Mutagenetix > Incidental Mutation

Incidental Mutation 'R6723:Pcsk1'

529713

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

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6723 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

75089826-75134861 bp(+) (GRCm38)

Type of Mutation

splice site

DNA Base Change (assembly)

T to A at 75093069 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

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 null
Transcript: ENSMUST00000022075

SMART Domains

Protein: ENSMUSP00000022075
Gene: ENSMUSG00000021587

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

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.3%
20x: 95.3%

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: 65 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4932415D10Rik	T	C	10: 82,289,823	Y2451C	possibly damaging	Het
Ahnak2	A	G	12: 112,778,793	S740P	probably damaging	Het
Akt3	A	T	1: 177,050,190	Y337*	probably null	Het
Bcl11a	C	A	11: 24,163,646	P330T	probably damaging	Het
Cyp2d12	A	T	15: 82,556,884	I124F	probably benign	Het
Dhdds	T	C	4: 133,994,265	T74A	probably damaging	Het
Dio3	G	A	12: 110,279,557	C109Y	possibly damaging	Het
Dnah8	G	A	17: 30,748,568	D2585N	probably benign	Het
Dock7	A	G	4: 99,003,916	V811A	possibly damaging	Het
Efcab3	A	T	11: 105,117,080	T329S	possibly damaging	Het
Esp1	A	T	17: 40,728,856	I11L	probably benign	Het
Fam13b	A	T	18: 34,498,026	H33Q	possibly damaging	Het
Fam13c	G	A	10: 70,554,525	D539N	probably damaging	Het
Fgd5	A	G	6: 91,988,030	T257A	probably benign	Het
Gm5134	A	G	10: 76,008,619	D603G	probably benign	Het
Gtpbp2	T	C	17: 46,168,276	V588A	probably benign	Het
Ift140	A	G	17: 25,033,116	I312M	probably benign	Het
Inpp5j	T	C	11: 3,500,640	N571S	probably damaging	Het
Iqgap1	T	G	7: 80,723,822	D1473A	probably benign	Het
Ivl	T	G	3: 92,571,387	K457T	unknown	Het
Kdm3b	T	C	18: 34,793,005	I66T	probably damaging	Het
Kif21a	A	T	15: 90,940,446	M1430K	probably damaging	Het
Klhl25	T	A	7: 75,865,991	L215Q	possibly damaging	Het
Lim2	T	A	7: 43,435,675	M163K	probably benign	Het
Lrig1	T	C	6: 94,626,405	D254G	probably damaging	Het
Mff	A	G	1: 82,751,666	I122V	possibly damaging	Het
Mrpl15	A	C	1: 4,782,566		probably null	Het
Mylk	A	G	16: 34,929,888	Y1199C	possibly damaging	Het
Nlrp3	G	A	11: 59,565,192	C938Y	probably damaging	Het
Notch1	T	C	2: 26,478,106	N623D	probably damaging	Het
Obscn	T	G	11: 59,054,998	E4129A	probably damaging	Het
Olfr1221	G	T	2: 89,112,296	T72N	possibly damaging	Het
Olfr1423	A	G	19: 12,036,275	S156P	probably damaging	Het
Olfr173	T	C	16: 58,797,432	K138R	probably benign	Het
Olfr517	A	T	7: 108,868,588	C189S	probably damaging	Het
Olfr808	A	T	10: 129,768,415	L306F	probably benign	Het
Parm1	C	T	5: 91,622,997	P291S	probably damaging	Het
Pi4ka	A	G	16: 17,376,982	L184P	possibly damaging	Het
Piezo1	T	G	8: 122,507,627	Q93H	probably benign	Het
Pkd2l2	A	T	18: 34,438,157	Y575F	probably damaging	Het
Plekhn1	A	C	4: 156,224,569	F258C	probably damaging	Het
Pole	C	T	5: 110,323,616	H1409Y	probably benign	Het
Rae1	T	C	2: 173,012,248	I273T	probably damaging	Het
Rag1	A	G	2: 101,643,645	V384A	probably damaging	Het
Rnaseh1	T	C	12: 28,649,762	L25P	probably damaging	Het
Serpinb12	A	G	1: 106,949,158	H68R	probably benign	Het
Sh3tc2	A	T	18: 61,977,954	I294F	probably damaging	Het
Sirpb1b	A	C	3: 15,548,798	L75V	possibly damaging	Het
Slc12a6	A	T	2: 112,337,942	T277S	probably damaging	Het
Slc7a12	A	T	3: 14,499,197	E43D	probably benign	Het
Spata31d1c	T	A	13: 65,035,944	D433E	probably benign	Het
Tbl2	A	T	5: 135,159,276	Y308F	probably damaging	Het
Tfec	T	C	6: 16,835,302	Y159C	probably damaging	Het
Tmem8	C	A	17: 26,120,636	T616N	probably damaging	Het
Top1mt	G	T	15: 75,667,433	T371K	probably benign	Het
Trim24	T	C	6: 37,951,468	V541A	probably benign	Het
Ttc16	T	C	2: 32,768,037	Y456C	possibly damaging	Het
Ttn	G	A	2: 76,770,097	R17204*	probably null	Het
Ugt1a6b	T	C	1: 88,107,717	V259A	probably benign	Het
Unc5a	T	C	13: 54,995,889	W129R	probably benign	Het
Vmn1r63	T	A	7: 5,802,949	H228L	probably damaging	Het
Whamm	G	T	7: 81,596,120	V775F	probably damaging	Het
Zfc3h1	T	A	10: 115,420,733	I1536N	probably benign	Het
Zfp1	T	C	8: 111,670,339	S317P	probably damaging	Het
Zfp58	T	C	13: 67,494,073	T52A	probably damaging	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
R2252:Pcsk1	UTSW	13	75126726	missense	probably benign	0.00
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
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'- TGAAGTGAGATATATACCAAGGGCC -3'
(R):5'- TATGAGCACGATTCCATAGAAGG -3'

Sequencing Primer
(F):5'- GTGAGATATATACCAAGGGCCATCTC -3'
(R):5'- TCTCTGTTGGGAGTCCTATAGAAAAC -3'

Posted On

2018-08-01