Mutagenetix > Incidental Mutation

Incidental Mutation 'R7807:Pcsk9'

600849

Institutional Source

Beutler Lab

Gene Symbol

Pcsk9

Ensembl Gene

ENSMUSG00000044254

Gene Name

proprotein convertase subtilisin/kexin type 9

Synonyms

Narc1

MMRRC Submission

045862-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R7807 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

106299531-106321522 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 106321092 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 6 (S6P)

Ref Sequence

ENSEMBL: ENSMUSP00000055757 (fasta)

Gene Model

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

AlphaFold

Q80W65

Predicted Effect

possibly damaging
Transcript: ENSMUST00000049507
AA Change: S6P

PolyPhen 2 Score 0.734 (Sensitivity: 0.85; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000055757
Gene: ENSMUSG00000044254
AA Change: S6P

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: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.0%

Validation Efficiency

100% (68/68)

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: 71 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
AB124611	C	A	9: 21,447,276 (GRCm39)	T146K	probably benign	Het
Alms1	T	A	6: 85,599,958 (GRCm39)	S1595T	possibly damaging	Het
Ankrd44	A	T	1: 54,831,635 (GRCm39)	I56N	probably damaging	Het
Anln	C	A	9: 22,272,176 (GRCm39)	V648F	probably damaging	Het
Arhgap29	A	G	3: 121,807,981 (GRCm39)	D1053G	probably benign	Het
Baalc	T	C	15: 38,797,412 (GRCm39)	S68P	probably benign	Het
Begain	T	C	12: 109,004,856 (GRCm39)	D52G	probably damaging	Het
Blmh	A	G	11: 76,837,040 (GRCm39)	I41V	probably benign	Het
Bpifc	T	A	10: 85,812,114 (GRCm39)	I365F	possibly damaging	Het
C2	G	T	17: 35,095,347 (GRCm39)	S199R	possibly damaging	Het
Ccbe1	T	A	18: 66,199,828 (GRCm39)	H298L	probably damaging	Het
Ccdc112	T	A	18: 46,423,826 (GRCm39)	K304I	probably damaging	Het
Ccdc15	T	C	9: 37,226,678 (GRCm39)	E432G	probably benign	Het
Cdh13	T	A	8: 119,010,594 (GRCm39)	M1K	probably null	Het
Cipc	T	C	12: 87,008,899 (GRCm39)	S253P	possibly damaging	Het
Clcn1	A	G	6: 42,287,282 (GRCm39)		probably null	Het
Clock	A	T	5: 76,390,982 (GRCm39)	N273K	probably benign	Het
Cyp19a1	T	C	9: 54,074,126 (GRCm39)	D476G	probably benign	Het
Dnaaf9	T	C	2: 130,552,785 (GRCm39)	K1092E	probably damaging	Het
Dnah7b	A	G	1: 46,253,527 (GRCm39)	I1811V	probably benign	Het
Fat1	C	A	8: 45,495,010 (GRCm39)	T4091K	probably damaging	Het
Gm10340	T	A	14: 14,826,724 (GRCm39)	N64K	probably damaging	Het
Hectd1	G	A	12: 51,792,171 (GRCm39)	R2523C	probably damaging	Het
Hgf	A	G	5: 16,782,009 (GRCm39)	H244R	probably damaging	Het
Hgs	G	T	11: 120,370,760 (GRCm39)	A567S	probably damaging	Het
Igdcc4	T	C	9: 65,041,077 (GRCm39)	V1036A	probably benign	Het
Keg1	G	A	19: 12,691,998 (GRCm39)		probably null	Het
Klhl8	A	T	5: 104,023,932 (GRCm39)	L156Q	probably damaging	Het
Lmln	T	C	16: 32,927,501 (GRCm39)	Y521H	probably benign	Het
Lrrc7	A	G	3: 157,866,124 (GRCm39)	S1206P	probably damaging	Het
Mad1l1	T	A	5: 140,074,541 (GRCm39)	I550F	probably benign	Het
Marf1	C	T	16: 13,971,753 (GRCm39)	W28*	probably null	Het
Mfsd11	T	G	11: 116,754,733 (GRCm39)	S215A	probably benign	Het
Mpped2	C	A	2: 106,575,085 (GRCm39)	H57N	possibly damaging	Het
Mslnl	A	G	17: 25,965,751 (GRCm39)	M542V	probably benign	Het
Myh6	G	T	14: 55,179,897 (GRCm39)	H1903Q	probably damaging	Het
Neo1	T	C	9: 58,897,777 (GRCm39)	T60A	probably benign	Het
Npm2	T	A	14: 70,889,947 (GRCm39)		probably null	Het
Or5b123	C	A	19: 13,597,285 (GRCm39)	T210K	probably damaging	Het
Or5d20-ps1	T	C	2: 87,931,909 (GRCm39)	S141G	probably benign	Het
Or7a39	T	A	10: 78,715,043 (GRCm39)	S12R	probably benign	Het
Pax9	A	T	12: 56,743,850 (GRCm39)	I166F	possibly damaging	Het
Pikfyve	A	G	1: 65,309,101 (GRCm39)	Y1893C	probably damaging	Het
Pirb	T	C	7: 3,722,864 (GRCm39)	T43A	possibly damaging	Het
Pou3f1	A	G	4: 124,552,074 (GRCm39)	D192G	possibly damaging	Het
Pus3	C	G	9: 35,478,021 (GRCm39)	R418G	probably damaging	Het
Rexo1	C	T	10: 80,385,970 (GRCm39)	V363I	probably benign	Het
Sdcbp	A	G	4: 6,393,688 (GRCm39)	T269A	probably damaging	Het
Sele	T	C	1: 163,881,462 (GRCm39)	V523A	probably benign	Het
Serpinb8	T	A	1: 107,532,457 (GRCm39)	M183K	probably damaging	Het
Sh2d4a	T	G	8: 68,735,033 (GRCm39)	S51A	probably benign	Het
Siglec15	A	G	18: 78,090,696 (GRCm39)	S201P	probably damaging	Het
Slc10a5	C	T	3: 10,400,529 (GRCm39)	V44I	probably benign	Het
Slc16a13	A	G	11: 70,111,388 (GRCm39)	V39A	probably damaging	Het
Slc25a13	G	A	6: 6,117,164 (GRCm39)	R184W	probably damaging	Het
Slc35f5	T	A	1: 125,512,278 (GRCm39)	D359E	probably damaging	Het
Slc3a1	A	G	17: 85,371,371 (GRCm39)	E641G	probably benign	Het
Slf1	T	C	13: 77,194,823 (GRCm39)	D834G	probably damaging	Het
Spata31f1e	A	C	4: 42,793,885 (GRCm39)	H82Q	probably benign	Het
Stim1	T	C	7: 102,076,348 (GRCm39)	I433T	probably damaging	Het
Stra6	T	A	9: 58,057,444 (GRCm39)	I418K	probably damaging	Het
Tanc2	A	G	11: 105,758,480 (GRCm39)	N747S	probably benign	Het
Tet2	T	C	3: 133,192,302 (GRCm39)	T711A	possibly damaging	Het
Trpm6	T	C	19: 18,807,220 (GRCm39)	I988T	probably benign	Het
Ttc41	T	A	10: 86,612,495 (GRCm39)	I1256N	probably benign	Het
Uba2	T	C	7: 33,862,638 (GRCm39)	D100G	possibly damaging	Het
Vmn1r43	A	G	6: 89,847,219 (GRCm39)	I89T	probably benign	Het
Vmn2r58	T	A	7: 41,521,910 (GRCm39)	Y62F	probably benign	Het
Ylpm1	C	T	12: 85,060,855 (GRCm39)	Q428*	probably null	Het
Zcrb1	T	C	15: 93,289,002 (GRCm39)	D88G	probably damaging	Het
Zmym1	A	C	4: 126,941,667 (GRCm39)	I907S	probably 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
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
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'- ACTTAGAGACCACCAGACGG -3'
(R):5'- ATCAGAGAGGATCTTCCGATGG -3'

Sequencing Primer
(F):5'- ATACCTTGGAGCAACGGC -3'
(R):5'- AGGATCTTCCGATGGGGCTC -3'

Posted On

2019-11-26