Mutagenetix > Incidental Mutation

Incidental Mutation 'R5905:Pcsk2'

456483

Institutional Source

Beutler Lab

Gene Symbol

Pcsk2

Ensembl Gene

ENSMUSG00000027419

Gene Name

proprotein convertase subtilisin/kexin type 2

Synonyms

Nec-2, PC2, Phpp-2, SPC2, Nec2, 6330411F23Rik, prohormone convertase 2

MMRRC Submission

044102-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.192) question?

Stock #

R5905 (G1)

Quality Score

153

Status

Not validated

Chromosome

Chromosomal Location

143388076-143658205 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 143591060 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Asparagine at position 186 (Y186N)

Ref Sequence

ENSEMBL: ENSMUSP00000028905 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028905]

AlphaFold

P21661

Predicted Effect

probably damaging
Transcript: ENSMUST00000028905
AA Change: Y186N

PolyPhen 2 Score 0.982 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000028905
Gene: ENSMUSG00000027419
AA Change: Y186N

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
Pfam:S8_pro-domain	32	108	2.9e-21	PFAM
Pfam:Peptidase_S8	157	444	5e-44	PFAM
Pfam:P_proprotein	503	590	4.3e-28	PFAM
low complexity region	617	630	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000153878

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000156362

Coding Region Coverage

1x: 99.8%
3x: 99.4%
10x: 97.1%
20x: 90.9%

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 protein undergoes an initial autocatalytic processing event and interacts with a neuroendocrine secretory protein in the ER, exits the ER and sorts to secretory granules, where it is cleaved and catalytically activated during intracellular transport. The encoded protease is packaged into and activated in dense core secretory granules and expressed in the neuroendocrine system and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It functions in the proteolytic activation of polypeptide hormones and neuropeptides precursors. Single nucleotide polymorphisms in this gene may increase susceptibility to myocardial infarction and type 2 diabetes. This gene may also play a role in tumor development and progression. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2014]
PHENOTYPE: Mice homozygous for disruptions of this gene display abnormalities in the maturation of peptide hormones leading to reduced female fertility, increased blood pressure on a high salt diet, and abnormal glucose metabolism. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 86 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1810062G17Rik	T	A	3: 36,533,718 (GRCm39)		probably null	Het
Acat1	A	T	9: 53,503,366 (GRCm39)	Y158N	probably damaging	Het
Adamtsl1	C	A	4: 86,260,561 (GRCm39)	A924E	probably damaging	Het
Alad	G	T	4: 62,428,359 (GRCm39)	T305K	probably benign	Het
Als2cl	G	T	9: 110,727,152 (GRCm39)	R906L	probably damaging	Het
Ap3d1	T	C	10: 80,558,761 (GRCm39)	N281S	possibly damaging	Het
Arf4	A	G	14: 26,375,079 (GRCm39)	T113A	probably benign	Het
Asah2	T	C	19: 31,993,914 (GRCm39)	D438G	probably damaging	Het
Cachd1	C	A	4: 100,840,753 (GRCm39)	N905K	probably damaging	Het
Catsperb	T	A	12: 101,568,959 (GRCm39)	M877K	possibly damaging	Het
Cc2d2a	A	T	5: 43,869,768 (GRCm39)	M890L	probably benign	Het
Cd180	A	T	13: 102,842,541 (GRCm39)	H529L	possibly damaging	Het
Cdh23	G	T	10: 60,370,314 (GRCm39)	D160E	probably damaging	Het
Chd7	C	A	4: 8,840,553 (GRCm39)	N1440K	possibly damaging	Het
Cntln	T	A	4: 84,889,410 (GRCm39)	S298T	probably benign	Het
Cplx3	A	G	9: 57,515,546 (GRCm39)	I443T	probably damaging	Het
Dmap1	G	T	4: 117,533,963 (GRCm39)	T132K	probably benign	Het
Dnah11	C	T	12: 117,918,659 (GRCm39)	G3424E	probably damaging	Het
Dnah5	T	A	15: 28,387,979 (GRCm39)	M3146K	probably damaging	Het
Egfr	A	T	11: 16,861,494 (GRCm39)	E1091V	probably damaging	Het
Eps8l2	T	C	7: 140,937,746 (GRCm39)	F422S	possibly damaging	Het
F2r	A	G	13: 95,741,121 (GRCm39)	V138A	possibly damaging	Het
Faf1	T	A	4: 109,748,126 (GRCm39)	M477K	probably benign	Het
Fam149b	C	T	14: 20,409,978 (GRCm39)	T235M	probably benign	Het
Fan1	C	A	7: 64,003,399 (GRCm39)	A808S	probably benign	Het
Fbxl20	A	G	11: 98,006,271 (GRCm39)	I38T	probably damaging	Het
Fnbp4	C	A	2: 90,581,478 (GRCm39)	T177K	probably benign	Het
Gm9747	T	C	1: 82,212,019 (GRCm39)		probably benign	Het
Grip1	A	G	10: 119,821,397 (GRCm39)	D354G	probably benign	Het
Grk4	A	C	5: 34,869,074 (GRCm39)	Y189S	probably damaging	Het
Hax1	GTCATCATCATCATCATC	GTCATCATCATCATCATCATC	3: 89,905,247 (GRCm39)		probably benign	Het
Hgfac	A	G	5: 35,199,706 (GRCm39)	N63D	probably benign	Het
Hk1	C	A	10: 62,188,837 (GRCm39)	K25N	probably null	Het
Hrc	G	A	7: 44,985,658 (GRCm39)	G270S	probably damaging	Het
Inhba	T	A	13: 16,191,893 (GRCm39)	W5R	probably benign	Het
Lipm	T	C	19: 34,089,311 (GRCm39)	S90P	probably benign	Het
Lmod3	T	A	6: 97,224,575 (GRCm39)	E415D	probably damaging	Het
Lrrc37	A	T	11: 103,505,081 (GRCm39)	S2296T	probably damaging	Het
Lrrc63	A	G	14: 75,323,614 (GRCm39)	S537P	possibly damaging	Het
Map9	T	A	3: 82,287,555 (GRCm39)		probably null	Het
Marf1	T	A	16: 13,945,113 (GRCm39)	Q1252L	probably damaging	Het
Mc3r	A	T	2: 172,091,129 (GRCm39)	D117V	probably damaging	Het
Mepce	A	G	5: 137,782,982 (GRCm39)	V448A	possibly damaging	Het
Mical1	A	T	10: 41,362,873 (GRCm39)	M973L	probably benign	Het
Mmp21	T	C	7: 133,280,443 (GRCm39)	T176A	probably benign	Het
Nacc2	A	G	2: 25,951,590 (GRCm39)	V415A	probably damaging	Het
Neb	G	A	2: 52,083,243 (GRCm39)	T1639I	probably damaging	Het
Nfia	A	G	4: 97,999,488 (GRCm39)	H485R	possibly damaging	Het
Nlrp9a	C	T	7: 26,257,762 (GRCm39)	T460I	probably benign	Het
Or10p21	A	T	10: 128,847,156 (GRCm39)	M1L	probably benign	Het
Or52z15	T	A	7: 103,332,781 (GRCm39)	N285K	probably damaging	Het
Or56b35	T	C	7: 104,964,158 (GRCm39)	Y316H	probably benign	Het
Or8g24	T	A	9: 38,989,379 (GRCm39)	I221F	probably damaging	Het
Or8k32	T	A	2: 86,369,113 (GRCm39)	I49F	possibly damaging	Het
Or9s13	T	A	1: 92,547,864 (GRCm39)	C79S	possibly damaging	Het
Otoa	T	A	7: 120,693,824 (GRCm39)	L68Q	probably damaging	Het
Pclo	A	T	5: 14,730,399 (GRCm39)		probably benign	Het
Pigz	A	G	16: 31,764,246 (GRCm39)	T435A	probably benign	Het
Pja2	T	C	17: 64,616,085 (GRCm39)	D270G	probably benign	Het
Polb	G	T	8: 23,130,011 (GRCm39)	S187*	probably null	Het
Popdc3	A	G	10: 45,194,015 (GRCm39)	D272G	probably benign	Het
Prr5	A	T	15: 84,626,178 (GRCm39)	K84N	possibly damaging	Het
Prss36	T	C	7: 127,532,744 (GRCm39)	D716G	probably benign	Het
Rapgef5	T	A	12: 117,712,161 (GRCm39)	D547E	probably damaging	Het
Slc4a11	T	A	2: 130,526,972 (GRCm39)	I719F	probably damaging	Het
Smpd2	A	G	10: 41,365,344 (GRCm39)	W51R	probably damaging	Het
Snrpb	T	A	2: 130,021,196 (GRCm39)		probably benign	Het
Sox9	A	G	11: 112,674,646 (GRCm39)	E148G	probably damaging	Het
Strbp	G	A	2: 37,515,267 (GRCm39)	T253I	probably damaging	Het
Sult1d1	A	T	5: 87,707,685 (GRCm39)	M145K	probably damaging	Het
Syt17	T	C	7: 118,036,141 (GRCm39)	D74G	probably benign	Het
Taf5l	A	C	8: 124,729,714 (GRCm39)		probably null	Het
Tas2r131	T	G	6: 132,934,639 (GRCm39)	I57L	probably benign	Het
Tcf25	A	G	8: 124,108,176 (GRCm39)	N77S	possibly damaging	Het
Tmem253	A	G	14: 52,255,268 (GRCm39)	T57A	possibly damaging	Het
Trrap	A	G	5: 144,786,730 (GRCm39)	K3170R	possibly damaging	Het
Tspan17	A	G	13: 54,941,111 (GRCm39)	N130S	probably damaging	Het
Vmn1r216	C	T	13: 23,283,367 (GRCm39)	L17F	probably damaging	Het
Vmn2r3	T	A	3: 64,182,698 (GRCm39)	T334S	probably benign	Het
Wnk2	G	T	13: 49,229,821 (GRCm39)	A901E	probably damaging	Het
Zc3hav1	T	C	6: 38,284,275 (GRCm39)	T947A	probably benign	Het
Zfhx3	C	T	8: 109,520,135 (GRCm39)	P419L	probably damaging	Het
Zfp292	A	G	4: 34,819,549 (GRCm39)	S258P	probably damaging	Het
Zfp354c	T	C	11: 50,706,253 (GRCm39)	Y274C	probably damaging	Het
Zfp652	G	A	11: 95,640,689 (GRCm39)	A205T	probably benign	Het
Zfp964	A	G	8: 70,116,563 (GRCm39)	T388A	unknown	Het

Other mutations in Pcsk2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00503:Pcsk2	APN	2	143,635,159 (GRCm39)	missense	probably damaging	1.00
IGL01609:Pcsk2	APN	2	143,643,078 (GRCm39)	missense	possibly damaging	0.88
IGL01690:Pcsk2	APN	2	143,529,490 (GRCm39)	missense	probably benign
IGL01833:Pcsk2	APN	2	143,529,500 (GRCm39)	missense	possibly damaging	0.62
IGL01962:Pcsk2	APN	2	143,655,552 (GRCm39)	nonsense	probably null
IGL02219:Pcsk2	APN	2	143,635,045 (GRCm39)	missense	probably damaging	1.00
IGL02572:Pcsk2	APN	2	143,532,262 (GRCm39)	missense	probably damaging	1.00
IGL02752:Pcsk2	APN	2	143,615,865 (GRCm39)	missense	probably benign	0.09
P0035:Pcsk2	UTSW	2	143,637,871 (GRCm39)	missense	probably damaging	1.00
R0092:Pcsk2	UTSW	2	143,642,944 (GRCm39)	missense	probably damaging	1.00
R1424:Pcsk2	UTSW	2	143,415,348 (GRCm39)	splice site	probably benign
R1470:Pcsk2	UTSW	2	143,388,438 (GRCm39)	nonsense	probably null
R1470:Pcsk2	UTSW	2	143,388,438 (GRCm39)	nonsense	probably null
R1832:Pcsk2	UTSW	2	143,635,189 (GRCm39)	missense	probably damaging	1.00
R1993:Pcsk2	UTSW	2	143,529,539 (GRCm39)	missense	probably benign	0.00
R4615:Pcsk2	UTSW	2	143,637,889 (GRCm39)	missense	probably damaging	1.00
R4783:Pcsk2	UTSW	2	143,529,599 (GRCm39)	critical splice donor site	probably null
R4796:Pcsk2	UTSW	2	143,655,345 (GRCm39)	missense	probably benign	0.16
R4827:Pcsk2	UTSW	2	143,643,099 (GRCm39)	nonsense	probably null
R5357:Pcsk2	UTSW	2	143,415,384 (GRCm39)	missense	probably benign	0.00
R5413:Pcsk2	UTSW	2	143,538,620 (GRCm39)	splice site	probably null
R5440:Pcsk2	UTSW	2	143,388,463 (GRCm39)	missense	probably benign	0.22
R5546:Pcsk2	UTSW	2	143,388,480 (GRCm39)	missense	probably benign	0.00
R5605:Pcsk2	UTSW	2	143,591,165 (GRCm39)	intron	probably benign
R5821:Pcsk2	UTSW	2	143,591,035 (GRCm39)	splice site	probably null
R6120:Pcsk2	UTSW	2	143,643,031 (GRCm39)	missense	probably damaging	1.00
R6135:Pcsk2	UTSW	2	143,415,460 (GRCm39)	missense	possibly damaging	0.63
R6657:Pcsk2	UTSW	2	143,532,286 (GRCm39)	missense	probably damaging	1.00
R6925:Pcsk2	UTSW	2	143,655,667 (GRCm39)	missense	probably damaging	1.00
R7223:Pcsk2	UTSW	2	143,532,253 (GRCm39)	missense	possibly damaging	0.95
R7289:Pcsk2	UTSW	2	143,532,343 (GRCm39)	missense	probably damaging	1.00
R8043:Pcsk2	UTSW	2	143,655,450 (GRCm39)	nonsense	probably null
R8803:Pcsk2	UTSW	2	143,637,870 (GRCm39)	missense	probably damaging	0.99
R8819:Pcsk2	UTSW	2	143,642,990 (GRCm39)	missense	probably damaging	0.99
R8820:Pcsk2	UTSW	2	143,642,990 (GRCm39)	missense	probably damaging	0.99
R9131:Pcsk2	UTSW	2	143,655,583 (GRCm39)	missense	possibly damaging	0.56
R9643:Pcsk2	UTSW	2	143,655,501 (GRCm39)	missense	probably damaging	1.00
R9753:Pcsk2	UTSW	2	143,635,150 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- ACCAGCTCTGTCACAATTTTGC -3'
(R):5'- TGAGGGGCATTGCAATACTGG -3'

Sequencing Primer
(F):5'- CCAGCTCTGTCACAATTTTGCAAATG -3'
(R):5'- GGCATTGCAATACTGGAAATCC -3'

Posted On

2017-02-15