Mutagenetix > Incidental Mutation

Incidental Mutation 'R9733:Pcsk4'

731562

Institutional Source

Beutler Lab

Gene Symbol

Pcsk4

Ensembl Gene

ENSMUSG00000020131

Gene Name

proprotein convertase subtilisin/kexin type 4

Synonyms

PC4, SPC5

MMRRC Submission

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R9733 (G1)

Quality Score

183.009

Status

Not validated

Chromosome

Chromosomal Location

80157117-80165332 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 80158034 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Cysteine at position 568 (Y568C)

Ref Sequence

ENSEMBL: ENSMUSP00000020340 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000020340] [ENSMUST00000020341] [ENSMUST00000020349] [ENSMUST00000105359] [ENSMUST00000128653] [ENSMUST00000135071]

AlphaFold

P29121

Predicted Effect

probably damaging
Transcript: ENSMUST00000020340
AA Change: Y568C

PolyPhen 2 Score 0.985 (Sensitivity: 0.74; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000020340
Gene: ENSMUSG00000020131
AA Change: Y568C

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: ENSMUST00000020349

SMART Domains

Protein: ENSMUSP00000020349
Gene: ENSMUSG00000020135

Domain	Start	End	E-Value	Type
PDB:1DEB\|B	4	57	9e-17	PDB
Pfam:Suppressor_APC	123	205	1.3e-28	PFAM
coiled coil region	214	236	N/A	INTRINSIC
low complexity region	242	261	N/A	INTRINSIC
ARM	300	355	2.95e0	SMART
ARM	417	468	2.22e-2	SMART
ARM	470	511	3.22e0	SMART
ARM	513	555	3.56e-1	SMART
ARM	557	602	2.1e1	SMART
ARM	607	647	1.82e-7	SMART
Blast:ARM	649	689	6e-18	BLAST
low complexity region	772	792	N/A	INTRINSIC
low complexity region	817	844	N/A	INTRINSIC
low complexity region	859	870	N/A	INTRINSIC
low complexity region	971	980	N/A	INTRINSIC
low complexity region	1057	1069	N/A	INTRINSIC
low complexity region	1087	1103	N/A	INTRINSIC
Pfam:APC_crr	1134	1159	4.4e-9	PFAM
low complexity region	1197	1208	N/A	INTRINSIC
Pfam:APC_crr	1244	1269	4.1e-8	PFAM
Pfam:SAMP	1323	1343	2.1e-10	PFAM
Pfam:APC_crr	1369	1394	5.8e-8	PFAM
low complexity region	1500	1516	N/A	INTRINSIC
Pfam:APC_crr	1540	1565	5.7e-8	PFAM
Pfam:SAMP	1594	1613	8.8e-11	PFAM
low complexity region	1673	1699	N/A	INTRINSIC
Pfam:APC_basic	1757	2093	1.1e-142	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000105359

SMART Domains

Protein: ENSMUSP00000100996
Gene: ENSMUSG00000020135

Domain	Start	End	E-Value	Type
signal peptide	1	19	N/A	INTRINSIC
Pfam:APC_N_CC	30	81	2.7e-34	PFAM
Pfam:Suppressor_APC	148	228	1.4e-27	PFAM
coiled coil region	238	260	N/A	INTRINSIC
low complexity region	266	285	N/A	INTRINSIC
ARM	324	379	2.95e0	SMART
ARM	446	497	2.22e-2	SMART
ARM	499	540	3.22e0	SMART
ARM	542	584	3.56e-1	SMART
ARM	586	631	2.1e1	SMART
ARM	636	676	1.82e-7	SMART
Blast:ARM	678	718	6e-18	BLAST
Pfam:Arm_APC_u3	719	977	1.1e-26	PFAM
low complexity region	1000	1009	N/A	INTRINSIC
low complexity region	1086	1098	N/A	INTRINSIC
low complexity region	1116	1132	N/A	INTRINSIC
Pfam:APC_crr	1164	1187	9.3e-8	PFAM
low complexity region	1226	1237	N/A	INTRINSIC
Pfam:APC_crr	1274	1297	7.9e-10	PFAM
Pfam:APC_crr	1399	1423	1.3e-9	PFAM
low complexity region	1529	1545	N/A	INTRINSIC
low complexity region	1585	1603	N/A	INTRINSIC
Pfam:SAMP	1624	1642	1.3e-11	PFAM
low complexity region	1702	1728	N/A	INTRINSIC
Pfam:APC_basic	1786	2122	1.3e-122	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

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

Coding Region Coverage

1x: 99.9%
3x: 99.7%
10x: 99.3%
20x: 98.3%

Validation Efficiency

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: 76 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2610042L04Rik	C	T	14: 15,712,825 (GRCm39)		probably benign	Het
4930595D18Rik	T	A	12: 111,128,254 (GRCm39)		probably benign	Het
Adam34l	T	C	8: 44,079,186 (GRCm39)	N346S	possibly damaging	Het
Alpi	C	T	1: 87,028,516 (GRCm39)	A125T	probably benign	Het
Alppl2	T	A	1: 87,014,957 (GRCm39)	H468L	probably damaging	Het
Arhgef12	A	T	9: 42,901,294 (GRCm39)	L836*	probably null	Het
Arv1	T	C	8: 125,458,658 (GRCm39)	Y261H	probably damaging	Het
Atf6	C	T	1: 170,662,402 (GRCm39)	S286N	probably benign	Het
Atl3	G	A	19: 7,509,705 (GRCm39)	G478R	probably damaging	Het
Avil	C	T	10: 126,843,711 (GRCm39)	R184C	probably damaging	Het
Bcl6b	A	G	11: 70,119,323 (GRCm39)	I131T	probably damaging	Het
Bltp1	T	A	3: 37,102,732 (GRCm39)	M1437K		Het
Catsper3	T	C	13: 55,946,752 (GRCm39)	S150P	probably damaging	Het
Cd7	A	G	11: 120,928,637 (GRCm39)	S132P	probably benign	Het
Cfh	T	C	1: 140,016,533 (GRCm39)	D1142G	probably damaging	Het
Clca4b	T	G	3: 144,621,272 (GRCm39)	K601Q	probably benign	Het
Cp	A	G	3: 20,033,126 (GRCm39)	H651R	probably damaging	Het
Cyp2s1	T	A	7: 25,507,529 (GRCm39)	T307S	probably damaging	Het
Dcaf11	A	G	14: 55,803,170 (GRCm39)	D328G	probably damaging	Het
Eapp	A	T	12: 54,739,741 (GRCm39)	S25R	probably damaging	Het
Ebag9	T	A	15: 44,491,033 (GRCm39)		probably null	Het
Exog	G	A	9: 119,291,586 (GRCm39)	E288K	possibly damaging	Het
Fads2	A	T	19: 10,047,940 (GRCm39)	Y265N	probably damaging	Het
Fam234b	T	A	6: 135,194,008 (GRCm39)	S220R	possibly damaging	Het
Fcgbp	T	A	7: 27,803,012 (GRCm39)	C1539S	probably damaging	Het
Fcsk	T	C	8: 111,615,563 (GRCm39)	T589A	probably benign	Het
Fv1	C	T	4: 147,954,621 (GRCm39)	R396W	probably damaging	Het
Fv1	T	C	4: 147,954,654 (GRCm39)	F407L	probably benign	Het
Glp2r	T	C	11: 67,648,367 (GRCm39)	T112A	probably benign	Het
Hydin	T	C	8: 111,262,011 (GRCm39)	I2704T	probably benign	Het
Ighm	T	A	12: 113,386,097 (GRCm39)	E84D	probably benign	Het
Ikzf5	A	G	7: 130,994,012 (GRCm39)	V205A	probably benign	Het
Kcnt1	G	T	2: 25,797,351 (GRCm39)	V844L	probably benign	Het
Kif2a	A	C	13: 107,106,304 (GRCm39)	S528R	probably damaging	Het
Klhl29	G	A	12: 5,190,641 (GRCm39)	T118M	probably damaging	Het
Krt4	C	A	15: 101,827,564 (GRCm39)	G492C	unknown	Het
Lama1	T	A	17: 68,116,940 (GRCm39)	I2441N		Het
Lin7a	T	C	10: 107,247,905 (GRCm39)	V192A	possibly damaging	Het
Marchf8	T	A	6: 116,378,990 (GRCm39)	V308D	probably damaging	Het
Mgat5b	T	C	11: 116,838,074 (GRCm39)	S238P	possibly damaging	Het
Mrps25	A	G	6: 92,155,715 (GRCm39)	S73P	probably damaging	Het
Muc6	G	T	7: 141,216,310 (GRCm39)	P2788T	unknown	Het
Ncf1	T	C	5: 134,250,899 (GRCm39)	T347A	probably benign	Het
Ndufaf4	T	C	4: 24,903,177 (GRCm39)	M122T	probably benign	Het
Nfil3	C	T	13: 53,121,591 (GRCm39)	A438T	probably damaging	Het
Noc2l	T	G	4: 156,328,022 (GRCm39)	I504S	probably damaging	Het
Nphs1	T	C	7: 30,166,955 (GRCm39)	C735R	probably damaging	Het
Or10g6	A	T	9: 39,934,171 (GRCm39)	S161C	probably benign	Het
Or2y10	T	C	11: 49,454,961 (GRCm39)	L71P	probably damaging	Het
Or5d38	C	A	2: 87,955,000 (GRCm39)	V110L	probably damaging	Het
Or6b9	A	C	7: 106,555,846 (GRCm39)	L99R	possibly damaging	Het
Pcdhac1	A	G	18: 37,225,506 (GRCm39)	H773R	probably benign	Het
Pcnt	A	G	10: 76,237,314 (GRCm39)	V1324A	probably benign	Het
Pdlim1	A	T	19: 40,219,040 (GRCm39)	M197K	probably damaging	Het
Plekho1	C	T	3: 95,903,091 (GRCm39)	G7S	probably benign	Het
Pramel17	A	G	4: 101,692,965 (GRCm39)	V345A	possibly damaging	Het
Prl7d1	A	C	13: 27,898,339 (GRCm39)	S57A	probably benign	Het
Prpf3	A	G	3: 95,741,512 (GRCm39)	V548A	possibly damaging	Het
Prss56	C	T	1: 87,111,219 (GRCm39)	P2L	possibly damaging	Het
Ric1	A	G	19: 29,580,030 (GRCm39)	D1277G	possibly damaging	Het
Rnf19b	T	A	4: 128,977,812 (GRCm39)	D676E	probably damaging	Het
Rph3a	T	A	5: 121,100,521 (GRCm39)	T126S	probably benign	Het
Sh3gl3	T	C	7: 81,917,562 (GRCm39)		probably null	Het
Slc14a1	C	A	18: 78,152,807 (GRCm39)	A367S	probably damaging	Het
Slc35f2	T	C	9: 53,708,385 (GRCm39)	V126A	probably benign	Het
Snrnp200	A	T	2: 127,068,240 (GRCm39)	Q860L	probably damaging	Het
Srbd1	T	C	17: 86,422,711 (GRCm39)	N435S	probably damaging	Het
Tab2	A	G	10: 7,795,214 (GRCm39)	S349P	possibly damaging	Het
Tie1	A	T	4: 118,330,183 (GRCm39)	W1040R	probably null	Het
Tnni3k	A	T	3: 154,562,244 (GRCm39)	Y678N	probably damaging	Het
Trav12-3	T	C	14: 53,859,474 (GRCm39)	V40A	possibly damaging	Het
Ttn	G	A	2: 76,576,379 (GRCm39)	S24838L	probably damaging	Het
Ttn	A	G	2: 76,725,660 (GRCm39)	W6158R	unknown	Het
Vegfa	T	C	17: 46,335,401 (GRCm39)	S298G	probably damaging	Het
Zer1	T	C	2: 29,997,643 (GRCm39)	K421R	probably benign	Het
Zfp959	C	A	17: 56,204,866 (GRCm39)	T301N	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
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
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
Z1176:Pcsk4	UTSW	10	80,158,560 (GRCm39)	missense	possibly damaging	0.94

Predicted Primers

PCR Primer
(F):5'- TCTGCATAGGGACAACATGG -3'
(R):5'- TGACCAGTGCAAACCAGGTG -3'

Sequencing Primer
(F):5'- AGTGAGGCTGCAGCTGG -3'
(R):5'- TGCCACCTACCTGGGAGATG -3'

Posted On

2022-11-14