Mutagenetix > Incidental Mutation

Incidental Mutation 'R5354:Pcsk4'

423987

Institutional Source

Beutler Lab

Gene Symbol

Pcsk4

Ensembl Gene

ENSMUSG00000020131

Gene Name

proprotein convertase subtilisin/kexin type 4

Synonyms

PC4, SPC5

MMRRC Submission

042933-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R5354 (G1)

Quality Score

175

Status

Validated

Chromosome

Chromosomal Location

80157117-80165332 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 80159523 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Asparagine to Lysine at position 416 (N416K)

Ref Sequence

ENSEMBL: ENSMUSP00000020340 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000020340] [ENSMUST00000020341] [ENSMUST00000128653] [ENSMUST00000135071]

AlphaFold

P29121

Predicted Effect

probably damaging
Transcript: ENSMUST00000020340
AA Change: N416K

PolyPhen 2 Score 0.984 (Sensitivity: 0.74; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000020340
Gene: ENSMUSG00000020131
AA Change: N416K

Domain	Start	End	E-Value	Type
signal peptide	1	26	N/A	INTRINSIC
Pfam:S8_pro-domain	34	110	1.2e-24	PFAM
Pfam:Peptidase_S8	146	429	3.1e-50	PFAM
Pfam:P_proprotein	488	574	5e-25	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000020341

SMART Domains

Protein: ENSMUSP00000020341
Gene: ENSMUSG00000020133

Domain	Start	End	E-Value	Type
Pfam:UPF0449	6	103	7.5e-40	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000128653

SMART Domains

Protein: ENSMUSP00000137809
Gene: ENSMUSG00000020131

Domain	Start	End	E-Value	Type
signal peptide	1	26	N/A	INTRINSIC
SCOP:d1kn6a_	31	102	8e-29	SMART
Pfam:Peptidase_S8	150	242	6.4e-18	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000130521

Predicted Effect

probably benign
Transcript: ENSMUST00000135071

SMART Domains

Protein: ENSMUSP00000137719
Gene: ENSMUSG00000020131

Domain	Start	End	E-Value	Type
SCOP:d1kn6a_	14	85	3e-27	SMART
Pfam:Peptidase_S8	133	187	1.7e-7	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000137177

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000147132

Meta Mutation Damage Score

0.8209

Coding Region Coverage

1x: 99.3%
3x: 98.6%
10x: 97.3%
20x: 95.4%

Validation Efficiency

100% (80/80)

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. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. The protease is expressed only in the testis, placenta, and ovary. It plays a critical role in fertilization, fetoplacental growth, and embryonic development and processes multiple prohormones including pro-pituitary adenylate cyclase-activating protein and pro-insulin-like growth factor II. [provided by RefSeq, Jan 2014]
PHENOTYPE: Inactivation of this locus results in significantly reduced male fertility, putatively due to impaired fertilization. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 73 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A630010A05Rik	A	G	16: 14,436,535 (GRCm39)	K196R	probably benign	Het
Ablim1	T	C	19: 57,119,355 (GRCm39)	E243G	probably benign	Het
Acat1	T	A	9: 53,500,483 (GRCm39)	E271V	possibly damaging	Het
Aco1	T	C	4: 40,180,290 (GRCm39)		probably null	Het
Adam22	C	A	5: 8,140,182 (GRCm39)	G202W	probably damaging	Het
Agbl3	T	A	6: 34,791,687 (GRCm39)	H596Q	probably benign	Het
Anxa7	A	G	14: 20,514,977 (GRCm39)	L177P	possibly damaging	Het
Atp11a	A	T	8: 12,856,753 (GRCm39)	N48I	probably damaging	Het
Bcas1	T	A	2: 170,191,316 (GRCm39)	N492I	possibly damaging	Het
Bclaf1	A	G	10: 20,209,278 (GRCm39)	Y498C	probably damaging	Het
Bltp3a	G	A	17: 28,106,489 (GRCm39)	S1005N	probably benign	Het
Bod1l	A	C	5: 41,988,880 (GRCm39)	V409G	probably damaging	Het
Ccdc170	G	A	10: 4,484,188 (GRCm39)	C338Y	probably benign	Het
Cdc45	C	T	16: 18,614,647 (GRCm39)	R205H	probably damaging	Het
Ckap2	A	C	8: 22,667,581 (GRCm39)	N93K	probably damaging	Het
Clca3a1	A	T	3: 144,442,766 (GRCm39)	S759R	possibly damaging	Het
Coro1c	A	T	5: 113,984,226 (GRCm39)	I347N	possibly damaging	Het
Cpox	A	G	16: 58,491,205 (GRCm39)	T139A	probably damaging	Het
Cyp4a12b	C	A	4: 115,290,661 (GRCm39)		probably null	Het
Dctn1	T	G	6: 83,160,108 (GRCm39)	V116G	possibly damaging	Het
Dhx38	A	G	8: 110,282,378 (GRCm39)	V683A	probably damaging	Het
Dnah12	G	A	14: 26,496,299 (GRCm39)		probably null	Het
Dnajb7	T	C	15: 81,292,208 (GRCm39)	E43G	probably damaging	Het
Dsc1	A	T	18: 20,220,632 (GRCm39)	V714E	probably damaging	Het
Dusp29	G	A	14: 21,727,091 (GRCm39)	R186W	probably benign	Het
Egfem1	T	C	3: 29,136,361 (GRCm39)		probably null	Het
Fchsd1	C	T	18: 38,092,926 (GRCm39)		probably benign	Het
Fmo1	T	C	1: 162,657,714 (GRCm39)	T476A	probably benign	Het
Gm10237	T	C	16: 35,741,099 (GRCm39)		noncoding transcript	Het
Gm14496	A	G	2: 181,642,602 (GRCm39)	S758G	probably damaging	Het
Gpat2	T	A	2: 127,270,643 (GRCm39)	L97Q	probably damaging	Het
Gpr162	T	C	6: 124,836,600 (GRCm39)	D357G	probably benign	Het
Hax1	A	T	3: 89,905,262 (GRCm39)	D34E	probably damaging	Het
Hmgcr	C	T	13: 96,791,404 (GRCm39)	V97M	probably benign	Het
Hsd3b2	T	C	3: 98,619,631 (GRCm39)	T105A	probably benign	Het
Ints1	A	G	5: 139,752,183 (GRCm39)		probably null	Het
Islr	T	C	9: 58,064,895 (GRCm39)	E204G	probably damaging	Het
Lrrc36	A	G	8: 106,151,996 (GRCm39)	N60D	probably damaging	Het
Maf1	T	C	15: 76,237,330 (GRCm39)		probably benign	Het
Mrgprb4	T	A	7: 47,848,077 (GRCm39)	R284W	probably benign	Het
Myh4	A	T	11: 67,146,551 (GRCm39)	N1508I	possibly damaging	Het
Nufip2	A	G	11: 77,577,103 (GRCm39)	H17R	unknown	Het
Oasl1	A	T	5: 115,075,055 (GRCm39)	I372L	probably damaging	Het
Or5ae1	T	A	7: 84,565,357 (GRCm39)	Y123*	probably null	Het
Or6p1	T	C	1: 174,258,252 (GRCm39)	L86P	probably damaging	Het
Pald1	A	T	10: 61,184,440 (GRCm39)	Y226N	probably damaging	Het
Pcdhb13	G	T	18: 37,577,844 (GRCm39)	G741C	probably damaging	Het
Pcdhga10	A	G	18: 37,881,259 (GRCm39)	D340G	probably damaging	Het
Pclo	C	A	5: 14,728,822 (GRCm39)		probably benign	Het
Pde10a	C	A	17: 9,180,812 (GRCm39)	R398S	probably damaging	Het
Plin1	T	A	7: 79,375,469 (GRCm39)	T227S	possibly damaging	Het
Pnpt1	A	G	11: 29,104,166 (GRCm39)	D542G	probably damaging	Het
Ppp4r3b	T	A	11: 29,161,646 (GRCm39)	D673E	probably benign	Het
Prr18	C	A	17: 8,559,892 (GRCm39)	P16Q	probably damaging	Het
Psmc3	T	A	2: 90,889,698 (GRCm39)	Y440N	probably damaging	Het
Rassf5	T	C	1: 131,108,385 (GRCm39)	I232V	probably benign	Het
Rims1	T	A	1: 22,577,592 (GRCm39)	D218V	probably damaging	Het
Skint10	T	C	4: 112,568,790 (GRCm39)	N309S	possibly damaging	Het
Slc6a1	T	C	6: 114,279,584 (GRCm39)	M121T	possibly damaging	Het
Slit3	A	G	11: 35,566,740 (GRCm39)	D1004G	probably damaging	Het
Snap91	C	T	9: 86,717,177 (GRCm39)	V215I	possibly damaging	Het
Son	T	C	16: 91,452,627 (GRCm39)	L458S	probably damaging	Het
St18	C	T	1: 6,914,395 (GRCm39)	A782V	probably damaging	Het
Synpo	A	G	18: 60,735,303 (GRCm39)		probably null	Het
Thbs3	A	G	3: 89,128,684 (GRCm39)	D458G	probably damaging	Het
Tpr	C	T	1: 150,321,675 (GRCm39)	R3C	probably damaging	Het
Trp63	A	G	16: 25,503,105 (GRCm39)		probably null	Het
Vmn1r27	C	A	6: 58,192,581 (GRCm39)	R141L	probably benign	Het
Wnk1	T	C	6: 119,945,484 (GRCm39)	I699V	probably benign	Het
Xkr6	A	G	14: 64,056,353 (GRCm39)	D88G	possibly damaging	Het
Zan	A	G	5: 137,379,050 (GRCm39)		probably benign	Het
Zbtb7b	T	C	3: 89,286,913 (GRCm39)		probably benign	Het
Zfp618	A	T	4: 62,998,265 (GRCm39)	D33V	probably damaging	Het

Other mutations in Pcsk4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00161:Pcsk4	APN	10	80,158,657 (GRCm39)	missense	probably damaging	1.00
IGL02818:Pcsk4	APN	10	80,158,626 (GRCm39)	missense	probably damaging	0.98
IGL03115:Pcsk4	APN	10	80,164,883 (GRCm39)	missense	probably damaging	1.00
IGL03354:Pcsk4	APN	10	80,161,893 (GRCm39)	missense	probably damaging	0.99
R0538:Pcsk4	UTSW	10	80,161,168 (GRCm39)	missense	probably damaging	1.00
R0760:Pcsk4	UTSW	10	80,161,775 (GRCm39)	unclassified	probably benign
R1462:Pcsk4	UTSW	10	80,161,815 (GRCm39)	missense	probably damaging	1.00
R1462:Pcsk4	UTSW	10	80,161,815 (GRCm39)	missense	probably damaging	1.00
R1554:Pcsk4	UTSW	10	80,157,785 (GRCm39)	missense	probably benign	0.01
R1728:Pcsk4	UTSW	10	80,159,404 (GRCm39)	missense	probably damaging	0.99
R1784:Pcsk4	UTSW	10	80,159,404 (GRCm39)	missense	probably damaging	0.99
R1886:Pcsk4	UTSW	10	80,164,794 (GRCm39)	missense	probably benign	0.32
R1981:Pcsk4	UTSW	10	80,161,613 (GRCm39)	missense	probably damaging	1.00
R2090:Pcsk4	UTSW	10	80,161,655 (GRCm39)	missense	probably benign	0.02
R2125:Pcsk4	UTSW	10	80,159,713 (GRCm39)	missense	probably benign	0.32
R2283:Pcsk4	UTSW	10	80,158,584 (GRCm39)	missense	probably damaging	1.00
R4183:Pcsk4	UTSW	10	80,160,845 (GRCm39)	missense	probably benign	0.12
R4283:Pcsk4	UTSW	10	80,165,287 (GRCm39)	unclassified	probably benign
R4798:Pcsk4	UTSW	10	80,158,938 (GRCm39)	missense	probably damaging	1.00
R4857:Pcsk4	UTSW	10	80,160,873 (GRCm39)	missense	probably damaging	1.00
R4990:Pcsk4	UTSW	10	80,161,215 (GRCm39)	missense	possibly damaging	0.74
R4991:Pcsk4	UTSW	10	80,161,215 (GRCm39)	missense	possibly damaging	0.74
R5020:Pcsk4	UTSW	10	80,161,869 (GRCm39)	missense	probably benign	0.00
R5123:Pcsk4	UTSW	10	80,157,979 (GRCm39)	missense	probably null	0.56
R6077:Pcsk4	UTSW	10	80,162,073 (GRCm39)	missense	probably damaging	0.99
R6102:Pcsk4	UTSW	10	80,161,651 (GRCm39)	nonsense	probably null
R6250:Pcsk4	UTSW	10	80,161,426 (GRCm39)	missense	probably benign	0.04
R6378:Pcsk4	UTSW	10	80,164,809 (GRCm39)	missense	probably benign	0.34
R6729:Pcsk4	UTSW	10	80,160,935 (GRCm39)	missense	probably damaging	0.99
R7308:Pcsk4	UTSW	10	80,159,007 (GRCm39)	missense	probably benign	0.41
R7595:Pcsk4	UTSW	10	80,157,935 (GRCm39)	missense	possibly damaging	0.84
R8004:Pcsk4	UTSW	10	80,158,674 (GRCm39)	missense	probably damaging	1.00
R8675:Pcsk4	UTSW	10	80,158,896 (GRCm39)	missense	probably damaging	1.00
R8777:Pcsk4	UTSW	10	80,159,557 (GRCm39)	missense	probably benign	0.29
R8777-TAIL:Pcsk4	UTSW	10	80,159,557 (GRCm39)	missense	probably benign	0.29
R9030:Pcsk4	UTSW	10	80,164,858 (GRCm39)	missense	probably damaging	1.00
R9262:Pcsk4	UTSW	10	80,160,864 (GRCm39)	missense	probably damaging	1.00
R9278:Pcsk4	UTSW	10	80,161,224 (GRCm39)	missense	probably damaging	1.00
R9526:Pcsk4	UTSW	10	80,161,800 (GRCm39)	missense	probably damaging	0.96
R9546:Pcsk4	UTSW	10	80,157,741 (GRCm39)	missense	possibly damaging	0.59
R9733:Pcsk4	UTSW	10	80,158,034 (GRCm39)	missense	probably damaging	0.99
Z1176:Pcsk4	UTSW	10	80,158,560 (GRCm39)	missense	possibly damaging	0.94

Predicted Primers

PCR Primer
(F):5'- GCACATTTCTTCTGAGGCTTAG -3'
(R):5'- ATTTCTCCATCTGGGCTGCG -3'

Sequencing Primer
(F):5'- TTAGTGGGCAGCCACACG -3'
(R):5'- ACTGAGCTCAAGGTCCCTCTG -3'

Posted On

2016-08-04