Mutagenetix > Incidental Mutation

Incidental Mutation 'R7223:Pcsk2'

561924

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

045295-MU

Accession Numbers

Essential gene?

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

Stock #

R7223 (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 G at 143532253 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 134 (T134A)

Ref Sequence

ENSEMBL: ENSMUSP00000028905 (fasta)

Gene Model

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

AlphaFold

P21661

Predicted Effect

possibly damaging
Transcript: ENSMUST00000028905
AA Change: T134A

PolyPhen 2 Score 0.951 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000028905
Gene: ENSMUSG00000027419
AA Change: T134A

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: 99.6%
20x: 98.8%

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: 82 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcb11	A	T	2: 69,104,487 (GRCm39)	V733E	probably benign	Het
Adam34	A	T	8: 44,105,041 (GRCm39)	N201K	probably benign	Het
Aldh3b2	A	C	19: 4,029,592 (GRCm39)	S322R	probably damaging	Het
Anpep	A	T	7: 79,475,058 (GRCm39)	L914Q	probably damaging	Het
Arhgap30	T	C	1: 171,235,139 (GRCm39)	F535S	probably damaging	Het
Baiap3	G	A	17: 25,462,814 (GRCm39)	R1075C	probably benign	Het
Baz2a	G	T	10: 127,948,475 (GRCm39)	G252V	probably damaging	Het
Brinp3	T	A	1: 146,776,812 (GRCm39)	S420T	possibly damaging	Het
Carmil3	T	C	14: 55,733,695 (GRCm39)	F359S	possibly damaging	Het
Ccdc124	A	T	8: 71,321,170 (GRCm39)	L190Q	probably damaging	Het
Ccr6	T	C	17: 8,474,972 (GRCm39)	V59A	probably damaging	Het
Ccr8	T	A	9: 119,923,683 (GRCm39)	I266N	probably damaging	Het
Cdh23	T	A	10: 60,167,596 (GRCm39)	E1798V	probably damaging	Het
Cdk5rap2	T	C	4: 70,153,684 (GRCm39)	N1713S	probably benign	Het
Cep19	T	A	16: 31,922,833 (GRCm39)	I33N	probably damaging	Het
Cers3	A	T	7: 66,433,163 (GRCm39)	Y196F	probably damaging	Het
Cidea	T	C	18: 67,499,491 (GRCm39)	I126T	probably damaging	Het
Copg2	A	T	6: 30,789,689 (GRCm39)	Y546*	probably null	Het
Cul3	A	T	1: 80,264,717 (GRCm39)	V261E	probably benign	Het
Cyp2g1	A	T	7: 26,514,057 (GRCm39)	D221V	probably damaging	Het
Cyp8b1	G	A	9: 121,744,163 (GRCm39)	H390Y	probably damaging	Het
Daam1	T	C	12: 72,035,717 (GRCm39)	F971L	probably damaging	Het
Dnajc24	G	A	2: 105,832,311 (GRCm39)	S24L	possibly damaging	Het
Dpysl3	T	C	18: 43,571,107 (GRCm39)	S56G	probably benign	Het
Esp1	A	G	17: 41,041,972 (GRCm39)	D88G	probably benign	Het
Fam171b	A	G	2: 83,708,574 (GRCm39)	T359A	probably damaging	Het
Fam186b	T	C	15: 99,177,718 (GRCm39)	E536G	possibly damaging	Het
Fbxo3	T	C	2: 103,873,357 (GRCm39)	V156A	possibly damaging	Het
Gls2	C	A	10: 128,035,063 (GRCm39)	H65Q	probably benign	Het
Gp2	A	G	7: 119,050,721 (GRCm39)		probably null	Het
Gpcpd1	T	A	2: 132,375,976 (GRCm39)	K435I	probably benign	Het
Gpx6	T	A	13: 21,501,840 (GRCm39)		probably null	Het
Hps3	A	T	3: 20,084,583 (GRCm39)	S202T	probably benign	Het
Htr1d	T	A	4: 136,170,812 (GRCm39)	L347H	probably damaging	Het
Igfals	T	C	17: 25,100,208 (GRCm39)	L433P	probably damaging	Het
Ilvbl	C	T	10: 78,419,530 (GRCm39)	H537Y	probably benign	Het
Iqgap2	A	T	13: 95,765,480 (GRCm39)	M1530K	probably damaging	Het
Jarid2	A	G	13: 45,049,798 (GRCm39)	T247A	possibly damaging	Het
L3hypdh	C	T	12: 72,120,783 (GRCm39)	V323I	possibly damaging	Het
Lama3	C	T	18: 12,715,665 (GRCm39)	T1707I	possibly damaging	Het
Map6	G	T	7: 98,917,232 (GRCm39)	A2S	probably damaging	Het
Mfap3	T	A	11: 57,421,066 (GRCm39)	I349K	probably benign	Het
Mybl2	A	G	2: 162,914,625 (GRCm39)	T248A	probably benign	Het
N6amt1	A	G	16: 87,159,548 (GRCm39)	*151W	probably null	Het
Nhlrc1	A	G	13: 47,167,684 (GRCm39)	V191A	probably benign	Het
Nkx2-5	T	C	17: 27,058,594 (GRCm39)	E120G	possibly damaging	Het
Or2y10	T	A	11: 49,454,925 (GRCm39)	M59K	probably damaging	Het
Or52r1b	C	A	7: 102,690,839 (GRCm39)	T46N	possibly damaging	Het
Or8b41	T	C	9: 38,055,049 (GRCm39)	V201A	probably benign	Het
Or8k28	T	A	2: 86,286,211 (GRCm39)	I135F	possibly damaging	Het
Pcdha8	T	G	18: 37,126,201 (GRCm39)	L228V	probably benign	Het
Phldb3	G	A	7: 24,324,078 (GRCm39)	R484Q	probably benign	Het
Pipox	A	G	11: 77,772,012 (GRCm39)	S371P	probably damaging	Het
Plekhg1	T	C	10: 3,823,343 (GRCm39)	S159P		Het
Psme4	C	T	11: 30,824,226 (GRCm39)	P1737S	probably benign	Het
Pygm	G	A	19: 6,438,893 (GRCm39)	D328N	probably benign	Het
Rabgef1	A	T	5: 130,219,801 (GRCm39)	E88V	probably benign	Het
Rims2	G	T	15: 39,300,428 (GRCm39)	R245L	probably benign	Het
Slc38a4	T	C	15: 96,908,226 (GRCm39)	I172V	probably damaging	Het
Slc4a10	T	A	2: 62,099,009 (GRCm39)	Y586N	probably damaging	Het
Snap91	C	T	9: 86,761,610 (GRCm39)		probably benign	Het
Sorcs1	C	T	19: 50,178,480 (GRCm39)	V881I	probably benign	Het
Spef2	A	T	15: 9,601,726 (GRCm39)	V1512E	unknown	Het
Sufu	T	C	19: 46,441,716 (GRCm39)	I292T	possibly damaging	Het
Tet1	T	C	10: 62,649,450 (GRCm39)	N87D	possibly damaging	Het
Tmem108	T	C	9: 103,376,733 (GRCm39)	T239A	not run	Het
Tmem121	A	T	12: 113,152,114 (GRCm39)	K111*	probably null	Het
Tpp2	T	A	1: 44,008,048 (GRCm39)	D417E	probably damaging	Het
Tpr	G	A	1: 150,315,007 (GRCm39)	E2025K	possibly damaging	Het
Trappc3	C	T	4: 126,168,945 (GRCm39)	A145V	possibly damaging	Het
Ttn	T	C	2: 76,721,325 (GRCm39)	D6754G	probably null	Het
Unc13c	T	A	9: 73,536,473 (GRCm39)	M1627L	probably benign	Het
Ush2a	A	G	1: 188,542,414 (GRCm39)	I3327V	probably benign	Het
Vmn1r74	C	T	7: 11,580,894 (GRCm39)	Q65*	probably null	Het
Wdr18	G	A	10: 79,796,202 (GRCm39)	R69H	probably damaging	Het
Zbed5	G	T	5: 129,929,279 (GRCm39)	D132Y	probably damaging	Het
Zfp644	A	T	5: 106,785,448 (GRCm39)	Y366*	probably null	Het
Zfyve26	T	C	12: 79,292,945 (GRCm39)	N2068S	probably damaging	Het
Zic2	T	C	14: 122,713,503 (GRCm39)	F139S	probably damaging	Het
Zmynd11	T	C	13: 9,760,198 (GRCm39)	Q141R	probably benign	Het
Zrsr2-ps1	A	G	11: 22,923,388 (GRCm39)	E54G	probably benign	Het
Zscan10	G	A	17: 23,828,456 (GRCm39)	D333N	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
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'- CAGCAATTTAGTTATGAGATGAGGG -3'
(R):5'- CCAACTCTTTGTGTTTGGAGGC -3'

Sequencing Primer
(F):5'- ATGAGGGGATTAGAGCAGTATTTG -3'
(R):5'- CTCTTTGTGTTTGGAGGCACGAAAG -3'

Posted On

2019-06-26