Mutagenetix > Incidental Mutation

Incidental Mutation 'R4657:Pcsk1'

352552

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

041917-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R4657 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

75089826-75134861 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 75132235 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glutamic Acid at position 726 (D726E)

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: D726E

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

SMART Domains

Protein: ENSMUSP00000022075
Gene: ENSMUSG00000021587
AA Change: D726E

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

Meta Mutation Damage Score

0.2813

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.4%
20x: 95.6%

Validation Efficiency

98% (105/107)

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: 102 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aatk	A	T	11: 120,013,478	V264E	possibly damaging	Het
Abcg1	T	A	17: 31,108,434	W368R	probably benign	Het
Acin1	A	G	14: 54,643,047	I476T	possibly damaging	Het
Acsm1	T	A	7: 119,640,694	I287N	possibly damaging	Het
Adgrv1	C	T	13: 81,405,364	V5464I	probably benign	Het
AI429214	T	A	8: 36,994,391	L231Q	probably damaging	Het
Akp3	A	G	1: 87,125,834		probably benign	Het
Amy2b	C	T	3: 113,153,477		noncoding transcript	Het
Apoa5	A	G	9: 46,269,872	Q82R	probably benign	Het
Arhgap44	A	G	11: 65,005,452		probably null	Het
Arhgef38	C	A	3: 133,234,681	G48V	probably damaging	Het
Bod1l	G	T	5: 41,818,612	N1786K	probably benign	Het
Cav2	A	T	6: 17,281,410	D17V	probably null	Het
Ccdc148	G	T	2: 59,001,888	N238K	probably benign	Het
Ccin	A	T	4: 43,984,981	I463F	probably damaging	Het
Cd8b1	C	T	6: 71,329,774	H162Y	possibly damaging	Het
Cdh16	T	A	8: 104,615,226		probably null	Het
Cfap65	T	A	1: 74,925,354		probably benign	Het
Clec4n	T	C	6: 123,232,196		probably null	Het
Cpne7	T	A	8: 123,134,575	*558R	probably null	Het
Cs	A	G	10: 128,353,137	I172V	probably benign	Het
Cyp2ab1	A	T	16: 20,313,072	L306Q	probably damaging	Het
D16Ertd472e	A	T	16: 78,547,926	V98E	probably damaging	Het
Dcaf15	A	C	8: 84,102,838	S92A	probably damaging	Het
Dkk3	T	C	7: 112,149,046		probably null	Het
Dnah11	A	T	12: 118,192,427	C163S	probably benign	Het
Eda2r	T	A	X: 97,341,633	Q171L	probably damaging	Het
Eml4	A	T	17: 83,450,948	K397*	probably null	Het
Eml6	A	T	11: 29,805,108	I889N	possibly damaging	Het
Etaa1	A	T	11: 17,946,964	D384E	possibly damaging	Het
Fzr1	T	A	10: 81,367,552		probably null	Het
Gm13889	G	T	2: 93,956,576	F61L	probably damaging	Het
Gm14149	A	T	2: 151,230,764		noncoding transcript	Het
Gm5828	T	A	1: 16,769,418		noncoding transcript	Het
Gm5866	G	A	5: 52,582,920		noncoding transcript	Het
Gp2	T	C	7: 119,457,168	I27M	probably benign	Het
Gpr83	G	A	9: 14,866,983		probably null	Het
Gucd1	T	C	10: 75,511,125	N97S	probably benign	Het
H2-Q7	T	A	17: 35,442,759	V326E	possibly damaging	Het
Haao	A	T	17: 83,832,345	D227E	possibly damaging	Het
Hipk3	C	T	2: 104,433,759	S819N	probably benign	Het
Hist3h2ba	C	T	11: 58,948,971	P11L	probably benign	Het
Hlcs	A	G	16: 94,262,698	V501A	probably benign	Het
Hmcn1	A	G	1: 150,624,550	Y3964H	probably damaging	Het
Ifi204	C	A	1: 173,760,361		probably benign	Het
Ifi211	A	G	1: 173,907,660	F68L	probably benign	Het
Ift57	A	G	16: 49,762,594		probably null	Het
Ighv5-12-4	A	T	12: 113,762,267	L112*	probably null	Het
Il1f6	T	A	2: 24,224,404	M97K	possibly damaging	Het
Il1rl2	CTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTATT	CTTTATTTTATTTTATTTTATTTTATTTTATTTTATT	1: 40,327,310		probably benign	Het
Itsn2	A	G	12: 4,713,197	*1686W	probably null	Het
Jkamp	G	T	12: 72,094,049	V123F	probably damaging	Het
Kat7	C	A	11: 95,277,598	V411L	probably damaging	Het
Kcnj5	A	G	9: 32,322,677	V114A	probably benign	Het
Krtap5-4	T	A	7: 142,303,754	C54S	unknown	Het
Lats1	T	A	10: 7,705,684	N744K	possibly damaging	Het
Lpo	T	C	11: 87,814,347	E387G	probably damaging	Het
Lrba	T	G	3: 86,737,164	M388R	probably damaging	Het
Lrp2	C	A	2: 69,466,993	R3208L	probably damaging	Het
Mterf1b	T	A	5: 4,197,176	C272*	probably null	Het
Mum1	T	A	10: 80,233,014	C331S	probably benign	Het
Myh15	A	T	16: 49,172,058	R1632*	probably null	Het
Myo3b	T	C	2: 70,238,899	V494A	possibly damaging	Het
Myo9a	T	C	9: 59,875,416		probably null	Het
Nelfa	T	G	5: 33,901,813	S233R	probably benign	Het
Nr4a3	A	T	4: 48,051,522	E121V	probably damaging	Het
Obscn	T	A	11: 59,042,290	E5406D	probably damaging	Het
Ofcc1	G	A	13: 40,015,388	T841I	probably damaging	Het
Olfr347	T	A	2: 36,734,403	Y27*	probably null	Het
Olfr873	A	C	9: 20,300,623	H142P	probably damaging	Het
Oxct2b	T	C	4: 123,117,133	L282P	probably damaging	Het
Pappa	G	A	4: 65,314,796		probably null	Het
Pcdhb14	A	G	18: 37,448,847	I335M	possibly damaging	Het
Pkhd1	T	A	1: 20,364,167	Q2349L	possibly damaging	Het
Pkhd1l1	G	A	15: 44,547,347	C2750Y	probably damaging	Het
Ppp2r3d	A	G	9: 124,476,821	C26R	unknown	Het
Prex2	T	A	1: 11,065,825	I74N	probably benign	Het
Ptgir	A	G	7: 16,907,146	D121G	probably benign	Het
Ralbp1	T	C	17: 65,852,691	S526G	probably null	Het
Ric8b	T	C	10: 84,992,137	Y442H	probably damaging	Het
Rpap1	C	T	2: 119,775,006	D385N	probably benign	Het
Sash1	T	C	10: 8,725,660	Y1177C	probably damaging	Het
Shroom1	T	C	11: 53,465,588	I363T	possibly damaging	Het
Slc26a9	T	C	1: 131,753,138	L95P	probably damaging	Het
Slc44a5	A	G	3: 154,256,584	T385A	possibly damaging	Het
Slc5a9	C	A	4: 111,891,744		probably null	Het
Slc7a1	T	A	5: 148,352,399	M13L	probably benign	Het
Snrpb2	A	G	2: 143,070,973	N172S	possibly damaging	Het
Spns1	G	T	7: 126,374,302		probably benign	Het
Srsf6	T	A	2: 162,933,427	S86R	probably benign	Het
Stk25	A	T	1: 93,625,656		probably benign	Het
Szt2	A	T	4: 118,397,669	C275S	probably benign	Het
Tcp10b	T	A	17: 13,073,617		probably null	Het
Tmem248	T	A	5: 130,231,774	L60H	probably damaging	Het
Trim27	T	C	13: 21,183,760	I182T	probably damaging	Het
Tspan10	A	G	11: 120,444,498	N145D	probably damaging	Het
Uhrf1bp1	T	A	17: 27,890,105	F1099L	probably benign	Het
Vps13d	A	G	4: 145,074,842	F487S	probably damaging	Het
Wdr86	A	T	5: 24,718,231	D154E	probably benign	Het
Wfdc18	C	A	11: 83,709,869	A32D	possibly damaging	Het
Wrn	A	T	8: 33,335,991		probably null	Het
Zfp811	C	A	17: 32,800,923	E7*	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
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

Predicted Primers

PCR Primer
(F):5'- CTGCGACTCCTACAAAGTGC -3'
(R):5'- ACGAATGATGAAGTTGGCTTTC -3'

Sequencing Primer
(F):5'- GCGACTCCTACAAAGTGCTTTTAG -3'
(R):5'- GAAACTCACTCCAAAGTACAGTTTG -3'

Posted On

2015-10-08