Mutagenetix > Incidental Mutation

Incidental Mutation 'R6378:Pcsk4'

515133

Institutional Source

Beutler Lab

Gene Symbol

Pcsk4

Ensembl Gene

ENSMUSG00000020131

Gene Name

proprotein convertase subtilisin/kexin type 4

Synonyms

PC4, SPC5

MMRRC Submission

044528-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R6378 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

80157117-80165332 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 80164809 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Asparagine at position 69 (H69N)

Ref Sequence

ENSEMBL: ENSMUSP00000137719 (fasta)

Gene Model

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

AlphaFold

P29121

Predicted Effect

probably benign
Transcript: ENSMUST00000020340
AA Change: H86N

PolyPhen 2 Score 0.202 (Sensitivity: 0.92; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000020340
Gene: ENSMUSG00000020131
AA Change: H86N

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: 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
AA Change: H86N

PolyPhen 2 Score 0.285 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000137809
Gene: ENSMUSG00000020131
AA Change: H86N

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
AA Change: H69N

PolyPhen 2 Score 0.339 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000137719
Gene: ENSMUSG00000020131
AA Change: H69N

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

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000153167

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000137177

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.3%
20x: 97.8%

Validation Efficiency

99% (80/81)

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: 80 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Ago2	A	T	15: 72,995,774 (GRCm39)	D408E	probably benign	Het
Agpat2	T	C	2: 26,486,147 (GRCm39)	N178S	probably benign	Het
Arsi	T	C	18: 61,049,573 (GRCm39)	F152S	probably damaging	Het
Atp13a2	T	A	4: 140,734,367 (GRCm39)	L1163Q	probably benign	Het
Bpifb2	T	A	2: 153,733,072 (GRCm39)	L385Q	possibly damaging	Het
C330018D20Rik	A	G	18: 57,095,579 (GRCm39)	L2P	probably damaging	Het
Cby3	A	G	11: 50,250,360 (GRCm39)	T189A	probably damaging	Het
Cdc42bpa	A	T	1: 179,921,561 (GRCm39)	D567V	possibly damaging	Het
Cdh5	T	A	8: 104,853,168 (GRCm39)		probably null	Het
Cela1	C	T	15: 100,585,071 (GRCm39)	V20I	probably benign	Het
Cmpk2	G	A	12: 26,519,415 (GRCm39)	G22E	possibly damaging	Het
Ctcf	T	A	8: 106,390,423 (GRCm39)	V10E	possibly damaging	Het
Dpp10	C	A	1: 123,339,468 (GRCm39)	C353F	probably damaging	Het
Efcab3	A	G	11: 104,999,620 (GRCm39)	S5546G	possibly damaging	Het
Elp3	G	T	14: 65,830,420 (GRCm39)	Y10*	probably null	Het
Eml2	G	A	7: 18,935,088 (GRCm39)	V432I	probably damaging	Het
Eml4	T	A	17: 83,755,646 (GRCm39)	W336R	probably damaging	Het
Erich6	T	C	3: 58,529,780 (GRCm39)		probably null	Het
Eya1	T	C	1: 14,373,027 (GRCm39)	N31D	possibly damaging	Het
Fam81a	T	A	9: 70,017,628 (GRCm39)	N106Y	probably damaging	Het
Frrs1	A	G	3: 116,694,639 (GRCm39)	T487A	possibly damaging	Het
Ganc	T	C	2: 120,264,307 (GRCm39)	M420T	probably damaging	Het
Gimap7	A	T	6: 48,701,116 (GRCm39)	E234V	probably damaging	Het
Gpbp1	T	C	13: 111,570,146 (GRCm39)	N400S	probably damaging	Het
Gucy2g	T	C	19: 55,229,377 (GRCm39)	S98G	probably benign	Het
Hoxd10	T	C	2: 74,524,678 (GRCm39)	I330T	possibly damaging	Het
Ik	T	A	18: 36,890,341 (GRCm39)	I539N	probably damaging	Het
Il17rb	G	A	14: 29,722,320 (GRCm39)	T237I	probably damaging	Het
Ing2	T	A	8: 48,122,293 (GRCm39)	Q85L	probably benign	Het
Lrp4	C	A	2: 91,324,174 (GRCm39)	N1208K	probably benign	Het
Lvrn	T	A	18: 47,028,024 (GRCm39)	S888R	probably benign	Het
Map2	T	C	1: 66,454,488 (GRCm39)	V1126A	probably damaging	Het
Mapkapk5	A	G	5: 121,677,233 (GRCm39)		probably null	Het
Mis18bp1	T	C	12: 65,196,021 (GRCm39)	D581G	probably benign	Het
Muc4	T	C	16: 32,599,320 (GRCm39)	V3289A	probably benign	Het
Myom2	T	A	8: 15,149,356 (GRCm39)	I609N	probably benign	Het
Nav1	A	T	1: 135,382,433 (GRCm39)	M1343K	probably damaging	Het
Ndufaf1	T	C	2: 119,486,207 (GRCm39)	I302V	probably damaging	Het
Neb	T	A	2: 52,183,733 (GRCm39)	K978N	probably damaging	Het
Nol8	A	G	13: 49,820,831 (GRCm39)	E878G	probably damaging	Het
Nrde2	A	T	12: 100,097,016 (GRCm39)	I928N	probably damaging	Het
Nxf1	T	A	19: 8,741,910 (GRCm39)	D145E	probably benign	Het
Obox3	T	A	7: 15,360,027 (GRCm39)	H214L	probably benign	Het
Obscn	T	C	11: 58,964,572 (GRCm39)	E3199G	probably damaging	Het
Ogfod3	T	C	11: 121,093,761 (GRCm39)	E83G	probably benign	Het
Or11a4	T	A	17: 37,536,688 (GRCm39)	V224E	probably benign	Het
Or2r3	T	G	6: 42,448,687 (GRCm39)	M142L	probably benign	Het
Or6b2	A	G	1: 92,408,178 (GRCm39)	L55P	probably damaging	Het
Or8s8	T	C	15: 98,354,425 (GRCm39)	V78A	probably benign	Het
Plcl2	C	T	17: 50,975,188 (GRCm39)		probably null	Het
Pmfbp1	T	C	8: 110,256,898 (GRCm39)	I534T	probably damaging	Het
Prss23	A	T	7: 89,159,241 (GRCm39)	I276N	probably damaging	Het
Ramac	A	G	7: 81,417,387 (GRCm39)	Y29C	probably damaging	Het
Rhd	T	A	4: 134,621,696 (GRCm39)	F403Y	possibly damaging	Het
Rsf1	CG	CGACGGCGGAG	7: 97,229,115 (GRCm39)		probably benign	Homo
Scg5	A	G	2: 113,657,737 (GRCm39)	V58A	possibly damaging	Het
Scn5a	C	T	9: 119,315,102 (GRCm39)	G1868R	probably damaging	Het
Secisbp2l	A	G	2: 125,610,245 (GRCm39)	S225P	possibly damaging	Het
Sema4f	A	T	6: 82,894,613 (GRCm39)	L486*	probably null	Het
Slc25a47	G	A	12: 108,822,069 (GRCm39)	R286H	probably damaging	Het
Slc5a8	A	C	10: 88,740,916 (GRCm39)	K277T	probably damaging	Het
Slc66a3	T	C	12: 17,047,644 (GRCm39)	Y96C	probably damaging	Het
Sorcs1	T	A	19: 50,213,615 (GRCm39)	E704V	possibly damaging	Het
Sptan1	T	C	2: 29,908,527 (GRCm39)	S1768P	probably damaging	Het
Srd5a2	C	T	17: 74,328,378 (GRCm39)		probably null	Het
Sytl2	A	T	7: 90,007,432 (GRCm39)	K65*	probably null	Het
Tas2r109	T	G	6: 132,957,844 (GRCm39)	I29L	probably benign	Het
Tfap2a	A	T	13: 40,876,717 (GRCm39)	V234E	possibly damaging	Het
Tgfbr3	G	A	5: 107,325,679 (GRCm39)	L128F	probably benign	Het
Trappc12	A	T	12: 28,797,082 (GRCm39)	L150Q	probably damaging	Het
Trim43b	T	A	9: 88,967,452 (GRCm39)	I395L	probably benign	Het
U2surp	C	T	9: 95,373,474 (GRCm39)	E232K	probably benign	Het
Vax1	T	C	19: 59,154,656 (GRCm39)	N327S	probably benign	Het
Vmn1r14	T	C	6: 57,210,587 (GRCm39)	V11A	probably benign	Het
Vmn1r60	A	G	7: 5,547,782 (GRCm39)	V106A	probably damaging	Het
Vmn2r106	T	C	17: 20,498,667 (GRCm39)	S415G	probably benign	Het
Vmn2r3	C	T	3: 64,182,517 (GRCm39)	G394D	probably damaging	Het
Ybx2	A	G	11: 69,831,179 (GRCm39)	E63G	possibly damaging	Het
Zfhx4	T	A	3: 5,308,410 (GRCm39)	N545K	probably benign	Het
Zp1	T	C	19: 10,892,217 (GRCm39)	T56A	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
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'- TGCATGAGACCTTCCATTCAGG -3'
(R):5'- CTGTGGCTGTCATATGGACC -3'

Sequencing Primer
(F):5'- ATCTGAGTCCCCCTGGATATTAAG -3'
(R):5'- CCCCTGGCTGAGGTGTATAAAGTC -3'

Posted On

2018-05-04