Mutagenetix > Incidental Mutation

Incidental Mutation 'R0894:Pcsk1'

83699

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

039057-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0894 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

75237945-75282980 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 75246096 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glycine to Aspartic acid at position 158 (G158D)

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 damaging
Transcript: ENSMUST00000022075
AA Change: G158D

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

SMART Domains

Protein: ENSMUSP00000022075
Gene: ENSMUSG00000021587
AA Change: G158D

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

noncoding transcript
Transcript: ENSMUST00000135349

Meta Mutation Damage Score

0.9543

Coding Region Coverage

1x: 99.5%
3x: 99.0%
10x: 97.7%
20x: 95.8%

Validation Efficiency

97% (102/105)

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: 104 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2210408I21Rik	A	G	13: 77,471,726 (GRCm39)	S1044G	probably benign	Het
Aanat	A	G	11: 116,487,730 (GRCm39)	H143R	probably benign	Het
Abca8a	A	G	11: 109,941,792 (GRCm39)	I1159T	probably benign	Het
Abcb1a	G	T	5: 8,724,856 (GRCm39)		probably benign	Het
Abcc1	T	C	16: 14,283,001 (GRCm39)	V1159A	possibly damaging	Het
Akr1e1	T	A	13: 4,645,071 (GRCm39)	Q204L	probably damaging	Het
Alk	T	C	17: 72,202,930 (GRCm39)	Y1135C	probably damaging	Het
Atad2b	C	T	12: 5,015,915 (GRCm39)	T547I	probably damaging	Het
Brd10	T	C	19: 29,697,974 (GRCm39)		probably benign	Het
C030005K15Rik	A	T	10: 97,561,648 (GRCm39)	S28T	unknown	Het
Cdk5rap3	A	G	11: 96,799,654 (GRCm39)	L387P	probably damaging	Het
Cfap95	T	C	19: 23,630,062 (GRCm39)	E10G	unknown	Het
Cfap96	A	G	8: 46,409,497 (GRCm39)	F274S	probably damaging	Het
Clec4f	T	A	6: 83,629,979 (GRCm39)	N193I	probably damaging	Het
Col4a4	A	T	1: 82,507,377 (GRCm39)		probably null	Het
Cplx4	T	G	18: 66,090,116 (GRCm39)	D101A	possibly damaging	Het
Cpne8	A	T	15: 90,533,474 (GRCm39)	D50E	probably damaging	Het
Csmd3	G	T	15: 47,721,316 (GRCm39)	D1542E	possibly damaging	Het
Ctdp1	A	G	18: 80,512,736 (GRCm39)	V9A	probably benign	Het
Ctnnd2	A	T	15: 30,332,301 (GRCm39)		probably benign	Het
Cyp7b1	C	T	3: 18,151,674 (GRCm39)	A180T	probably benign	Het
Dcun1d5	C	T	9: 7,203,379 (GRCm39)		probably benign	Het
Dgat1	G	T	15: 76,387,199 (GRCm39)	L363I	possibly damaging	Het
Dipk2b	T	A	X: 18,289,791 (GRCm39)	I224F	possibly damaging	Het
Dlg1	T	A	16: 31,561,965 (GRCm39)	H120Q	probably benign	Het
Dnah6	T	C	6: 73,101,740 (GRCm39)	N1928S	probably benign	Het
Dnai4	T	C	4: 102,906,583 (GRCm39)		probably benign	Het
Dync2h1	A	T	9: 7,041,734 (GRCm39)		probably benign	Het
Ednra	T	G	8: 78,446,649 (GRCm39)		probably benign	Het
Efcab6	A	T	15: 83,802,493 (GRCm39)	C845S	probably benign	Het
Egln1	A	T	8: 125,642,435 (GRCm39)	C303S	probably damaging	Het
Eomes	T	C	9: 118,311,368 (GRCm39)		probably null	Het
Epha1	A	G	6: 42,340,756 (GRCm39)	V568A	probably benign	Het
Ercc6	T	A	14: 32,238,985 (GRCm39)	N24K	probably benign	Het
Esco2	T	C	14: 66,064,726 (GRCm39)	Q338R	probably benign	Het
Fbxo46	T	C	7: 18,869,654 (GRCm39)	V91A	probably damaging	Het
Fryl	A	T	5: 73,198,675 (GRCm39)		probably benign	Het
Gab3	A	C	X: 74,077,024 (GRCm39)	D43E	probably damaging	Het
Gltpd2	T	A	11: 70,410,535 (GRCm39)		probably benign	Het
Gm17333	G	T	16: 77,649,711 (GRCm39)		noncoding transcript	Het
Gm7353	T	C	7: 3,160,570 (GRCm39)		noncoding transcript	Het
Grik4	T	C	9: 42,599,405 (GRCm39)		probably benign	Het
Gtpbp2	G	T	17: 46,476,895 (GRCm39)	A358S	possibly damaging	Het
Hyls1	C	T	9: 35,472,528 (GRCm39)	C296Y	probably damaging	Het
Igf2r	C	T	17: 12,910,988 (GRCm39)	M1943I	probably benign	Het
Iqca1l	T	C	5: 24,755,731 (GRCm39)		probably null	Het
Ireb2	T	A	9: 54,803,861 (GRCm39)	N517K	probably damaging	Het
Itga10	A	G	3: 96,560,976 (GRCm39)	S614G	possibly damaging	Het
Kdm2b	A	G	5: 123,122,523 (GRCm39)		probably null	Het
Kif17	T	C	4: 138,025,542 (GRCm39)	M948T	possibly damaging	Het
Klhl33	A	T	14: 51,129,583 (GRCm39)	N347K	probably damaging	Het
Llph	T	A	10: 120,064,086 (GRCm39)	C67*	probably null	Het
Lrrn3	T	C	12: 41,504,033 (GRCm39)	T95A	probably damaging	Het
Map3k12	C	A	15: 102,410,613 (GRCm39)	A455S	probably damaging	Het
Mex3d	T	C	10: 80,217,376 (GRCm39)	T149A	probably benign	Het
Myo7b	A	G	18: 32,133,123 (GRCm39)	W409R	probably damaging	Het
Nbea	A	G	3: 55,916,761 (GRCm39)	M833T	possibly damaging	Het
Ncapg	A	G	5: 45,837,236 (GRCm39)	T436A	probably null	Het
Nkx1-2	C	A	7: 132,201,042 (GRCm39)	D72Y	probably null	Het
Or11g27	T	C	14: 50,771,159 (GRCm39)	S97P	possibly damaging	Het
Or2d3b	T	A	7: 106,514,317 (GRCm39)	I304K	probably benign	Het
Or6c217	T	A	10: 129,737,751 (GRCm39)	N276I	probably damaging	Het
Pcdh15	A	G	10: 74,460,087 (GRCm39)	Y1308C	probably damaging	Het
Pcnx2	A	G	8: 126,613,665 (GRCm39)		probably benign	Het
Phkb	A	T	8: 86,744,070 (GRCm39)	D573V	probably damaging	Het
Pik3r4	A	G	9: 105,544,970 (GRCm39)	K150E	possibly damaging	Het
Ppp2r5e	C	G	12: 75,516,341 (GRCm39)	A239P	probably damaging	Het
Ppp4r4	C	T	12: 103,566,754 (GRCm39)	A67V	probably damaging	Het
Prex2	A	G	1: 11,252,122 (GRCm39)	T1056A	probably benign	Het
Prkca	A	T	11: 107,903,518 (GRCm39)	Y285N	possibly damaging	Het
Psd	T	C	19: 46,301,880 (GRCm39)	E903G	probably damaging	Het
Psg19	T	C	7: 18,527,987 (GRCm39)	E252G	probably benign	Het
Psg20	T	A	7: 18,414,969 (GRCm39)	K306*	probably null	Het
Pygl	T	G	12: 70,241,148 (GRCm39)		probably benign	Het
Rasgrf2	A	G	13: 92,130,890 (GRCm39)	S724P	probably damaging	Het
Reck	C	A	4: 43,922,967 (GRCm39)	A414D	probably damaging	Het
Scn10a	C	A	9: 119,459,213 (GRCm39)	V1150L	probably damaging	Het
Shc2	A	T	10: 79,465,751 (GRCm39)	I187N	probably damaging	Het
Sipa1l3	T	A	7: 29,086,716 (GRCm39)	K625*	probably null	Het
Slc44a4	T	C	17: 35,147,466 (GRCm39)	L583P	possibly damaging	Het
Slc5a11	G	C	7: 122,857,643 (GRCm39)	R244P	possibly damaging	Het
Slfn8	T	A	11: 82,894,407 (GRCm39)	Q744L	probably benign	Het
Snx2	G	T	18: 53,309,488 (GRCm39)	V13L	probably benign	Het
Spmip5	A	T	19: 58,776,015 (GRCm39)	L138Q	probably damaging	Het
Spsb1	C	T	4: 149,990,872 (GRCm39)		probably null	Het
Stfa2l1	A	T	16: 35,977,228 (GRCm39)	I8L	probably benign	Het
Svil	G	T	18: 5,097,494 (GRCm39)	R1659L	probably damaging	Het
Tbccd1	A	T	16: 22,640,995 (GRCm39)	L461M	probably benign	Het
Tmem9	A	T	1: 135,961,926 (GRCm39)	T174S	possibly damaging	Het
Tnks2	T	C	19: 36,867,450 (GRCm39)		probably null	Het
Tnrc18	C	A	5: 142,800,869 (GRCm39)	V30L	probably benign	Het
Tomm7	A	G	5: 24,049,025 (GRCm39)	F16S	probably damaging	Het
Ttf2	A	G	3: 100,876,865 (GRCm39)		probably benign	Het
Ubr7	C	A	12: 102,735,450 (GRCm39)	T303N	probably damaging	Het
Ushbp1	A	T	8: 71,842,868 (GRCm39)		probably null	Het
Vmn1r177	C	A	7: 23,565,475 (GRCm39)	V134F	probably benign	Het
Vmn2r12	A	G	5: 109,235,716 (GRCm39)		probably null	Het
Vmn2r53	T	G	7: 12,335,141 (GRCm39)	H173P	probably benign	Het
Yars1	A	T	4: 129,090,948 (GRCm39)	M119L	probably damaging	Het
Zcrb1	A	T	15: 93,295,038 (GRCm39)		probably benign	Het
Zfp267	T	A	3: 36,218,935 (GRCm39)	Y319*	probably null	Het
Zfp319	C	A	8: 96,056,250 (GRCm39)		probably benign	Het
Zfp783	C	G	6: 47,920,320 (GRCm39)		noncoding transcript	Het
Zfyve26	A	G	12: 79,320,372 (GRCm39)	I1024T	possibly 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
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
R7487:Pcsk1	UTSW	13	75,259,002 (GRCm39)	missense	probably benign	0.01
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'- GGCTATTTGGCTTGGACCCTCAAC -3'
(R):5'- CAGTTCTAAATACAGTGTGGCTCCTGG -3'

Sequencing Primer
(F):5'- GCTTGGACCCTCAACTTTGTG -3'
(R):5'- CATTTAGACAGACTGATAGCAGGC -3'

Posted On

2013-11-08