Mutagenetix > Incidental Mutation

Incidental Mutation 'R4739:Pcsk9'

359499

Institutional Source

Beutler Lab

Gene Symbol

Pcsk9

Ensembl Gene

ENSMUSG00000044254

Gene Name

proprotein convertase subtilisin/kexin type 9

Synonyms

Narc1

MMRRC Submission

042025-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R4739 (G1)

Quality Score

203

Status

Validated

Chromosome

Chromosomal Location

106299531-106321522 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 106304353 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glycine to Arginine at position 496 (G496R)

Ref Sequence

ENSEMBL: ENSMUSP00000055757 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000049507]

AlphaFold

Q80W65

Predicted Effect

probably damaging
Transcript: ENSMUST00000049507
AA Change: G496R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000055757
Gene: ENSMUSG00000044254
AA Change: G496R

Domain	Start	End	E-Value	Type
low complexity region	12	27	N/A	INTRINSIC
Pfam:Peptidase_S8	180	438	3.1e-34	PFAM
low complexity region	471	481	N/A	INTRINSIC
low complexity region	490	500	N/A	INTRINSIC

Meta Mutation Damage Score

0.1593

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 96.9%
20x: 94.5%

Validation Efficiency

96% (102/106)

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 autocatalytic processing event with its prosegment in the ER and is constitutively secreted as an inactive protease into the extracellular matrix and trans-Golgi network. It is expressed in liver, intestine and kidney tissues and escorts specific receptors for lysosomal degradation. It plays a role in cholesterol and fatty acid metabolism. Mutations in this gene have been associated with autosomal dominant familial hypercholesterolemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]
PHENOTYPE: Homozygous null mice exhibit increased clearance of circulating cholesterol and decreased plasma cholesterol levels. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 98 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1600012P17Rik	C	T	1: 158,796,904 (GRCm39)		noncoding transcript	Het
2300002M23Rik	A	G	17: 35,878,403 (GRCm39)		probably benign	Het
Aadat	T	C	8: 60,993,140 (GRCm39)	V360A	probably benign	Het
Abcc5	T	A	16: 20,218,376 (GRCm39)	D283V	probably damaging	Het
Abraxas1	T	A	5: 100,959,886 (GRCm39)	K155N	probably damaging	Het
Acot3	T	C	12: 84,105,364 (GRCm39)	I277T	probably benign	Het
Ankrd45	G	A	1: 160,982,960 (GRCm39)	C157Y	probably damaging	Het
Apol10a	C	T	15: 77,372,841 (GRCm39)	T159I	possibly damaging	Het
Arhgef11	G	A	3: 87,605,306 (GRCm39)	V214M	possibly damaging	Het
Ash1l	A	C	3: 88,890,152 (GRCm39)	N677T	probably benign	Het
Atg13	A	G	2: 91,515,040 (GRCm39)	S254P	probably damaging	Het
Atg16l2	A	G	7: 100,946,385 (GRCm39)	L129P	probably damaging	Het
Avl9	T	A	6: 56,703,294 (GRCm39)	V120D	probably damaging	Het
Castor1	A	G	11: 4,169,004 (GRCm39)	E57G	possibly damaging	Het
Cc2d1b	T	C	4: 108,485,239 (GRCm39)	V527A	probably benign	Het
Ccnl1	A	G	3: 65,854,092 (GRCm39)		probably benign	Het
Cenpl	T	A	1: 160,910,837 (GRCm39)	D261E	probably damaging	Het
Cep192	T	G	18: 67,984,803 (GRCm39)	I1604M	probably benign	Het
Cep95	A	G	11: 106,706,560 (GRCm39)	I573V	probably benign	Het
Cfap100	A	G	6: 90,389,825 (GRCm39)		probably null	Het
Ciao3	A	T	17: 26,000,283 (GRCm39)	H322L	probably damaging	Het
Cmc1	T	A	9: 117,904,245 (GRCm39)	M49L	probably benign	Het
Cyfip2	G	T	11: 46,170,820 (GRCm39)	N176K	probably damaging	Het
Cyp2w1	T	C	5: 139,342,430 (GRCm39)	F408L	probably damaging	Het
D630045J12Rik	G	A	6: 38,172,971 (GRCm39)	S399F	possibly damaging	Het
Dcbld2	T	A	16: 58,281,339 (GRCm39)	L528Q	probably damaging	Het
Dip2b	T	C	15: 100,105,658 (GRCm39)	V1138A	probably damaging	Het
Dip2c	T	A	13: 9,583,375 (GRCm39)	L119Q	probably damaging	Het
Dnah3	T	C	7: 119,677,169 (GRCm39)	D444G	possibly damaging	Het
Dsg1c	A	T	18: 20,408,246 (GRCm39)	N432Y	possibly damaging	Het
Dst	T	A	1: 34,230,228 (GRCm39)	I2785N	probably benign	Het
Dynap	A	T	18: 70,374,296 (GRCm39)	Y77N	possibly damaging	Het
Eif4g3	T	C	4: 137,910,510 (GRCm39)	L1330P	possibly damaging	Het
Eif4g3	T	A	4: 137,925,408 (GRCm39)	S1584T	probably benign	Het
Enpp1	A	T	10: 24,555,146 (GRCm39)	C67S	probably null	Het
Enpp5	C	T	17: 44,392,027 (GRCm39)	T152I	probably damaging	Het
Erbb4	T	C	1: 68,383,059 (GRCm39)	M313V	probably damaging	Het
Erc2	T	G	14: 27,498,838 (GRCm39)	L238R	probably damaging	Het
Eya3	T	A	4: 132,448,698 (GRCm39)		probably benign	Het
Farp1	T	C	14: 121,476,199 (GRCm39)	F339L	probably damaging	Het
Fsip2	A	C	2: 82,805,697 (GRCm39)	D672A	possibly damaging	Het
Gap43	G	T	16: 42,112,581 (GRCm39)	P60Q	probably benign	Het
Gpr37l1	T	A	1: 135,094,783 (GRCm39)	I154F	probably damaging	Het
Greb1	A	G	12: 16,746,329 (GRCm39)	S1314P	probably damaging	Het
Hectd4	A	T	5: 121,486,505 (GRCm39)	M3167L	probably benign	Het
Hps3	C	T	3: 20,084,574 (GRCm39)		probably null	Het
Hps5	A	G	7: 46,436,013 (GRCm39)	C178R	probably benign	Het
Hspg2	T	A	4: 137,297,384 (GRCm39)		probably benign	Het
Impdh2-ps	A	G	8: 100,757,839 (GRCm39)		noncoding transcript	Het
Josd2	T	A	7: 44,120,678 (GRCm39)	N138K	probably damaging	Het
Mtmr6	T	G	14: 60,529,546 (GRCm39)	M315R	probably damaging	Het
Mtrf1	G	A	14: 79,650,520 (GRCm39)	V323M	probably damaging	Het
Myo16	G	T	8: 10,423,527 (GRCm39)	G288W	probably damaging	Het
Myo18a	T	C	11: 77,714,149 (GRCm39)	Y748H	probably damaging	Het
Nek1	A	T	8: 61,551,545 (GRCm39)	N853I	probably benign	Het
Npnt	T	G	3: 132,610,452 (GRCm39)	T272P	possibly damaging	Het
Obi1	C	T	14: 104,747,819 (GRCm39)	D43N	probably damaging	Het
Or2ag1b	C	A	7: 106,288,351 (GRCm39)	E196*	probably null	Het
Or2b6	T	A	13: 21,823,340 (GRCm39)	M118L	possibly damaging	Het
Or2y17	G	A	11: 49,232,148 (GRCm39)	G263D	probably benign	Het
Or51e1	T	A	7: 102,359,378 (GRCm39)	I304N	probably damaging	Het
Or52n2c	G	A	7: 104,574,017 (GRCm39)	T318I	possibly damaging	Het
Or5a1	A	G	19: 12,097,234 (GRCm39)	Y269H	possibly damaging	Het
Pappa2	T	C	1: 158,784,582 (GRCm39)	R143G	probably benign	Het
Pappa2	T	G	1: 158,784,572 (GRCm39)	D146A	probably damaging	Het
Pes1	A	G	11: 3,914,058 (GRCm39)	K8E	probably damaging	Het
Phlpp2	G	A	8: 110,667,052 (GRCm39)	G1194S	probably damaging	Het
Pkn1	A	C	8: 84,398,378 (GRCm39)	V763G	probably damaging	Het
Pkp2	C	A	16: 16,048,588 (GRCm39)	A331E	probably damaging	Het
Plb1	T	A	5: 32,507,023 (GRCm39)		probably null	Het
Plxna1	A	T	6: 89,309,657 (GRCm39)		probably null	Het
Polq	C	T	16: 36,862,109 (GRCm39)	T264M	probably damaging	Het
Prkag3	T	C	1: 74,779,864 (GRCm39)	*490W	probably null	Het
Prl2c1	T	C	13: 28,041,661 (GRCm39)	C228R	probably damaging	Het
Pus7l	T	C	15: 94,438,591 (GRCm39)	S85G	probably benign	Het
Rfc3	A	C	5: 151,568,241 (GRCm39)		probably benign	Het
Riox2	A	G	16: 59,309,732 (GRCm39)	N362S	probably benign	Het
Scaper	A	T	9: 55,650,932 (GRCm39)	D904E	probably damaging	Het
Scn11a	T	C	9: 119,583,627 (GRCm39)	M1663V	probably benign	Het
Slc13a3	A	T	2: 165,272,209 (GRCm39)	I278N	possibly damaging	Het
Slc22a7	T	C	17: 46,745,923 (GRCm39)	E278G	probably damaging	Het
Snrnp48	T	A	13: 38,393,893 (GRCm39)	M66K	probably damaging	Het
Styk1	T	G	6: 131,277,429 (GRCm39)	E404A	probably damaging	Het
Synj1	T	A	16: 90,752,307 (GRCm39)	H1016L	probably benign	Het
Tbc1d8	G	A	1: 39,441,959 (GRCm39)	T211I	possibly damaging	Het
Tjp2	T	C	19: 24,097,475 (GRCm39)		probably null	Het
Tmem87a	A	G	2: 120,190,518 (GRCm39)		probably null	Het
Trappc9	T	G	15: 72,808,909 (GRCm39)	Y718S	probably damaging	Het
Ttn	A	T	2: 76,641,587 (GRCm39)	L5176Q	possibly damaging	Het
Ubqlnl	C	T	7: 103,798,925 (GRCm39)	V191M	probably benign	Het
Ugt2a3	C	T	5: 87,475,054 (GRCm39)	G397R	probably damaging	Het
Wdr33	T	A	18: 32,019,139 (GRCm39)	M454K	probably benign	Het
Wdtc1	G	T	4: 133,029,110 (GRCm39)	N325K	possibly damaging	Het
Whrn	T	C	4: 63,336,402 (GRCm39)	H720R	probably damaging	Het
Xirp2	A	T	2: 67,349,609 (GRCm39)	D3268V	probably damaging	Het
Zc3h7a	A	T	16: 10,959,573 (GRCm39)	H793Q	probably damaging	Het
Zfp518b	C	T	5: 38,831,841 (GRCm39)	A55T	possibly damaging	Het
Zmynd8	G	A	2: 165,647,249 (GRCm39)	T901M	probably damaging	Het

Other mutations in Pcsk9

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02140:Pcsk9	APN	4	106,311,843 (GRCm39)	missense	probably benign	0.00
IGL02709:Pcsk9	APN	4	106,304,886 (GRCm39)	splice site	probably benign
IGL02804:Pcsk9	APN	4	106,314,161 (GRCm39)	missense	probably damaging	1.00
IGL02850:Pcsk9	APN	4	106,316,062 (GRCm39)	missense	probably damaging	1.00
IGL03009:Pcsk9	APN	4	106,311,542 (GRCm39)	missense	probably damaging	1.00
IGL03294:Pcsk9	APN	4	106,303,967 (GRCm39)	missense	probably benign
R0271:Pcsk9	UTSW	4	106,306,246 (GRCm39)	splice site	probably benign
R0321:Pcsk9	UTSW	4	106,301,891 (GRCm39)	missense	probably benign
R0413:Pcsk9	UTSW	4	106,311,538 (GRCm39)	missense	probably damaging	1.00
R0426:Pcsk9	UTSW	4	106,307,274 (GRCm39)	missense	possibly damaging	0.77
R0783:Pcsk9	UTSW	4	106,307,314 (GRCm39)	missense	probably benign	0.00
R2136:Pcsk9	UTSW	4	106,303,967 (GRCm39)	missense	probably benign	0.00
R4056:Pcsk9	UTSW	4	106,301,899 (GRCm39)	missense	probably benign	0.02
R4438:Pcsk9	UTSW	4	106,316,156 (GRCm39)	missense	probably benign	0.00
R4683:Pcsk9	UTSW	4	106,316,092 (GRCm39)	missense	possibly damaging	0.59
R4801:Pcsk9	UTSW	4	106,304,766 (GRCm39)	missense	probably benign	0.43
R4802:Pcsk9	UTSW	4	106,304,766 (GRCm39)	missense	probably benign	0.43
R5249:Pcsk9	UTSW	4	106,320,950 (GRCm39)	missense	probably benign	0.01
R5307:Pcsk9	UTSW	4	106,304,371 (GRCm39)	missense	probably damaging	1.00
R5320:Pcsk9	UTSW	4	106,320,988 (GRCm39)	missense	probably benign	0.00
R5653:Pcsk9	UTSW	4	106,316,113 (GRCm39)	missense	probably damaging	1.00
R5827:Pcsk9	UTSW	4	106,306,144 (GRCm39)	missense	probably damaging	1.00
R6010:Pcsk9	UTSW	4	106,311,469 (GRCm39)	missense	possibly damaging	0.92
R6019:Pcsk9	UTSW	4	106,314,073 (GRCm39)	missense	probably benign	0.02
R6393:Pcsk9	UTSW	4	106,304,793 (GRCm39)	missense	probably benign	0.00
R7472:Pcsk9	UTSW	4	106,316,094 (GRCm39)	missense	probably benign	0.08
R7614:Pcsk9	UTSW	4	106,304,763 (GRCm39)	missense	probably benign	0.34
R7807:Pcsk9	UTSW	4	106,321,092 (GRCm39)	missense	possibly damaging	0.73
R8036:Pcsk9	UTSW	4	106,311,536 (GRCm39)	missense	possibly damaging	0.88
R8735:Pcsk9	UTSW	4	106,311,808 (GRCm39)	missense	probably damaging	1.00
R9258:Pcsk9	UTSW	4	106,316,047 (GRCm39)	missense	possibly damaging	0.63
R9404:Pcsk9	UTSW	4	106,311,723 (GRCm39)	missense	probably damaging	1.00
R9684:Pcsk9	UTSW	4	106,307,386 (GRCm39)	missense	probably benign	0.29
Z1176:Pcsk9	UTSW	4	106,316,138 (GRCm39)	missense	probably damaging	0.96

Predicted Primers

PCR Primer
(F):5'- GCTTCCAGCAGAGACAATGG -3'
(R):5'- GCCATCAACTGAGGCAATCC -3'

Sequencing Primer
(F):5'- GGTGGCTAATACCCCAGCTC -3'
(R):5'- TGAGGCAATCCCTAACATCTCTGG -3'

Posted On

2015-11-11