Mutagenetix > Incidental Mutation

Incidental Mutation 'R2269:Vcp'

242290

Institutional Source

Beutler Lab

Gene Symbol

Vcp

Ensembl Gene

ENSMUSG00000028452

Gene Name

valosin containing protein

Synonyms

CDC48, p97, AAA ATPase p97, p97/VCP

MMRRC Submission

040269-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R2269 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

42979964-43000507 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 42980833 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Alanine to Valine at position 759 (A759V)

Ref Sequence

ENSEMBL: ENSMUSP00000030164 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000030164] [ENSMUST00000139127]

AlphaFold

Q01853

PDB Structure

STRUCTURE OF THE N-TERMINAL DOMAIN AND THE D1 AAA DOMAIN OF MEMBRANE FUSION ATPASE P97 [X-RAY DIFFRACTION]
The crystal structure of murine p97/VCP at 3.6A [X-RAY DIFFRACTION]
Crystal structure of AAA ATPase p97/VCP ND1 in complex with p47 C [X-RAY DIFFRACTION]
Strctural Model of the p97 N domain- npl4 UBD complex [SOLUTION NMR]
Structure of D2 subdomain of P97/VCP in complex with ADP [X-RAY DIFFRACTION]
Structure of P97/vcp in complex with ADP/ADP.alfx [X-RAY DIFFRACTION]
Structure of P97/vcp in complex with ADP/AMP-PNP [X-RAY DIFFRACTION]
Structure of P97/vcp in complex with ADP [X-RAY DIFFRACTION]

Predicted Effect

possibly damaging
Transcript: ENSMUST00000030164
AA Change: A759V

PolyPhen 2 Score 0.925 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000030164
Gene: ENSMUSG00000028452
AA Change: A759V

Domain	Start	End	E-Value	Type
CDC48_N	25	108	6.85e-27	SMART
CDC48_2	125	191	3.77e-15	SMART
AAA	237	373	7.87e-24	SMART
AAA	510	649	2e-25	SMART
Pfam:Vps4_C	710	762	3.5e-7	PFAM
low complexity region	775	794	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000139127

SMART Domains

Protein: ENSMUSP00000116415
Gene: ENSMUSG00000028451

Domain	Start	End	E-Value	Type
low complexity region	38	55	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000154541

Meta Mutation Damage Score

0.1281

Coding Region Coverage

1x: 99.2%
3x: 98.7%
10x: 97.5%
20x: 95.7%

Validation Efficiency

98% (79/81)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a member of a family that includes putative ATP-binding proteins involved in vesicle transport and fusion, 26S proteasome function, and assembly of peroxisomes. This protein, as a structural protein, is associated with clathrin, and heat-shock protein Hsc70, to form a complex. It has been implicated in a number of cellular events that are regulated during mitosis, including homotypic membrane fusion, spindle pole body function, and ubiquitin-dependent protein degradation. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous mutation of this gene results in lethality before weaning. Mice homozygous for a knock-in allele exhibit progressive muscle weakness, myopathy, decreased bone density, increased osteoclast genesis, and seizures. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca16	A	G	7: 120,030,383 (GRCm39)	D165G	probably benign	Het
Abca8a	A	C	11: 109,917,718 (GRCm39)	F1574V	probably damaging	Het
Adh6a	A	T	3: 138,034,857 (GRCm39)	I329L	probably benign	Het
Agap2	T	A	10: 126,918,297 (GRCm39)		probably benign	Het
Ager	A	T	17: 34,818,124 (GRCm39)	I185F	probably damaging	Het
Agrn	C	T	4: 156,263,675 (GRCm39)	G173R	probably damaging	Het
Arhgef16	T	A	4: 154,369,490 (GRCm39)	H329L	probably damaging	Het
Astn1	T	C	1: 158,329,669 (GRCm39)	Y175H	probably damaging	Het
Banp	A	G	8: 122,702,662 (GRCm39)	T70A	probably benign	Het
Bcl11b	T	C	12: 107,881,910 (GRCm39)	T802A	possibly damaging	Het
Ces2a	A	T	8: 105,466,822 (GRCm39)	I65F	probably benign	Het
Cflar	G	A	1: 58,780,206 (GRCm39)		probably null	Het
Clec16a	G	A	16: 10,462,650 (GRCm39)	R656H	probably damaging	Het
Cntn1	A	G	15: 92,192,863 (GRCm39)		probably benign	Het
Coasy	A	G	11: 100,976,708 (GRCm39)	T493A	probably benign	Het
Col16a1	C	A	4: 129,946,711 (GRCm39)	H111Q	probably benign	Het
Commd8	A	G	5: 72,322,765 (GRCm39)	W51R	probably damaging	Het
Cyp3a41b	A	T	5: 145,514,976 (GRCm39)	V83D	probably benign	Het
D2hgdh	C	T	1: 93,763,157 (GRCm39)	A314V	probably damaging	Het
Dcun1d4	T	A	5: 73,638,618 (GRCm39)		probably benign	Het
Decr2	C	A	17: 26,302,858 (GRCm39)	V173L	probably benign	Het
Defb11	A	G	8: 22,395,444 (GRCm39)	*78Q	probably null	Het
Dock3	C	A	9: 106,818,525 (GRCm39)	V1190F	probably damaging	Het
Dusp1	A	T	17: 26,726,093 (GRCm39)	I200N	probably damaging	Het
Efna1	G	A	3: 89,183,646 (GRCm39)	A60V	possibly damaging	Het
Egfl8	C	T	17: 34,832,832 (GRCm39)	V253M	probably damaging	Het
Epb41	T	A	4: 131,691,458 (GRCm39)	N623I	probably benign	Het
Fbxw22	C	T	9: 109,213,062 (GRCm39)	R295K	probably benign	Het
Foxn4	T	C	5: 114,393,662 (GRCm39)	T486A	probably damaging	Het
Gbe1	C	T	16: 70,233,840 (GRCm39)	A239V	probably damaging	Het
Gpatch3	C	T	4: 133,311,118 (GRCm39)	A518V	possibly damaging	Het
Gpc6	A	T	14: 118,125,932 (GRCm39)		probably null	Het
Hdhd2	C	T	18: 77,052,866 (GRCm39)	T172M	probably benign	Het
Heatr5a	T	C	12: 51,940,528 (GRCm39)	D1444G	possibly damaging	Het
Hnrnpul1	A	G	7: 25,450,299 (GRCm39)	Y138H	probably damaging	Het
Itgal	A	G	7: 126,905,873 (GRCm39)	I352V	possibly damaging	Het
Klhl31	A	G	9: 77,557,440 (GRCm39)	D52G	possibly damaging	Het
Klk1b21	T	C	7: 43,753,863 (GRCm39)	I49T	possibly damaging	Het
Lama2	T	A	10: 26,868,932 (GRCm39)	I2838F	probably damaging	Het
Lrrc43	A	T	5: 123,641,354 (GRCm39)	T513S	probably damaging	Het
Lsmem1	GTACATACATACATACATACATACATACA	GTACATACATACATACATACATACATACATACA	12: 40,235,260 (GRCm39)		probably null	Het
Mamdc2	A	T	19: 23,281,267 (GRCm39)		probably benign	Het
Mpdz	A	G	4: 81,301,628 (GRCm39)	S266P	probably damaging	Het
Mrc2	G	A	11: 105,239,257 (GRCm39)		probably null	Het
Mroh5	T	C	15: 73,664,997 (GRCm39)	N258D	probably benign	Het
Mrpl28	T	C	17: 26,345,285 (GRCm39)	V235A	probably benign	Het
Mtbp	G	A	15: 55,432,556 (GRCm39)		probably null	Het
Mtss2	A	G	8: 111,455,362 (GRCm39)	K92E	possibly damaging	Het
Muc4	C	A	16: 32,754,529 (GRCm38)	H1468N	probably benign	Het
Nav1	A	T	1: 135,399,974 (GRCm39)	L532*	probably null	Het
Or10ak16	A	T	4: 118,751,071 (GRCm39)	R264W	probably damaging	Het
Or1e23	A	G	11: 73,407,309 (GRCm39)	S239P	probably damaging	Het
Or51f1d	G	A	7: 102,701,344 (GRCm39)	V280I	probably benign	Het
Pappa2	A	G	1: 158,684,841 (GRCm39)	M766T	probably damaging	Het
Pkhd1	C	T	1: 20,604,759 (GRCm39)		probably null	Het
Plch2	T	C	4: 155,077,461 (GRCm39)	E423G	probably benign	Het
Prrc1	G	T	18: 57,514,718 (GRCm39)	D312Y	probably damaging	Het
Pxdn	T	A	12: 30,055,774 (GRCm39)	V1220E	probably damaging	Het
Robo1	T	A	16: 72,775,660 (GRCm39)	F728L	probably benign	Het
Rtel1	G	T	2: 180,977,796 (GRCm39)	Q292H	probably benign	Het
Sh3bp4	G	A	1: 89,073,314 (GRCm39)	V721I	possibly damaging	Het
Slc2a10	T	A	2: 165,356,701 (GRCm39)	C120*	probably null	Het
Srd5a2	T	C	17: 74,331,485 (GRCm39)	R171G	probably damaging	Het
Srsf4	T	C	4: 131,624,993 (GRCm39)	V130A	probably damaging	Het
Styk1	T	C	6: 131,289,539 (GRCm39)	E25G	probably benign	Het
Taar8b	T	C	10: 23,967,270 (GRCm39)	N308S	probably damaging	Het
Tbc1d14	A	G	5: 36,700,561 (GRCm39)	L269P	possibly damaging	Het
Tbx1	T	C	16: 18,400,744 (GRCm39)		probably null	Het
Tmem233	G	C	5: 116,189,517 (GRCm39)		probably benign	Het
Tmem252	T	C	19: 24,651,455 (GRCm39)	I8T	probably benign	Het
Vmn2r107	T	C	17: 20,595,817 (GRCm39)	I790T	possibly damaging	Het
Vmn2r77	T	C	7: 86,460,897 (GRCm39)	V741A	probably benign	Het
Vps13c	T	C	9: 67,828,229 (GRCm39)	V1461A	possibly damaging	Het
Ylpm1	T	A	12: 85,061,824 (GRCm39)	V575E	unknown	Het
Zbp1	T	A	2: 173,060,616 (GRCm39)		probably benign	Het
Zfp280d	C	A	9: 72,209,052 (GRCm39)		probably benign	Het
Zkscan5	A	G	5: 145,142,277 (GRCm39)	Y58C	probably damaging	Het

Other mutations in Vcp

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01460:Vcp	APN	4	42,996,040 (GRCm39)	missense	possibly damaging	0.69
IGL02251:Vcp	APN	4	42,988,728 (GRCm39)	missense	possibly damaging	0.49
H8562:Vcp	UTSW	4	42,982,596 (GRCm39)	missense	probably damaging	1.00
R0627:Vcp	UTSW	4	42,983,011 (GRCm39)	missense	possibly damaging	0.83
R0639:Vcp	UTSW	4	42,982,565 (GRCm39)	missense	probably benign	0.00
R0711:Vcp	UTSW	4	42,986,201 (GRCm39)	missense	probably benign	0.22
R0766:Vcp	UTSW	4	42,988,728 (GRCm39)	missense	possibly damaging	0.49
R1312:Vcp	UTSW	4	42,988,728 (GRCm39)	missense	possibly damaging	0.49
R1702:Vcp	UTSW	4	42,990,840 (GRCm39)	missense	probably damaging	1.00
R2071:Vcp	UTSW	4	42,995,894 (GRCm39)	critical splice donor site	probably null
R2192:Vcp	UTSW	4	42,982,547 (GRCm39)	missense	probably benign
R2262:Vcp	UTSW	4	42,980,828 (GRCm39)	missense	probably benign	0.04
R2265:Vcp	UTSW	4	42,980,833 (GRCm39)	missense	possibly damaging	0.93
R2268:Vcp	UTSW	4	42,980,833 (GRCm39)	missense	possibly damaging	0.93
R2443:Vcp	UTSW	4	42,983,385 (GRCm39)	missense	probably damaging	1.00
R2937:Vcp	UTSW	4	42,980,846 (GRCm39)	missense	probably damaging	1.00
R2973:Vcp	UTSW	4	42,996,315 (GRCm39)	missense	probably damaging	1.00
R4004:Vcp	UTSW	4	42,983,028 (GRCm39)	missense	probably damaging	1.00
R4488:Vcp	UTSW	4	42,993,826 (GRCm39)	missense	probably damaging	0.96
R4546:Vcp	UTSW	4	42,988,813 (GRCm39)	intron	probably benign
R4578:Vcp	UTSW	4	42,984,565 (GRCm39)	missense	probably benign	0.41
R4817:Vcp	UTSW	4	42,983,486 (GRCm39)	missense	probably damaging	1.00
R4869:Vcp	UTSW	4	42,993,691 (GRCm39)	missense	probably benign	0.00
R5014:Vcp	UTSW	4	42,980,828 (GRCm39)	missense	probably benign	0.04
R6128:Vcp	UTSW	4	42,980,941 (GRCm39)	missense	probably benign	0.00
R6594:Vcp	UTSW	4	42,993,826 (GRCm39)	missense	probably damaging	0.96
R7105:Vcp	UTSW	4	42,985,991 (GRCm39)	missense	probably damaging	1.00
R7470:Vcp	UTSW	4	42,982,891 (GRCm39)	missense	probably damaging	1.00
R8006:Vcp	UTSW	4	42,985,993 (GRCm39)	missense	probably benign	0.04
R8234:Vcp	UTSW	4	42,985,242 (GRCm39)	missense	probably damaging	1.00
R8313:Vcp	UTSW	4	42,988,728 (GRCm39)	missense	possibly damaging	0.49
R8751:Vcp	UTSW	4	42,984,658 (GRCm39)	missense	probably damaging	1.00
R8992:Vcp	UTSW	4	42,980,828 (GRCm39)	missense	probably benign	0.04
R9506:Vcp	UTSW	4	42,983,383 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TGTACACACTGCCACCTGTG -3'
(R):5'- TTAGAGTGCAAGCTGGATCCTAAC -3'

Sequencing Primer
(F):5'- CCTGAAGGGAATCTGTATACACAAG -3'
(R):5'- CTGGATCCTAACTAGCATAGTGGTC -3'

Posted On

2014-10-16