Mutagenetix > Incidental Mutation

Incidental Mutation 'IGL02795:Pcsk1'

359948

Institutional Source

Australian Phenomics Network (link to record)

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

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

IGL02795

Quality Score

Status

Chromosome

Chromosomal Location

75089826-75134861 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 75112620 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Glycine to Cysteine at position 321 (G321C)

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: G321C

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

SMART Domains

Protein: ENSMUSP00000022075
Gene: ENSMUSG00000021587
AA Change: G321C

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

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
Abca12	A	G	1: 71,288,748	L1391P	probably damaging	Het
Abcc3	G	A	11: 94,361,642		probably benign	Het
Acvr1	A	G	2: 58,462,952	I332T	probably damaging	Het
Atp8a2	C	T	14: 60,033,742	V247M	probably damaging	Het
Btn1a1	T	C	13: 23,460,616		probably null	Het
Btnl9	A	T	11: 49,174,867		probably benign	Het
Dbx1	T	A	7: 49,636,577	I47F	probably benign	Het
Dnaja3	A	G	16: 4,690,073		probably benign	Het
Dnmt1	T	C	9: 20,927,111	S220G	probably benign	Het
Dock9	A	T	14: 121,639,978	M451K	probably benign	Het
Eml3	A	G	19: 8,933,778	Y257C	probably benign	Het
Fbxw19	C	A	9: 109,495,818	M10I	possibly damaging	Het
Flg2	C	T	3: 93,203,613	R983W	unknown	Het
Galnt5	C	A	2: 58,027,871	P707H	probably damaging	Het
Gba2	G	T	4: 43,578,331	P6Q	probably damaging	Het
Gm13199	A	G	2: 5,862,673		probably benign	Het
Gpr45	C	T	1: 43,032,493	R99C	possibly damaging	Het
Hecw1	G	A	13: 14,322,517	S302L	probably damaging	Het
Hrg	T	C	16: 22,957,553		probably benign	Het
Kdelc2	A	G	9: 53,392,105	D99G	probably damaging	Het
Lama1	A	G	17: 67,738,894		probably null	Het
Lgr4	T	C	2: 110,008,210		probably benign	Het
Lrrc9	C	T	12: 72,478,768	T830M	probably damaging	Het
Mdga2	T	C	12: 66,689,432	T341A	probably benign	Het
Mms19	C	T	19: 41,952,406		probably null	Het
Nectin1	A	G	9: 43,803,552	S362G	probably benign	Het
Nlrc3	G	T	16: 3,965,285	H87N	probably damaging	Het
Oit1	T	A	14: 8,355,497	M113L	probably benign	Het
Olfr1018	T	A	2: 85,823,512	C180*	probably null	Het
Olfr142	A	G	2: 90,252,562	L142P	probably damaging	Het
Olfr183	G	T	16: 59,000,277	L197F	possibly damaging	Het
Olfr23	G	A	11: 73,940,929	V228I	probably benign	Het
Olfr243	T	A	7: 103,716,883	F96L	probably benign	Het
Prrc2c	G	T	1: 162,714,299	P374T	probably benign	Het
Rusc1	A	T	3: 89,091,950	L175Q	probably damaging	Het
Ryr2	T	C	13: 11,595,190	N4250S	probably benign	Het
Scara5	A	C	14: 65,730,680	N134T	possibly damaging	Het
Sema4d	T	C	13: 51,703,411	K595R	probably benign	Het
Serpinb6a	A	C	13: 33,931,593	L15R	probably damaging	Het
Setdb1	A	T	3: 95,327,373	N1006K	probably damaging	Het
Slc18a2	G	A	19: 59,274,490		probably benign	Het
Slc22a30	C	T	19: 8,400,895	C139Y	probably damaging	Het
Slc25a27	T	A	17: 43,647,112	Y269F	probably damaging	Het
Slc9c1	A	T	16: 45,575,419	D611V	probably benign	Het
Spag6	G	T	2: 18,733,083	V255F	probably benign	Het
St5	T	C	7: 109,556,364	Y393C	probably damaging	Het
Svep1	C	A	4: 58,123,223	G698W	probably damaging	Het
Syne2	T	C	12: 75,966,549	L2839P	probably damaging	Het
Tfb2m	T	C	1: 179,545,959	E58G	possibly damaging	Het
Trim24	A	T	6: 37,919,389	E260D	probably damaging	Het
Ugt2b1	T	A	5: 86,917,701	D493V	probably damaging	Het
Vmn1r27	A	G	6: 58,215,302	V189A	possibly damaging	Het
Vmn2r91	A	G	17: 18,085,277	Q74R	probably benign	Het
Vps25	A	G	11: 101,256,090	Y64C	probably damaging	Het
Xirp2	G	A	2: 67,509,136	G574S	probably damaging	Het
Ythdc2	A	G	18: 44,837,438	E273G	possibly 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
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
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

Posted On

2015-12-18