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

MMRRC Submission

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R8171 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

75089826-75134861 bp(+) (GRCm38)

Type of Mutation

nonsense

DNA Base Change (assembly)

T to A at 75090091 bp (GRCm38)

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: 32,662,025	A661E	probably benign	Het
4932438A13Rik	T	C	3: 36,975,713	V2423A	probably benign	Het
4933425L06Rik	T	A	13: 105,109,783	V284E	probably benign	Het
Abhd14a	T	A	9: 106,440,761	T142S	probably benign	Het
Actn1	A	G	12: 80,196,393		probably null	Het
Adss	T	C	1: 177,796,351	N15S	probably benign	Het
Alpk2	A	G	18: 65,305,983	S780P	probably benign	Het
Asap1	G	T	15: 64,110,966	L830M	probably damaging	Het
Atic	T	C	1: 71,569,873	V319A	possibly damaging	Het
Atp8a2	A	T	14: 60,046,044	I87N	probably damaging	Het
Bace2	G	T	16: 97,424,586	V407L	possibly damaging	Het
Bmp3	A	T	5: 98,872,669	Y317F	probably damaging	Het
Ccdc159	A	G	9: 21,933,711	E291G	possibly damaging	Het
Cct8l1	T	A	5: 25,516,554	L89Q	probably damaging	Het
Cep83	T	A	10: 94,768,935	N503K	possibly damaging	Het
Ces4a	A	G	8: 105,147,207	Y436C	probably damaging	Het
Cftr	T	A	6: 18,258,288	D579E	probably damaging	Het
Chd9	T	A	8: 91,025,387	V1751D	possibly damaging	Het
Clasp2	A	T	9: 113,903,906	T937S	possibly damaging	Het
Clock	T	A	5: 76,266,414	D17V	possibly damaging	Het
Cpm	T	C	10: 117,683,315	L376P	probably damaging	Het
Crocc2	T	C	1: 93,189,001		probably null	Het
Csnk1g2	A	G	10: 80,639,802	D401G	probably damaging	Het
Cyb5r4	C	T	9: 87,042,810	L206F	possibly damaging	Het
Cyp1a1	T	A	9: 57,700,196	W36R	probably benign	Het
Cyp3a59	A	T	5: 146,085,774	H30L	probably damaging	Het
Dab2	G	A	15: 6,423,926	V182I	probably benign	Het
Dnah1	G	T	14: 31,297,110	F1342L	probably damaging	Het
Draxin	A	T	4: 148,115,666	L109Q	possibly damaging	Het
Elfn1	G	A	5: 139,971,357	V39M	probably damaging	Het
Erlin1	A	G	19: 44,069,329	I19T	probably benign	Het
F830016B08Rik	T	A	18: 60,300,078	S78T	possibly damaging	Het
Fer1l4	A	G	2: 156,048,231	V258A	probably benign	Het
Fgb	T	C	3: 83,042,515	D445G	probably damaging	Het
Fgd6	T	C	10: 94,074,332		probably null	Het
Frem3	T	A	8: 80,615,240	D1387E	probably damaging	Het
Gdf3	T	C	6: 122,609,903	T22A	probably benign	Het
Glcci1	C	T	6: 8,593,167	A511V	probably benign	Het
Gldc	A	T	19: 30,133,761	N538K	probably benign	Het
Glipr1l1	C	T	10: 112,078,384	P217S	probably benign	Het
Gm15800	A	G	5: 121,318,756	E728G	possibly damaging	Het
Gm35339	C	A	15: 76,363,619	F1614L		Het
Gpr161	A	G	1: 165,306,436	N89S	probably damaging	Het
Gypa	T	A	8: 80,509,463	S166T	probably benign	Het
Hcar1	A	G	5: 123,879,089	S180P	probably damaging	Het
Hcn1	T	C	13: 117,602,734	S11P	unknown	Het
Itih1	A	T	14: 30,937,090	M323K	possibly damaging	Het
Ivl	A	G	3: 92,571,778	S327P	probably damaging	Het
Kcnt2	T	A	1: 140,509,465	N545K	probably benign	Het
Kdm4b	A	T	17: 56,389,534	R417W	probably damaging	Het
Kif13a	T	C	13: 46,778,968	E1083G	probably damaging	Het
Klhl40	A	T	9: 121,778,557	H261L	probably benign	Het
Kpnb1	A	G	11: 97,175,747		probably null	Het
Lamc3	C	A	2: 31,914,971	T621N	probably benign	Het
Lingo3	T	C	10: 80,834,761	H445R	probably benign	Het
Ly75	G	A	2: 60,314,228	T1297I	possibly damaging	Het
Lypd6	C	T	2: 50,190,747	T149M	possibly damaging	Het
Mcrs1	A	T	15: 99,248,732	D139E	probably damaging	Het
Muc5b	G	A	7: 141,861,000	S2561N	unknown	Het
Mybpc1	C	T	10: 88,523,003	G1095R	probably damaging	Het
Myh1	A	G	11: 67,202,572	Y163C	probably damaging	Het
Notch4	T	A	17: 34,582,509	C1110*	probably null	Het
Olfr1257	A	G	2: 89,881,065	I80V	probably benign	Het
Olfr527	A	T	7: 140,336,230	I123F	probably damaging	Het
Olfr705	C	T	7: 106,714,618	S21N	probably benign	Het
Olfr705	T	A	7: 106,714,619	S21C		Het
Pdlim5	A	T	3: 142,312,187	S107T	probably benign	Het
Plac8l1	T	A	18: 42,180,380	D99V	probably damaging	Het
Plin2	A	T	4: 86,657,112	V400E	probably damaging	Het
Plxna1	G	A	6: 89,357,120	P176S	probably benign	Het
Pnn	A	G	12: 59,070,437	K238R	probably damaging	Het
Pou5f1	A	G	17: 35,510,036	E231G	probably benign	Het
Ppara	A	T	15: 85,797,876	M258L	probably benign	Het
Prune2	G	A	19: 17,120,518	D1129N	probably damaging	Het
Rai14	G	A	15: 10,633,163	T47M	probably damaging	Het
Rdh5	T	C	10: 128,918,100	I117V	probably benign	Het
Rpain	G	A	11: 70,973,898	C137Y	probably damaging	Het
Scn3a	A	G	2: 65,530,810	V126A	possibly damaging	Het
Senp7	G	T	16: 56,111,726	L129F	probably damaging	Het
Setd1a	A	G	7: 127,791,227	D1025G	unknown	Het
Sirt4	A	T	5: 115,483,023	V30E	probably damaging	Het
Slit1	C	A	19: 41,727,073	R113L	probably damaging	Het
Stxbp5l	G	A	16: 37,208,054	T549I	noncoding transcript	Het
Sytl2	A	G	7: 90,409,470	M926V	probably damaging	Het
Tgfbr2	C	T	9: 116,130,006	W113*	probably null	Het
Tmem86a	A	G	7: 47,053,764	Y213C	probably damaging	Het
Tpo	T	A	12: 30,104,046	Y220F	probably damaging	Het
Ttc6	C	A	12: 57,673,310	A889E	probably damaging	Het
Tyw1	A	G	5: 130,300,014	D547G	probably benign	Het
Ubtfl1	A	G	9: 18,409,227	K17R	probably benign	Het
Usp46	T	A	5: 74,002,693	I331F	probably benign	Het
Vmn2r111	T	C	17: 22,573,092	H61R	probably benign	Het
Vwa9	A	T	9: 64,973,250	H213L	possibly damaging	Het
Wdr75	T	A	1: 45,822,546	N715K	probably benign	Het
Zfp772	A	T	7: 7,204,097	C198*	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
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
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
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'- TCGGGAGACTGAAGCACTTTAG -3'
(R):5'- CGAAAGTGGAAACTCTTACCTG -3'

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

Posted On

2020-07-13