Mutagenetix > Incidental Mutations

Incidental Mutation 'R6019:Pcsk9'

478772

Institutional Source

Beutler Lab

Gene Symbol

Pcsk9

Ensembl Gene

ENSMUSG00000044254

Gene Name

proprotein convertase subtilisin/kexin type 9

Synonyms

Narc1

MMRRC Submission

044193-MU

Accession Numbers

Is this an essential gene?

Non essential (E-score: 0.000) question?

Stock #

R6019 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

106442329-106464329 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 106456876 bp

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Alanine at position 174 (D174A)

Ref Sequence

ENSEMBL: ENSMUSP00000055757 (fasta)

Gene Model

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

Predicted Effect

probably benign
Transcript: ENSMUST00000049507
AA Change: D174A

PolyPhen 2 Score 0.019 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000055757
Gene: ENSMUSG00000044254
AA Change: D174A

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

0.0898

Coding Region Coverage

1x: 99.9%
3x: 99.4%
10x: 97.2%
20x: 91.1%

Validation Efficiency

96% (81/84)

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: 83 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcf3	C	T	16: 20,552,451	H436Y	possibly damaging	Het
Acad10	A	T	5: 121,634,801	H472Q	possibly damaging	Het
Ano8	G	A	8: 71,482,380	R393C	probably damaging	Het
Arhgap18	T	A	10: 26,860,650	V163E	probably damaging	Het
AW209491	C	T	13: 14,637,780	A406V	probably benign	Het
Brix1	C	T	15: 10,476,589	R267H	probably benign	Het
Cacng5	T	C	11: 107,884,388	M52V	probably benign	Het
Casz1	T	C	4: 148,947,038	C1249R	probably damaging	Het
Cenpj	C	T	14: 56,534,815	S1086N	probably benign	Het
Chil1	T	C	1: 134,189,572	F367S	probably benign	Het
Copg2	A	T	6: 30,810,933	I610N	possibly damaging	Het
Cpa6	T	C	1: 10,595,643	K57E	possibly damaging	Het
D5Ertd579e	C	T	5: 36,629,692	A111T	possibly damaging	Het
Dgat2	A	G	7: 99,154,631	M361T	probably benign	Het
Dnm3	G	T	1: 162,134,501	F46L	probably damaging	Het
Dph7	T	A	2: 24,963,540	C122*	probably null	Het
Dspp	A	T	5: 104,178,039	D756V	unknown	Het
Ep300	T	A	15: 81,641,382	M1469K	unknown	Het
Fsip2	T	C	2: 82,987,939	I4672T	possibly damaging	Het
Gapdh	A	T	6: 125,163,033	L67*	probably null	Het
Gm11639	T	C	11: 105,042,902		probably null	Het
Gm14025	T	C	2: 129,037,690	Q772R	probably benign	Het
Gm21994	T	A	2: 150,255,212	H99L	probably damaging	Het
Gm3259	G	A	5: 95,340,213	S2N	probably damaging	Het
Gm9495	A	T	8: 69,429,314	C337S	probably benign	Het
Gpr75	A	G	11: 30,891,640	R182G	probably benign	Het
Gsr	G	T	8: 33,693,807	A366S	probably damaging	Het
Gypc	A	G	18: 32,530,195	I33T	probably damaging	Het
Hapln1	A	G	13: 89,608,100	D341G	probably benign	Het
Hnrnpd	A	G	5: 99,967,236	S148P	probably benign	Het
Hydin	A	T	8: 110,566,620	T3450S	probably benign	Het
Kif20b	T	C	19: 34,950,464	V1002A	probably benign	Het
Kif5c	T	C	2: 49,735,509	V597A	probably benign	Het
Kntc1	A	G	5: 123,762,516	T226A	probably benign	Het
Krt75	C	A	15: 101,573,723	V37L	probably benign	Het
L3mbtl2	A	G	15: 81,686,942	I668V	probably benign	Het
Lrp1b	G	A	2: 41,302,970	A480V	probably damaging	Het
Lrp1b	T	A	2: 41,476,809	D485V	probably damaging	Het
Lrrc37a	T	C	11: 103,456,596	H3091R	unknown	Het
Msi1	A	G	5: 115,451,491	Y361C	probably damaging	Het
Mtus1	G	T	8: 41,083,040	N546K	probably benign	Het
Mup17	T	A	4: 61,593,699	T113S	probably benign	Het
Myh11	T	A	16: 14,206,074	D1479V	probably damaging	Het
Ncor1	C	T	11: 62,373,161	E198K	probably benign	Het
Nrde2	A	G	12: 100,132,242	V722A	probably benign	Het
Olfr206	C	T	16: 59,345,435	D89N	possibly damaging	Het
Olfr564	C	T	7: 102,804,284	R269*	probably null	Het
Olfr61	T	C	7: 140,638,012	F104L	probably benign	Het
Otog	A	G	7: 46,288,950	M2028V	probably benign	Het
Paox	T	A	7: 140,131,742	V169E	probably damaging	Het
Pde4b	A	G	4: 102,570,769	E41G	possibly damaging	Het
Pip4k2c	A	G	10: 127,199,074	I419T	probably damaging	Het
Plekhg3	G	T	12: 76,577,941	E1186*	probably null	Het
Pole	C	A	5: 110,324,514	P1548T	probably benign	Het
Pole	C	T	5: 110,324,515	P1548L	probably benign	Het
Polq	A	G	16: 37,061,764	E1430G	probably damaging	Het
Ptgr2	T	C	12: 84,298,146	S98P	probably damaging	Het
Ralgapa1	A	G	12: 55,684,042	Y1903H	possibly damaging	Het
Rasgrp1	T	C	2: 117,291,895	D338G	probably damaging	Het
Rif1	C	G	2: 52,095,844	L614V	probably damaging	Het
Rnase13	C	T	14: 51,922,403	C93Y	probably damaging	Het
Rnd2	C	T	11: 101,468,999	L57F	probably damaging	Het
S100z	T	A	13: 95,477,426	M59L	probably benign	Het
Ska1	T	A	18: 74,199,921	D142V	probably benign	Het
Slc16a3	T	C	11: 120,957,105		probably null	Het
Snd1	T	C	6: 28,880,234	V669A	probably benign	Het
Snrpd3	A	T	10: 75,532,195	T49S	probably damaging	Het
Sort1	T	C	3: 108,357,233	L856P	possibly damaging	Het
Srek1ip1	T	A	13: 104,834,322		probably null	Het
Ssrp1	T	C	2: 85,045,452	S552P	probably damaging	Het
Stab2	A	G	10: 87,003,022	V60A	probably benign	Het
Stard9	GCCC	GCC	2: 120,693,715		probably null	Het
Tll1	A	C	8: 64,041,491	H743Q	possibly damaging	Het
Tpo	G	T	12: 30,094,981	R590S	possibly damaging	Het
Trbv12-1	A	T	6: 41,113,846	T51S	probably benign	Het
Trbv30	C	T	6: 41,281,774	A40V	probably benign	Het
Tulp4	T	A	17: 6,233,215	V1173E	possibly damaging	Het
Upk1a	A	T	7: 30,612,385		probably null	Het
Vmn1r199	A	G	13: 22,382,599	D21G	possibly damaging	Het
Vmn2r7	T	C	3: 64,716,222	T317A	probably damaging	Het
Wdfy3	A	G	5: 101,849,423	V3112A	probably damaging	Het
Zbtb8os	T	C	4: 129,340,749	V40A	possibly damaging	Het
Zwint	A	G	10: 72,656,853	K108E	possibly damaging	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
R5307:Pcsk9	UTSW	4	106447174	missense	probably damaging	1.00
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
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

Predicted Primers

PCR Primer
(F):5'- ATGAAGCCAACACGGATGC -3'
(R):5'- AGAAATGAGGACACTGGCCC -3'

Sequencing Primer
(F):5'- CGAAGCTGGAGGAGAGGG -3'
(R):5'- CCCCAGGAGGAAGACTTTGTG -3'

Posted On

2017-06-26