Mutagenetix > Incidental Mutation

Incidental Mutation 'R7289:Pcsk2'

566208

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

045396-MU

Accession Numbers

Essential gene?

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

Stock #

R7289 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

143388076-143658205 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 143532343 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Phenylalanine at position 164 (I164F)

Ref Sequence

ENSEMBL: ENSMUSP00000028905 (fasta)

Gene Model

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

AlphaFold

P21661

Predicted Effect

probably damaging
Transcript: ENSMUST00000028905
AA Change: I164F

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

SMART Domains

Protein: ENSMUSP00000028905
Gene: ENSMUSG00000027419
AA Change: I164F

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

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.0%

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: 93 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aars2	G	A	17: 45,818,550 (GRCm39)	D112N	probably damaging	Het
Abca7	T	A	10: 79,845,778 (GRCm39)	I1580K	probably damaging	Het
Aebp1	A	G	11: 5,815,059 (GRCm39)	D234G	probably damaging	Het
Agap1	T	A	1: 89,383,153 (GRCm39)	M1K	probably null	Het
Agrn	A	T	4: 156,263,389 (GRCm39)	L345H	probably damaging	Het
Amfr	A	G	8: 94,725,754 (GRCm39)	M209T	possibly damaging	Het
Angel2	G	A	1: 190,673,371 (GRCm39)	R338H	possibly damaging	Het
Ankrd27	C	T	7: 35,330,674 (GRCm39)	A866V	probably damaging	Het
Apc	G	A	18: 34,448,324 (GRCm39)	R1740Q	probably damaging	Het
Arhgap32	A	T	9: 32,168,233 (GRCm39)	S739C	possibly damaging	Het
Arhgap32	G	C	9: 32,168,234 (GRCm39)	S739T	probably benign	Het
Arhgef2	C	T	3: 88,543,192 (GRCm39)	S418L	probably benign	Het
Arhgef25	T	C	10: 127,019,641 (GRCm39)	T472A	possibly damaging	Het
Atrnl1	C	T	19: 57,638,846 (GRCm39)	S328F	probably benign	Het
Bahcc1	C	T	11: 120,171,000 (GRCm39)	A1514V	probably benign	Het
Calcoco2	C	T	11: 95,990,823 (GRCm39)	E305K	unknown	Het
Ccn1	C	T	3: 145,354,428 (GRCm39)	W161*	probably null	Het
Cdc42bpa	A	T	1: 179,889,362 (GRCm39)	K203*	probably null	Het
Cmc1	A	T	9: 117,904,250 (GRCm39)	I47N	possibly damaging	Het
Cntln	A	G	4: 84,964,540 (GRCm39)	E656G	possibly damaging	Het
Dcun1d3	T	C	7: 119,458,864 (GRCm39)	K57R	possibly damaging	Het
Ddx23	T	C	15: 98,546,492 (GRCm39)	E559G	probably damaging	Het
Dennd6a	G	A	14: 26,333,193 (GRCm39)	R367Q	probably damaging	Het
Desi2	A	T	1: 178,083,702 (GRCm39)		probably benign	Het
Dido1	T	C	2: 180,301,424 (GRCm39)	D2160G	unknown	Het
Efcab3	T	C	11: 104,929,184 (GRCm39)	M4838T	probably benign	Het
Epb41	A	G	4: 131,718,520 (GRCm39)		probably null	Het
Esrrb	T	A	12: 86,517,331 (GRCm39)		probably null	Het
Fabp1	C	A	6: 71,180,111 (GRCm39)	T94N	probably benign	Het
Fam120a	A	T	13: 49,045,482 (GRCm39)	C785S	probably damaging	Het
Fam243	T	C	16: 92,117,710 (GRCm39)	I193V	probably damaging	Het
Foxc1	A	G	13: 31,991,243 (GRCm39)	Y18C	probably damaging	Het
Fshr	T	C	17: 89,293,272 (GRCm39)	T469A	probably benign	Het
Gm14399	T	A	2: 174,972,204 (GRCm39)	H517L	unknown	Het
Gm39115	G	T	7: 141,689,297 (GRCm39)	Q159K	unknown	Het
Gm7347	T	A	5: 26,262,306 (GRCm39)	I72F	possibly damaging	Het
Hmcn1	A	G	1: 150,559,466 (GRCm39)	V2395A	possibly damaging	Het
Ighv5-17	T	G	12: 113,822,858 (GRCm39)	T88P	probably damaging	Het
Insm2	T	A	12: 55,647,329 (GRCm39)	Y358N	probably damaging	Het
Kazn	A	T	4: 141,844,486 (GRCm39)	L409Q		Het
Kcnj5	A	C	9: 32,234,045 (GRCm39)	L90R	probably damaging	Het
Kcnv2	A	T	19: 27,311,084 (GRCm39)	T484S	probably damaging	Het
Kdm3b	T	C	18: 34,927,557 (GRCm39)	Y140H	probably benign	Het
Kifbp	A	C	10: 62,401,895 (GRCm39)	C261W	probably damaging	Het
Krt25	C	T	11: 99,212,098 (GRCm39)	A180T	probably benign	Het
Mmp1a	A	G	9: 7,467,294 (GRCm39)	E290G	probably damaging	Het
Muc21	G	A	17: 35,929,761 (GRCm39)	A1475V	unknown	Het
Nr3c1	T	C	18: 39,547,654 (GRCm39)	T755A	probably benign	Het
Nr3c1	A	T	18: 39,555,786 (GRCm39)	I517N	probably benign	Het
Nxpe2	A	G	9: 48,234,339 (GRCm39)		probably null	Het
Oaz1	C	A	10: 80,662,673 (GRCm39)	T27K	possibly damaging	Het
Or4p7	A	T	2: 88,222,050 (GRCm39)	H153L	probably damaging	Het
Or51f5	T	C	7: 102,424,634 (GRCm39)	I301T	probably damaging	Het
Or5t5	G	T	2: 86,617,034 (GRCm39)	C320F	probably benign	Het
Or6z3	T	A	7: 6,463,777 (GRCm39)	W90R	probably benign	Het
Or8k21	A	G	2: 86,145,369 (GRCm39)	M87T	probably benign	Het
Or8s5	A	G	15: 98,237,943 (GRCm39)	V309A	probably damaging	Het
Pafah2	A	T	4: 134,147,308 (GRCm39)	K319M	probably damaging	Het
Pask	A	T	1: 93,259,309 (GRCm39)	V236E	probably damaging	Het
Pcdh1	T	C	18: 38,322,966 (GRCm39)	T956A	probably damaging	Het
Pcdhb18	C	A	18: 37,623,700 (GRCm39)	N343K	probably damaging	Het
Phf1	T	C	17: 27,154,289 (GRCm39)	Y169H	probably damaging	Het
Pkdrej	T	A	15: 85,705,301 (GRCm39)	I212F	probably benign	Het
Pnkp	T	A	7: 44,508,114 (GRCm39)	W146R	probably damaging	Het
Prkcb	A	T	7: 122,143,910 (GRCm39)	I325F	probably benign	Het
Ptpn21	C	T	12: 98,670,450 (GRCm39)	D239N	probably benign	Het
Ptprb	A	G	10: 116,164,070 (GRCm39)	T626A	probably damaging	Het
Pttg1	T	C	11: 43,311,916 (GRCm39)	N180D	probably benign	Het
Raly	G	A	2: 154,703,774 (GRCm39)	R115Q	probably damaging	Het
Rims2	A	T	15: 39,301,114 (GRCm39)	M474L	probably benign	Het
Sash1	A	T	10: 8,605,960 (GRCm39)	I810N	probably damaging	Het
Scnn1g	T	A	7: 121,337,304 (GRCm39)	L55*	probably null	Het
Sema6b	A	T	17: 56,432,573 (GRCm39)	D543E	possibly damaging	Het
Serpina11	C	T	12: 103,952,761 (GRCm39)	G5E	unknown	Het
Sesn3	A	T	9: 14,187,848 (GRCm39)	M1L	probably benign	Het
Sez6	T	A	11: 77,865,149 (GRCm39)	I632N	possibly damaging	Het
Sgo2b	A	T	8: 64,394,192 (GRCm39)	I49N	probably damaging	Het
Slc30a2	A	T	4: 134,071,524 (GRCm39)	I86F	possibly damaging	Het
Slc38a6	T	A	12: 73,333,786 (GRCm39)	W30R	probably benign	Het
Spata31g1	A	T	4: 42,972,379 (GRCm39)	T571S	probably benign	Het
Spata31g1	A	T	4: 42,973,252 (GRCm39)	I862F	possibly damaging	Het
Stk31	T	G	6: 49,415,393 (GRCm39)	V576G	probably benign	Het
Szt2	G	A	4: 118,233,075 (GRCm39)	T2297I	unknown	Het
Tmem208	T	C	8: 106,061,418 (GRCm39)	F148S	possibly damaging	Het
Tprg1l	A	G	4: 154,245,031 (GRCm39)	L19P	possibly damaging	Het
Tubg2	C	A	11: 101,050,897 (GRCm39)	N207K	probably damaging	Het
Ube2n	G	T	10: 95,377,612 (GRCm39)	K130N	probably benign	Het
Usp36	T	C	11: 118,164,355 (GRCm39)	Y384C	probably damaging	Het
Vcan	A	T	13: 89,840,852 (GRCm39)	L1564*	probably null	Het
Xkr6	A	T	14: 64,035,748 (GRCm39)	D283V	unknown	Het
Zfp654	T	C	16: 64,605,523 (GRCm39)	H352R	probably benign	Het
Zfp819	T	A	7: 43,266,506 (GRCm39)	C330S	probably damaging	Het
Zfp970	G	T	2: 177,167,086 (GRCm39)	C220F	probably damaging	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
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
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'- CACCCAAAAGCATGTTTCATGAAG -3'
(R):5'- TGTTGAGAGCATCACCAACTG -3'

Sequencing Primer
(F):5'- AAGCATGTTTCATGAAGGGTGTAGC -3'
(R):5'- GTTGAGAGCATCACCAACTGATCAG -3'

Posted On

2019-06-26