Mutagenetix > Incidental Mutation

Incidental Mutation 'R6537:Pcsk1'

520498

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

044663-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6537 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

75237945-75282980 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 75280358 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Phenylalanine to Leucine at position 728 (F728L)

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: F728L

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000022075
Gene: ENSMUSG00000021587
AA Change: F728L

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: 99.6%
20x: 98.6%

Validation Efficiency

100% (30/30)

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: 29 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Anapc4	T	C	5: 53,000,898 (GRCm39)	S224P	probably damaging	Het
Col6a4	G	A	9: 105,945,153 (GRCm39)	T987M	possibly damaging	Het
Cort	C	T	4: 149,211,081 (GRCm39)	G8E	probably benign	Het
Ctdp1	G	T	18: 80,492,766 (GRCm39)	D576E	probably benign	Het
Ctsq	A	T	13: 61,183,140 (GRCm39)	I334N	probably damaging	Het
Cwc15	A	G	9: 14,413,284 (GRCm39)	D22G	probably damaging	Het
Dnmt3l	G	A	10: 77,887,898 (GRCm39)	G136R	probably null	Het
Fxyd6	A	G	9: 45,302,092 (GRCm39)	I37V	possibly damaging	Het
Gm10604	A	C	4: 11,980,221 (GRCm39)	S28A	unknown	Het
Gm43302	A	G	5: 105,438,861 (GRCm39)	I9T	possibly damaging	Het
Hmcn2	T	C	2: 31,305,280 (GRCm39)	V3151A	probably benign	Het
Kif1b	T	C	4: 149,277,053 (GRCm39)	M1337V	probably benign	Het
Kyat3	A	G	3: 142,435,573 (GRCm39)	T282A	probably benign	Het
Lrp6	T	C	6: 134,457,458 (GRCm39)	E782G	probably benign	Het
Lrrc3b	T	C	14: 15,357,946 (GRCm38)	Y220C	probably damaging	Het
Macf1	C	T	4: 123,386,518 (GRCm39)	S1033N	probably damaging	Het
Mdm1	A	G	10: 117,994,481 (GRCm39)	T452A	probably benign	Het
Nrn1l	G	T	8: 106,621,350 (GRCm39)	R99L	probably damaging	Het
Pappa	T	A	4: 65,215,519 (GRCm39)	I1142N	probably damaging	Het
Ptcd3	T	C	6: 71,874,094 (GRCm39)		probably null	Het
Siglecf	C	T	7: 43,005,423 (GRCm39)	T461I	probably benign	Het
Slc7a8	C	T	14: 54,972,576 (GRCm39)	A282T	probably benign	Het
Srcap	T	C	7: 127,141,392 (GRCm39)	V1724A	probably damaging	Het
Tafa2	T	A	10: 123,429,401 (GRCm39)	M5K	possibly damaging	Het
Tek	A	G	4: 94,725,561 (GRCm39)	Q609R	probably benign	Het
Trim45	C	T	3: 100,832,712 (GRCm39)	A315V	probably benign	Het
Ttbk1	C	T	17: 46,781,236 (GRCm39)	V446M	probably damaging	Het
Wrap53	T	C	11: 69,454,694 (GRCm39)	D225G	possibly damaging	Het
Znhit6	A	G	3: 145,300,374 (GRCm39)	I193V	probably benign	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
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
R8171:Pcsk1	UTSW	13	75,238,210 (GRCm39)	nonsense	probably null
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'- GCTGCGACTCCTACAAAGTG -3'
(R):5'- CTCACTCCAAAGTACAGTTTGAAAG -3'

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

Posted On

2018-06-06