Mutagenetix > Incidental Mutation

Incidental Mutation 'R0784:Pcsk5'

76800

Institutional Source

Beutler Lab

Gene Symbol

Pcsk5

Ensembl Gene

ENSMUSG00000024713

Gene Name

proprotein convertase subtilisin/kexin type 5

Synonyms

PC5A, PC5/6A, PC6, b2b1549Clo, b2b585Clo, SPC6

MMRRC Submission

038964-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0784 (G1)

Quality Score

217

Status

Validated

Chromosome

Chromosomal Location

17409683-17814996 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 17692133 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Valine at position 184 (M184V)

Ref Sequence

ENSEMBL: ENSMUSP00000050272 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000025618] [ENSMUST00000050715]

AlphaFold

Q04592

Predicted Effect

probably benign
Transcript: ENSMUST00000025618
AA Change: M184V

PolyPhen 2 Score 0.056 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000025618
Gene: ENSMUSG00000024713
AA Change: M184V

Domain	Start	End	E-Value	Type
low complexity region	17	29	N/A	INTRINSIC
Pfam:S8_pro-domain	40	116	4.6e-27	PFAM
Pfam:Peptidase_S8	164	447	2.1e-46	PFAM
Pfam:P_proprotein	507	597	2.1e-33	PFAM
FU	632	682	4.92e-13	SMART
FU	685	732	4.84e-12	SMART
EGF_like	690	723	3.29e1	SMART
FU	736	779	1.29e-7	SMART
FU	781	826	5.74e-14	SMART
FU	834	881	2.23e-11	SMART
EGF_like	839	870	3.43e1	SMART
FU	884	929	1.84e-12	SMART
FU	931	981	1.47e-11	SMART
FU	984	1030	1e-4	SMART
EGF_like	989	1020	2.92e1	SMART
FU	1034	1079	5.04e-10	SMART
FU	1081	1123	3.08e-5	SMART
FU	1127	1168	4.88e-8	SMART
FU	1206	1248	2.7e-10	SMART
EGF_like	1211	1239	5.91e1	SMART
FU	1252	1299	1.48e-7	SMART
EGF	1264	1305	1.69e1	SMART
FU	1301	1345	2.31e-9	SMART
FU	1347	1390	8.98e-7	SMART
EGF_like	1352	1381	7.23e1	SMART
FU	1392	1438	1.04e-11	SMART
FU	1442	1487	6.8e-7	SMART
EGF	1447	1476	2.16e1	SMART
FU	1491	1536	3.37e-11	SMART
FU	1540	1585	9.32e-14	SMART
EGF_like	1545	1576	2.8e1	SMART
FU	1589	1636	1.39e-12	SMART
FU	1640	1685	6.49e-13	SMART
EGF_like	1645	1676	6.67e1	SMART
FU	1691	1738	7.01e-9	SMART
transmembrane domain	1770	1789	N/A	INTRINSIC
low complexity region	1827	1840	N/A	INTRINSIC
low complexity region	1858	1876	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000050715
AA Change: M184V

PolyPhen 2 Score 0.056 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000050272
Gene: ENSMUSG00000024713
AA Change: M184V

Domain	Start	End	E-Value	Type
low complexity region	17	29	N/A	INTRINSIC
PDB:1KN6\|A	35	116	6e-11	PDB
Pfam:Peptidase_S8	168	456	2.9e-59	PFAM
Pfam:P_proprotein	507	597	1.5e-34	PFAM
FU	632	682	4.92e-13	SMART
FU	685	732	4.84e-12	SMART
EGF_like	690	723	3.29e1	SMART
FU	736	779	1.29e-7	SMART
FU	781	826	5.74e-14	SMART
FU	834	884	1.4e-8	SMART
EGF_like	839	870	3.43e1	SMART

Meta Mutation Damage Score

0.0704

Coding Region Coverage

1x: 99.6%
3x: 98.9%
10x: 96.9%
20x: 92.1%

Validation Efficiency

97% (59/61)

MGI Phenotype

FUNCTION: This gene encodes a subtilisin-like proprotein convertase that mediates posttranslational endoproteolytic processing of various proprotein substrates traversing the secretory pathway. The encoded protein is an inactive zymogen that undergoes autoproteolytic processing in the endoplasmic reticulum and the Golgi network to generate an active enzyme. Mice lacking the encoded protein die at an early embryonic stage. Conditional inactivation this gene in the epiblast but not in the extraembryonic tissue bypasses embryonic lethality but results in death at birth. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2015]
PHENOTYPE: Mice homozygous for a null mutation in this gene display embryonic lethality between E4.5-E7.5. Mice homozygous for ENU-induced mutations exhibit heterotaxia with congenital heart defects and immotile respiratory cilia. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 58 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acin1	T	C	14: 54,890,985 (GRCm39)		probably benign	Het
Adamts2	C	T	11: 50,558,830 (GRCm39)	R182W	probably damaging	Het
Ahr	C	T	12: 35,558,141 (GRCm39)	G293D	possibly damaging	Het
Akna	G	T	4: 63,295,125 (GRCm39)	T1028K	probably benign	Het
Akp3	G	A	1: 87,055,593 (GRCm39)	G547R	unknown	Het
Aoc1l3	T	A	6: 48,964,235 (GRCm39)	M81K	possibly damaging	Het
Asic2	T	A	11: 80,784,815 (GRCm39)	M324L	possibly damaging	Het
Atf6	A	G	1: 170,537,516 (GRCm39)	F635L	probably benign	Het
Atp8b2	A	T	3: 89,864,380 (GRCm39)	V195E	probably damaging	Het
Bicd1	T	A	6: 149,414,861 (GRCm39)	C525S	probably damaging	Het
Cbfa2t3	A	G	8: 123,377,226 (GRCm39)		probably benign	Het
Cd46	G	A	1: 194,774,502 (GRCm39)	T11M	possibly damaging	Het
Cecr2	A	G	6: 120,735,110 (GRCm39)	H754R	possibly damaging	Het
Clcn3	G	T	8: 61,382,237 (GRCm39)	D450E	probably benign	Het
Cobl	T	G	11: 12,216,843 (GRCm39)		probably benign	Het
Cyba	T	A	8: 123,154,422 (GRCm39)	T34S	probably benign	Het
Dennd1a	A	G	2: 37,911,426 (GRCm39)	L187P	probably damaging	Het
Dennd4c	A	T	4: 86,763,145 (GRCm39)	Q1817L	probably benign	Het
Drosha	T	C	15: 12,867,764 (GRCm39)		probably benign	Het
Dync1li2	A	G	8: 105,169,130 (GRCm39)	S34P	probably damaging	Het
Emilin2	T	A	17: 71,582,282 (GRCm39)	D148V	possibly damaging	Het
Galnt11	A	G	5: 25,463,907 (GRCm39)	D393G	probably damaging	Het
Gm5435	T	A	12: 82,542,954 (GRCm39)		noncoding transcript	Het
Gpr176	C	T	2: 118,203,533 (GRCm39)	V46M	possibly damaging	Het
Gpr85	T	A	6: 13,836,748 (GRCm39)	H52L	probably benign	Het
Grn	T	C	11: 102,325,328 (GRCm39)	M246T	possibly damaging	Het
Hnrnpul2	T	C	19: 8,802,416 (GRCm39)	F428L	possibly damaging	Het
Hoxa13	G	C	6: 52,236,917 (GRCm39)	N278K	probably damaging	Het
Irx5	A	G	8: 93,087,118 (GRCm39)	D350G	probably benign	Het
Kat2a	C	T	11: 100,601,667 (GRCm39)	M249I	probably benign	Het
Klhl29	T	C	12: 5,131,251 (GRCm39)	Y782C	probably damaging	Het
Kmt2c	A	T	5: 25,515,893 (GRCm39)	F2650Y	probably benign	Het
Lrp2	A	G	2: 69,348,709 (GRCm39)	I754T	probably benign	Het
LTO1	A	T	7: 144,473,014 (GRCm39)	Y108F	probably benign	Het
Mpl	G	A	4: 118,303,603 (GRCm39)	P472S	possibly damaging	Het
Mtnr1b	A	G	9: 15,774,081 (GRCm39)	I326T	probably benign	Het
Myh9	A	G	15: 77,661,209 (GRCm39)		probably benign	Het
Mylk	G	C	16: 34,699,845 (GRCm39)	E403Q	possibly damaging	Het
Myo9a	A	G	9: 59,803,828 (GRCm39)		probably benign	Het
Or2z2	T	A	11: 58,346,131 (GRCm39)	I215F	possibly damaging	Het
Or4ac1-ps1	T	A	2: 88,370,511 (GRCm39)		noncoding transcript	Het
Piezo2	T	A	18: 63,216,306 (GRCm39)	D1143V	probably damaging	Het
Prr36	G	T	8: 4,263,771 (GRCm39)		probably benign	Het
Rnf220	C	A	4: 117,135,195 (GRCm39)		probably benign	Het
Senp3	A	G	11: 69,571,274 (GRCm39)	L131P	probably damaging	Het
Shc4	A	C	2: 125,499,416 (GRCm39)	W354G	probably benign	Het
Slc6a15	A	G	10: 103,252,661 (GRCm39)		probably benign	Het
Smtnl2	T	C	11: 72,290,763 (GRCm39)	D394G	probably damaging	Het
Sry	G	T	Y: 2,662,731 (GRCm39)	Q310K	unknown	Het
St7l	A	G	3: 104,778,240 (GRCm39)	M126V	probably benign	Het
St8sia3	T	C	18: 64,404,772 (GRCm39)	W350R	probably damaging	Het
Stk35	A	T	2: 129,652,722 (GRCm39)	K408*	probably null	Het
Thsd7b	T	C	1: 129,523,096 (GRCm39)		probably benign	Het
Tmem106b	T	C	6: 13,084,252 (GRCm39)	V252A	probably damaging	Het
Trpm7	A	G	2: 126,687,992 (GRCm39)		probably null	Het
Ttf2	T	C	3: 100,870,026 (GRCm39)	D349G	probably benign	Het
Zfp386	T	A	12: 116,023,540 (GRCm39)	C419*	probably null	Het
Zfp541	A	G	7: 15,816,917 (GRCm39)		probably benign	Het

Other mutations in Pcsk5

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00418:Pcsk5	APN	19	17,488,785 (GRCm39)	missense	possibly damaging	0.49
IGL00423:Pcsk5	APN	19	17,619,923 (GRCm39)	missense	probably benign	0.23
IGL01315:Pcsk5	APN	19	17,429,322 (GRCm39)	missense	probably damaging	1.00
IGL01372:Pcsk5	APN	19	17,595,108 (GRCm39)	missense	probably damaging	1.00
IGL01738:Pcsk5	APN	19	17,411,144 (GRCm39)	splice site	probably benign
IGL01874:Pcsk5	APN	19	17,573,041 (GRCm39)	missense	probably damaging	0.96
IGL02070:Pcsk5	APN	19	17,416,406 (GRCm39)	missense	probably benign	0.25
IGL02311:Pcsk5	APN	19	17,410,784 (GRCm39)	nonsense	probably null
IGL02436:Pcsk5	APN	19	17,542,072 (GRCm39)	critical splice donor site	probably null
IGL02498:Pcsk5	APN	19	17,488,920 (GRCm39)	missense	probably damaging	0.99
IGL02504:Pcsk5	APN	19	17,455,236 (GRCm39)	critical splice donor site	probably null
IGL02664:Pcsk5	APN	19	17,434,134 (GRCm39)	missense	probably damaging	1.00
IGL02735:Pcsk5	APN	19	17,652,832 (GRCm39)	missense	probably damaging	1.00
IGL02941:Pcsk5	APN	19	17,424,865 (GRCm39)	missense	probably damaging	1.00
PIT4377001:Pcsk5	UTSW	19	17,416,466 (GRCm39)	missense	probably damaging	1.00
R0007:Pcsk5	UTSW	19	17,632,225 (GRCm39)	missense	probably damaging	1.00
R0007:Pcsk5	UTSW	19	17,632,225 (GRCm39)	missense	probably damaging	1.00
R0032:Pcsk5	UTSW	19	17,542,179 (GRCm39)	missense	possibly damaging	0.81
R0032:Pcsk5	UTSW	19	17,542,179 (GRCm39)	missense	possibly damaging	0.81
R0373:Pcsk5	UTSW	19	17,632,213 (GRCm39)	missense	probably damaging	1.00
R0843:Pcsk5	UTSW	19	17,632,182 (GRCm39)	missense	probably damaging	1.00
R1014:Pcsk5	UTSW	19	17,542,194 (GRCm39)	missense	probably damaging	1.00
R1221:Pcsk5	UTSW	19	17,814,512 (GRCm39)	missense	possibly damaging	0.85
R1435:Pcsk5	UTSW	19	17,541,246 (GRCm39)	nonsense	probably null
R1471:Pcsk5	UTSW	19	17,545,688 (GRCm39)	missense	probably damaging	1.00
R1564:Pcsk5	UTSW	19	17,632,120 (GRCm39)	missense	probably damaging	1.00
R1597:Pcsk5	UTSW	19	17,413,964 (GRCm39)	missense	probably benign	0.00
R1614:Pcsk5	UTSW	19	17,492,620 (GRCm39)	missense	probably damaging	1.00
R1661:Pcsk5	UTSW	19	17,424,938 (GRCm39)	missense	probably damaging	0.98
R1671:Pcsk5	UTSW	19	17,432,232 (GRCm39)	missense	probably damaging	1.00
R1703:Pcsk5	UTSW	19	17,729,458 (GRCm39)	missense	probably benign	0.15
R1793:Pcsk5	UTSW	19	17,432,114 (GRCm39)	missense	possibly damaging	0.83
R1855:Pcsk5	UTSW	19	17,492,556 (GRCm39)	missense	possibly damaging	0.93
R1909:Pcsk5	UTSW	19	17,410,825 (GRCm39)	missense	probably benign	0.00
R1959:Pcsk5	UTSW	19	17,410,782 (GRCm39)	missense	unknown
R2006:Pcsk5	UTSW	19	17,455,280 (GRCm39)	missense	probably benign	0.32
R2045:Pcsk5	UTSW	19	17,558,508 (GRCm39)	missense	possibly damaging	0.48
R2061:Pcsk5	UTSW	19	17,432,236 (GRCm39)	missense	probably benign	0.03
R2110:Pcsk5	UTSW	19	17,450,423 (GRCm39)	missense	probably damaging	1.00
R2402:Pcsk5	UTSW	19	17,452,198 (GRCm39)	nonsense	probably null
R2496:Pcsk5	UTSW	19	17,443,522 (GRCm39)	nonsense	probably null
R4115:Pcsk5	UTSW	19	17,410,783 (GRCm39)	missense	unknown
R4504:Pcsk5	UTSW	19	17,429,319 (GRCm39)	missense	probably damaging	1.00
R4616:Pcsk5	UTSW	19	17,538,114 (GRCm39)	missense	probably benign	0.00
R4683:Pcsk5	UTSW	19	17,450,405 (GRCm39)	missense	probably damaging	1.00
R4717:Pcsk5	UTSW	19	17,502,631 (GRCm39)	missense	probably damaging	1.00
R4761:Pcsk5	UTSW	19	17,814,512 (GRCm39)	missense	possibly damaging	0.85
R4789:Pcsk5	UTSW	19	17,410,963 (GRCm39)	missense	probably benign	0.09
R4880:Pcsk5	UTSW	19	17,425,054 (GRCm39)	missense	probably damaging	1.00
R5100:Pcsk5	UTSW	19	17,492,499 (GRCm39)	critical splice donor site	probably null
R5114:Pcsk5	UTSW	19	17,652,949 (GRCm39)	missense	probably damaging	1.00
R5116:Pcsk5	UTSW	19	17,440,798 (GRCm39)	missense	possibly damaging	0.87
R5193:Pcsk5	UTSW	19	17,542,174 (GRCm39)	missense	possibly damaging	0.79
R5279:Pcsk5	UTSW	19	17,573,022 (GRCm39)	splice site	probably null
R5334:Pcsk5	UTSW	19	17,439,215 (GRCm39)	missense	probably benign	0.00
R5369:Pcsk5	UTSW	19	17,558,619 (GRCm39)	missense	probably damaging	1.00
R5451:Pcsk5	UTSW	19	17,440,720 (GRCm39)	missense	possibly damaging	0.91
R5547:Pcsk5	UTSW	19	17,729,488 (GRCm39)	missense	probably benign	0.08
R5630:Pcsk5	UTSW	19	17,553,195 (GRCm39)	missense	probably benign	0.04
R5805:Pcsk5	UTSW	19	17,434,193 (GRCm39)	missense	probably benign	0.01
R6063:Pcsk5	UTSW	19	17,432,045 (GRCm39)	critical splice donor site	probably null
R6130:Pcsk5	UTSW	19	17,488,920 (GRCm39)	missense	probably damaging	0.99
R6153:Pcsk5	UTSW	19	17,488,856 (GRCm39)	missense	probably damaging	0.98
R6163:Pcsk5	UTSW	19	17,450,405 (GRCm39)	missense	probably damaging	1.00
R6164:Pcsk5	UTSW	19	17,814,317 (GRCm39)	critical splice donor site	probably null
R6228:Pcsk5	UTSW	19	17,558,631 (GRCm39)	missense	possibly damaging	0.91
R6426:Pcsk5	UTSW	19	17,595,093 (GRCm39)	missense	probably damaging	1.00
R6601:Pcsk5	UTSW	19	17,488,744 (GRCm39)	missense	probably benign	0.00
R6648:Pcsk5	UTSW	19	17,553,185 (GRCm39)	missense	probably damaging	0.99
R6789:Pcsk5	UTSW	19	17,434,150 (GRCm39)	missense	possibly damaging	0.93
R6807:Pcsk5	UTSW	19	17,549,986 (GRCm39)	splice site	probably null
R6837:Pcsk5	UTSW	19	17,416,448 (GRCm39)	missense	probably benign	0.01
R6998:Pcsk5	UTSW	19	17,450,476 (GRCm39)	missense	probably benign	0.20
R7051:Pcsk5	UTSW	19	17,411,095 (GRCm39)	missense	probably benign	0.00
R7164:Pcsk5	UTSW	19	17,429,349 (GRCm39)	missense	probably damaging	1.00
R7173:Pcsk5	UTSW	19	17,455,241 (GRCm39)	missense	possibly damaging	0.85
R7348:Pcsk5	UTSW	19	17,434,182 (GRCm39)	nonsense	probably null
R7360:Pcsk5	UTSW	19	17,492,577 (GRCm39)	missense	probably benign	0.00
R7407:Pcsk5	UTSW	19	17,652,880 (GRCm39)	missense	probably damaging	1.00
R7447:Pcsk5	UTSW	19	17,487,600 (GRCm39)	missense	probably benign	0.31
R7521:Pcsk5	UTSW	19	17,432,196 (GRCm39)	missense	probably benign	0.29
R7525:Pcsk5	UTSW	19	17,619,954 (GRCm39)	missense	probably damaging	1.00
R7560:Pcsk5	UTSW	19	17,814,336 (GRCm39)	missense	probably benign	0.01
R7566:Pcsk5	UTSW	19	17,549,821 (GRCm39)	missense	probably benign
R7631:Pcsk5	UTSW	19	17,542,144 (GRCm39)	missense	probably damaging	1.00
R7654:Pcsk5	UTSW	19	17,434,168 (GRCm39)	missense	possibly damaging	0.46
R7677:Pcsk5	UTSW	19	17,558,593 (GRCm39)	missense	possibly damaging	0.59
R7711:Pcsk5	UTSW	19	17,416,444 (GRCm39)	missense	possibly damaging	0.82
R7903:Pcsk5	UTSW	19	17,549,847 (GRCm39)	missense	probably damaging	0.98
R7938:Pcsk5	UTSW	19	17,443,549 (GRCm39)	critical splice acceptor site	probably null
R8025:Pcsk5	UTSW	19	17,538,415 (GRCm39)	intron	probably benign
R8032:Pcsk5	UTSW	19	17,692,151 (GRCm39)	missense	probably damaging	0.98
R8064:Pcsk5	UTSW	19	17,692,225 (GRCm39)	missense	probably damaging	1.00
R8115:Pcsk5	UTSW	19	17,487,530 (GRCm39)	critical splice donor site	probably null
R8193:Pcsk5	UTSW	19	17,563,415 (GRCm39)	missense	possibly damaging	0.64
R8408:Pcsk5	UTSW	19	17,410,809 (GRCm39)	missense	probably benign	0.00
R8466:Pcsk5	UTSW	19	17,549,864 (GRCm39)	nonsense	probably null
R8739:Pcsk5	UTSW	19	17,432,138 (GRCm39)	missense	probably benign	0.00
R8753:Pcsk5	UTSW	19	17,446,408 (GRCm39)	missense	probably benign	0.00
R8797:Pcsk5	UTSW	19	17,443,472 (GRCm39)	missense	probably benign	0.00
R8944:Pcsk5	UTSW	19	17,452,275 (GRCm39)	missense	probably damaging	0.96
R9041:Pcsk5	UTSW	19	17,538,132 (GRCm39)	nonsense	probably null
R9135:Pcsk5	UTSW	19	17,563,472 (GRCm39)	missense
R9288:Pcsk5	UTSW	19	17,814,345 (GRCm39)	missense	probably benign	0.10
R9406:Pcsk5	UTSW	19	17,771,097 (GRCm39)	missense	probably benign	0.14
R9581:Pcsk5	UTSW	19	17,432,196 (GRCm39)	missense	probably benign
R9592:Pcsk5	UTSW	19	17,652,899 (GRCm39)	nonsense	probably null
R9659:Pcsk5	UTSW	19	17,455,245 (GRCm39)	missense	probably benign	0.00
R9788:Pcsk5	UTSW	19	17,455,245 (GRCm39)	missense	probably benign	0.00
X0023:Pcsk5	UTSW	19	17,452,236 (GRCm39)	missense	possibly damaging	0.66
X0063:Pcsk5	UTSW	19	17,424,968 (GRCm39)	missense	probably damaging	1.00
Z1088:Pcsk5	UTSW	19	17,440,738 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TTGAAGGCCACCCCATCAAAGG -3'
(R):5'- TCGTCTCACAGGAACATACCTCTGG -3'

Sequencing Primer
(F):5'- ATCTTGTGATCCCTGTGCTATAAGTG -3'
(R):5'- CAGTTACCCTCTTGAGGTAGATAACG -3'

Posted On

2013-10-16