Mutagenetix > Incidental Mutation

Incidental Mutation 'R2252:Pcsk1'

241769

Institutional Source

Beutler Lab

Gene Symbol

Pcsk1

Ensembl Gene

ENSMUSG00000021587

Gene Name

proprotein convertase subtilisin/kexin type 1

Synonyms

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

MMRRC Submission

040252-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R2252 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

75089826-75134861 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 75126726 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Alanine to Aspartic acid at position 478 (A478D)

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: A478D

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000022075
Gene: ENSMUSG00000021587
AA Change: A478D

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

probably benign
Transcript: ENSMUST00000222727

Coding Region Coverage

1x: 99.1%
3x: 98.6%
10x: 97.3%
20x: 95.1%

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 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: 56 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700129C05Rik	G	A	14: 59,142,612	S79F	probably damaging	Het
Acaca	G	T	11: 84,371,532	V1987L	probably damaging	Het
B3gnt3	A	T	8: 71,692,818	M302K	probably damaging	Het
BC048507	T	C	13: 67,863,507	M1T	probably null	Het
Bckdk	C	A	7: 127,905,418	R105S	probably damaging	Het
Casp3	G	T	8: 46,637,955	W214L	probably damaging	Het
Cd180	A	T	13: 102,706,398	K651*	probably null	Het
Cdh15	T	A	8: 122,857,422	D87E	probably damaging	Het
Cldn24	G	T	8: 47,822,328	R62S	probably benign	Het
Cnot1	A	G	8: 95,763,186	V463A	probably benign	Het
Cspg4	C	T	9: 56,898,046	T2047I	probably damaging	Het
Cul2	A	T	18: 3,399,876	L3F	probably damaging	Het
Cwc27	A	T	13: 104,631,729	H419Q	probably damaging	Het
Dgkg	A	T	16: 22,622,260	M1K	probably null	Het
Dock5	A	T	14: 67,784,812	L1171H	probably damaging	Het
Drc1	G	T	5: 30,342,731	V103F	probably benign	Het
Ep400	A	T	5: 110,719,091	N1062K	unknown	Het
Faap20	A	C	4: 155,250,553	E37A	possibly damaging	Het
Foxa2	A	G	2: 148,044,166	F243S	probably damaging	Het
Gzf1	T	C	2: 148,683,936	M109T	probably damaging	Het
Itch	T	A	2: 155,212,339	M701K	probably benign	Het
Kpna1	T	C	16: 36,021,569	Y280H	possibly damaging	Het
L1td1	A	G	4: 98,737,637		probably null	Het
Lrrc37a	T	C	11: 103,501,467	Q1044R	probably benign	Het
Lrrc52	A	T	1: 167,466,368	I116N	probably damaging	Het
Mbd5	A	G	2: 49,257,686	E636G	probably damaging	Het
Mrpl40	T	C	16: 18,875,375	H29R	probably benign	Het
Nrip1	T	C	16: 76,291,285	Y1128C	probably damaging	Het
Olfr1279	A	G	2: 111,306,310	Y35C	probably damaging	Het
Olfr143	A	G	9: 38,253,830	I135V	probably benign	Het
Olfr958	G	T	9: 39,549,977	A298D	probably damaging	Het
Olfr988	A	G	2: 85,353,858	S23P	possibly damaging	Het
Pard3	A	T	8: 127,610,599	E1232V	probably damaging	Het
Pcif1	A	G	2: 164,890,879	E628G	probably benign	Het
Pkd1l2	T	C	8: 117,057,438	Y700C	probably damaging	Het
Pknox2	T	C	9: 36,910,520	N270D	probably benign	Het
Plcb2	T	C	2: 118,723,765	N69S	probably benign	Het
Reep1	T	A	6: 71,756,442		probably null	Het
Sash1	A	T	10: 8,729,977	M883K	probably benign	Het
Secisbp2l	C	T	2: 125,740,737	G933D	possibly damaging	Het
Sept4	A	G	11: 87,589,811	N405D	possibly damaging	Het
Serpinb3b	T	C	1: 107,155,478	I231M	possibly damaging	Het
Serping1	A	G	2: 84,769,851	S322P	probably damaging	Het
Slc7a2	T	C	8: 40,905,621	Y334H	probably benign	Het
Spink5	G	T	18: 44,020,824	E1013*	probably null	Het
Thoc3	A	T	13: 54,467,833	N139K	probably benign	Het
Tns2	C	T	15: 102,108,934	R281C	probably damaging	Het
Tubb2b	T	A	13: 34,130,215	I7F	possibly damaging	Het
Upf2	A	G	2: 5,961,460	D297G	unknown	Het
Vmn2r18	T	C	5: 151,584,976	I228V	possibly damaging	Het
Vmn2r98	A	C	17: 19,080,436	S567R	probably benign	Het
Vwa5a	T	C	9: 38,728,080	I369T	probably damaging	Het
Yjefn3	A	C	8: 69,889,445	F42V	probably damaging	Het
Zfp472	A	T	17: 32,976,283	R69*	probably null	Het
Zfp536	T	C	7: 37,479,389	S200G	probably benign	Het
Zfp970	T	A	2: 177,474,821		probably null	Het

Other mutations in Pcsk1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00324:Pcsk1	APN	13	75132087	missense	probably benign
IGL01554:Pcsk1	APN	13	75132307	missense	probably benign
IGL01960:Pcsk1	APN	13	75093167	missense	possibly damaging	0.82
IGL02026:Pcsk1	APN	13	75112653	missense	probably benign	0.16
IGL02047:Pcsk1	APN	13	75097989	missense	probably benign	0.33
IGL02264:Pcsk1	APN	13	75105959	missense	probably damaging	1.00
IGL02441:Pcsk1	APN	13	75132163	missense	probably benign	0.16
IGL02795:Pcsk1	APN	13	75112620	missense	probably damaging	1.00
IGL02829:Pcsk1	APN	13	75126836	missense	probably damaging	1.00
IGL03116:Pcsk1	APN	13	75132216	missense	probably damaging	0.99
IGL03156:Pcsk1	APN	13	75131951	missense	probably benign
clipper	UTSW	13	75130070	missense	probably damaging	1.00
spareribs	UTSW	13	75115255	missense	possibly damaging	0.88
swivel	UTSW	13	75125984	missense	probably damaging	1.00
Tweeze	UTSW	13	75126839	missense	probably benign	0.00
PIT4453001:Pcsk1	UTSW	13	75112650	missense	probably damaging	1.00
R0771:Pcsk1	UTSW	13	75132162	missense	probably benign	0.31
R0894:Pcsk1	UTSW	13	75097977	missense	probably damaging	1.00
R1014:Pcsk1	UTSW	13	75132234	missense	probably damaging	1.00
R1035:Pcsk1	UTSW	13	75132119	missense	probably benign
R1199:Pcsk1	UTSW	13	75096413	splice site	probably benign
R1517:Pcsk1	UTSW	13	75098047	nonsense	probably null
R1625:Pcsk1	UTSW	13	75126852	missense	probably benign	0.11
R1691:Pcsk1	UTSW	13	75132225	missense	possibly damaging	0.65
R1717:Pcsk1	UTSW	13	75110828	missense	probably damaging	0.99
R2168:Pcsk1	UTSW	13	75112534	intron	probably benign
R2400:Pcsk1	UTSW	13	75090126	missense	probably benign	0.00
R4110:Pcsk1	UTSW	13	75096369	missense	probably damaging	0.99
R4358:Pcsk1	UTSW	13	75112719	missense	possibly damaging	0.58
R4359:Pcsk1	UTSW	13	75112719	missense	possibly damaging	0.58
R4657:Pcsk1	UTSW	13	75132235	missense	probably damaging	1.00
R5195:Pcsk1	UTSW	13	75126855	missense	probably damaging	1.00
R5669:Pcsk1	UTSW	13	75130102	missense	probably benign	0.01
R5671:Pcsk1	UTSW	13	75097907	missense	possibly damaging	0.63
R5745:Pcsk1	UTSW	13	75131960	missense	probably benign	0.03
R6107:Pcsk1	UTSW	13	75127848	missense	probably benign	0.09
R6200:Pcsk1	UTSW	13	75115255	missense	possibly damaging	0.88
R6326:Pcsk1	UTSW	13	75132179	missense	possibly damaging	0.89
R6537:Pcsk1	UTSW	13	75132239	missense	probably damaging	1.00
R6541:Pcsk1	UTSW	13	75125984	missense	probably damaging	1.00
R6567:Pcsk1	UTSW	13	75130070	missense	probably damaging	1.00
R6723:Pcsk1	UTSW	13	75093069	splice site	probably null
R7258:Pcsk1	UTSW	13	75093186	missense	probably damaging	1.00
R7357:Pcsk1	UTSW	13	75125960	missense	probably damaging	0.96
R7487:Pcsk1	UTSW	13	75110883	missense	probably benign	0.01
R7519:Pcsk1	UTSW	13	75110865	missense	probably damaging	0.99
R7647:Pcsk1	UTSW	13	75132210	missense	possibly damaging	0.73
R7787:Pcsk1	UTSW	13	75132158	missense	possibly damaging	0.88
R7944:Pcsk1	UTSW	13	75132092	missense	probably benign
R7945:Pcsk1	UTSW	13	75132092	missense	probably benign
R7961:Pcsk1	UTSW	13	75126839	missense	probably benign	0.00
R8009:Pcsk1	UTSW	13	75126839	missense	probably benign	0.00
R8022:Pcsk1	UTSW	13	75099293	missense	possibly damaging	0.77
R8171:Pcsk1	UTSW	13	75090091	nonsense	probably null
R8489:Pcsk1	UTSW	13	75126002	missense	probably damaging	1.00
R9310:Pcsk1	UTSW	13	75090072	missense	probably benign
R9404:Pcsk1	UTSW	13	75132223	missense	probably benign	0.11
R9544:Pcsk1	UTSW	13	75110920	missense	probably damaging	0.99
R9588:Pcsk1	UTSW	13	75110920	missense	probably damaging	0.99
R9706:Pcsk1	UTSW	13	75099354	critical splice donor site	probably null
Z1176:Pcsk1	UTSW	13	75098042	missense	probably damaging	1.00
Z1177:Pcsk1	UTSW	13	75125864	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TTGATATCCTTGTCATGGACCAC -3'
(R):5'- GAGTGGTTGTTGAAGTTTACCAAC -3'

Sequencing Primer
(F):5'- GGACCACTTTTGTTGAATTGAAGAC -3'
(R):5'- TGTTGAAGTTTACCAACAGCAG -3'

Posted On

2014-10-16