Mutagenetix > Incidental Mutation

Incidental Mutation 'R5307:Pcsk9'

404623

Institutional Source

Beutler Lab

Gene Symbol

Pcsk9

Ensembl Gene

ENSMUSG00000044254

Gene Name

proprotein convertase subtilisin/kexin type 9

Synonyms

Narc1

MMRRC Submission

042890-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R5307 (G1)

Quality Score

120

Status

Not validated

Chromosome

Chromosomal Location

106442329-106464329 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 106447174 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 490 (S490P)

Ref Sequence

ENSEMBL: ENSMUSP00000055757 (fasta)

Gene Model

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

AlphaFold

Q80W65

Predicted Effect

probably damaging
Transcript: ENSMUST00000049507
AA Change: S490P

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

SMART Domains

Protein: ENSMUSP00000055757
Gene: ENSMUSG00000044254
AA Change: S490P

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

Coding Region Coverage

1x: 99.3%
3x: 98.6%
10x: 97.2%
20x: 95.1%

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 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: 78 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700006A11Rik	C	G	3: 124,406,350	G531A	probably damaging	Het
2410089E03Rik	G	A	15: 8,260,690		probably null	Het
Abca8b	C	A	11: 109,977,813	G175V	probably damaging	Het
Ank3	G	A	10: 70,002,565	R1566K	possibly damaging	Het
Ap3d1	T	C	10: 80,723,549	T264A	probably benign	Het
Arhgef17	C	G	7: 100,929,428	G771A	probably benign	Het
Atg2b	T	A	12: 105,658,329	D637V	probably benign	Het
Atp10b	A	G	11: 43,212,475	E562G	probably damaging	Het
Atp1a1	A	G	3: 101,589,964	V342A	probably damaging	Het
Atp2a2	A	G	5: 122,461,747	I527T	probably benign	Het
Atr	T	A	9: 95,878,544	N1022K	probably benign	Het
Bach2	T	A	4: 32,562,683	D383E	probably benign	Het
Casq1	A	T	1: 172,219,416	L92Q	probably damaging	Het
Chd1	T	A	17: 15,732,570	Y371N	probably damaging	Het
Chd9	G	A	8: 90,997,149	A617T	probably damaging	Het
Cntrob	T	A	11: 69,314,750	R419S	possibly damaging	Het
Corin	C	A	5: 72,356,978	G318C	probably damaging	Het
Cpa3	A	G	3: 20,227,163		probably null	Het
Crybg1	T	C	10: 44,003,714	S493G	probably benign	Het
Ddc	A	G	11: 11,876,321	F80S	probably damaging	Het
Dhrs2	A	G	14: 55,236,144	S87G	possibly damaging	Het
Dnah12	A	G	14: 26,693,486	E14G	possibly damaging	Het
Dtd1	A	G	2: 144,747,022	E200G	possibly damaging	Het
Dync2h1	T	C	9: 7,155,099	E895G	probably damaging	Het
Ehhadh	A	C	16: 21,762,692	S517A	probably benign	Het
Ephb2	C	A	4: 136,693,787	Q417H	possibly damaging	Het
Ephb4	A	G	5: 137,363,312	T526A	probably damaging	Het
Fam222b	G	A	11: 78,153,768	V52I	probably damaging	Het
Galm	G	A	17: 80,144,987	W118*	probably null	Het
Galm	G	T	17: 80,144,988	W118C	probably damaging	Het
Gcfc2	A	G	6: 81,944,386	N458D	probably damaging	Het
Gm11595	G	A	11: 99,772,555	R100C	unknown	Het
Gykl1	A	C	18: 52,694,651	R310S	possibly damaging	Het
Gzmn	A	C	14: 56,167,946	V27G	probably damaging	Het
H2-T23	T	A	17: 36,032,216	M90L	probably benign	Het
Hnrnpu	T	C	1: 178,337,312	E87G	unknown	Het
Hps3	G	A	3: 20,012,701	S567L	possibly damaging	Het
Igfn1	A	T	1: 135,964,938	V2148E	probably damaging	Het
Ighv1-75	T	C	12: 115,833,952	R117G	probably damaging	Het
Itgae	C	T	11: 73,145,638	A1134V	probably benign	Het
Kmt2b	C	T	7: 30,581,673	A1294T	possibly damaging	Het
Leng8	C	T	7: 4,145,473	T748I	probably damaging	Het
Lrig3	G	C	10: 126,006,690	D495H	probably damaging	Het
Mctp1	G	A	13: 76,712,079		probably null	Het
Mfsd3	T	A	15: 76,702,171	L168*	probably null	Het
Nlrp4d	C	A	7: 10,362,782	G921*	probably null	Het
Nsun4	G	A	4: 116,034,138	T348I	probably damaging	Het
Nucb1	T	C	7: 45,498,418	T246A	probably damaging	Het
Nynrin	A	C	14: 55,863,806	S311R	probably damaging	Het
Olfr1019	T	G	2: 85,841,014	Y259S	probably damaging	Het
Olfr1281	T	A	2: 111,328,396		probably null	Het
Ovch2	C	A	7: 107,792,134	R303L	probably benign	Het
Pi4ka	A	G	16: 17,323,030	F859L	probably benign	Het
Pkd1l3	A	G	8: 109,640,792	D1207G	probably damaging	Het
Pnpla7	G	A	2: 25,021,952	R710Q	possibly damaging	Het
Prex2	T	G	1: 11,200,032	S1314A	probably damaging	Het
Rnf216	A	G	5: 143,093,002	L64P	probably damaging	Het
Sh3bp5	C	A	14: 31,377,495	R265L	probably benign	Het
Slc6a20b	T	G	9: 123,603,834	S374R	possibly damaging	Het
Slc8a1	G	T	17: 81,649,224	N128K	probably damaging	Het
Slc9a3r1	T	A	11: 115,163,761	I79N	probably damaging	Het
Slfn5	A	T	11: 82,956,385	D32V	probably damaging	Het
Snrnp35	T	C	5: 124,490,490	I122T	possibly damaging	Het
Snx24	C	T	18: 53,340,211	Q76*	probably null	Het
Sspo	T	A	6: 48,454,850	H692Q	probably damaging	Het
Stxbp3	T	C	3: 108,793,798	D585G	probably damaging	Het
Svep1	T	C	4: 58,072,677	N2211D	possibly damaging	Het
Tnfrsf18	G	A	4: 156,028,424		probably null	Het
Tnik	T	G	3: 28,541,972	D171E	probably damaging	Het
Ttc23l	T	A	15: 10,533,659	H266L	probably damaging	Het
Ttn	G	T	2: 76,894,770	S2037*	probably null	Het
Tuba3a	G	A	6: 125,281,310	T239I	probably damaging	Het
Usp25	T	A	16: 77,093,706	D767E	probably benign	Het
Whrn	G	T	4: 63,431,843	H546N	probably benign	Het
Xirp2	C	T	2: 67,511,162	T1249I	probably damaging	Het
Zbtb1	T	A	12: 76,386,240	D333E	probably damaging	Het
Zfp689	T	G	7: 127,448,815	E15A	possibly damaging	Het
Zhx3	A	G	2: 160,779,868	M793T	probably benign	Het

Other mutations in Pcsk9

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02140:Pcsk9	APN	4	106454646	missense	probably benign	0.00
IGL02709:Pcsk9	APN	4	106447689	splice site	probably benign
IGL02804:Pcsk9	APN	4	106456964	missense	probably damaging	1.00
IGL02850:Pcsk9	APN	4	106458865	missense	probably damaging	1.00
IGL03009:Pcsk9	APN	4	106454345	missense	probably damaging	1.00
IGL03294:Pcsk9	APN	4	106446770	missense	probably benign
R0271:Pcsk9	UTSW	4	106449049	splice site	probably benign
R0321:Pcsk9	UTSW	4	106444694	missense	probably benign
R0413:Pcsk9	UTSW	4	106454341	missense	probably damaging	1.00
R0426:Pcsk9	UTSW	4	106450077	missense	possibly damaging	0.77
R0783:Pcsk9	UTSW	4	106450117	missense	probably benign	0.00
R2136:Pcsk9	UTSW	4	106446770	missense	probably benign	0.00
R4056:Pcsk9	UTSW	4	106444702	missense	probably benign	0.02
R4438:Pcsk9	UTSW	4	106458959	missense	probably benign	0.00
R4683:Pcsk9	UTSW	4	106458895	missense	possibly damaging	0.59
R4739:Pcsk9	UTSW	4	106447156	missense	probably damaging	1.00
R4801:Pcsk9	UTSW	4	106447569	missense	probably benign	0.43
R4802:Pcsk9	UTSW	4	106447569	missense	probably benign	0.43
R5249:Pcsk9	UTSW	4	106463753	missense	probably benign	0.01
R5320:Pcsk9	UTSW	4	106463791	missense	probably benign	0.00
R5653:Pcsk9	UTSW	4	106458916	missense	probably damaging	1.00
R5827:Pcsk9	UTSW	4	106448947	missense	probably damaging	1.00
R6010:Pcsk9	UTSW	4	106454272	missense	possibly damaging	0.92
R6019:Pcsk9	UTSW	4	106456876	missense	probably benign	0.02
R6393:Pcsk9	UTSW	4	106447596	missense	probably benign	0.00
R7472:Pcsk9	UTSW	4	106458897	missense	probably benign	0.08
R7614:Pcsk9	UTSW	4	106447566	missense	probably benign	0.34
R7807:Pcsk9	UTSW	4	106463895	missense	possibly damaging	0.73
R8036:Pcsk9	UTSW	4	106454339	missense	possibly damaging	0.88
R8735:Pcsk9	UTSW	4	106454611	missense	probably damaging	1.00
R9258:Pcsk9	UTSW	4	106458850	missense	possibly damaging	0.63
R9404:Pcsk9	UTSW	4	106454526	missense	probably damaging	1.00
R9684:Pcsk9	UTSW	4	106450189	missense	probably benign	0.29
Z1176:Pcsk9	UTSW	4	106458941	missense	probably damaging	0.96

Predicted Primers

PCR Primer
(F):5'- TTCCAGCAGAGACAATGGGTG -3'
(R):5'- TGCCATCAACTGAGGCAATCC -3'

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

Posted On

2016-07-22