Mutagenetix > Incidental Mutation

Incidental Mutation 'R6925:Pcsk2'

541058

Institutional Source

Beutler Lab

Gene Symbol

Pcsk2

Ensembl Gene

ENSMUSG00000027419

Gene Name

proprotein convertase subtilisin/kexin type 2

Synonyms

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

MMRRC Submission

Accession Numbers

Is this an essential gene?

Probably non essential (E-score: 0.196) question?

Stock #

R6925 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

143546156-143816285 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 143813747 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Glycine at position 617 (E617G)

Ref Sequence

ENSEMBL: ENSMUSP00000028905 (fasta)

Gene Model

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

AlphaFold

P21661

Predicted Effect

probably damaging
Transcript: ENSMUST00000028905
AA Change: E617G

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000028905
Gene: ENSMUSG00000027419
AA Change: E617G

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

0.1107

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.4%
20x: 98.0%

Validation Efficiency

100% (91/91)

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: 90 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
5430419D17Rik	A	G	7: 131,222,707	Q177R	possibly damaging	Het
Acat1	A	T	9: 53,592,029	V170E	probably benign	Het
Atp2b2	T	A	6: 113,760,720	I902F	probably damaging	Het
Cacna1d	A	G	14: 30,051,637	V1697A	probably benign	Het
Ccdc14	T	A	16: 34,690,749	F31Y	probably benign	Het
Ccdc17	T	A	4: 116,598,210	V250E	probably damaging	Het
Cct7	A	G	6: 85,459,182	N25S	probably damaging	Het
Cep19	G	C	16: 32,103,942	G9R	probably damaging	Het
Ces5a	A	T	8: 93,523,057		probably null	Het
Chd1l	T	G	3: 97,582,826	E471A	probably damaging	Het
Chd6	A	G	2: 161,013,127	I787T	probably damaging	Het
Cntnap5c	A	C	17: 58,395,266	T1194P	probably benign	Het
Col6a3	T	A	1: 90,816,002	M208L	probably benign	Het
Coro7	A	T	16: 4,628,674		probably null	Het
Csrnp2	T	C	15: 100,481,958	K484R	probably benign	Het
Cyp2c39	T	A	19: 39,513,195	V64E	probably damaging	Het
Ddr2	T	C	1: 169,998,132	K300E	probably benign	Het
Ddx56	T	C	11: 6,263,980	E393G	probably damaging	Het
Diaph1	A	C	18: 37,853,679	Y1084*	probably null	Het
Disp1	A	T	1: 183,086,478	F1459L	probably benign	Het
Dnajc8	G	A	4: 132,544,113	A80T	probably damaging	Het
Elfn1	T	A	5: 139,971,685	M148K	probably benign	Het
Emcn	T	A	3: 137,419,002	I154N	probably damaging	Het
Enah	C	G	1: 181,905,898		probably null	Het
Enah	T	A	1: 181,905,899		probably null	Het
Ep300	C	A	15: 81,649,981	Q2080K	probably benign	Het
Epha2	T	A	4: 141,308,757	M168K	probably benign	Het
Ercc6	T	A	14: 32,562,608	I776N	probably damaging	Het
Fan1	T	A	7: 64,372,486	N340Y	probably damaging	Het
Fat4	G	T	3: 38,996,204		probably null	Het
G3bp1	A	G	11: 55,497,960	R333G	possibly damaging	Het
Gm3604	A	G	13: 62,369,390	F385L	probably benign	Het
Gm5800	T	C	14: 51,713,700	I147M	possibly damaging	Het
Hipk1	A	G	3: 103,778,245	F18S	unknown	Het
Ighv3-8	A	T	12: 114,322,330	C131S	probably benign	Het
Il23r	T	G	6: 67,423,493	T618P	probably damaging	Het
Il31ra	G	A	13: 112,527,529	T538I	possibly damaging	Het
Kcns2	A	G	15: 34,839,913	D474G	unknown	Het
Klc4	T	C	17: 46,636,229	T407A	possibly damaging	Het
Klra5	C	T	6: 129,911,457	S2N	probably benign	Het
Krt10	T	C	11: 99,388,851	Y161C	probably damaging	Het
Kxd1	A	T	8: 70,523,278	M1K	probably null	Het
Lgals1	A	C	15: 78,928,040	D27A	possibly damaging	Het
Lgr5	T	C	10: 115,466,346	S308G	probably benign	Het
Lrp1	G	A	10: 127,556,988	S2736L	probably benign	Het
Lrpap1	G	T	5: 35,102,536	H73N	probably benign	Het
Mcpt1	C	A	14: 56,019,065	T86K	probably damaging	Het
Megf6	A	T	4: 154,254,587	D527V	probably damaging	Het
Mical3	A	T	6: 120,959,390	S1392T	probably benign	Het
Mmp2	A	T	8: 92,839,382	D437V	probably damaging	Het
Mob4	T	A	1: 55,152,722	Y166*	probably null	Het
Mrap2	G	A	9: 87,182,474	M89I	possibly damaging	Het
Mug1	G	A	6: 121,881,787	A1155T	probably damaging	Het
Myh2	G	T	11: 67,193,218	A1556S	probably benign	Het
Nfatc3	A	G	8: 106,119,322	D1028G	probably benign	Het
Ngef	T	G	1: 87,503,263		probably null	Het
Nlrp1a	A	T	11: 71,092,513	L1209Q	probably null	Het
Npr2	C	T	4: 43,647,553	R819C	probably damaging	Het
Nsd2	A	T	5: 33,879,110	D646V	probably damaging	Het
Nsun7	A	G	5: 66,277,072	H252R	probably damaging	Het
Olfr267	A	T	4: 58,785,647	I25N	possibly damaging	Het
Olfr447	T	A	6: 42,911,857	C111*	probably null	Het
Olfr642	C	T	7: 104,049,740	V205I	probably benign	Het
Olfr951	A	T	9: 39,393,860	Q20L	probably benign	Het
Olfr951	G	T	9: 39,393,861	Q20H	probably benign	Het
Pcdhga2	A	T	18: 37,670,585	D494V	probably damaging	Het
Pdc	T	C	1: 150,333,180	I138T	probably damaging	Het
Phc2	T	A	4: 128,748,134	S750T	probably damaging	Het
Pkd2l1	T	A	19: 44,191,508	N88Y	possibly damaging	Het
Plcl1	C	T	1: 55,406,598	R71*	probably null	Het
Prag1	C	A	8: 36,103,894	L544M	probably damaging	Het
Prkg2	A	G	5: 98,966,510		probably null	Het
Psd2	G	A	18: 35,979,711	S153N	probably damaging	Het
Rab11fip1	A	T	8: 27,152,972	S600T	probably damaging	Het
Rbms1	T	G	2: 60,762,304	T222P	probably benign	Het
Slfn8	A	T	11: 83,013,417	Y382*	probably null	Het
Socs4	T	A	14: 47,289,738	C43*	probably null	Het
Sorl1	T	A	9: 42,033,626	T868S	probably damaging	Het
St6gal1	A	G	16: 23,356,213	Y267C	probably damaging	Het
Syne1	A	G	10: 5,126,682	V6879A	probably benign	Het
Syne2	C	A	12: 75,854,132	H22N	possibly damaging	Het
Tmeff2	T	A	1: 50,928,021	L25Q	probably damaging	Het
Tmprss11g	G	T	5: 86,487,426	D396E	probably benign	Het
Tmprss11g	T	A	5: 86,487,436	H393L	probably benign	Het
Vmn2r23	A	G	6: 123,704,553	E140G	probably damaging	Het
Wapl	T	C	14: 34,677,363	S130P	probably benign	Het
Zeb2	T	A	2: 44,994,529	K982M	probably damaging	Het
Zfhx3	C	G	8: 108,956,821	H3631D	unknown	Het
Zfp719	T	C	7: 43,590,706	S573P	probably damaging	Het
Zfp979	A	T	4: 147,613,542	C237S	possibly damaging	Het

Other mutations in Pcsk2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00503:Pcsk2	APN	2	143793239	missense	probably damaging	1.00
IGL01609:Pcsk2	APN	2	143801158	missense	possibly damaging	0.88
IGL01690:Pcsk2	APN	2	143687570	missense	probably benign
IGL01833:Pcsk2	APN	2	143687580	missense	possibly damaging	0.62
IGL01962:Pcsk2	APN	2	143813632	nonsense	probably null
IGL02219:Pcsk2	APN	2	143793125	missense	probably damaging	1.00
IGL02572:Pcsk2	APN	2	143690342	missense	probably damaging	1.00
IGL02752:Pcsk2	APN	2	143773945	missense	probably benign	0.09
P0035:Pcsk2	UTSW	2	143795951	missense	probably damaging	1.00
R0092:Pcsk2	UTSW	2	143801024	missense	probably damaging	1.00
R1424:Pcsk2	UTSW	2	143573428	splice site	probably benign
R1470:Pcsk2	UTSW	2	143546518	nonsense	probably null
R1470:Pcsk2	UTSW	2	143546518	nonsense	probably null
R1832:Pcsk2	UTSW	2	143793269	missense	probably damaging	1.00
R1993:Pcsk2	UTSW	2	143687619	missense	probably benign	0.00
R4615:Pcsk2	UTSW	2	143795969	missense	probably damaging	1.00
R4783:Pcsk2	UTSW	2	143687679	critical splice donor site	probably null
R4796:Pcsk2	UTSW	2	143813425	missense	probably benign	0.16
R4827:Pcsk2	UTSW	2	143801179	nonsense	probably null
R5357:Pcsk2	UTSW	2	143573464	missense	probably benign	0.00
R5413:Pcsk2	UTSW	2	143696700	splice site	probably null
R5440:Pcsk2	UTSW	2	143546543	missense	probably benign	0.22
R5546:Pcsk2	UTSW	2	143546560	missense	probably benign	0.00
R5605:Pcsk2	UTSW	2	143749245	intron	probably benign
R5821:Pcsk2	UTSW	2	143749115	splice site	probably null
R5905:Pcsk2	UTSW	2	143749140	missense	probably damaging	0.98
R6120:Pcsk2	UTSW	2	143801111	missense	probably damaging	1.00
R6135:Pcsk2	UTSW	2	143573540	missense	possibly damaging	0.63
R6657:Pcsk2	UTSW	2	143690366	missense	probably damaging	1.00
R7223:Pcsk2	UTSW	2	143690333	missense	possibly damaging	0.95
R7289:Pcsk2	UTSW	2	143690423	missense	probably damaging	1.00
R8043:Pcsk2	UTSW	2	143813530	nonsense	probably null
R8803:Pcsk2	UTSW	2	143795950	missense	probably damaging	0.99
R8819:Pcsk2	UTSW	2	143801070	missense	probably damaging	0.99
R8820:Pcsk2	UTSW	2	143801070	missense	probably damaging	0.99
R9131:Pcsk2	UTSW	2	143813663	missense	possibly damaging	0.56
R9643:Pcsk2	UTSW	2	143813581	missense	probably damaging	1.00
R9753:Pcsk2	UTSW	2	143793230	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- AGTGGCCTTTCATGACCAC -3'
(R):5'- AGCAAAGCTTGAGACCAGGC -3'

Sequencing Primer
(F):5'- TTTCATGACCACCCACACCTGG -3'
(R):5'- TGAGACCAGGCTGGGATTGC -3'

Posted On

2018-11-28