Mutagenetix > Incidental Mutation

Incidental Mutation 'R0321:Pcsk9'

35850

Institutional Source

Beutler Lab

Gene Symbol

Pcsk9

Ensembl Gene

ENSMUSG00000044254

Gene Name

proprotein convertase subtilisin/kexin type 9

Synonyms

Narc1

MMRRC Submission

038531-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R0321 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

106299531-106321522 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 106301891 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 619 (S619P)

Ref Sequence

ENSEMBL: ENSMUSP00000055757 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000049507] [ENSMUST00000094933] [ENSMUST00000165709]

AlphaFold

Q80W65

Predicted Effect

probably benign
Transcript: ENSMUST00000049507
AA Change: S619P

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000055757
Gene: ENSMUSG00000044254
AA Change: S619P

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

Predicted Effect

probably benign
Transcript: ENSMUST00000094933

SMART Domains

Protein: ENSMUSP00000092538
Gene: ENSMUSG00000028514

Domain	Start	End	E-Value	Type
Blast:UBA	5	43	2e-16	BLAST
low complexity region	57	96	N/A	INTRINSIC
SCOP:d1gw5a_	348	882	6e-7	SMART
low complexity region	1031	1059	N/A	INTRINSIC
low complexity region	1124	1150	N/A	INTRINSIC
low complexity region	1365	1378	N/A	INTRINSIC
Pfam:UCH	1685	2036	3.7e-54	PFAM
Pfam:UCH_1	1686	1993	1.8e-27	PFAM
low complexity region	2066	2081	N/A	INTRINSIC
low complexity region	2256	2267	N/A	INTRINSIC
low complexity region	2576	2592	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000165709

SMART Domains

Protein: ENSMUSP00000133095
Gene: ENSMUSG00000028514

Domain	Start	End	E-Value	Type
Blast:UBA	5	43	2e-16	BLAST
low complexity region	57	96	N/A	INTRINSIC
SCOP:d1gw5a_	348	883	8e-7	SMART
low complexity region	1032	1060	N/A	INTRINSIC
low complexity region	1125	1151	N/A	INTRINSIC
low complexity region	1366	1379	N/A	INTRINSIC
Pfam:UCH	1686	2037	2e-49	PFAM
Pfam:UCH_1	1687	1994	4e-24	PFAM
low complexity region	2067	2082	N/A	INTRINSIC
low complexity region	2257	2268	N/A	INTRINSIC
low complexity region	2577	2593	N/A	INTRINSIC

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.2%
3x: 98.4%
10x: 96.5%
20x: 93.7%

Validation Efficiency

100% (79/79)

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: 73 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4921509C19Rik	T	C	2: 151,314,620 (GRCm39)	T353A	probably benign	Het
4933402N03Rik	T	A	7: 130,747,956 (GRCm39)	Y12F	probably benign	Het
Acbd3	T	G	1: 180,579,870 (GRCm39)	F505V	probably damaging	Het
Acod1	T	C	14: 103,292,565 (GRCm39)	V363A	probably benign	Het
Adam28	T	C	14: 68,855,200 (GRCm39)	Q647R	probably damaging	Het
Akr1c18	T	A	13: 4,185,243 (GRCm39)	L296F	probably damaging	Het
Ap1b1	G	A	11: 4,982,464 (GRCm39)	A588T	probably benign	Het
Armc8	A	T	9: 99,415,230 (GRCm39)	I150K	probably damaging	Het
Bahcc1	T	C	11: 120,164,251 (GRCm39)		probably null	Het
Bltp1	T	C	3: 36,960,937 (GRCm39)		probably null	Het
Carmil3	C	A	14: 55,739,698 (GRCm39)	D928E	possibly damaging	Het
Ccrl2	T	C	9: 110,885,279 (GRCm39)	N73S	probably damaging	Het
Cdk9	C	A	2: 32,602,698 (GRCm39)		probably benign	Het
Cel	G	T	2: 28,451,160 (GRCm39)	Q66K	probably benign	Het
D930028M14Rik	T	A	7: 24,854,991 (GRCm39)		noncoding transcript	Het
Dgka	G	C	10: 128,556,952 (GRCm39)		probably benign	Het
Dlg1	T	C	16: 31,676,854 (GRCm39)	V801A	probably damaging	Het
Dnah10	A	G	5: 124,900,416 (GRCm39)	D3834G	probably benign	Het
Dnajc15	C	T	14: 78,112,273 (GRCm39)	A23T	possibly damaging	Het
Ell2	T	A	13: 75,910,007 (GRCm39)	L119Q	probably damaging	Het
Epha2	T	C	4: 141,035,716 (GRCm39)	W51R	probably damaging	Het
F10	T	C	8: 13,103,413 (GRCm39)	F266L	possibly damaging	Het
Fam110a	T	C	2: 151,812,587 (GRCm39)	N61S	probably benign	Het
Fam83c	C	T	2: 155,671,620 (GRCm39)	S605N	probably benign	Het
Fbxw15	C	T	9: 109,394,453 (GRCm39)	V121I	probably benign	Het
Gart	G	A	16: 91,419,925 (GRCm39)		probably benign	Het
Gfi1b	A	G	2: 28,503,897 (GRCm39)	F101S	probably damaging	Het
Gimap5	C	G	6: 48,727,449 (GRCm39)		probably benign	Het
Gpr180	T	C	14: 118,385,699 (GRCm39)		probably null	Het
Gsn	T	C	2: 35,180,408 (GRCm39)	F188L	probably benign	Het
Hivep3	T	A	4: 119,952,788 (GRCm39)	I368N	possibly damaging	Het
Itih3	T	A	14: 30,634,063 (GRCm39)	I153F	probably damaging	Het
Kdm8	A	T	7: 125,060,178 (GRCm39)	Q360L	probably damaging	Het
Lars1	T	C	18: 42,335,697 (GRCm39)	K1140E	probably damaging	Het
Mocs1	A	G	17: 49,740,286 (GRCm39)	Y71C	probably damaging	Het
Mroh5	C	T	15: 73,661,892 (GRCm39)	G433E	probably damaging	Het
Mrpl45	T	A	11: 97,217,764 (GRCm39)		probably benign	Het
Mtcl1	T	A	17: 66,686,426 (GRCm39)	T827S	probably damaging	Het
Muc5b	T	C	7: 141,415,972 (GRCm39)	S2973P	probably benign	Het
Mynn	T	C	3: 30,661,706 (GRCm39)	S263P	probably benign	Het
Myo1f	A	C	17: 33,811,986 (GRCm39)	D595A	probably benign	Het
Necab1	A	T	4: 14,960,083 (GRCm39)	I288N	probably damaging	Het
Nutm2	T	G	13: 50,626,991 (GRCm39)	M382R	probably damaging	Het
Oprm1	T	C	10: 6,779,183 (GRCm39)	S131P	probably damaging	Het
Phkg1	A	T	5: 129,898,365 (GRCm39)	M1K	probably null	Het
Pigc	C	T	1: 161,798,668 (GRCm39)	Q217*	probably null	Het
Pik3r4	T	A	9: 105,525,906 (GRCm39)	F259I	probably damaging	Het
Pkdcc	A	T	17: 83,529,541 (GRCm39)		probably benign	Het
Pnpla5	G	T	15: 84,004,920 (GRCm39)	L144M	probably damaging	Het
Prtg	A	T	9: 72,755,307 (GRCm39)	I259F	possibly damaging	Het
Prune2	T	G	19: 17,098,291 (GRCm39)	L1265R	possibly damaging	Het
Prune2	C	T	19: 17,099,818 (GRCm39)	A1774V	probably benign	Het
Rcn3	A	G	7: 44,738,139 (GRCm39)		probably benign	Het
Rnf213	C	T	11: 119,328,931 (GRCm39)	Q2067*	probably null	Het
Sec14l1	T	A	11: 117,041,568 (GRCm39)		probably benign	Het
Serpinb3a	C	T	1: 106,975,212 (GRCm39)	W198*	probably null	Het
Smpdl3b	A	T	4: 132,468,755 (GRCm39)	V154E	probably damaging	Het
Spag17	T	C	3: 100,008,719 (GRCm39)	S1950P	probably damaging	Het
Sprr1a	T	C	3: 92,391,609 (GRCm39)	T131A	probably benign	Het
Tatdn2	T	G	6: 113,686,462 (GRCm39)	L690W	probably damaging	Het
Tbc1d1	T	C	5: 64,496,937 (GRCm39)	F864L	probably damaging	Het
Tmem8b	C	A	4: 43,674,444 (GRCm39)	R243S	probably damaging	Het
Tnfrsf11a	T	A	1: 105,772,583 (GRCm39)	C623*	probably null	Het
Tprg1l	T	C	4: 154,243,812 (GRCm39)	N115D	probably damaging	Het
Ube2t	C	T	1: 134,895,538 (GRCm39)	A4V	possibly damaging	Het
Vps41	G	A	13: 19,026,465 (GRCm39)		probably benign	Het
Wdr17	C	T	8: 55,149,303 (GRCm39)		probably null	Het
Wwc1	G	A	11: 35,732,637 (GRCm39)	Q1024*	probably null	Het
Zfand5	T	A	19: 21,253,879 (GRCm39)	N27K	probably damaging	Het
Zfp142	A	T	1: 74,608,873 (GRCm39)	C1641S	probably damaging	Het
Zfyve16	A	G	13: 92,629,042 (GRCm39)	I1465T	probably damaging	Het
Zswim1	G	A	2: 164,667,947 (GRCm39)	G400S	probably benign	Het
Zswim3	C	T	2: 164,662,279 (GRCm39)	A253V	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
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
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'- ACAAATGCACACATGCTGTGCC -3'
(R):5'- ATCCTGACGCCAGCACCATTTC -3'

Sequencing Primer
(F):5'- ATGCTGTGCCTACAACAGG -3'
(R):5'- cgccagcaccatttctactc -3'

Posted On

2013-05-09