Mutagenetix > Incidental Mutation

Incidental Mutation 'R8803:Pcsk2'

671602

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

068640-MU

Accession Numbers

Essential gene?

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

Stock #

R8803 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

143388076-143658205 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 143637870 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 369 (T369A)

Ref Sequence

ENSEMBL: ENSMUSP00000028905 (fasta)

Gene Model

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

AlphaFold

P21661

Predicted Effect

probably damaging
Transcript: ENSMUST00000028905
AA Change: T369A

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000028905
Gene: ENSMUSG00000027419
AA Change: T369A

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: 99.9%
10x: 99.7%
20x: 98.9%

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 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: 69 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aadat	T	A	8: 60,998,290 (GRCm39)	S431T	probably benign	Het
Acot7	T	G	4: 152,302,272 (GRCm39)	V128G	probably damaging	Het
Actn3	T	C	19: 4,914,691 (GRCm39)	D508G	probably benign	Het
Adam18	T	C	8: 25,137,878 (GRCm39)	I321V	probably benign	Het
Ak1	T	C	2: 32,523,490 (GRCm39)	V186A	probably benign	Het
Aldh3a2	A	G	11: 61,139,756 (GRCm39)	F459L	probably benign	Het
Atp11a	T	C	8: 12,875,721 (GRCm39)	L256P	probably benign	Het
Bcan	T	C	3: 87,903,999 (GRCm39)	E162G	probably benign	Het
Birc6	A	G	17: 74,959,033 (GRCm39)	Q3850R	probably damaging	Het
Btf3l4	T	G	4: 108,689,084 (GRCm39)		probably benign	Het
Btla	A	G	16: 45,059,430 (GRCm39)	T45A	probably benign	Het
Cad	T	G	5: 31,226,908 (GRCm39)	S1222A	probably damaging	Het
Cbarp	A	G	10: 79,972,976 (GRCm39)	V39A	possibly damaging	Het
Cct2	A	C	10: 116,894,090 (GRCm39)	D221E	probably benign	Het
Cmya5	T	C	13: 93,177,991 (GRCm39)	D3621G	probably damaging	Het
Col20a1	G	T	2: 180,643,131 (GRCm39)	R867L	possibly damaging	Het
Cops3	A	G	11: 59,718,802 (GRCm39)	V164A	probably benign	Het
Crygf	A	G	1: 65,967,148 (GRCm39)	R91G	probably damaging	Het
Csmd2	T	A	4: 128,440,477 (GRCm39)	S3181T		Het
Cyb5r1	G	T	1: 134,333,696 (GRCm39)		probably benign	Het
Dennd6b	T	A	15: 89,070,383 (GRCm39)	I429F	probably benign	Het
Dock1	A	G	7: 134,475,816 (GRCm39)	T864A	probably benign	Het
Eea1	A	T	10: 95,859,853 (GRCm39)	D713V	probably benign	Het
Fam78b	G	A	1: 166,829,160 (GRCm39)	C9Y	probably damaging	Het
Gga2	A	C	7: 121,597,002 (GRCm39)	D371E	probably benign	Het
Gtpbp6	A	T	5: 110,255,186 (GRCm39)	V2E	unknown	Het
Hectd4	A	T	5: 121,461,994 (GRCm39)	M954L	probably benign	Het
Hmcn1	A	G	1: 150,610,248 (GRCm39)	C1474R	probably damaging	Het
Igkv1-99	G	T	6: 68,519,370 (GRCm39)	G109V		Het
Izumo3	T	C	4: 92,033,310 (GRCm39)		probably null	Het
Kremen1	T	C	11: 5,144,981 (GRCm39)	D465G	probably benign	Het
Ksr1	T	C	11: 79,036,882 (GRCm39)	E75G	probably benign	Het
Mmp17	G	T	5: 129,675,773 (GRCm39)	E311*	probably null	Het
Mmrn1	T	A	6: 60,965,271 (GRCm39)	F1101I	probably damaging	Het
Muc13	G	A	16: 33,633,287 (GRCm39)		probably benign	Het
Myl4	T	A	11: 104,475,403 (GRCm39)	M147K	probably damaging	Het
Myo1a	T	A	10: 127,546,856 (GRCm39)	N334K	probably benign	Het
Myo3b	T	C	2: 70,083,338 (GRCm39)	S664P	probably benign	Het
Nptxr	T	C	15: 79,678,655 (GRCm39)	N211D	probably damaging	Het
Ntf5	A	G	7: 45,065,485 (GRCm39)	T206A	probably benign	Het
Obscn	T	A	11: 58,945,229 (GRCm39)	E4596D	probably benign	Het
Or4d10c	T	C	19: 12,065,469 (GRCm39)	E229G	probably benign	Het
Or4f14d	T	C	2: 111,960,427 (GRCm39)	H243R	probably damaging	Het
Or5ak20	T	A	2: 85,184,078 (GRCm39)	Q64L	probably damaging	Het
Or5ak25	T	A	2: 85,268,981 (GRCm39)	I174F	probably damaging	Het
Or5b3	A	T	19: 13,388,037 (GRCm39)	I35F	probably damaging	Het
Or7e169	A	T	9: 19,757,462 (GRCm39)	I151N	possibly damaging	Het
Paip2	A	G	18: 35,749,273 (GRCm39)	N114D	possibly damaging	Het
Pcnx1	T	C	12: 82,039,925 (GRCm39)	S2071P	possibly damaging	Het
Ppp1r12b	A	C	1: 134,818,492 (GRCm39)		probably benign	Het
Ppp1r35	T	A	5: 137,777,731 (GRCm39)	D132E	possibly damaging	Het
Pramel7	A	T	2: 87,320,405 (GRCm39)	V296E	probably benign	Het
Prh1	C	T	6: 132,548,948 (GRCm39)	P152S	unknown	Het
Pygl	T	C	12: 70,242,390 (GRCm39)	T689A	probably damaging	Het
Rasgef1b	T	C	5: 99,369,269 (GRCm39)	S450G	probably benign	Het
Rtn4ip1	G	T	10: 43,783,842 (GRCm39)	R121L	probably damaging	Het
Scarf2	A	T	16: 17,620,695 (GRCm39)	H121L	probably damaging	Het
Selenbp1	C	A	3: 94,851,821 (GRCm39)	A454E	possibly damaging	Het
Slc7a9	A	G	7: 35,163,143 (GRCm39)	I449M	possibly damaging	Het
Snapc2	C	T	8: 4,305,558 (GRCm39)	H278Y	probably damaging	Het
Stambp	C	T	6: 83,524,212 (GRCm39)		probably null	Het
Syne1	T	C	10: 5,311,535 (GRCm39)	Y550C	probably damaging	Het
Tas2r113	T	C	6: 132,870,104 (GRCm39)	V44A	possibly damaging	Het
Trpv4	T	C	5: 114,772,816 (GRCm39)	T305A	probably benign	Het
Twf1	T	C	15: 94,479,136 (GRCm39)	Y241C	probably damaging	Het
Ugt2a3	T	C	5: 87,484,389 (GRCm39)	K212E	probably damaging	Het
Ush2a	A	T	1: 188,676,998 (GRCm39)	H4770L	probably benign	Het
Zfc3h1	T	C	10: 115,247,800 (GRCm39)	V1001A	probably benign	Het
Zfp335	C	T	2: 164,751,290 (GRCm39)	R92Q	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
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
R7289:Pcsk2	UTSW	2	143,532,343 (GRCm39)	missense	probably damaging	1.00
R8043:Pcsk2	UTSW	2	143,655,450 (GRCm39)	nonsense	probably null
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'- TCATGATGAAAGTCCAAAAGCC -3'
(R):5'- CTAGGTGCTCATATCCATGCCTG -3'

Sequencing Primer
(F):5'- GTCCAAAAGCCAAGCTCAGTG -3'
(R):5'- TCTCTGTGGACACCTGGCATG -3'

Posted On

2021-04-30