Mutagenetix > Incidental Mutation

Incidental Mutation 'R8171:Pcsk1'

634144

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

067597-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R8171 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

75237945-75282980 bp(+) (GRCm39)

Type of Mutation

nonsense

DNA Base Change (assembly)

T to A at 75238210 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Cysteine to Stop codon at position 10 (C10*)

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
AA Change: C10*

SMART Domains

Protein: ENSMUSP00000022075
Gene: ENSMUSG00000021587
AA Change: C10*

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.4%
20x: 97.9%

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: 95 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
3425401B19Rik	G	T	14: 32,383,982 (GRCm39)	A661E	probably benign	Het
Abhd14a	T	A	9: 106,317,960 (GRCm39)	T142S	probably benign	Het
Actn1	A	G	12: 80,243,167 (GRCm39)		probably null	Het
Adss2	T	C	1: 177,623,917 (GRCm39)	N15S	probably benign	Het
Alpk2	A	G	18: 65,439,054 (GRCm39)	S780P	probably benign	Het
Asap1	G	T	15: 63,982,815 (GRCm39)	L830M	probably damaging	Het
Atic	T	C	1: 71,609,032 (GRCm39)	V319A	possibly damaging	Het
Atp8a2	A	T	14: 60,283,493 (GRCm39)	I87N	probably damaging	Het
Bace2	G	T	16: 97,225,786 (GRCm39)	V407L	possibly damaging	Het
Bltp1	T	C	3: 37,029,862 (GRCm39)	V2423A	probably benign	Het
Bmp3	A	T	5: 99,020,528 (GRCm39)	Y317F	probably damaging	Het
Ccdc159	A	G	9: 21,845,007 (GRCm39)	E291G	possibly damaging	Het
Cct8l1	T	A	5: 25,721,552 (GRCm39)	L89Q	probably damaging	Het
Cep83	T	A	10: 94,604,797 (GRCm39)	N503K	possibly damaging	Het
Ces4a	A	G	8: 105,873,839 (GRCm39)	Y436C	probably damaging	Het
Cftr	T	A	6: 18,258,287 (GRCm39)	D579E	probably damaging	Het
Chd9	T	A	8: 91,752,015 (GRCm39)	V1751D	possibly damaging	Het
Clasp2	A	T	9: 113,732,974 (GRCm39)	T937S	possibly damaging	Het
Clock	T	A	5: 76,414,261 (GRCm39)	D17V	possibly damaging	Het
Cpm	T	C	10: 117,519,220 (GRCm39)	L376P	probably damaging	Het
Crocc2	T	C	1: 93,116,723 (GRCm39)		probably null	Het
Csnk1g2	A	G	10: 80,475,636 (GRCm39)	D401G	probably damaging	Het
Cyb5r4	C	T	9: 86,924,863 (GRCm39)	L206F	possibly damaging	Het
Cyp1a1	T	A	9: 57,607,479 (GRCm39)	W36R	probably benign	Het
Cyp3a59	A	T	5: 146,022,584 (GRCm39)	H30L	probably damaging	Het
Dab2	G	A	15: 6,453,407 (GRCm39)	V182I	probably benign	Het
Dnah1	G	T	14: 31,019,067 (GRCm39)	F1342L	probably damaging	Het
Draxin	A	T	4: 148,200,123 (GRCm39)	L109Q	possibly damaging	Het
Elfn1	G	A	5: 139,957,112 (GRCm39)	V39M	probably damaging	Het
Erlin1	A	G	19: 44,057,768 (GRCm39)	I19T	probably benign	Het
F830016B08Rik	T	A	18: 60,433,150 (GRCm39)	S78T	possibly damaging	Het
Fer1l4	A	G	2: 155,890,151 (GRCm39)	V258A	probably benign	Het
Fgb	T	C	3: 82,949,822 (GRCm39)	D445G	probably damaging	Het
Fgd6	T	C	10: 93,910,194 (GRCm39)		probably null	Het
Frem3	T	A	8: 81,341,869 (GRCm39)	D1387E	probably damaging	Het
Gdf3	T	C	6: 122,586,862 (GRCm39)	T22A	probably benign	Het
Glcci1	C	T	6: 8,593,167 (GRCm39)	A511V	probably benign	Het
Gldc	A	T	19: 30,111,161 (GRCm39)	N538K	probably benign	Het
Glipr1l1	C	T	10: 111,914,289 (GRCm39)	P217S	probably benign	Het
Gpr161	A	G	1: 165,134,005 (GRCm39)	N89S	probably damaging	Het
Gypa	T	A	8: 81,236,092 (GRCm39)	S166T	probably benign	Het
Hcar1	A	G	5: 124,017,152 (GRCm39)	S180P	probably damaging	Het
Hcn1	T	C	13: 117,739,270 (GRCm39)	S11P	unknown	Het
Hectd4	A	G	5: 121,456,819 (GRCm39)	E728G	possibly damaging	Het
Ints14	A	T	9: 64,880,532 (GRCm39)	H213L	possibly damaging	Het
Itih1	A	T	14: 30,659,047 (GRCm39)	M323K	possibly damaging	Het
Ivl	A	G	3: 92,479,085 (GRCm39)	S327P	probably damaging	Het
Kcnt2	T	A	1: 140,437,203 (GRCm39)	N545K	probably benign	Het
Kdm4b	A	T	17: 56,696,534 (GRCm39)	R417W	probably damaging	Het
Kif13a	T	C	13: 46,932,444 (GRCm39)	E1083G	probably damaging	Het
Klhl40	A	T	9: 121,607,623 (GRCm39)	H261L	probably benign	Het
Kpnb1	A	G	11: 97,066,573 (GRCm39)		probably null	Het
Lamc3	C	A	2: 31,804,983 (GRCm39)	T621N	probably benign	Het
Lingo3	T	C	10: 80,670,595 (GRCm39)	H445R	probably benign	Het
Ly75	G	A	2: 60,144,572 (GRCm39)	T1297I	possibly damaging	Het
Lypd6	C	T	2: 50,080,759 (GRCm39)	T149M	possibly damaging	Het
Mcrs1	A	T	15: 99,146,613 (GRCm39)	D139E	probably damaging	Het
Muc5b	G	A	7: 141,414,737 (GRCm39)	S2561N	unknown	Het
Mybpc1	C	T	10: 88,358,865 (GRCm39)	G1095R	probably damaging	Het
Myh1	A	G	11: 67,093,398 (GRCm39)	Y163C	probably damaging	Het
Notch4	T	A	17: 34,801,483 (GRCm39)	C1110*	probably null	Het
Nt5el	T	A	13: 105,246,291 (GRCm39)	V284E	probably benign	Het
Or12j2	A	T	7: 139,916,143 (GRCm39)	I123F	probably damaging	Het
Or2ag1	C	T	7: 106,313,825 (GRCm39)	S21N	probably benign	Het
Or2ag1	T	A	7: 106,313,826 (GRCm39)	S21C		Het
Or4c10b	A	G	2: 89,711,409 (GRCm39)	I80V	probably benign	Het
Pdlim5	A	T	3: 142,017,948 (GRCm39)	S107T	probably benign	Het
Plac8l1	T	A	18: 42,313,445 (GRCm39)	D99V	probably damaging	Het
Plin2	A	T	4: 86,575,349 (GRCm39)	V400E	probably damaging	Het
Plxna1	G	A	6: 89,334,102 (GRCm39)	P176S	probably benign	Het
Pnn	A	G	12: 59,117,223 (GRCm39)	K238R	probably damaging	Het
Pou5f1	A	G	17: 35,820,933 (GRCm39)	E231G	probably benign	Het
Ppara	A	T	15: 85,682,077 (GRCm39)	M258L	probably benign	Het
Prune2	G	A	19: 17,097,882 (GRCm39)	D1129N	probably damaging	Het
Rai14	G	A	15: 10,633,249 (GRCm39)	T47M	probably damaging	Het
Rdh5	T	C	10: 128,753,969 (GRCm39)	I117V	probably benign	Het
Rpain	G	A	11: 70,864,724 (GRCm39)	C137Y	probably damaging	Het
Scn3a	A	G	2: 65,361,154 (GRCm39)	V126A	possibly damaging	Het
Senp7	G	T	16: 55,932,089 (GRCm39)	L129F	probably damaging	Het
Setd1a	A	G	7: 127,390,399 (GRCm39)	D1025G	unknown	Het
Sirt4	A	T	5: 115,621,082 (GRCm39)	V30E	probably damaging	Het
Slit1	C	A	19: 41,715,512 (GRCm39)	R113L	probably damaging	Het
Stxbp5l	G	A	16: 37,028,416 (GRCm39)	T549I	noncoding transcript	Het
Sytl2	A	G	7: 90,058,678 (GRCm39)	M926V	probably damaging	Het
Tgfbr2	C	T	9: 115,959,074 (GRCm39)	W113*	probably null	Het
Tmem86a	A	G	7: 46,703,512 (GRCm39)	Y213C	probably damaging	Het
Tpo	T	A	12: 30,154,045 (GRCm39)	Y220F	probably damaging	Het
Ttc6	C	A	12: 57,720,096 (GRCm39)	A889E	probably damaging	Het
Tyw1	A	G	5: 130,328,855 (GRCm39)	D547G	probably benign	Het
Ubtfl1	A	G	9: 18,320,523 (GRCm39)	K17R	probably benign	Het
Usp46	T	A	5: 74,163,354 (GRCm39)	I331F	probably benign	Het
Vmn2r111	T	C	17: 22,792,073 (GRCm39)	H61R	probably benign	Het
Wdr75	T	A	1: 45,861,706 (GRCm39)	N715K	probably benign	Het
Wdr97	C	A	15: 76,247,819 (GRCm39)	F1614L		Het
Zfp772	A	T	7: 7,207,096 (GRCm39)	C198*	probably null	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
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
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'- TCGGGAGACTGAAGCACTTTAG -3'
(R):5'- CGAAAGTGGAAACTCTTACCTG -3'

Sequencing Primer
(F):5'- ACTTTAGTGAGCGCTCGC -3'
(R):5'- GTGGAAACTCTTACCTGACCCAAAAG -3'

Posted On

2020-07-13