Mutagenetix > Incidental Mutation

Incidental Mutation 'R4995:Pkp1'

385142

Institutional Source

Beutler Lab

Gene Symbol

Pkp1

Ensembl Gene

ENSMUSG00000026413

Gene Name

plakophilin 1

Synonyms

MMRRC Submission

042589-MU

Accession Numbers

NCBI RefSeq: NM_019645.2; MGI: 1328359

Essential gene?

Possibly essential (E-score: 0.503) question?

Stock #

R4995 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

135871395-135919207 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 135880855 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 458 (I458N)

Ref Sequence

ENSEMBL: ENSMUSP00000128418 (fasta)

Gene Model

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

AlphaFold

P97350

Predicted Effect

possibly damaging
Transcript: ENSMUST00000027667
AA Change: I458N

PolyPhen 2 Score 0.913 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000027667
Gene: ENSMUSG00000026413
AA Change: I458N

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

noncoding transcript
Transcript: ENSMUST00000132793

Predicted Effect

possibly damaging
Transcript: ENSMUST00000163260
AA Change: I458N

PolyPhen 2 Score 0.913 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000128418
Gene: ENSMUSG00000026413
AA Change: I458N

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

SMART Domains

Protein: ENSMUSP00000140883
Gene: ENSMUSG00000026413

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

Meta Mutation Damage Score

0.1795

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.7%
20x: 93.6%

Validation Efficiency

99% (86/87)

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: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4921504E06Rik	G	A	2: 19,494,184	Q333*	probably null	Het
4930505A04Rik	C	T	11: 30,426,349	V173M	probably damaging	Het
Acvrl1	G	A	15: 101,135,860	R141H	probably benign	Het
Adprm	A	G	11: 67,041,610	F158L	possibly damaging	Het
Aldoart2	C	T	12: 55,566,253	T321M	probably benign	Het
Ap3m2	A	G	8: 22,803,776	V86A	probably benign	Het
Arhgef19	T	A	4: 141,247,515		probably null	Het
Armc4	G	A	18: 7,223,663	T460M	probably damaging	Het
Bcl2l12	T	G	7: 44,994,191		probably null	Het
Bptf	T	C	11: 107,054,565	Q2501R	probably damaging	Het
C230029F24Rik	A	T	1: 49,338,136		noncoding transcript	Het
C7	C	T	15: 5,049,592	G78D	probably damaging	Het
Caly	T	C	7: 140,070,625	T135A	probably benign	Het
Cbl	A	G	9: 44,153,811	M740T	possibly damaging	Het
Cbx4	A	G	11: 119,081,211	V446A	probably benign	Het
Celsr1	C	A	15: 85,937,911	R1735L	probably damaging	Het
Cep250	A	G	2: 155,988,316	D135G	probably damaging	Het
Cgn	T	C	3: 94,779,936	T19A	probably damaging	Het
Chic2	A	T	5: 75,044,204	V32D	probably damaging	Het
Cntln	A	G	4: 85,049,883	K780E	probably benign	Het
Col8a2	A	T	4: 126,310,788	D197V	probably damaging	Het
Crot	A	T	5: 8,974,000	V372E	probably damaging	Het
Cyb561d2	C	T	9: 107,541,548	V26M	probably damaging	Het
Ddx5	G	A	11: 106,785,236	T237I	probably damaging	Het
Dmxl2	G	T	9: 54,501,441		probably benign	Het
Dock8	T	A	19: 25,158,383	S1188R	probably benign	Het
Ehbp1	T	A	11: 22,101,073	H493L	probably damaging	Het
Eif5b	T	A	1: 38,051,711	*1217K	probably null	Het
Eprs	A	G	1: 185,410,139		probably benign	Het
Etfdh	T	C	3: 79,605,788	D376G	probably benign	Het
Fam186a	T	C	15: 99,945,099	Q1088R	probably benign	Het
Fbxw16	G	T	9: 109,441,250	T141N	probably damaging	Het
Fgf11	G	A	11: 69,798,759	H138Y	probably damaging	Het
Gm1673	G	A	5: 33,984,926	R79H	probably damaging	Het
Htra3	T	C	5: 35,671,074	E154G	probably damaging	Het
Hydin	T	A	8: 110,569,642	V3601D	probably damaging	Het
Jup	G	T	11: 100,379,541	S380*	probably null	Het
Klrg1	T	A	6: 122,278,275	D66V	probably benign	Het
Llgl1	C	T	11: 60,709,724	A633V	probably benign	Het
Lmln	T	A	16: 33,074,097	Y203*	probably null	Het
Lrrc58	T	G	16: 37,877,056	C165G	probably benign	Het
Lss	T	C	10: 76,547,537	V557A	probably benign	Het
Mast4	T	C	13: 102,905,754		probably benign	Het
Med13l	C	A	5: 118,730,949	P754Q	possibly damaging	Het
Mga	C	T	2: 119,932,582	R1240*	probably null	Het
Mgat5b	T	A	11: 116,974,199		probably null	Het
Mtor	A	G	4: 148,525,752	D1572G	probably damaging	Het
Muc4	T	A	16: 32,754,214	S1363T	probably benign	Het
Muc4	T	A	16: 32,754,041	S1306T	probably benign	Het
Myo18b	A	G	5: 112,760,392	V2005A	probably damaging	Het
Myo1e	G	A	9: 70,353,272	D571N	probably benign	Het
Mypn	T	C	10: 63,119,968		probably null	Het
Ndufb10	T	C	17: 24,722,757		probably null	Het
Nelfb	G	T	2: 25,206,196	D300E	probably benign	Het
Olfr1389	T	A	11: 49,430,655	Y60N	probably damaging	Het
Olfr1507	A	T	14: 52,490,531	C61*	probably null	Het
Olfr625-ps1	T	A	7: 103,683,367	D206E	probably damaging	Het
Olfr668	T	A	7: 104,925,735	T10S	probably benign	Het
Pcdha11	C	T	18: 37,011,027	T57M	probably benign	Het
Prr12	T	A	7: 45,051,229		probably benign	Het
Prrc2c	A	T	1: 162,705,310		probably benign	Het
Psd4	T	C	2: 24,397,247	F397S	probably benign	Het
Pygm	T	C	19: 6,398,139	I737T	probably damaging	Het
Rfx1	T	A	8: 84,080,114		probably null	Het
Rsl1	A	G	13: 67,182,249	T254A	possibly damaging	Het
Sh3rf3	A	G	10: 59,086,824	Q574R	probably benign	Het
Spire1	T	C	18: 67,552,779		probably null	Het
St6galnac4	G	A	2: 32,594,063	G91D	probably damaging	Het
Sytl2	T	C	7: 90,382,257		probably benign	Het
Tbpl2	T	A	2: 24,093,860	K188N	possibly damaging	Het
Tenm3	A	T	8: 48,229,137	M2486K	possibly damaging	Het
Tgoln1	A	C	6: 72,616,140	V119G	possibly damaging	Het
Tpgs1	A	T	10: 79,669,491	N28Y	probably benign	Het
U2surp	A	C	9: 95,462,794		probably benign	Het
Vmn2r103	A	G	17: 19,773,511	H50R	probably benign	Het
Vmn2r19	A	G	6: 123,329,910	N459S	probably benign	Het
Vmn2r72	T	C	7: 85,738,485	S624G	probably damaging	Het
Vps13c	A	G	9: 67,919,321	T1415A	probably benign	Het
Vwa5b1	G	A	4: 138,608,843	P147S	probably damaging	Het

Other mutations in Pkp1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00943:Pkp1	APN	1	135878184	missense	probably damaging	0.96
IGL02113:Pkp1	APN	1	135883914	missense	possibly damaging	0.92
IGL02149:Pkp1	APN	1	135886747	missense	probably benign	0.00
IGL02582:Pkp1	APN	1	135889926	missense	probably damaging	0.99
IGL02655:Pkp1	APN	1	135889773	missense	probably benign	0.14
IGL03166:Pkp1	APN	1	135878124	missense	probably damaging	1.00
P0008:Pkp1	UTSW	1	135875683	missense	probably benign	0.00
R0180:Pkp1	UTSW	1	135886800	missense	probably benign	0.00
R0368:Pkp1	UTSW	1	135875683	missense	probably benign
R0368:Pkp1	UTSW	1	135886852	missense	probably benign	0.00
R0601:Pkp1	UTSW	1	135878182	missense	probably damaging	1.00
R0725:Pkp1	UTSW	1	135880740	missense	probably benign	0.02
R1414:Pkp1	UTSW	1	135884085	splice site	probably benign
R1926:Pkp1	UTSW	1	135877673	missense	probably benign
R2082:Pkp1	UTSW	1	135884976	missense	possibly damaging	0.48
R2190:Pkp1	UTSW	1	135879971	missense	probably benign	0.02
R2249:Pkp1	UTSW	1	135880807	missense	probably damaging	1.00
R4457:Pkp1	UTSW	1	135875624	makesense	probably null
R4838:Pkp1	UTSW	1	135882588	missense	probably damaging	1.00
R4885:Pkp1	UTSW	1	135918952	missense	possibly damaging	0.92
R5436:Pkp1	UTSW	1	135918918	missense	probably damaging	1.00
R5440:Pkp1	UTSW	1	135882492	missense	probably benign	0.41
R5652:Pkp1	UTSW	1	135882597	critical splice acceptor site	probably null
R5898:Pkp1	UTSW	1	135882521	missense	probably damaging	1.00
R5908:Pkp1	UTSW	1	135918883	nonsense	probably null
R6006:Pkp1	UTSW	1	135877668	splice site	probably null
R6013:Pkp1	UTSW	1	135883910	missense	probably damaging	1.00
R6218:Pkp1	UTSW	1	135879908	missense	probably damaging	0.96
R6232:Pkp1	UTSW	1	135886861	missense	probably benign	0.01
R7000:Pkp1	UTSW	1	135889954	missense	probably benign	0.41
R7799:Pkp1	UTSW	1	135889957	missense	possibly damaging	0.94
R7883:Pkp1	UTSW	1	135884903	critical splice donor site	probably null
R8486:Pkp1	UTSW	1	135918976	missense	probably damaging	1.00
R8822:Pkp1	UTSW	1	135879923	missense	probably benign	0.00
R8848:Pkp1	UTSW	1	135879914	missense	probably damaging	1.00
R9099:Pkp1	UTSW	1	135877691	missense	probably benign
R9498:Pkp1	UTSW	1	135890082	missense	probably benign

Predicted Primers

PCR Primer
(F):5'- TTTCTGGGTCCAAGAAGAGGG -3'
(R):5'- GGGCCTAGTGCATAATCTACCC -3'

Sequencing Primer
(F):5'- TCCAAGAAGAGGGCTACGG -3'
(R):5'- AGGCTAGCCCATTTTACAGTG -3'

Posted On

2016-05-10