Mutagenetix > Incidental Mutation

Incidental Mutation 'R7487:Pcsk1'

580277

Institutional Source

Beutler Lab

Gene Symbol

Pcsk1

Ensembl Gene

ENSMUSG00000021587

Gene Name

proprotein convertase subtilisin/kexin type 1

Synonyms

PC3, Nec1, Phpp-1, Nec-1, SPC3, prohormone convertase 1/3, PC1

MMRRC Submission

045561-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7487 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

75237945-75282980 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 75259002 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glycine to Serine at position 259 (G259S)

Ref Sequence

ENSEMBL: ENSMUSP00000022075 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000022075]

AlphaFold

P63239

PDB Structure

Solution Structure of the Mouse Prohormone Convertase 1 Pro-Domain [SOLUTION NMR]
PC1/3 DCSG sorting domain structure in DPC [SOLUTION NMR]
PC1/3 DCSG sorting domain in CHAPS [SOLUTION NMR]

Predicted Effect

probably benign
Transcript: ENSMUST00000022075
AA Change: G259S

PolyPhen 2 Score 0.011 (Sensitivity: 0.96; Specificity: 0.78)

SMART Domains

Protein: ENSMUSP00000022075
Gene: ENSMUSG00000021587
AA Change: G259S

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC
Pfam:S8_pro-domain	34	110	6.4e-26	PFAM
Pfam:Peptidase_S8	158	442	2.2e-49	PFAM
Pfam:P_proprotein	504	591	6.1e-30	PFAM
low complexity region	679	694	N/A	INTRINSIC
Pfam:Proho_convert	713	751	4.3e-26	PFAM

Predicted Effect

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.3%

Validation Efficiency

100% (89/89)

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 encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER and sorts to subcellular compartments where a second autocatalytic even takes place and the catalytic activity is acquired. The 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. Mutations in this gene have been associated with susceptibility to obesity and proprotein convertase 1/3 deficiency. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene [provided by RefSeq, Jan 2014]
PHENOTYPE: Homozygotes for a null allele show pre- and postnatal death, low weight, diarrhea, hypoglycemia, low insulin and GHRH levels, and lack mature glucagon and ACTH levels. Homozygotes for another null allele die prior to implantation. ENU mutants show obesity, polyphagia and higher metabolic efficiency. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 87 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1110002E22Rik	A	T	3: 137,772,629 (GRCm39)	D606V	probably damaging	Het
1700009N14Rik	T	A	4: 39,450,929 (GRCm39)	V45E	probably damaging	Het
2510009E07Rik	C	T	16: 21,472,479 (GRCm39)	V74M	probably damaging	Het
Abca2	C	T	2: 25,327,915 (GRCm39)	T739M	probably benign	Het
Abra	T	C	15: 41,732,949 (GRCm39)	E39G	probably damaging	Het
Adam34	A	T	8: 44,104,191 (GRCm39)	C485S	probably damaging	Het
Add2	G	T	6: 86,070,432 (GRCm39)	V175F	possibly damaging	Het
Alk	T	A	17: 72,256,893 (GRCm39)	K655N	probably benign	Het
Ap3m1	A	G	14: 21,088,107 (GRCm39)	V317A	probably benign	Het
Astn1	A	G	1: 158,438,352 (GRCm39)		probably null	Het
Atm	A	T	9: 53,435,654 (GRCm39)	Y219N	probably benign	Het
Cep128	C	T	12: 90,966,404 (GRCm39)	A1068T	probably benign	Het
Cep20	T	C	16: 14,128,968 (GRCm39)	D85G	probably benign	Het
Cnksr3	T	C	10: 7,085,097 (GRCm39)	Q250R	probably benign	Het
Cst7	A	G	2: 150,419,624 (GRCm39)	T97A	probably benign	Het
Ctps1	G	A	4: 120,415,997 (GRCm39)	L209F	probably damaging	Het
Cyp2d10	A	T	15: 82,288,793 (GRCm39)	F230I	probably benign	Het
Daam2	T	C	17: 49,793,510 (GRCm39)	N336D	probably benign	Het
Dchs2	T	C	3: 83,263,613 (GRCm39)	S3294P	probably damaging	Het
Dhx36	G	T	3: 62,391,623 (GRCm39)	N574K	possibly damaging	Het
Dock10	G	T	1: 80,562,765 (GRCm39)	Q533K	probably benign	Het
Dync2h1	A	G	9: 7,132,041 (GRCm39)	S1589P	probably benign	Het
Enpp3	T	A	10: 24,681,821 (GRCm39)	Y295F	probably benign	Het
Esrrg	T	A	1: 187,878,620 (GRCm39)	Y234N	probably benign	Het
Fadd	A	C	7: 144,134,462 (GRCm39)	V141G	probably damaging	Het
Fam114a2	C	T	11: 57,404,515 (GRCm39)	G83D	probably damaging	Het
Fam170b	T	A	14: 32,557,776 (GRCm39)	C204S	probably damaging	Het
Fam186a	T	A	15: 99,840,017 (GRCm39)	I2076F	possibly damaging	Het
Fdxacb1	G	A	9: 50,681,519 (GRCm39)	V147I	possibly damaging	Het
Frem2	C	A	3: 53,561,970 (GRCm39)	V846F	probably benign	Het
Fry	G	A	5: 150,338,039 (GRCm39)	S1449N	possibly damaging	Het
Gucy1b2	A	G	14: 62,685,672 (GRCm39)	F98L	probably damaging	Het
Hps1	T	C	19: 42,744,700 (GRCm39)	Y658C	probably damaging	Het
Igkv3-9	T	A	6: 70,565,506 (GRCm39)	L35Q	probably damaging	Het
Irx2	A	G	13: 72,778,739 (GRCm39)	Y101C	probably damaging	Het
Kcnj11	G	T	7: 45,748,265 (GRCm39)	R353S	probably benign	Het
Kyat3	C	T	3: 142,431,955 (GRCm39)	Q228*	probably null	Het
Lama3	T	A	18: 12,552,294 (GRCm39)	D415E	probably benign	Het
Lcn3	G	A	2: 25,656,174 (GRCm39)		probably null	Het
Lin7b	T	C	7: 45,019,364 (GRCm39)	E68G	possibly damaging	Het
Lmbr1	T	A	5: 29,459,262 (GRCm39)	K379M	probably benign	Het
Lrig1	A	G	6: 94,583,099 (GRCm39)	S1006P	probably benign	Het
Lrrc37a	T	G	11: 103,389,045 (GRCm39)	T2127P	unknown	Het
Map4	A	G	9: 109,856,783 (GRCm39)	D151G	probably damaging	Het
Marchf1	A	T	8: 66,908,726 (GRCm39)	T149S	probably benign	Het
Msh4	A	T	3: 153,569,147 (GRCm39)	F809I	probably damaging	Het
Muc16	G	A	9: 18,496,095 (GRCm39)	P6699S	possibly damaging	Het
Mxi1	A	T	19: 53,360,088 (GRCm39)	D270V	probably damaging	Het
Myh6	A	T	14: 55,190,953 (GRCm39)	C907*	probably null	Het
Myo18b	T	C	5: 112,982,299 (GRCm39)	R1145G	possibly damaging	Het
Nkx2-6	A	C	14: 69,409,389 (GRCm39)	N47H	probably benign	Het
Nol7	G	A	13: 43,552,076 (GRCm39)	A66T	probably damaging	Het
Ntrk3	T	C	7: 77,900,461 (GRCm39)	N626S	probably damaging	Het
Nwd1	A	G	8: 73,393,266 (GRCm39)	Y77C	unknown	Het
Or12d17	G	T	17: 37,777,457 (GRCm39)	R120L	probably damaging	Het
Or12k5	A	C	2: 36,894,786 (GRCm39)	V280G	probably damaging	Het
Or8c14-ps1	A	G	9: 38,101,356 (GRCm39)	S112G	probably damaging	Het
Or8j3b	A	T	2: 86,205,475 (GRCm39)	Y94N	probably damaging	Het
Or9s23	G	A	1: 92,501,517 (GRCm39)	G208D	possibly damaging	Het
Otop3	A	G	11: 115,235,826 (GRCm39)	D486G	probably benign	Het
Pak1ip1	A	G	13: 41,162,731 (GRCm39)	K178R	probably benign	Het
Pde6a	A	G	18: 61,383,031 (GRCm39)	D338G	probably damaging	Het
Pias4	A	T	10: 80,999,806 (GRCm39)	D82E	probably benign	Het
Plekha5	C	A	6: 140,516,059 (GRCm39)	Q771K	probably benign	Het
Plekhh3	C	A	11: 101,056,405 (GRCm39)	A397S	possibly damaging	Het
Prg4	G	T	1: 150,331,656 (GRCm39)	T339N	unknown	Het
Prss22	A	T	17: 24,216,971 (GRCm39)	I3N	probably damaging	Het
Rasgrp1	T	C	2: 117,118,424 (GRCm39)	I522V	probably damaging	Het
Rspo2	T	C	15: 42,941,510 (GRCm39)	T138A	probably benign	Het
Rtcb	C	T	10: 85,789,333 (GRCm39)	G70S	probably benign	Het
Selenov	A	T	7: 27,989,803 (GRCm39)	S234T	probably damaging	Het
Shtn1	T	C	19: 58,992,292 (GRCm39)	T429A	probably damaging	Het
Slc4a3	G	T	1: 75,530,021 (GRCm39)	R622L	probably benign	Het
Smc2	T	C	4: 52,478,448 (GRCm39)	I1015T	probably damaging	Het
Spata9	G	T	13: 76,115,959 (GRCm39)	V3F	possibly damaging	Het
Tlr4	T	C	4: 66,842,659 (GRCm39)	I105T	probably benign	Het
Trav6d-4	A	T	14: 52,991,096 (GRCm39)	Y47F	possibly damaging	Het
Ttn	A	T	2: 76,657,377 (GRCm39)	I12450N	unknown	Het
Umad1	G	T	6: 8,270,560 (GRCm39)	A21S	probably damaging	Het
Unc5a	G	A	13: 55,144,362 (GRCm39)	R229H	probably benign	Het
Vmn1r216	A	T	13: 23,284,030 (GRCm39)	M238L	probably damaging	Het
Vps16	T	A	2: 130,280,977 (GRCm39)	C255*	probably null	Het
Wdr89	A	G	12: 75,679,388 (GRCm39)	F289L	probably benign	Het
Zfp180	A	T	7: 23,805,525 (GRCm39)	H648L	probably damaging	Het
Zfp735	A	G	11: 73,581,154 (GRCm39)	K64E	possibly damaging	Het
Zfp990	G	A	4: 145,264,157 (GRCm39)	C385Y	probably damaging	Het
Zswim3	G	T	2: 164,662,135 (GRCm39)	S205I	probably damaging	Het

Other mutations in Pcsk1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00324:Pcsk1	APN	13	75,280,206 (GRCm39)	missense	probably benign
IGL01554:Pcsk1	APN	13	75,280,426 (GRCm39)	missense	probably benign
IGL01960:Pcsk1	APN	13	75,241,286 (GRCm39)	missense	possibly damaging	0.82
IGL02026:Pcsk1	APN	13	75,260,772 (GRCm39)	missense	probably benign	0.16
IGL02047:Pcsk1	APN	13	75,246,108 (GRCm39)	missense	probably benign	0.33
IGL02264:Pcsk1	APN	13	75,254,078 (GRCm39)	missense	probably damaging	1.00
IGL02441:Pcsk1	APN	13	75,280,282 (GRCm39)	missense	probably benign	0.16
IGL02795:Pcsk1	APN	13	75,260,739 (GRCm39)	missense	probably damaging	1.00
IGL02829:Pcsk1	APN	13	75,274,955 (GRCm39)	missense	probably damaging	1.00
IGL03116:Pcsk1	APN	13	75,280,335 (GRCm39)	missense	probably damaging	0.99
IGL03156:Pcsk1	APN	13	75,280,070 (GRCm39)	missense	probably benign
clipper	UTSW	13	75,278,189 (GRCm39)	missense	probably damaging	1.00
spareribs	UTSW	13	75,263,374 (GRCm39)	missense	possibly damaging	0.88
swivel	UTSW	13	75,274,103 (GRCm39)	missense	probably damaging	1.00
Tweeze	UTSW	13	75,274,958 (GRCm39)	missense	probably benign	0.00
PIT4453001:Pcsk1	UTSW	13	75,260,769 (GRCm39)	missense	probably damaging	1.00
R0771:Pcsk1	UTSW	13	75,280,281 (GRCm39)	missense	probably benign	0.31
R0894:Pcsk1	UTSW	13	75,246,096 (GRCm39)	missense	probably damaging	1.00
R1014:Pcsk1	UTSW	13	75,280,353 (GRCm39)	missense	probably damaging	1.00
R1035:Pcsk1	UTSW	13	75,280,238 (GRCm39)	missense	probably benign
R1199:Pcsk1	UTSW	13	75,244,532 (GRCm39)	splice site	probably benign
R1517:Pcsk1	UTSW	13	75,246,166 (GRCm39)	nonsense	probably null
R1625:Pcsk1	UTSW	13	75,274,971 (GRCm39)	missense	probably benign	0.11
R1691:Pcsk1	UTSW	13	75,280,344 (GRCm39)	missense	possibly damaging	0.65
R1717:Pcsk1	UTSW	13	75,258,947 (GRCm39)	missense	probably damaging	0.99
R2168:Pcsk1	UTSW	13	75,260,653 (GRCm39)	intron	probably benign
R2252:Pcsk1	UTSW	13	75,274,845 (GRCm39)	missense	probably benign	0.00
R2400:Pcsk1	UTSW	13	75,238,245 (GRCm39)	missense	probably benign	0.00
R4110:Pcsk1	UTSW	13	75,244,488 (GRCm39)	missense	probably damaging	0.99
R4358:Pcsk1	UTSW	13	75,260,838 (GRCm39)	missense	possibly damaging	0.58
R4359:Pcsk1	UTSW	13	75,260,838 (GRCm39)	missense	possibly damaging	0.58
R4657:Pcsk1	UTSW	13	75,280,354 (GRCm39)	missense	probably damaging	1.00
R5195:Pcsk1	UTSW	13	75,274,974 (GRCm39)	missense	probably damaging	1.00
R5669:Pcsk1	UTSW	13	75,278,221 (GRCm39)	missense	probably benign	0.01
R5671:Pcsk1	UTSW	13	75,246,026 (GRCm39)	missense	possibly damaging	0.63
R5745:Pcsk1	UTSW	13	75,280,079 (GRCm39)	missense	probably benign	0.03
R6107:Pcsk1	UTSW	13	75,275,967 (GRCm39)	missense	probably benign	0.09
R6200:Pcsk1	UTSW	13	75,263,374 (GRCm39)	missense	possibly damaging	0.88
R6326:Pcsk1	UTSW	13	75,280,298 (GRCm39)	missense	possibly damaging	0.89
R6537:Pcsk1	UTSW	13	75,280,358 (GRCm39)	missense	probably damaging	1.00
R6541:Pcsk1	UTSW	13	75,274,103 (GRCm39)	missense	probably damaging	1.00
R6567:Pcsk1	UTSW	13	75,278,189 (GRCm39)	missense	probably damaging	1.00
R6723:Pcsk1	UTSW	13	75,241,188 (GRCm39)	splice site	probably null
R7258:Pcsk1	UTSW	13	75,241,305 (GRCm39)	missense	probably damaging	1.00
R7357:Pcsk1	UTSW	13	75,274,079 (GRCm39)	missense	probably damaging	0.96
R7519:Pcsk1	UTSW	13	75,258,984 (GRCm39)	missense	probably damaging	0.99
R7647:Pcsk1	UTSW	13	75,280,329 (GRCm39)	missense	possibly damaging	0.73
R7787:Pcsk1	UTSW	13	75,280,277 (GRCm39)	missense	possibly damaging	0.88
R7944:Pcsk1	UTSW	13	75,280,211 (GRCm39)	missense	probably benign
R7945:Pcsk1	UTSW	13	75,280,211 (GRCm39)	missense	probably benign
R7961:Pcsk1	UTSW	13	75,274,958 (GRCm39)	missense	probably benign	0.00
R8009:Pcsk1	UTSW	13	75,274,958 (GRCm39)	missense	probably benign	0.00
R8022:Pcsk1	UTSW	13	75,247,412 (GRCm39)	missense	possibly damaging	0.77
R8171:Pcsk1	UTSW	13	75,238,210 (GRCm39)	nonsense	probably null
R8489:Pcsk1	UTSW	13	75,274,121 (GRCm39)	missense	probably damaging	1.00
R9310:Pcsk1	UTSW	13	75,238,191 (GRCm39)	missense	probably benign
R9404:Pcsk1	UTSW	13	75,280,342 (GRCm39)	missense	probably benign	0.11
R9544:Pcsk1	UTSW	13	75,259,039 (GRCm39)	missense	probably damaging	0.99
R9588:Pcsk1	UTSW	13	75,259,039 (GRCm39)	missense	probably damaging	0.99
R9706:Pcsk1	UTSW	13	75,247,473 (GRCm39)	critical splice donor site	probably null
Z1176:Pcsk1	UTSW	13	75,246,161 (GRCm39)	missense	probably damaging	1.00
Z1177:Pcsk1	UTSW	13	75,273,983 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- AGTCCCTTAAGACCGTGATTG -3'
(R):5'- ACCATGTTAGACCCACATGTG -3'

Sequencing Primer
(F):5'- CCCTTAAGACCGTGATTGTTACGAG -3'
(R):5'- GTGCATTTAAAGTTGTGAAAGGC -3'

Posted On

2019-10-07