Mutagenetix > Incidental Mutations

Incidental Mutation 'R2136:Pcsk9'

235791

Institutional Source

Beutler Lab

Gene Symbol

Pcsk9

Ensembl Gene

ENSMUSG00000044254

Gene Name

proprotein convertase subtilisin/kexin type 9

Synonyms

Narc1

MMRRC Submission

040139-MU

Accession Numbers

Is this an essential gene?

Non essential (E-score: 0.000) question?

Stock #

R2136 (G1)

Quality Score

212

Status

Not validated

Chromosome

Chromosomal Location

106442329-106464329 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 106446770 bp

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Valine at position 506 (I506V)

Ref Sequence

ENSEMBL: ENSMUSP00000055757 (fasta)

Gene Model

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

Predicted Effect

probably benign
Transcript: ENSMUST00000049507
AA Change: I506V

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000055757
Gene: ENSMUSG00000044254
AA Change: I506V

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: 99.2%
3x: 98.7%
10x: 97.6%
20x: 95.9%

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: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2210010C04Rik	A	G	6: 41,035,462	F6S	probably benign	Het
2810474O19Rik	T	A	6: 149,328,822	I1122K	probably benign	Het
A930003A15Rik	T	G	16: 19,883,780		noncoding transcript	Het
Abca5	T	C	11: 110,319,832	T174A	probably benign	Het
Abcg3	G	A	5: 104,966,814	S279L	probably benign	Het
Acap3	T	C	4: 155,896,912	L85P	probably damaging	Het
Adgrl3	A	G	5: 81,512,254	K290R	probably damaging	Het
Ankhd1	A	G	18: 36,647,621	T1909A	probably benign	Het
Asap1	T	C	15: 64,110,959	D832G	probably damaging	Het
Atp6v0a2	T	A	5: 124,718,488	L702Q	possibly damaging	Het
Bsn	A	G	9: 108,113,231	V1774A	probably damaging	Het
Cd209e	T	C	8: 3,853,248	E48G	probably benign	Het
Cdadc1	T	C	14: 59,568,044		probably null	Het
Cfap65	C	CA	1: 74,917,273		probably null	Het
Cln3	A	C	7: 126,582,799	S30R	probably benign	Het
Cluap1	C	T	16: 3,933,772	R332W	probably damaging	Het
Crb1	A	T	1: 139,337,425	V85E	probably benign	Het
Crocc	G	A	4: 141,032,954	R789W	probably damaging	Het
Cwh43	A	G	5: 73,415,054	I212V	probably benign	Het
Cyp2t4	C	A	7: 27,158,160	F391L	probably benign	Het
Dhx35	G	T	2: 158,831,861	R404L	probably damaging	Het
Disp1	A	G	1: 183,088,378	L826S	probably damaging	Het
Dync2h1	T	A	9: 7,122,772	E2061D	probably damaging	Het
Ep300	T	A	15: 81,640,447	Y1393N	unknown	Het
Fap	C	T	2: 62,524,207	G446D	possibly damaging	Het
Fat3	A	G	9: 16,377,051	I392T	probably benign	Het
Fpr-rs4	CAGGAA	CA	17: 18,022,334		probably null	Het
Glipr1l1	T	C	10: 112,060,476	V56A	probably damaging	Het
Grsf1	A	G	5: 88,672,658	V7A	probably benign	Het
Hmcn1	G	A	1: 150,633,659	A3646V	probably damaging	Het
Ipo9	A	T	1: 135,394,285	I569N	probably damaging	Het
Irs1	G	T	1: 82,290,042	P151Q	probably damaging	Het
Kalrn	T	C	16: 34,307,724	D491G	possibly damaging	Het
Kctd7	T	C	5: 130,152,366	L210P	probably damaging	Het
Lifr	C	A	15: 7,181,857	D625E	possibly damaging	Het
Lrguk	T	C	6: 34,043,519	V201A	probably benign	Het
Mark1	A	G	1: 184,919,573	V135A	probably damaging	Het
Mical2	T	A	7: 112,271,515	D70E	possibly damaging	Het
Mrc1	T	C	2: 14,270,189	Y434H	probably damaging	Het
Myh10	C	A	11: 68,804,714	Q1556K	probably damaging	Het
Nav1	G	A	1: 135,454,436	T1400I	probably null	Het
Olfr1173	T	C	2: 88,274,240	K270E	probably damaging	Het
Olfr1178	T	A	2: 88,391,319	I24N	probably benign	Het
Olfr1289	T	C	2: 111,483,616	V62A	probably damaging	Het
Olfr13	A	G	6: 43,174,501	K172E	probably benign	Het
Olfr142	A	C	2: 90,252,253	V245G	probably damaging	Het
Olfr339	A	G	2: 36,421,938	D180G	probably damaging	Het
Olfr513	G	A	7: 108,755,223	M122I	possibly damaging	Het
Osmr	T	A	15: 6,852,462	Q67L	probably damaging	Het
Pan2	T	G	10: 128,313,637	V522G	possibly damaging	Het
Pard3	T	G	8: 127,376,885		probably null	Het
Pcdhgc5	G	T	18: 37,820,113	A147S	possibly damaging	Het
Polr3d	GCCCCC	GCCCC	14: 70,443,047		probably null	Het
Prdm4	G	A	10: 85,893,351	R731*	probably null	Het
Prdx6b	T	A	2: 80,293,163	D105E	probably damaging	Het
Rab42	A	G	4: 132,302,479	L144P	probably damaging	Het
Ralbp1	T	A	17: 65,864,666	K104M	probably damaging	Het
Rrp12	A	G	19: 41,892,599	V131A	probably damaging	Het
Sbno1	C	T	5: 124,387,534		probably null	Het
Sbno2	A	T	10: 80,062,693	I645N	probably damaging	Het
Scfd2	T	C	5: 74,206,367	K624R	probably benign	Het
Sgk2	C	A	2: 162,999,179		probably null	Het
Sirt4	A	G	5: 115,479,701	S299P	probably benign	Het
Slit2	C	T	5: 48,304,225	A1521V	probably benign	Het
Socs7	T	G	11: 97,373,107	V275G	possibly damaging	Het
Spink11	G	A	18: 44,190,487	P102S	probably benign	Het
Tacc3	A	G	5: 33,671,404	N534D	probably damaging	Het
Tas2r115	T	C	6: 132,737,346	Y214C	probably damaging	Het
Tcaf1	A	T	6: 42,673,520	M875K	probably benign	Het
Ttc22	T	A	4: 106,622,672	L41Q	possibly damaging	Het
Ttc37	T	C	13: 76,173,354	S1322P	possibly damaging	Het
Vasn	T	A	16: 4,649,795	C535*	probably null	Het
Vcan	T	A	13: 89,689,737	I2563F	probably damaging	Het
Vmn2r63	T	G	7: 42,926,873	Q505H	probably damaging	Het
Vmn2r65	T	G	7: 84,943,573	Q475H	probably damaging	Het
Zbtb43	T	C	2: 33,454,520	Y231C	probably damaging	Het
Zfp292	A	G	4: 34,810,266	V931A	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
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
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
Z1176:Pcsk9	UTSW	4	106458941	missense	probably damaging	0.96

Predicted Primers

PCR Primer
(F):5'- ACCACGGTCTGGAATCAACATG -3'
(R):5'- CTGGAGATAGAACAGTCTGCCTC -3'

Sequencing Primer
(F):5'- TAGACTCCTACCTGTGAGAACATGG -3'
(R):5'- TCAGGCCTGGGCAAATGACTC -3'

Posted On

2014-10-01