign |
|
R1236:Pkp2
|
UTSW |
16 |
16,043,766 (GRCm39) |
missense |
probably benign |
|
R1265:Pkp2
|
UTSW |
16 |
16,043,168 (GRCm39) |
missense |
probably benign |
0.00 |
R1674:Pkp2
|
UTSW |
16 |
16,058,422 (GRCm39) |
missense |
possibly damaging |
0.50 |
R1687:Pkp2
|
UTSW |
16 |
16,086,573 (GRCm39) |
critical splice donor site |
probably null |
|
R1769:Pkp2
|
UTSW |
16 |
16,080,561 (GRCm39) |
missense |
probably damaging |
1.00 |
R2094:Pkp2
|
UTSW |
16 |
16,064,831 (GRCm39) |
missense |
probably damaging |
1.00 |
R4360:Pkp2
|
UTSW |
16 |
16,086,546 (GRCm39) |
missense |
probably benign |
0.03 |
R4739:Pkp2
|
UTSW |
16 |
16,048,588 (GRCm39) |
missense |
probably damaging |
0.99 |
R5162:Pkp2
|
UTSW |
16 |
16,078,200 (GRCm39) |
missense |
probably damaging |
1.00 |
R5607:Pkp2
|
UTSW |
16 |
16,078,239 (GRCm39) |
missense |
probably damaging |
0.98 |
R6334:Pkp2
|
UTSW |
16 |
16,043,933 (GRCm39) |
missense |
probably damaging |
0.99 |
R6918:Pkp2
|
UTSW |
16 |
16,090,082 (GRCm39) |
missense |
probably damaging |
1.00 |
R7274:Pkp2
|
UTSW |
16 |
16,064,793 (GRCm39) |
missense |
possibly damaging |
0.92 |
R7408:Pkp2
|
UTSW |
16 |
16,079,537 (GRCm39) |
missense |
possibly damaging |
0.50 |
R7698:Pkp2
|
UTSW |
16 |
16,058,523 (GRCm39) |
missense |
probably benign |
0.01 |
R7788:Pkp2
|
UTSW |
16 |
16,043,272 (GRCm39) |
missense |
probably benign |
0.01 |
R8030:Pkp2
|
UTSW |
16 |
16,064,774 (GRCm39) |
missense |
probably benign |
|
R8056:Pkp2
|
UTSW |
16 |
16,031,264 (GRCm39) |
missense |
probably benign |
0.28 |
R8161:Pkp2
|
UTSW |
16 |
16,031,313 (GRCm39) |
missense |
probably damaging |
0.99 |
R8253:Pkp2
|
UTSW |
16 |
16,086,406 (GRCm39) |
missense |
probably damaging |
1.00 |
R8681:Pkp2
|
UTSW |
16 |
16,048,545 (GRCm39) |
missense |
probably benign |
|
R9259:Pkp2
|
UTSW |
16 |
16,043,714 (GRCm39) |
missense |
probably damaging |
1.00 |
R9570:Pkp2
|
UTSW |
16 |
16,078,278 (GRCm39) |
missense |
possibly damaging |
0.71 |
R9720:Pkp2
|
UTSW |
16 |
16,087,584 (GRCm39) |
missense |
probably benign |
0.18 |
Z1176:Pkp2
|
UTSW |
16 |
16,048,564 (GRCm39) |
missense |
probably benign |
|
|
Protein Function and Prediction |
Plakophilin 2 (Pkp2) links the cytoplasmic tails of cadherins to the intermediate filament cytoskeleton (1).
|
Expression/Localization |
Northern blot analysis of PKP2 detected transcripts in epithelial and nonepithelial cell lines and tissues (2). In human tissues and cell lines, western blot analysis detected PKP2 at the desmosomal plaque in simple epithelia, some stratified epithelia, and some nonepithelial cells. PKP2 is also enriched in the karyoplasm of cells of various types, including those lacking desmosomes (2).
|
Background |
Heterozygous mutations in PKP2 can cause arrhythmogenic right ventricular dysplasia 9 [ARVD9; OMIM #609040); (3)], a disorder characterized by arrhythmia with a left branch block pattern.
Pkp2tm1Wbm/tm1Wbm; MGI:3487374
involves: C57BL/6
Homozygous embryos begin to die around E11.5 and exhibit thinner atrial walls, abnormal adhering junctions between the cardiomyoctes, pericardial edem, edema, and poor circulation (4).
|
References |
3. Gerull, B., Heuser, A., Wichter, T., Paul, M., Basson, C. T., McDermott, D. A., Lerman, B. B., Markowitz, S. M., Ellinor, P. T., MacRae, C. A., Peters, S., Grossmann, K. S., Drenckhahn, J., Michely, B., Sasse-Klaassen, S., Birchmeier, W., Dietz, R., Breithardt, G., Schulze-Bahr, E., and Thierfelder, L. (2004) Mutations in the Desmosomal Protein Plakophilin-2 are Common in Arrhythmogenic Right Ventricular Cardiomyopathy. Nat Genet. 36, 1162-1164.
4. Grossmann, K. S., Grund, C., Huelsken, J., Behrend, M., Erdmann, B., Franke, W. W., and Birchmeier, W. (2004) Requirement of Plakophilin 2 for Heart Morphogenesis and Cardiac Junction Formation. J Cell Biol. 167, 149-160.
|
Posted On |
2012-10-05 |
Science Writer |
Anne Murray |