Mutagenetix > Incidental Mutation

Incidental Mutation 'R4857:Pcsk4'

374073

Institutional Source

Beutler Lab

Gene Symbol

Pcsk4

Ensembl Gene

ENSMUSG00000020131

Gene Name

proprotein convertase subtilisin/kexin type 4

Synonyms

PC4, SPC5

MMRRC Submission

042468-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R4857 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

80157117-80165332 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 80160873 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 318 (S318P)

Ref Sequence

ENSEMBL: ENSMUSP00000020340 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000020340] [ENSMUST00000020341] [ENSMUST00000105354] [ENSMUST00000105355] [ENSMUST00000105357] [ENSMUST00000105358] [ENSMUST00000128653] [ENSMUST00000135071]

AlphaFold

P29121

Predicted Effect

probably damaging
Transcript: ENSMUST00000020340
AA Change: S318P

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

SMART Domains

Protein: ENSMUSP00000020340
Gene: ENSMUSG00000020131
AA Change: S318P

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: ENSMUST00000105354

SMART Domains

Protein: ENSMUSP00000100991
Gene: ENSMUSG00000035504

Domain	Start	End	E-Value	Type
Pfam:TB2_DP1_HVA22	50	144	5e-36	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000105355

SMART Domains

Protein: ENSMUSP00000100992
Gene: ENSMUSG00000035504

Domain	Start	End	E-Value	Type
Pfam:TB2_DP1_HVA22	50	144	3.4e-36	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000105357

SMART Domains

Protein: ENSMUSP00000100994
Gene: ENSMUSG00000035504

Domain	Start	End	E-Value	Type
low complexity region	22	61	N/A	INTRINSIC
low complexity region	108	129	N/A	INTRINSIC
low complexity region	297	319	N/A	INTRINSIC
low complexity region	340	352	N/A	INTRINSIC
low complexity region	411	428	N/A	INTRINSIC
SCOP:d1gkub1	434	465	1e-3	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000105358

SMART Domains

Protein: ENSMUSP00000100995
Gene: ENSMUSG00000035504

Domain	Start	End	E-Value	Type
low complexity region	22	61	N/A	INTRINSIC
low complexity region	108	129	N/A	INTRINSIC
low complexity region	324	346	N/A	INTRINSIC
low complexity region	367	379	N/A	INTRINSIC
low complexity region	438	455	N/A	INTRINSIC
SCOP:d1gkub1	461	492	8e-4	SMART

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: ENSMUST00000147132

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000130521

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000137177

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

Meta Mutation Damage Score

0.5738

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.3%
20x: 92.3%

Validation Efficiency

97% (115/119)

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: 101 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930548G14Rik	C	T	15: 46,488,927 (GRCm39)		noncoding transcript	Het
Aasdh	A	T	5: 77,035,131 (GRCm39)	F428L	probably benign	Het
Abca13	A	G	11: 9,244,143 (GRCm39)	N2002S	probably benign	Het
Acot7	T	G	4: 152,322,211 (GRCm39)	F248V	possibly damaging	Het
Acsf2	A	G	11: 94,460,164 (GRCm39)	I396T	probably benign	Het
Agbl1	A	G	7: 76,069,583 (GRCm39)	N372D	probably benign	Het
Ahctf1	A	T	1: 179,626,922 (GRCm39)		probably benign	Het
Akap11	T	C	14: 78,736,300 (GRCm39)	D1830G		Het
Bcl7b	A	G	5: 135,202,033 (GRCm39)	*59W	probably null	Het
Bdh1	A	G	16: 31,266,366 (GRCm39)		probably null	Het
Bin3	A	G	14: 70,366,344 (GRCm39)	N69S	probably benign	Het
Bltp3b	A	T	10: 89,615,825 (GRCm39)	N156I	probably damaging	Het
Bsdc1	T	C	4: 129,365,685 (GRCm39)		probably benign	Het
Cacna1i	T	C	15: 80,253,863 (GRCm39)	V700A	probably damaging	Het
Calcr	T	C	6: 3,708,511 (GRCm39)	N225S	probably benign	Het
Cby2	C	T	14: 75,830,478 (GRCm39)	E8K	probably damaging	Het
Cdh23	A	G	10: 60,227,563 (GRCm39)	S1173P	probably damaging	Het
Cftr	C	T	6: 18,320,974 (GRCm39)	T1428M	possibly damaging	Het
Chd1l	T	C	3: 97,479,975 (GRCm39)	K591E	probably benign	Het
Chrd	C	T	16: 20,557,508 (GRCm39)	P709L	possibly damaging	Het
Ckap4	T	C	10: 84,369,352 (GRCm39)	R127G	possibly damaging	Het
Cnbd2	T	C	2: 156,209,485 (GRCm39)	F476S	probably benign	Het
Dclk3	T	C	9: 111,297,716 (GRCm39)	V420A	probably benign	Het
Dnah5	A	G	15: 28,345,953 (GRCm39)	D2431G	probably benign	Het
Duox1	T	A	2: 122,146,212 (GRCm39)	I10N	probably benign	Het
Ece2	T	A	16: 20,436,556 (GRCm39)	V126D	probably damaging	Het
Elfn1	T	C	5: 139,958,840 (GRCm39)	Y615H	probably damaging	Het
Epha1	T	C	6: 42,338,416 (GRCm39)	D720G	probably benign	Het
Fras1	A	G	5: 96,926,018 (GRCm39)	I3741V	probably benign	Het
Gm53	A	T	11: 96,142,562 (GRCm39)		noncoding transcript	Het
Grb10	G	T	11: 11,901,469 (GRCm39)		probably benign	Het
Grid2ip	A	G	5: 143,368,384 (GRCm39)	H568R	probably damaging	Het
Gsap	A	T	5: 21,492,797 (GRCm39)		probably null	Het
Gse1	T	C	8: 121,299,496 (GRCm39)		probably benign	Het
Gstm1	T	C	3: 107,923,724 (GRCm39)	R94G	possibly damaging	Het
Gtf2ird1	A	G	5: 134,391,398 (GRCm39)	F866L	probably damaging	Het
Haao	T	A	17: 84,146,009 (GRCm39)		probably null	Het
Hcn4	A	T	9: 58,766,853 (GRCm39)	I805F	unknown	Het
Hemk1	A	T	9: 107,206,647 (GRCm39)		probably benign	Het
Il12rb1	A	T	8: 71,263,232 (GRCm39)	Y33F	possibly damaging	Het
Il19	T	A	1: 130,863,683 (GRCm39)	I103F	probably damaging	Het
Itpr1	A	G	6: 108,387,828 (GRCm39)	N1522S	probably benign	Het
Klhdc8a	A	G	1: 132,230,843 (GRCm39)	Y236C	probably damaging	Het
Klhl3	C	T	13: 58,166,620 (GRCm39)	G404S	probably damaging	Het
Large2	T	C	2: 92,196,979 (GRCm39)		probably benign	Het
Lgi1	C	A	19: 38,294,698 (GRCm39)	A490E	probably damaging	Het
Lmbr1	A	G	5: 29,528,807 (GRCm39)	L112P	probably damaging	Het
Lmo7	T	A	14: 102,124,784 (GRCm39)		probably null	Het
Lpin1	A	C	12: 16,613,631 (GRCm39)	I479S	possibly damaging	Het
Lrrc40	T	A	3: 157,771,866 (GRCm39)		probably benign	Het
Lrrc9	A	G	12: 72,546,466 (GRCm39)	N1218S	possibly damaging	Het
Map3k9	A	G	12: 81,771,401 (GRCm39)	V729A	probably benign	Het
Marf1	A	T	16: 13,946,475 (GRCm39)	Y1215*	probably null	Het
Moap1	T	A	12: 102,708,824 (GRCm39)	I242L	probably benign	Het
Mpo	A	G	11: 87,687,107 (GRCm39)	K218E	probably benign	Het
Mpz	C	T	1: 170,986,379 (GRCm39)	R98C	probably damaging	Het
Neb	T	G	2: 52,091,992 (GRCm39)	K5024T	probably damaging	Het
Nlrp4b	C	T	7: 10,449,225 (GRCm39)	T109I	probably benign	Het
Noc3l	T	A	19: 38,781,244 (GRCm39)		probably null	Het
Nosip	G	A	7: 44,726,102 (GRCm39)	V220I	probably benign	Het
Nyap1	A	C	5: 137,733,840 (GRCm39)	S398A	probably damaging	Het
Or12d17	A	G	17: 37,777,714 (GRCm39)	M206V	possibly damaging	Het
Or4a68	T	G	2: 89,269,967 (GRCm39)	I219L	probably damaging	Het
Or4f54	A	G	2: 111,123,488 (GRCm39)	N292D	possibly damaging	Het
Osbpl7	T	C	11: 96,947,495 (GRCm39)		probably benign	Het
Pard3	A	T	8: 128,050,535 (GRCm39)	Y199F	probably damaging	Het
Pcdha11	G	A	18: 37,144,505 (GRCm39)	V199I	probably benign	Het
Pcdhga8	A	T	18: 37,859,967 (GRCm39)	N341I	probably damaging	Het
Phldb1	C	A	9: 44,607,389 (GRCm39)	R1272L	probably damaging	Het
Phlpp2	A	G	8: 110,603,642 (GRCm39)	T103A	probably damaging	Het
Pibf1	T	A	14: 99,423,937 (GRCm39)	Y503*	probably null	Het
Pkn1	A	T	8: 84,410,856 (GRCm39)		probably null	Het
Pramel22	A	T	4: 143,383,158 (GRCm39)	N20K	possibly damaging	Het
Ptprf	A	G	4: 118,074,394 (GRCm39)		probably benign	Het
Rbm19	C	A	5: 120,270,898 (GRCm39)		probably benign	Het
Rcan1	T	C	16: 92,262,794 (GRCm39)	D5G	possibly damaging	Het
Recql5	A	T	11: 115,819,038 (GRCm39)	L176Q	probably damaging	Het
Rev3l	T	A	10: 39,714,455 (GRCm39)	L2393Q	probably damaging	Het
Rp1	C	A	1: 4,422,539 (GRCm39)	K180N	probably damaging	Het
Rp1	T	A	1: 4,422,540 (GRCm39)	K180M	probably damaging	Het
Sdk1	T	C	5: 142,147,531 (GRCm39)	V1461A	probably benign	Het
Sdk2	A	T	11: 113,712,208 (GRCm39)	L1653*	probably null	Het
Shroom3	G	T	5: 93,090,945 (GRCm39)	V1151F	probably damaging	Het
Skint10	A	T	4: 112,603,830 (GRCm39)	V119D	possibly damaging	Het
Sncaip	T	C	18: 53,002,297 (GRCm39)	S273P	probably benign	Het
Sp1	T	G	15: 102,339,409 (GRCm39)	I449S	probably damaging	Het
Spata31h1	T	C	10: 82,119,682 (GRCm39)	T4443A	possibly damaging	Het
Spats2	T	C	15: 99,072,301 (GRCm39)	L78P	probably damaging	Het
Stambp	T	A	6: 83,533,348 (GRCm39)	N305I	probably benign	Het
Stim2	A	T	5: 54,275,888 (GRCm39)	S688C	probably damaging	Het
Sytl3	A	G	17: 7,003,980 (GRCm39)	N355S	probably damaging	Het
Taf4b	C	T	18: 14,937,635 (GRCm39)	A236V	probably null	Het
Tnfaip6	A	G	2: 51,941,086 (GRCm39)		probably null	Het
Trpc2	T	A	7: 101,733,176 (GRCm39)	S416T	probably benign	Het
Ttn	T	C	2: 76,569,210 (GRCm39)	T27228A	probably damaging	Het
Ush2a	T	A	1: 188,269,917 (GRCm39)	D1721E	probably benign	Het
Usp47	T	A	7: 111,681,759 (GRCm39)	H523Q	probably damaging	Het
Vmn1r8	A	T	6: 57,013,338 (GRCm39)	I130F	probably benign	Het
Vps13b	A	G	15: 35,456,800 (GRCm39)	S749G	probably benign	Het
Xrcc5	C	A	1: 72,365,424 (GRCm39)	T283K	possibly damaging	Het
Ydjc	A	G	16: 16,966,002 (GRCm39)		probably benign	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
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
R5354:Pcsk4	UTSW	10	80,159,523 (GRCm39)	missense	probably damaging	0.98
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'- TCTTCAGAGAGCCTCCATGTG -3'
(R):5'- TAACCAAGGTGACCAGGAAC -3'

Sequencing Primer
(F):5'- TGGCACAGATCTTGCCCGAG -3'
(R):5'- AGGAACCACACCCTGGG -3'

Posted On

2016-03-01