Mutagenetix > Incidental Mutation

Incidental Mutation 'IGL02441:Pcsk1'

293957

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 #

IGL02441

Quality Score

Status

Chromosome

Chromosomal Location

75089826-75134861 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 75132163 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Aspartic acid at position 702 (E702D)

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: E702D

PolyPhen 2 Score 0.159 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000022075
Gene: ENSMUSG00000021587
AA Change: E702D

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

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: 58 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Alg8	C	T	7: 97,380,297	R179C	probably benign	Het
Als2	A	G	1: 59,215,472	M242T	probably damaging	Het
Atad1	C	T	19: 32,706,948	V17I	probably benign	Het
Bag4	A	G	8: 25,768,108	V397A	probably damaging	Het
Brd7	A	G	8: 88,343,590	V396A	probably damaging	Het
Cdc45	C	T	16: 18,798,729	M200I	probably benign	Het
Cdhr4	T	A	9: 107,993,267	I123N	possibly damaging	Het
Cep68	A	G	11: 20,239,186	F609L	probably benign	Het
Clec3b	C	A	9: 123,151,113	P24T	possibly damaging	Het
Ctsg	T	A	14: 56,102,412	T9S	probably benign	Het
Dalrd3	A	T	9: 108,571,526		probably benign	Het
Dock6	A	T	9: 21,841,926	V286E	possibly damaging	Het
Dpep2	G	A	8: 105,985,091	A568V	probably benign	Het
Dph5	A	C	3: 115,926,741	Q192P	possibly damaging	Het
Eppin	T	A	2: 164,591,778	R37*	probably null	Het
Esyt1	A	G	10: 128,512,424	L865P	possibly damaging	Het
Exoc6b	A	G	6: 85,005,008	L102P	probably damaging	Het
Foxo6	A	G	4: 120,268,035	I521T	possibly damaging	Het
Guca1a	A	T	17: 47,394,653		probably benign	Het
Hpx	A	G	7: 105,592,223	F327S	probably damaging	Het
Hspa12b	A	G	2: 131,138,595	M145V	probably null	Het
Hspa4	A	T	11: 53,270,982	S448T	probably benign	Het
Kbtbd6	T	C	14: 79,453,319	Y422H	probably benign	Het
Lama4	A	T	10: 39,061,445	D677V	probably benign	Het
Ldb1	C	T	19: 46,035,756	E111K	probably damaging	Het
Macf1	A	G	4: 123,387,236	S3823P	probably damaging	Het
Man1a2	G	A	3: 100,591,873	T415I	probably benign	Het
Map3k2	T	C	18: 32,200,046		probably benign	Het
Morn5	T	A	2: 36,055,026	Y87*	probably null	Het
Mpp3	T	C	11: 102,009,675	D326G	probably benign	Het
Mrgprx1	T	C	7: 48,021,588	H137R	probably benign	Het
Nav2	C	A	7: 49,452,512	P292T	probably damaging	Het
Nlrp2	C	A	7: 5,335,567		probably null	Het
Noxo1	G	A	17: 24,699,056	S112N	probably damaging	Het
Nudt9	G	T	5: 104,065,019	K319N	probably benign	Het
Olfr885	A	T	9: 38,061,937	I206L	probably benign	Het
Osbpl7	C	A	11: 97,067,702	Q728K	probably damaging	Het
Piezo2	T	C	18: 63,072,862	D1492G	probably damaging	Het
Plekhg1	A	G	10: 3,958,103	K1007E	possibly damaging	Het
Ppp6r3	G	A	19: 3,464,693	P141S	probably benign	Het
Prrt3	T	C	6: 113,497,016	T354A	probably damaging	Het
Ptk2	C	A	15: 73,320,826	W181L	probably benign	Het
Rif1	T	A	2: 52,105,515	H915Q	probably benign	Het
Selenbp2	G	T	3: 94,704,064	V361L	probably benign	Het
Slamf7	A	G	1: 171,641,057	L89P	probably damaging	Het
Slc6a21	G	A	7: 45,288,081	V599M	probably damaging	Het
Sltm	G	T	9: 70,587,185	S921I	probably damaging	Het
Smc4	C	A	3: 69,006,211	A44E	probably damaging	Het
Tdrd5	A	T	1: 156,259,943		probably benign	Het
Tead2	T	A	7: 45,217,421	I68N	probably damaging	Het
Tnks1bp1	T	A	2: 85,071,799	S1680T	probably damaging	Het
Topbp1	T	C	9: 103,320,239	V386A	possibly damaging	Het
Tpx2	C	A	2: 152,882,287	P328T	possibly damaging	Het
Ttn	T	A	2: 76,745,988	I24854F	probably damaging	Het
Zbtb11	G	A	16: 55,974,189	R43H	possibly damaging	Het
Zfp609	A	G	9: 65,703,329	L784S	possibly damaging	Het
Zfp703	T	C	8: 26,980,008	S567P	probably damaging	Het
Zfp750	A	G	11: 121,513,629	I140T	probably benign	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
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
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

2015-04-16