Mutagenetix > Incidental Mutation

Incidental Mutation 'R7000:Pkp1'

544432

Institutional Source

Beutler Lab

Gene Symbol

Pkp1

Ensembl Gene

ENSMUSG00000026413

Gene Name

plakophilin 1

Synonyms

MMRRC Submission

045105-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.640) question?

Stock #

R7000 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

135799133-135846945 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 135817692 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Valine at position 148 (M148V)

Ref Sequence

ENSEMBL: ENSMUSP00000140883 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000027667] [ENSMUST00000163260] [ENSMUST00000189805]

AlphaFold

P97350

Predicted Effect

probably benign
Transcript: ENSMUST00000027667
AA Change: M148V

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000027667
Gene: ENSMUSG00000026413
AA Change: M148V

Domain	Start	End	E-Value	Type
low complexity region	52	60	N/A	INTRINSIC
ARM	277	317	2.65e-9	SMART
ARM	319	360	3.47e-4	SMART
ARM	361	416	1.3e1	SMART
ARM	417	464	5.59e1	SMART
ARM	516	557	8.48e1	SMART
ARM	565	604	3.85e0	SMART
ARM	605	650	5.76e1	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000163260
AA Change: M148V

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000128418
Gene: ENSMUSG00000026413
AA Change: M148V

Domain	Start	End	E-Value	Type
low complexity region	52	60	N/A	INTRINSIC
ARM	277	317	2.65e-9	SMART
ARM	319	360	3.47e-4	SMART
ARM	361	416	1.3e1	SMART
ARM	417	464	5.59e1	SMART
ARM	516	557	8.48e1	SMART
ARM	565	604	3.85e0	SMART
ARM	605	650	5.76e1	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000189805
AA Change: M148V

PolyPhen 2 Score 0.411 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000140883
Gene: ENSMUSG00000026413
AA Change: M148V

Domain	Start	End	E-Value	Type
low complexity region	52	60	N/A	INTRINSIC

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.3%

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 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 protein may be involved in molecular recruitment and stabilization during desmosome formation. Mutations in this gene have been associated with the ectodermal dysplasia/skin fragility syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit reduced birth weight, absent whiskers, and neonatal lethality associated with skin fragility, skin lesions, loss of desmosomal adhesion, and impaired skin barrier function due to abnormal tight junction formation. [provided by MGI curators]

Allele List at MGI

All alleles(4) : Targeted(4)

Other mutations in this stock

Total: 82 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcb1a	G	A	5: 8,752,823 (GRCm39)	A525T	probably benign	Het
Abcc6	A	G	7: 45,654,946 (GRCm39)	I515T	possibly damaging	Het
Abi1	G	A	2: 22,832,053 (GRCm39)	A420V	probably damaging	Het
Abtb2	A	T	2: 103,542,787 (GRCm39)	I887F	possibly damaging	Het
Acap3	G	A	4: 155,988,306 (GRCm39)	G602S	possibly damaging	Het
Auts2	T	A	5: 131,469,056 (GRCm39)	T754S	probably benign	Het
AW551984	T	C	9: 39,512,085 (GRCm39)	R12G	probably benign	Het
Bcan	G	A	3: 87,895,686 (GRCm39)	R817*	probably null	Het
Bmp10	A	G	6: 87,411,175 (GRCm39)	T323A	probably benign	Het
Bpnt1	T	C	1: 185,082,053 (GRCm39)	L165P	probably damaging	Het
Casz1	G	A	4: 149,013,693 (GRCm39)	A86T	probably damaging	Het
Ccn3	A	T	15: 54,615,743 (GRCm39)	T303S	probably damaging	Het
Cd1d2	T	C	3: 86,895,080 (GRCm39)	F189L	probably benign	Het
Cep72	A	G	13: 74,206,444 (GRCm39)	M126T	probably damaging	Het
Cep85l	T	A	10: 53,174,295 (GRCm39)	T483S	probably damaging	Het
Cfi	C	A	3: 129,666,522 (GRCm39)	T415K	probably damaging	Het
Chrna7	A	G	7: 62,755,787 (GRCm39)	L253S	probably damaging	Het
Col4a4	T	C	1: 82,475,051 (GRCm39)	H596R	unknown	Het
Cplx3	G	C	9: 57,523,231 (GRCm39)	Q109E	probably benign	Het
Cyp2j8	A	T	4: 96,335,588 (GRCm39)	M402K	probably benign	Het
Cyp3a16	T	A	5: 145,399,980 (GRCm39)		probably null	Het
Dhdh	T	C	7: 45,124,698 (GRCm39)	K332E	possibly damaging	Het
Dnah11	C	A	12: 117,981,396 (GRCm39)	C2590F	probably damaging	Het
Dnah17	T	C	11: 117,916,528 (GRCm39)		probably null	Het
Dtx1	A	G	5: 120,833,148 (GRCm39)	Y97H	probably damaging	Het
Duxf1	T	C	10: 58,058,814 (GRCm39)	T647A	possibly damaging	Het
Elf1	A	G	14: 79,808,208 (GRCm39)	D183G	probably damaging	Het
Esyt3	A	C	9: 99,204,206 (GRCm39)	L94R	probably damaging	Het
Exoc3	A	G	13: 74,330,285 (GRCm39)	Y521H	probably benign	Het
F5	C	T	1: 164,007,075 (GRCm39)	T293M	probably damaging	Het
Fam118b	A	T	9: 35,146,560 (GRCm39)	H102Q	probably damaging	Het
Flad1	T	C	3: 89,309,549 (GRCm39)		probably benign	Het
Flrt3	G	A	2: 140,502,804 (GRCm39)	R275*	probably null	Het
Fndc7	G	A	3: 108,783,964 (GRCm39)	A215V	probably benign	Het
Fscn1	T	A	5: 142,946,382 (GRCm39)	V60E	probably damaging	Het
Gm17175	A	T	14: 51,811,418 (GRCm39)	M1K	probably null	Het
Gpatch2l	G	A	12: 86,290,958 (GRCm39)	R47H	probably damaging	Het
Gprc6a	T	C	10: 51,491,143 (GRCm39)	S694G	probably benign	Het
Iglon5	A	T	7: 43,126,254 (GRCm39)		probably null	Het
Iqch	T	C	9: 63,361,892 (GRCm39)	T874A	probably benign	Het
Lamc2	T	A	1: 153,041,873 (GRCm39)	H87L	possibly damaging	Het
Ldlrad1	T	A	4: 107,066,777 (GRCm39)	D37E	probably benign	Het
Loxhd1	T	C	18: 77,460,129 (GRCm39)		probably null	Het
Lxn	T	G	3: 67,369,704 (GRCm39)	E60D	probably benign	Het
Man2b2	A	G	5: 36,979,213 (GRCm39)	W276R	probably damaging	Het
Mast1	T	C	8: 85,655,598 (GRCm39)	Y182C	probably damaging	Het
Mroh8	C	T	2: 157,058,897 (GRCm39)	R923Q	probably benign	Het
Obscn	A	G	11: 59,026,864 (GRCm39)	L113P	probably damaging	Het
Ocln	C	T	13: 100,671,470 (GRCm39)		probably null	Het
Oog2	A	T	4: 143,921,897 (GRCm39)	Q269L	probably damaging	Het
Or52e8	G	A	7: 104,624,338 (GRCm39)	P285S	probably damaging	Het
Or5b113	A	G	19: 13,341,987 (GRCm39)		probably benign	Het
Osbpl3	A	G	6: 50,274,137 (GRCm39)	S826P	probably damaging	Het
Otogl	T	C	10: 107,615,692 (GRCm39)	N1869S	probably benign	Het
Pamr1	G	A	2: 102,441,968 (GRCm39)	D186N	probably damaging	Het
Pcdhga8	T	A	18: 37,859,946 (GRCm39)	I334K	probably benign	Het
Pde7b	A	G	10: 20,319,038 (GRCm39)	S95P	probably damaging	Het
Pik3cg	A	T	12: 32,242,128 (GRCm39)	V994E	probably damaging	Het
Plbd1	T	G	6: 136,589,836 (GRCm39)	K461Q	probably benign	Het
Pmfbp1	A	G	8: 110,257,221 (GRCm39)	E594G	possibly damaging	Het
Pold3	A	T	7: 99,755,865 (GRCm39)	H60Q	probably damaging	Het
Polr3gl	C	T	3: 96,487,783 (GRCm39)	R52Q	possibly damaging	Het
Ptgds	A	G	2: 25,357,828 (GRCm39)		probably null	Het
Scarb2	T	C	5: 92,601,934 (GRCm39)	D320G	probably benign	Het
Sdk2	T	C	11: 113,693,995 (GRCm39)	Y1812C	probably damaging	Het
Skint8	C	A	4: 111,794,222 (GRCm39)	T204N	probably benign	Het
Slc23a2	T	C	2: 131,936,123 (GRCm39)	Q49R	possibly damaging	Het
Slc26a7	T	C	4: 14,552,476 (GRCm39)	Q227R	probably benign	Het
Sntn	C	T	14: 13,679,108 (GRCm38)	T94I	probably damaging	Het
Spem2	C	T	11: 69,708,582 (GRCm39)	G128S	probably benign	Het
Supt16	A	T	14: 52,408,907 (GRCm39)	S822R	probably damaging	Het
Syn3	T	C	10: 85,916,116 (GRCm39)	Y290C	probably damaging	Het
Tdrd6	C	G	17: 43,938,599 (GRCm39)	E816D	probably benign	Het
Tln1	A	T	4: 43,556,302 (GRCm39)	M72K	probably damaging	Het
Tlnrd1	A	G	7: 83,531,987 (GRCm39)	V148A	probably damaging	Het
Trim24	C	A	6: 37,935,613 (GRCm39)	T832K	probably benign	Het
Ubr4	C	T	4: 139,141,715 (GRCm39)	A1267V	probably damaging	Het
Usp17lb	A	T	7: 104,490,492 (GRCm39)	M145K	probably damaging	Het
Vmn1r178	T	A	7: 23,593,762 (GRCm39)	M270K	probably benign	Het
Vmn2r70	A	T	7: 85,208,819 (GRCm39)	C553S	probably damaging	Het
Vps37c	G	T	19: 10,687,693 (GRCm39)	E51D	probably damaging	Het
Zfp62	T	G	11: 49,107,206 (GRCm39)	Y432*	probably null	Het

Other mutations in Pkp1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00943:Pkp1	APN	1	135,805,922 (GRCm39)	missense	probably damaging	0.96
IGL02113:Pkp1	APN	1	135,811,652 (GRCm39)	missense	possibly damaging	0.92
IGL02149:Pkp1	APN	1	135,814,485 (GRCm39)	missense	probably benign	0.00
IGL02582:Pkp1	APN	1	135,817,664 (GRCm39)	missense	probably damaging	0.99
IGL02655:Pkp1	APN	1	135,817,511 (GRCm39)	missense	probably benign	0.14
IGL03166:Pkp1	APN	1	135,805,862 (GRCm39)	missense	probably damaging	1.00
P0008:Pkp1	UTSW	1	135,803,421 (GRCm39)	missense	probably benign	0.00
R0180:Pkp1	UTSW	1	135,814,538 (GRCm39)	missense	probably benign	0.00
R0368:Pkp1	UTSW	1	135,814,590 (GRCm39)	missense	probably benign	0.00
R0368:Pkp1	UTSW	1	135,803,421 (GRCm39)	missense	probably benign
R0601:Pkp1	UTSW	1	135,805,920 (GRCm39)	missense	probably damaging	1.00
R0725:Pkp1	UTSW	1	135,808,478 (GRCm39)	missense	probably benign	0.02
R1414:Pkp1	UTSW	1	135,811,823 (GRCm39)	splice site	probably benign
R1926:Pkp1	UTSW	1	135,805,411 (GRCm39)	missense	probably benign
R2082:Pkp1	UTSW	1	135,812,714 (GRCm39)	missense	possibly damaging	0.48
R2190:Pkp1	UTSW	1	135,807,709 (GRCm39)	missense	probably benign	0.02
R2249:Pkp1	UTSW	1	135,808,545 (GRCm39)	missense	probably damaging	1.00
R4457:Pkp1	UTSW	1	135,803,362 (GRCm39)	makesense	probably null
R4838:Pkp1	UTSW	1	135,810,326 (GRCm39)	missense	probably damaging	1.00
R4885:Pkp1	UTSW	1	135,846,690 (GRCm39)	missense	possibly damaging	0.92
R4995:Pkp1	UTSW	1	135,808,593 (GRCm39)	missense	possibly damaging	0.91
R5436:Pkp1	UTSW	1	135,846,656 (GRCm39)	missense	probably damaging	1.00
R5440:Pkp1	UTSW	1	135,810,230 (GRCm39)	missense	probably benign	0.41
R5652:Pkp1	UTSW	1	135,810,335 (GRCm39)	critical splice acceptor site	probably null
R5898:Pkp1	UTSW	1	135,810,259 (GRCm39)	missense	probably damaging	1.00
R5908:Pkp1	UTSW	1	135,846,621 (GRCm39)	nonsense	probably null
R6006:Pkp1	UTSW	1	135,805,406 (GRCm39)	splice site	probably null
R6013:Pkp1	UTSW	1	135,811,648 (GRCm39)	missense	probably damaging	1.00
R6218:Pkp1	UTSW	1	135,807,646 (GRCm39)	missense	probably damaging	0.96
R6232:Pkp1	UTSW	1	135,814,599 (GRCm39)	missense	probably benign	0.01
R7799:Pkp1	UTSW	1	135,817,695 (GRCm39)	missense	possibly damaging	0.94
R7883:Pkp1	UTSW	1	135,812,641 (GRCm39)	critical splice donor site	probably null
R8486:Pkp1	UTSW	1	135,846,714 (GRCm39)	missense	probably damaging	1.00
R8822:Pkp1	UTSW	1	135,807,661 (GRCm39)	missense	probably benign	0.00
R8848:Pkp1	UTSW	1	135,807,652 (GRCm39)	missense	probably damaging	1.00
R9099:Pkp1	UTSW	1	135,805,429 (GRCm39)	missense	probably benign
R9498:Pkp1	UTSW	1	135,817,820 (GRCm39)	missense	probably benign

Predicted Primers

PCR Primer
(F):5'- CACATACACCGGGTCTTGCTTG -3'
(R):5'- TTGTGGACAGCTAGATCCAGG -3'

Sequencing Primer
(F):5'- CTTGGAGGTGCAGGAGGGC -3'
(R):5'- TAGATCCAGGCTCCCAGTC -3'

Posted On

2019-05-13