Mutagenetix > Incidental Mutation

Incidental Mutation 'R9262:Pcsk4'

702327

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 #

R9262 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

80157117-80165332 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 80160864 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Cysteine at position 321 (S321C)

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: S321C

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

SMART Domains

Protein: ENSMUSP00000020340
Gene: ENSMUSG00000020131
AA Change: S321C

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

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: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.6%

Validation Efficiency

97% (73/75)

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: 75 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4933409G03Rik	A	T	2: 68,443,375 (GRCm39)	H192L	unknown	Het
Abca4	T	A	3: 121,964,639 (GRCm39)	C2149S	probably damaging	Het
Abl2	G	A	1: 156,469,820 (GRCm39)	G1028D	possibly damaging	Het
Adgre1	A	G	17: 57,754,941 (GRCm39)	T680A	probably damaging	Het
Amn	G	A	12: 111,237,585 (GRCm39)	W10*	probably null	Het
Ankhd1	G	T	18: 36,765,799 (GRCm39)	V140F		Het
Asnsd1	A	T	1: 53,383,934 (GRCm39)	N613K	probably benign	Het
Bbs2	A	T	8: 94,807,543 (GRCm39)	I417N	probably damaging	Het
Cad	T	A	5: 31,225,009 (GRCm39)	W971R	probably null	Het
Cand2	A	T	6: 115,759,730 (GRCm39)	I134F	probably benign	Het
Ccdc154	C	A	17: 25,389,160 (GRCm39)	H453N	probably damaging	Het
Ccdc168	A	G	1: 44,096,269 (GRCm39)	S1610P	possibly damaging	Het
Ccdc7a	T	A	8: 129,486,277 (GRCm39)	H1601L	possibly damaging	Het
Ccdc9	A	C	7: 16,012,400 (GRCm39)	S261A	probably benign	Het
Cdkl3	T	A	11: 51,916,702 (GRCm39)	S277T	probably benign	Het
Cipc	T	A	12: 86,999,497 (GRCm39)	Y8*	probably null	Het
Cramp1	A	G	17: 25,232,920 (GRCm39)	S27P	probably damaging	Het
Csf1r	A	T	18: 61,243,406 (GRCm39)	M141L	probably benign	Het
Csf2rb2	G	T	15: 78,168,535 (GRCm39)	F873L	probably damaging	Het
Dchs1	G	A	7: 105,404,833 (GRCm39)	R2570W	probably damaging	Het
Dmxl1	A	T	18: 49,976,919 (GRCm39)	N94Y	probably benign	Het
Dnajc10	A	G	2: 80,176,965 (GRCm39)	K640R	probably benign	Het
Epha8	A	C	4: 136,658,995 (GRCm39)	H886Q	probably benign	Het
Fcgbp	G	C	7: 27,819,952 (GRCm39)	D2560H	probably damaging	Het
Fry	T	G	5: 150,305,109 (GRCm39)	F605V	probably damaging	Het
Fsip2	A	G	2: 82,807,662 (GRCm39)	N1327S	probably benign	Het
Gm12117	T	C	11: 33,226,001 (GRCm39)	T112A	probably benign	Het
Gm3604	A	T	13: 62,517,697 (GRCm39)	N220K	probably damaging	Het
Gm572	T	C	4: 148,735,652 (GRCm39)	V27A	probably benign	Het
Gpr39	A	G	1: 125,800,524 (GRCm39)	K425R	probably benign	Het
Heatr3	A	G	8: 88,883,097 (GRCm39)	D349G	probably benign	Het
Hip1	A	G	5: 135,478,541 (GRCm39)	S248P	probably damaging	Het
Itga11	A	G	9: 62,659,678 (GRCm39)		probably benign	Het
Itga3	C	T	11: 94,956,625 (GRCm39)	V210I	probably benign	Het
Jmjd1c	T	C	10: 67,083,793 (GRCm39)	I2173T	probably benign	Het
Klf13	G	A	7: 63,574,456 (GRCm39)	Q21*	probably null	Het
Kmt2a	A	T	9: 44,731,222 (GRCm39)	S3032T	probably benign	Het
Krt34	T	C	11: 99,930,851 (GRCm39)	R184G	probably benign	Het
Krtap16-1	T	C	11: 99,876,994 (GRCm39)	T137A	probably benign	Het
Ldc1	A	G	4: 130,114,153 (GRCm39)	V88A	possibly damaging	Het
Mgam	T	C	6: 40,723,422 (GRCm39)		probably null	Het
Mog	T	C	17: 37,325,648 (GRCm39)	T196A	possibly damaging	Het
Ms4a6d	T	C	19: 11,579,216 (GRCm39)	Y87C	possibly damaging	Het
Ndrg4	C	T	8: 96,435,812 (GRCm39)		probably benign	Het
Nsd1	T	A	13: 55,394,871 (GRCm39)	M927K	possibly damaging	Het
Or11l3	T	A	11: 58,516,282 (GRCm39)	M197L	probably benign	Het
Or4a73	G	T	2: 89,421,435 (GRCm39)	T8K	probably damaging	Het
Ovgp1	T	C	3: 105,893,883 (GRCm39)		probably benign	Het
Pcdhac2	A	G	18: 37,279,095 (GRCm39)	R692G	possibly damaging	Het
Pi4ka	A	G	16: 17,120,859 (GRCm39)	F1292L		Het
Pigv	G	T	4: 133,397,110 (GRCm39)	P6Q	possibly damaging	Het
Pkhd1	A	C	1: 20,618,351 (GRCm39)	S927A	probably benign	Het
Pnpla3	A	T	15: 84,055,363 (GRCm39)	I90F	probably benign	Het
Pole	C	A	5: 110,473,422 (GRCm39)	L1739I	probably damaging	Het
Pole	T	A	5: 110,473,423 (GRCm39)	L1739H	probably damaging	Het
Rbm12	A	T	2: 155,939,317 (GRCm39)	N318K	possibly damaging	Het
Rpl18a	A	T	8: 71,348,179 (GRCm39)	L168Q	probably benign	Het
Ryr2	T	C	13: 11,765,854 (GRCm39)	N1294S	probably damaging	Het
Sema5b	T	C	16: 35,453,223 (GRCm39)	L98P	possibly damaging	Het
Slco1a8	G	T	6: 141,926,594 (GRCm39)	F597L	probably damaging	Het
Smg7	A	G	1: 152,721,262 (GRCm39)	V650A	probably damaging	Het
Spata31d1e	T	C	13: 59,890,402 (GRCm39)	M473V	probably benign	Het
Strada	C	T	11: 106,075,444 (GRCm39)	R13Q	probably damaging	Het
Sun1	T	C	5: 139,200,918 (GRCm39)	S37P	unknown	Het
Syce1l	T	C	8: 114,380,738 (GRCm39)		probably null	Het
Tdg	T	A	10: 82,480,507 (GRCm39)	F263L	probably damaging	Het
Tead3	G	T	17: 28,560,495 (GRCm39)	S36R	probably benign	Het
Timm44	A	G	8: 4,310,621 (GRCm39)	L377P	probably damaging	Het
Tk1	C	T	11: 117,716,581 (GRCm39)	V9M	probably benign	Het
Trim36	A	G	18: 46,300,506 (GRCm39)	Y722H	probably benign	Het
Ttn	A	T	2: 76,640,232 (GRCm39)	M13792K	possibly damaging	Het
Unc80	A	G	1: 66,594,411 (GRCm39)		probably benign	Het
Usp46	G	T	5: 74,189,965 (GRCm39)	A133E	probably benign	Het
Wnk2	T	A	13: 49,221,430 (GRCm39)	R1240S	probably benign	Het
Zfp821	G	A	8: 110,450,982 (GRCm39)	R325Q	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
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
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'- GTTCTTCAGAGAGCCTCCATG -3'
(R):5'- TAACCAAGGTGACCAGGAAC -3'

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

Posted On

2022-03-25