Mutagenetix > Incidental Mutation

Incidental Mutation 'R0092:Pcsk2'

20258

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

038379-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.205) question?

Stock #

R0092 (G1)

Quality Score

225

Status

Validated (trace)

Chromosome

Chromosomal Location

143388076-143658205 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 143642944 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 407 (D407G)

Ref Sequence

ENSEMBL: ENSMUSP00000028905 (fasta)

Gene Model

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

AlphaFold

P21661

Predicted Effect

probably damaging
Transcript: ENSMUST00000028905
AA Change: D407G

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000028905
Gene: ENSMUSG00000027419
AA Change: D407G

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

Meta Mutation Damage Score

0.9668

Coding Region Coverage

1x: 98.9%
3x: 97.9%
10x: 95.1%
20x: 88.6%

Validation Efficiency

99% (112/113)

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: 94 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcg2	T	A	6: 58,662,762 (GRCm39)	S535T	probably benign	Het
Acad11	A	T	9: 103,967,540 (GRCm39)		probably benign	Het
Acadm	A	T	3: 153,647,512 (GRCm39)		probably benign	Het
Acot12	T	A	13: 91,889,684 (GRCm39)	M12K	probably damaging	Het
Actr2	A	T	11: 20,044,308 (GRCm39)	N99K	probably benign	Het
Adam2	G	A	14: 66,291,336 (GRCm39)	A314V	probably damaging	Het
Agl	C	T	3: 116,587,453 (GRCm39)	R34Q	probably damaging	Het
Agrn	C	T	4: 156,263,410 (GRCm39)	R338H	probably damaging	Het
AI661453	A	G	17: 47,778,440 (GRCm39)		probably benign	Het
Alpk3	A	G	7: 80,742,301 (GRCm39)	D706G	probably benign	Het
Apbb1	T	C	7: 105,208,361 (GRCm39)	E648G	probably damaging	Het
Astn2	C	A	4: 66,322,219 (GRCm39)	A127S	unknown	Het
Asxl2	T	C	12: 3,546,313 (GRCm39)	S366P	probably benign	Het
Bdh1	A	T	16: 31,266,380 (GRCm39)	K92*	probably null	Het
Bltp1	A	G	3: 37,082,308 (GRCm39)	D3790G	probably benign	Het
Cacna1g	C	T	11: 94,348,090 (GRCm39)	S666N	probably damaging	Het
Ces2b	A	G	8: 105,563,144 (GRCm39)	T361A	possibly damaging	Het
Col6a4	T	A	9: 105,890,513 (GRCm39)	E1927V	probably benign	Het
Ctnnb1	T	G	9: 120,781,929 (GRCm39)	I314S	possibly damaging	Het
Cyp2c66	T	C	19: 39,172,224 (GRCm39)		probably benign	Het
Dennd4c	T	A	4: 86,699,844 (GRCm39)	F232I	probably damaging	Het
Dennd5a	T	C	7: 109,499,013 (GRCm39)	N950S	possibly damaging	Het
Dhx30	T	C	9: 109,914,078 (GRCm39)	N14S	possibly damaging	Het
Dip2b	T	A	15: 100,100,146 (GRCm39)	V1004D	probably damaging	Het
Dnah1	A	C	14: 30,993,566 (GRCm39)	S2872A	probably benign	Het
Dnajc10	T	C	2: 80,156,026 (GRCm39)	V233A	probably damaging	Het
E230025N22Rik	A	G	18: 36,822,277 (GRCm39)	L162P	probably damaging	Het
Elmod3	T	C	6: 72,543,792 (GRCm39)	D333G	probably benign	Het
Epb41l3	T	A	17: 69,593,745 (GRCm39)	M846K	probably damaging	Het
Frem2	A	G	3: 53,497,217 (GRCm39)	Y1766H	probably benign	Het
Fxr2	T	C	11: 69,532,972 (GRCm39)		probably benign	Het
Gmpr2	A	G	14: 55,915,402 (GRCm39)	R258G	probably benign	Het
Helb	T	C	10: 119,925,713 (GRCm39)	Y888C	probably damaging	Het
Hephl1	TTCCAGATGTCC	TTCC	9: 15,001,899 (GRCm39)		probably null	Het
Hipk2	T	C	6: 38,720,164 (GRCm39)	D482G	probably damaging	Het
Itgb4	G	T	11: 115,869,950 (GRCm39)	R44L	probably damaging	Het
Itih1	T	C	14: 30,662,820 (GRCm39)		probably benign	Het
Kit	T	A	5: 75,808,414 (GRCm39)	S719R	possibly damaging	Het
Krt13	G	A	11: 100,012,258 (GRCm39)	Q22*	probably null	Het
L3mbtl4	A	C	17: 68,732,698 (GRCm39)	R59S	probably benign	Het
Lpp	A	G	16: 24,580,352 (GRCm39)	S23G	probably benign	Het
Magi3	G	A	3: 103,958,280 (GRCm39)	Q602*	probably null	Het
Man2a1	A	G	17: 64,966,079 (GRCm39)		probably benign	Het
Muc5ac	A	G	7: 141,372,367 (GRCm39)	E2667G	possibly damaging	Het
Myef2l	G	A	3: 10,153,633 (GRCm39)	C134Y	possibly damaging	Het
Myo15b	C	G	11: 115,753,812 (GRCm39)	S842C	possibly damaging	Het
Naf1	T	A	8: 67,341,760 (GRCm39)	S462T	probably benign	Het
Necab3	T	C	2: 154,400,659 (GRCm39)	D34G	possibly damaging	Het
Nisch	C	A	14: 30,913,410 (GRCm39)		probably benign	Het
Nlrc5	T	C	8: 95,216,222 (GRCm39)		probably benign	Het
Nmt1	T	C	11: 102,937,319 (GRCm39)	F119L	probably damaging	Het
Nod1	T	G	6: 54,921,526 (GRCm39)	D264A	probably damaging	Het
Nol8	C	T	13: 49,815,923 (GRCm39)	A677V	possibly damaging	Het
Nt5e	T	A	9: 88,252,338 (GRCm39)	F567I	probably benign	Het
Obscn	A	T	11: 58,942,073 (GRCm39)	M4434K	possibly damaging	Het
Opa1	A	T	16: 29,444,412 (GRCm39)	D866V	probably damaging	Het
Or10a3m	T	C	7: 108,313,031 (GRCm39)	V145A	probably benign	Het
Or10al3	T	G	17: 38,011,696 (GRCm39)	L45R	probably damaging	Het
Or10p1	A	G	10: 129,444,090 (GRCm39)	S87P	probably damaging	Het
Or1j21	A	G	2: 36,683,508 (GRCm39)	T87A	probably benign	Het
Or51ai2	T	C	7: 103,586,934 (GRCm39)	S116P	probably damaging	Het
Otop1	T	A	5: 38,457,174 (GRCm39)	V311E	probably damaging	Het
Pdcd1	A	G	1: 93,980,149 (GRCm39)	W23R	possibly damaging	Het
Pigp	A	G	16: 94,166,321 (GRCm39)	V129A	probably damaging	Het
Pik3r5	A	G	11: 68,383,629 (GRCm39)	R483G	probably benign	Het
Pink1	A	G	4: 138,047,309 (GRCm39)	V225A	probably benign	Het
Plcl1	C	G	1: 55,735,924 (GRCm39)	Q422E	probably damaging	Het
Plec	T	C	15: 76,067,943 (GRCm39)	E1222G	probably benign	Het
Polr1a	T	C	6: 71,944,439 (GRCm39)		probably benign	Het
Prokr2	C	T	2: 132,215,517 (GRCm39)	V154M	probably damaging	Het
Rasgrp4	A	G	7: 28,844,557 (GRCm39)	R280G	possibly damaging	Het
Rmnd5b	T	C	11: 51,520,419 (GRCm39)	E8G	possibly damaging	Het
Sbf2	T	A	7: 109,920,013 (GRCm39)		probably benign	Het
Sec23b	A	G	2: 144,408,830 (GRCm39)	M172V	probably benign	Het
Setx	T	C	2: 29,036,305 (GRCm39)	V930A	probably benign	Het
Sft2d2	G	A	1: 165,006,829 (GRCm39)	A159V	possibly damaging	Het
Sh3gl1	G	T	17: 56,325,088 (GRCm39)	R250S	probably benign	Het
Skor1	C	A	9: 63,053,277 (GRCm39)	D231Y	probably damaging	Het
Slc24a1	T	G	9: 64,856,034 (GRCm39)	E291A	unknown	Het
Slc28a2b	G	T	2: 122,348,078 (GRCm39)		probably benign	Het
Smc1b	A	T	15: 84,951,925 (GRCm39)		probably benign	Het
Tbccd1	A	T	16: 22,644,844 (GRCm39)	N177K	possibly damaging	Het
Tdp1	T	A	12: 99,921,248 (GRCm39)	Y595N	probably damaging	Het
Tle5	G	A	10: 81,397,054 (GRCm39)	G10D	possibly damaging	Het
Tmem108	T	C	9: 103,366,504 (GRCm39)	K496E	possibly damaging	Het
Tmprss7	T	C	16: 45,487,959 (GRCm39)	D490G	probably damaging	Het
Tnrc6b	A	T	15: 80,802,729 (GRCm39)	N1511Y	probably damaging	Het
Top2b	G	A	14: 16,409,263 (GRCm38)	R802Q	probably damaging	Het
Trip10	A	T	17: 57,557,798 (GRCm39)	K27N	possibly damaging	Het
Txlnb	A	G	10: 17,718,503 (GRCm39)	N445D	possibly damaging	Het
Txnrd1	T	A	10: 82,715,636 (GRCm39)	I159N	probably damaging	Het
Ulk1	C	A	5: 110,944,193 (GRCm39)	A164S	probably null	Het
Vmn2r83	T	C	10: 79,327,798 (GRCm39)	V802A	probably damaging	Het
Zbtb4	A	G	11: 69,670,177 (GRCm39)	I967V	probably benign	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
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
R5905:Pcsk2	UTSW	2	143,591,060 (GRCm39)	missense	probably damaging	0.98
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'- AGATAACACACAAATGCCTTCCTTGAGT -3'
(R):5'- TGCATCTCTATAGCTTTCCCCAGAAGTC -3'

Sequencing Primer
(F):5'- TGagttaaaagttcacagatgttcc -3'
(R):5'- GAAGAAGTTCTGCCCCTACTTAC -3'

Posted On

2013-04-11