Mutagenetix > Incidental Mutation

Incidental Mutation 'R0426:Pcsk9'

38631

Institutional Source

Beutler Lab

Gene Symbol

Pcsk9

Ensembl Gene

ENSMUSG00000044254

Gene Name

proprotein convertase subtilisin/kexin type 9

Synonyms

Narc1

MMRRC Submission

038628-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R0426 (G1)

Quality Score

166

Status

Validated

Chromosome

Chromosomal Location

106299531-106321522 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 106307274 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 323 (D323G)

Ref Sequence

ENSEMBL: ENSMUSP00000055757 (fasta)

Gene Model

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

AlphaFold

Q80W65

Predicted Effect

possibly damaging
Transcript: ENSMUST00000049507
AA Change: D323G

PolyPhen 2 Score 0.766 (Sensitivity: 0.85; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000055757
Gene: ENSMUSG00000044254
AA Change: D323G

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

0.1268

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.7%
20x: 93.9%

Validation Efficiency

96% (86/90)

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: 87 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca8b	G	T	11: 109,845,853 (GRCm39)		probably benign	Het
Acadl	A	T	1: 66,880,805 (GRCm39)	F320L	probably damaging	Het
Acsbg1	T	C	9: 54,530,030 (GRCm39)	D222G	probably benign	Het
Anapc15	A	G	7: 101,547,240 (GRCm39)	T39A	probably benign	Het
Ano3	A	T	2: 110,491,519 (GRCm39)	V919E	probably damaging	Het
Arhgef12	T	C	9: 42,882,286 (GRCm39)		probably null	Het
Atad5	T	A	11: 80,003,658 (GRCm39)	I1091N	probably benign	Het
Atf1	A	T	15: 100,130,708 (GRCm39)	H26L	possibly damaging	Het
Atp10a	T	C	7: 58,434,482 (GRCm39)	M252T	probably benign	Het
Btbd8	C	T	5: 107,658,239 (GRCm39)	T1603I	probably damaging	Het
Cd55	C	T	1: 130,376,109 (GRCm39)	R347H	probably benign	Het
Cdc27	A	C	11: 104,403,853 (GRCm39)		probably null	Het
Cdh9	G	A	15: 16,823,540 (GRCm39)		probably null	Het
Cdk11b	T	C	4: 155,726,969 (GRCm39)		probably benign	Het
Cep70	A	G	9: 99,179,737 (GRCm39)	D567G	probably benign	Het
Cep78	A	T	19: 15,948,334 (GRCm39)	Y382*	probably null	Het
Cgas	G	A	9: 78,343,020 (GRCm39)		probably benign	Het
Col9a2	T	C	4: 120,901,857 (GRCm39)		probably benign	Het
Cyp2d12	G	A	15: 82,443,164 (GRCm39)	D409N	probably benign	Het
Ddx39a	A	G	8: 84,448,398 (GRCm39)	T217A	probably benign	Het
Dennd1b	T	A	1: 139,097,934 (GRCm39)	D733E	probably benign	Het
Dicer1	A	G	12: 104,668,801 (GRCm39)	S1294P	probably damaging	Het
Dnah3	T	C	7: 119,542,795 (GRCm39)	E3539G	probably benign	Het
Dnmbp	A	G	19: 43,840,875 (GRCm39)		probably benign	Het
Dysf	T	C	6: 84,126,739 (GRCm39)	L1332P	probably damaging	Het
F5	A	G	1: 164,010,409 (GRCm39)	D380G	probably damaging	Het
Fam171a1	T	C	2: 3,226,433 (GRCm39)	V522A	probably benign	Het
Fhip1b	A	C	7: 105,038,680 (GRCm39)	C186W	probably damaging	Het
Galr2	C	A	11: 116,172,517 (GRCm39)	A69D	probably damaging	Het
Grk2	T	C	19: 4,340,628 (GRCm39)		probably null	Het
Gtf3c1	A	T	7: 125,262,188 (GRCm39)	Y1119*	probably null	Het
Hgd	A	T	16: 37,409,047 (GRCm39)		probably benign	Het
Ildr2	G	T	1: 166,136,468 (GRCm39)	V436L	probably benign	Het
Intu	G	A	3: 40,629,735 (GRCm39)	C355Y	probably damaging	Het
Irf2bpl	G	T	12: 86,929,870 (GRCm39)	P268T	probably benign	Het
Jarid2	T	C	13: 44,994,358 (GRCm39)		probably null	Het
Jup	A	T	11: 100,263,227 (GRCm39)	M716K	probably benign	Het
Kank1	G	A	19: 25,388,837 (GRCm39)	V809I	probably damaging	Het
Kdm1b	T	A	13: 47,217,720 (GRCm39)		probably benign	Het
Kdm3a	C	T	6: 71,577,739 (GRCm39)	C687Y	probably damaging	Het
Kdm5d	T	A	Y: 942,437 (GRCm39)		probably benign	Het
Kifap3	T	A	1: 163,693,121 (GRCm39)		probably benign	Het
Macf1	T	A	4: 123,377,453 (GRCm39)	K1400*	probably null	Het
Majin	A	G	19: 6,262,147 (GRCm39)		probably benign	Het
Mctp1	A	G	13: 77,168,940 (GRCm39)	I846V	probably benign	Het
Mrgpra2b	T	A	7: 47,113,875 (GRCm39)	I286F	possibly damaging	Het
Neil3	T	G	8: 54,062,431 (GRCm39)		probably benign	Het
Nox3	G	T	17: 3,745,838 (GRCm39)	N23K	probably damaging	Het
Nt5c3	T	C	6: 56,860,797 (GRCm39)	K219E	probably benign	Het
Or1e29	T	A	11: 73,667,263 (GRCm39)	M297L	probably benign	Het
Or52b4i	T	A	7: 102,191,893 (GRCm39)	I250N	probably damaging	Het
Or5b105	G	A	19: 13,080,642 (GRCm39)	R3C	possibly damaging	Het
Or6b13	A	C	7: 139,782,029 (GRCm39)	F218C	possibly damaging	Het
Or6d13	A	T	6: 116,517,446 (GRCm39)	N11Y	probably damaging	Het
Or8g34	T	C	9: 39,372,889 (GRCm39)	L54P	probably damaging	Het
Pacsin2	A	G	15: 83,263,996 (GRCm39)	V347A	possibly damaging	Het
Pcdhb7	A	T	18: 37,475,857 (GRCm39)	E331V	probably damaging	Het
Pcid2	A	C	8: 13,131,262 (GRCm39)		probably null	Het
Pdhb	T	C	14: 8,169,801 (GRCm38)	E203G	probably damaging	Het
Phlpp2	A	G	8: 110,655,095 (GRCm39)	Y630C	probably benign	Het
Pidd1	C	T	7: 141,019,046 (GRCm39)	A812T	probably damaging	Het
Plau	G	A	14: 20,892,382 (GRCm39)	R389H	probably benign	Het
Plekhg6	G	A	6: 125,341,592 (GRCm39)		probably null	Het
Ppox	T	C	1: 171,105,322 (GRCm39)	Y321C	probably damaging	Het
Pxdn	A	G	12: 30,037,065 (GRCm39)	N281S	possibly damaging	Het
Pycr3	A	T	15: 75,790,237 (GRCm39)	M138K	probably benign	Het
Radil	T	C	5: 142,483,628 (GRCm39)	Y526C	probably damaging	Het
Ranbp3	C	A	17: 57,014,169 (GRCm39)	D233E	probably benign	Het
Rhpn1	A	G	15: 75,583,721 (GRCm39)	Q402R	possibly damaging	Het
Sec23b	T	A	2: 144,410,532 (GRCm39)		probably benign	Het
Sel1l2	A	T	2: 140,082,832 (GRCm39)	L602*	probably null	Het
Sema5b	G	A	16: 35,466,725 (GRCm39)	G209D	probably damaging	Het
Svep1	T	C	4: 58,073,333 (GRCm39)	Y1992C	possibly damaging	Het
Syncrip	T	A	9: 88,338,312 (GRCm39)		probably benign	Het
Synj1	G	T	16: 90,764,242 (GRCm39)	A65E	probably damaging	Het
Taar2	G	A	10: 23,817,393 (GRCm39)	R311H	probably benign	Het
Tecrl	T	C	5: 83,502,610 (GRCm39)		probably benign	Het
Tenm4	G	T	7: 96,427,058 (GRCm39)	G698C	probably damaging	Het
Tmem209	G	A	6: 30,491,181 (GRCm39)	L259F	probably damaging	Het
Tmem247	G	A	17: 87,225,931 (GRCm39)	E124K	possibly damaging	Het
Tnks2	C	A	19: 36,830,221 (GRCm39)	A218E	probably damaging	Het
Tppp	T	A	13: 74,169,430 (GRCm39)	F57I	probably damaging	Het
Trim36	A	G	18: 46,305,592 (GRCm39)	W452R	probably damaging	Het
Vars2	A	T	17: 35,975,476 (GRCm39)	V262E	probably damaging	Het
Vmn2r92	C	T	17: 18,388,219 (GRCm39)	A408V	probably damaging	Het
Zfp516	G	T	18: 82,973,897 (GRCm39)	A32S	probably benign	Het
Zfy2	G	T	Y: 2,107,348 (GRCm39)	L429I	possibly 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
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
R4739:Pcsk9	UTSW	4	106,304,353 (GRCm39)	missense	probably damaging	1.00
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'- TCTGCCTTCCAAGGGACAGAAGAG -3'
(R):5'- TCGGAAGAGTCAGCTAATCCAGCC -3'

Sequencing Primer
(F):5'- CCAGGATCATAGGTATGGCTGC -3'
(R):5'- AGCTAATCCAGCCCTCGG -3'

Posted On

2013-05-23