Mutagenetix > Incidental Mutation

Incidental Mutation 'R0538:Pcsk4'

49606

Institutional Source

Beutler Lab

Gene Symbol

Pcsk4

Ensembl Gene

ENSMUSG00000020131

Gene Name

proprotein convertase subtilisin/kexin type 4

Synonyms

PC4, SPC5

MMRRC Submission

038730-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R0538 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

80321283-80329498 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 80325334 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Leucine at position 249 (I249L)

Ref Sequence

ENSEMBL: ENSMUSP00000020340 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000020340] [ENSMUST00000020341] [ENSMUST00000040081] [ENSMUST00000105354] [ENSMUST00000105355] [ENSMUST00000105357] [ENSMUST00000105358] [ENSMUST00000128653] [ENSMUST00000135071] [ENSMUST00000186864]

AlphaFold

P29121

Predicted Effect

probably damaging
Transcript: ENSMUST00000020340
AA Change: I249L

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000020340
Gene: ENSMUSG00000020131
AA Change: I249L

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: ENSMUST00000040081

SMART Domains

Protein: ENSMUSP00000043722
Gene: ENSMUSG00000035504

Domain	Start	End	E-Value	Type
Pfam:TB2_DP1_HVA22	50	118	8e-28	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: 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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000153167

Predicted Effect

probably benign
Transcript: ENSMUST00000186864

SMART Domains

Protein: ENSMUSP00000140840
Gene: ENSMUSG00000035504

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

Meta Mutation Damage Score

0.3193

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.3%
20x: 92.7%

Validation Efficiency

98% (126/129)

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: 129 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930578I07Rik	A	T	14: 66,938,374	H6L	unknown	Het
Abca13	G	A	11: 9,267,622		probably null	Het
Acad12	C	T	5: 121,607,448	R260Q	possibly damaging	Het
Actn1	G	A	12: 80,260,100		probably benign	Het
Acvrl1	A	G	15: 101,136,149	T182A	probably damaging	Het
Adam23	T	C	1: 63,567,844		probably benign	Het
Adamtsl1	A	T	4: 86,343,121	T1190S	probably benign	Het
Adh6b	A	T	3: 138,357,650	Y330F	probably benign	Het
Ak7	A	G	12: 105,766,617	E540G	probably damaging	Het
Akr1c19	T	A	13: 4,237,100	L106Q	probably damaging	Het
Ankrd12	A	T	17: 66,049,852	S57T	probably damaging	Het
Aoc3	G	A	11: 101,332,138	R400Q	possibly damaging	Het
Arel1	A	T	12: 84,941,837	I46N	probably damaging	Het
Armc5	A	G	7: 128,244,291	D752G	probably damaging	Het
Atp11b	T	C	3: 35,837,014	V812A	probably damaging	Het
Axin1	A	G	17: 26,184,241	H131R	possibly damaging	Het
Bpifb3	A	G	2: 153,923,869	E184G	probably benign	Het
Cacna2d2	T	C	9: 107,524,383		probably benign	Het
Catsperd	T	C	17: 56,662,828	F641L	probably benign	Het
Ccdc83	A	C	7: 90,228,383	L284V	probably damaging	Het
Ccnt2	T	A	1: 127,803,165	V593E	probably damaging	Het
Cd53	T	A	3: 106,762,128	I185F	probably benign	Het
Cep350	A	T	1: 155,848,620	D3077E	possibly damaging	Het
Ces1h	C	A	8: 93,357,000		probably null	Het
Chrna3	T	A	9: 55,016,006	T173S	probably benign	Het
Clca4b	T	C	3: 144,921,956	D418G	probably benign	Het
Col11a2	T	C	17: 34,051,328		probably benign	Het
Coq2	T	A	5: 100,668,023	I97F	possibly damaging	Het
Cr2	A	G	1: 195,160,359		probably benign	Het
Ctgf	T	A	10: 24,596,466	C136S	probably damaging	Het
D2hgdh	A	G	1: 93,826,377	Y24C	probably damaging	Het
D630045J12Rik	G	A	6: 38,191,693	R974C	probably damaging	Het
Dach1	A	G	14: 97,903,279	V429A	possibly damaging	Het
Ddr1	G	A	17: 35,685,007	T660I	probably damaging	Het
Dlg1	A	C	16: 31,796,864		probably null	Het
Dmbt1	T	C	7: 131,049,901		probably benign	Het
Dmxl2	A	T	9: 54,393,836	D2330E	probably benign	Het
Doc2a	A	G	7: 126,848,811	T5A	probably benign	Het
Dock2	G	A	11: 34,704,718		probably benign	Het
Dok4	T	A	8: 94,865,238	Y290F	probably damaging	Het
Dopey1	A	G	9: 86,485,497	D11G	probably damaging	Het
E230025N22Rik	T	C	18: 36,688,934	H235R	probably benign	Het
Ear6	A	G	14: 51,854,452	D152G	probably damaging	Het
Ecscr	T	A	18: 35,713,636		probably benign	Het
Eml6	A	T	11: 29,760,010		probably benign	Het
Epha4	T	A	1: 77,388,541	Q607L	probably damaging	Het
Exoc4	A	G	6: 33,972,063	N947S	probably benign	Het
Flg	A	G	3: 93,279,460	E73G	probably damaging	Het
Fndc1	C	T	17: 7,784,341		probably benign	Het
Gad1-ps	T	C	10: 99,444,992		noncoding transcript	Het
Gata6	A	G	18: 11,064,771	T528A	probably benign	Het
Gjd4	T	C	18: 9,280,244	E278G	probably benign	Het
Gm13101	T	A	4: 143,965,083	T357S	possibly damaging	Het
Gm20091	T	A	10: 96,409,002		noncoding transcript	Het
Gnb3	G	A	6: 124,835,696	Q266*	probably null	Het
Grm3	A	G	5: 9,512,446	V468A	possibly damaging	Het
Igf1r	C	T	7: 68,207,826	R1085C	probably damaging	Het
Igsf10	T	C	3: 59,320,106	T2049A	probably damaging	Het
Jak3	A	T	8: 71,685,482	D859V	probably benign	Het
Kcnb2	G	T	1: 15,712,884		probably benign	Het
Kcnh3	G	A	15: 99,240,958	G858D	probably benign	Het
Kif1a	C	A	1: 93,043,638	R1006L	probably damaging	Het
Klhl23	C	T	2: 69,824,413	A209V	probably benign	Het
Mapk13	T	C	17: 28,775,255	Y104H	probably damaging	Het
Mbd4	A	G	6: 115,849,482	S183P	probably damaging	Het
Mga	T	C	2: 119,919,706		probably null	Het
Mipol1	G	A	12: 57,414,411		probably null	Het
Mmp14	A	G	14: 54,438,709	T299A	possibly damaging	Het
Mmrn1	A	G	6: 60,976,469	E578G	probably benign	Het
Mov10l1	G	A	15: 88,994,860	C193Y	possibly damaging	Het
Mppe1	A	G	18: 67,237,477	C50R	probably damaging	Het
Msantd1	C	A	5: 34,917,725	R44S	probably damaging	Het
Myt1l	T	C	12: 29,842,571	V69A	possibly damaging	Het
Nav1	A	T	1: 135,464,692		probably benign	Het
Ncan	A	G	8: 70,108,602	S572P	possibly damaging	Het
Nck2	T	C	1: 43,569,144		probably benign	Het
Nemf	A	T	12: 69,356,314	D31E	probably damaging	Het
Nlrp12	T	C	7: 3,249,262	D93G	possibly damaging	Het
Nsmaf	A	T	4: 6,419,930		probably null	Het
Nup98	T	C	7: 102,186,685	T184A	probably damaging	Het
Olfr1415	A	T	1: 92,491,333	C141S	possibly damaging	Het
Olfr46	A	T	7: 140,610,384	N73Y	probably damaging	Het
Olfr522	A	T	7: 140,162,231	S240T	probably damaging	Het
Oog2	C	A	4: 144,196,084	Y306*	probably null	Het
Osmr	A	G	15: 6,841,938		probably benign	Het
P2rx6	A	G	16: 17,568,298	N275S	probably benign	Het
Papd4	A	T	13: 93,175,615		probably benign	Het
Pbxip1	G	T	3: 89,447,619	G482W	possibly damaging	Het
Pou4f2	C	T	8: 78,435,662	G104E	probably damaging	Het
Prkdc	G	T	16: 15,833,788	R3763L	probably damaging	Het
Ptpre	A	T	7: 135,663,315	I207F	probably damaging	Het
Rapgef3	A	T	15: 97,757,817		probably benign	Het
Rasgrp1	T	G	2: 117,284,947	K685T	probably benign	Het
Rnf148	C	T	6: 23,654,238	R253Q	probably damaging	Het
Rock1	T	C	18: 10,132,227	I241V	possibly damaging	Het
Rp1l1	T	G	14: 64,022,092	V61G	probably damaging	Het
Scin	A	C	12: 40,081,771	S255A	probably damaging	Het
Scn8a	A	T	15: 101,035,624	K1570*	probably null	Het
Sec14l4	A	C	11: 4,040,018	M106L	probably benign	Het
Sec63	G	A	10: 42,798,799	R226H	probably benign	Het
Sept2	T	A	1: 93,501,623	N271K	probably damaging	Het
Serac1	G	T	17: 6,048,826		probably benign	Het
Shc2	T	A	10: 79,630,140		probably benign	Het
Sipa1l1	T	A	12: 82,425,099	D1284E	probably benign	Het
Slc11a2	A	G	15: 100,408,216	L105P	probably damaging	Het
Slc1a3	T	A	15: 8,650,922	T151S	probably benign	Het
Smarca2	G	T	19: 26,691,362	K920N	probably damaging	Het
Sugp2	G	A	8: 70,258,948	E964K	probably damaging	Het
Tas2r122	A	C	6: 132,711,815	N38K	probably benign	Het
Tecpr1	G	A	5: 144,206,274	R730C	probably damaging	Het
Themis3	G	T	17: 66,593,270	N34K	possibly damaging	Het
Traf3ip1	A	G	1: 91,499,619	T104A	unknown	Het
Trappc11	A	G	8: 47,503,412	V843A	probably benign	Het
Trmt61a	T	A	12: 111,678,927	L99Q	probably damaging	Het
Trp53tg5	T	A	2: 164,471,481	K91N	probably damaging	Het
Ufsp2	T	C	8: 45,992,150	S339P	probably damaging	Het
Usp20	T	A	2: 31,004,450	V126E	probably damaging	Het
Vmn1r75	T	A	7: 11,880,870	N176K	probably damaging	Het
Vmn2r24	A	G	6: 123,816,053	S780G	probably benign	Het
Vmn2r89	A	G	14: 51,457,591		probably null	Het
Vps13d	A	T	4: 145,045,095	S4038T	probably damaging	Het
Vwa7	A	G	17: 35,022,651	T421A	probably damaging	Het
Wdr78	T	C	4: 103,096,618	N128S	possibly damaging	Het
Wdr95	C	A	5: 149,580,806	L332I	probably damaging	Het
Wrn	T	A	8: 33,336,091	K181I	probably damaging	Het
Zc3h6	T	A	2: 129,017,223	I1058N	possibly damaging	Het
Zfp423	T	A	8: 87,782,085	I544F	probably damaging	Het
Zfp446	T	A	7: 12,979,589	S161T	possibly damaging	Het
Zmym6	T	A	4: 127,123,369	M889K	probably benign	Het

Other mutations in Pcsk4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00161:Pcsk4	APN	10	80322823	missense	probably damaging	1.00
IGL02818:Pcsk4	APN	10	80322792	missense	probably damaging	0.98
IGL03115:Pcsk4	APN	10	80329049	missense	probably damaging	1.00
IGL03354:Pcsk4	APN	10	80326059	missense	probably damaging	0.99
R0760:Pcsk4	UTSW	10	80325941	unclassified	probably benign
R1462:Pcsk4	UTSW	10	80325981	missense	probably damaging	1.00
R1462:Pcsk4	UTSW	10	80325981	missense	probably damaging	1.00
R1554:Pcsk4	UTSW	10	80321951	missense	probably benign	0.01
R1728:Pcsk4	UTSW	10	80323570	missense	probably damaging	0.99
R1784:Pcsk4	UTSW	10	80323570	missense	probably damaging	0.99
R1886:Pcsk4	UTSW	10	80328960	missense	probably benign	0.32
R1981:Pcsk4	UTSW	10	80325779	missense	probably damaging	1.00
R2090:Pcsk4	UTSW	10	80325821	missense	probably benign	0.02
R2125:Pcsk4	UTSW	10	80323879	missense	probably benign	0.32
R2283:Pcsk4	UTSW	10	80322750	missense	probably damaging	1.00
R4183:Pcsk4	UTSW	10	80325011	missense	probably benign	0.12
R4283:Pcsk4	UTSW	10	80329453	unclassified	probably benign
R4798:Pcsk4	UTSW	10	80323104	missense	probably damaging	1.00
R4857:Pcsk4	UTSW	10	80325039	missense	probably damaging	1.00
R4990:Pcsk4	UTSW	10	80325381	missense	possibly damaging	0.74
R4991:Pcsk4	UTSW	10	80325381	missense	possibly damaging	0.74
R5020:Pcsk4	UTSW	10	80326035	missense	probably benign	0.00
R5123:Pcsk4	UTSW	10	80322145	missense	probably null	0.56
R5354:Pcsk4	UTSW	10	80323689	missense	probably damaging	0.98
R6077:Pcsk4	UTSW	10	80326239	missense	probably damaging	0.99
R6102:Pcsk4	UTSW	10	80325817	nonsense	probably null
R6250:Pcsk4	UTSW	10	80325592	missense	probably benign	0.04
R6378:Pcsk4	UTSW	10	80328975	missense	probably benign	0.34
R6729:Pcsk4	UTSW	10	80325101	missense	probably damaging	0.99
R7308:Pcsk4	UTSW	10	80323173	missense	probably benign	0.41
R7595:Pcsk4	UTSW	10	80322101	missense	possibly damaging	0.84
R8004:Pcsk4	UTSW	10	80322840	missense	probably damaging	1.00
R8675:Pcsk4	UTSW	10	80323062	missense	probably damaging	1.00
R8777:Pcsk4	UTSW	10	80323723	missense	probably benign	0.29
R8777-TAIL:Pcsk4	UTSW	10	80323723	missense	probably benign	0.29
R9030:Pcsk4	UTSW	10	80329024	missense	probably damaging	1.00
R9262:Pcsk4	UTSW	10	80325030	missense	probably damaging	1.00
R9278:Pcsk4	UTSW	10	80325390	missense	probably damaging	1.00
R9526:Pcsk4	UTSW	10	80325966	missense	probably damaging	0.96
R9546:Pcsk4	UTSW	10	80321907	missense	possibly damaging	0.59
R9733:Pcsk4	UTSW	10	80322200	missense	probably damaging	0.99
Z1176:Pcsk4	UTSW	10	80322726	missense	possibly damaging	0.94

Predicted Primers

PCR Primer
(F):5'- TGACCCGAGAGAACAGAGTCAGTC -3'
(R):5'- AGGTGTCTGCCACAGCTAACAAC -3'

Sequencing Primer
(F):5'- GAGAACAGAGTCAGTCCTCCAAC -3'
(R):5'- CAGCTAACAACGGTTTCTGTG -3'

Posted On

2013-06-12