Mutagenetix > Incidental Mutations

Incidental Mutation 'R0373:Pcsk5'

30661

Institutional Source

Beutler Lab

Gene Symbol

Pcsk5

Ensembl Gene

ENSMUSG00000024713

Gene Name

proprotein convertase subtilisin/kexin type 5

Synonyms

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

MMRRC Submission

038579-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R0373 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

17432832-17837632 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 17654849 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Tryptophan at position 318 (R318W)

Ref Sequence

ENSEMBL: ENSMUSP00000050272 (fasta)

Gene Model

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

AlphaFold

Q04592

Predicted Effect

probably damaging
Transcript: ENSMUST00000025618
AA Change: R318W

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

SMART Domains

Protein: ENSMUSP00000025618
Gene: ENSMUSG00000024713
AA Change: R318W

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 damaging
Transcript: ENSMUST00000050715
AA Change: R318W

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

SMART Domains

Protein: ENSMUSP00000050272
Gene: ENSMUSG00000024713
AA Change: R318W

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

Coding Region Coverage

1x: 99.1%
3x: 98.1%
10x: 95.8%
20x: 91.5%

Validation Efficiency

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: 93 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930579F01Rik	A	T	3: 138,173,582	L235Q	probably damaging	Het
Adam6b	T	A	12: 113,490,655	V364D	probably benign	Het
Akap13	T	C	7: 75,609,929	L767P	probably benign	Het
Akap13	T	A	7: 75,730,500	S2193T	probably damaging	Het
Anapc11	T	C	11: 120,605,377	V69A	probably benign	Het
Ankmy1	C	T	1: 92,896,190	R118Q	probably damaging	Het
Ankrd27	T	C	7: 35,638,053	S931P	probably benign	Het
Atp6v1c2	G	A	12: 17,288,168	R280C	probably damaging	Het
Bbs10	T	A	10: 111,300,052	I342N	probably damaging	Het
Calhm2	T	C	19: 47,132,950	D260G	possibly damaging	Het
Camk2a	A	G	18: 60,958,238	E264G	probably damaging	Het
Ccdc146	T	A	5: 21,319,545	M270L	probably benign	Het
Cdc16	A	G	8: 13,779,264	T517A	probably benign	Het
Ces1g	T	C	8: 93,331,193	H160R	probably benign	Het
Chst4	T	C	8: 110,030,394	N196S	probably damaging	Het
Ciz1	A	T	2: 32,367,467	N175Y	probably damaging	Het
Cyb5r4	G	A	9: 87,027,040	V57I	probably damaging	Het
Cyth3	A	G	5: 143,684,426		probably benign	Het
Def6	A	G	17: 28,220,180	E255G	probably damaging	Het
Dhtkd1	T	G	2: 5,911,870	Q665P	probably damaging	Het
Dsg3	A	C	18: 20,539,747	D825A	probably damaging	Het
Eif3m	T	C	2: 105,005,000	T242A	probably benign	Het
Emilin3	A	G	2: 160,909,817	F101L	probably benign	Het
Epha7	A	G	4: 28,935,700		probably null	Het
Fam205a1	T	C	4: 42,851,161	I332V	probably benign	Het
Fbxo45	A	T	16: 32,238,405	Y224N	probably damaging	Het
Fhod3	A	T	18: 25,090,104	M836L	possibly damaging	Het
Fut4	C	A	9: 14,751,210	V263F	probably damaging	Het
Ggt1	C	T	10: 75,579,270	T206M	probably benign	Het
Gls	T	C	1: 52,188,699	R79G	probably damaging	Het
Gm436	A	T	4: 144,686,220	M50K	possibly damaging	Het
Grhl1	T	C	12: 24,581,515	S156P	probably benign	Het
Ipo8	C	T	6: 148,775,042	S983N	probably benign	Het
Kcna7	C	T	7: 45,409,444	A385V	probably damaging	Het
Kpnb1	A	T	11: 97,185,090	L40Q	probably damaging	Het
Matn1	A	T	4: 130,950,106	S209C	probably damaging	Het
Mcc	A	G	18: 44,475,222	I501T	probably benign	Het
Mdp1	A	T	14: 55,659,375	F104L	probably damaging	Het
Mib2	A	T	4: 155,656,288	N626K	probably damaging	Het
Mrgprh	T	C	17: 12,876,956	S28P	possibly damaging	Het
Mup-ps23	T	A	4: 61,856,149		noncoding transcript	Het
Myh15	A	G	16: 49,182,959	T1794A	possibly damaging	Het
Myo18a	C	G	11: 77,821,042	P680A	probably benign	Het
Myom2	G	T	8: 15,098,419	D532Y	possibly damaging	Het
Ndufaf5	A	G	2: 140,170,881	N57S	probably benign	Het
Nectin3	C	T	16: 46,458,187	V282M	probably damaging	Het
Nup188	G	T	2: 30,330,988	D997Y	probably damaging	Het
Olfm3	T	C	3: 115,122,805	V462A	probably damaging	Het
Olfr1044	A	C	2: 86,171,706	F37C	probably damaging	Het
Olfr1225	A	T	2: 89,170,413	F266L	probably benign	Het
Olfr305	A	T	7: 86,363,805	C177*	probably null	Het
Opcml	A	G	9: 28,813,398	H164R	possibly damaging	Het
Pacrg	A	G	17: 10,403,418	I209T	probably damaging	Het
Pcf11	T	C	7: 92,661,215	M522V	probably benign	Het
Pck1	T	A	2: 173,153,390	M1K	probably null	Het
Pcm1	G	T	8: 41,276,111	E707*	probably null	Het
Phf11d	A	T	14: 59,353,344	M188K	possibly damaging	Het
Ppip5k2	A	T	1: 97,740,537	C615*	probably null	Het
Prkdc	T	A	16: 15,791,927	S3132T	probably damaging	Het
Prl2c5	A	T	13: 13,183,024		probably benign	Het
Prpsap2	A	G	11: 61,741,000	I177T	possibly damaging	Het
Rad50	A	G	11: 53,650,519	S1297P	probably damaging	Het
Rasip1	T	A	7: 45,635,244	N678K	possibly damaging	Het
Rubcn	A	G	16: 32,835,980	S544P	probably damaging	Het
Rwdd2a	A	T	9: 86,574,400	T210S	possibly damaging	Het
Scd2	A	G	19: 44,303,040	D306G	probably damaging	Het
Sema3b	T	C	9: 107,602,918	N207S	probably benign	Het
Sf3b2	C	T	19: 5,274,824	D845N	probably damaging	Het
Sipa1l2	C	A	8: 125,464,410	C947F	probably damaging	Het
Slc12a1	A	T	2: 125,226,031	T1013S	probably damaging	Het
Slc18a2	A	T	19: 59,287,367	I461L	probably benign	Het
Slc1a6	C	A	10: 78,801,922	Y427*	probably null	Het
Slc30a4	A	T	2: 122,689,399	I231K	probably damaging	Het
Sos1	G	T	17: 80,453,763	A168D	probably damaging	Het
Sptb	T	C	12: 76,621,371	S651G	probably benign	Het
Stk36	T	C	1: 74,633,620	L1007P	probably damaging	Het
Tek	A	T	4: 94,804,341	N229Y	probably damaging	Het
Tep1	A	G	14: 50,836,768	F1887L	possibly damaging	Het
Tet1	A	T	10: 62,878,209	C602*	probably null	Het
Tnfrsf19	A	G	14: 60,972,036	S262P	possibly damaging	Het
Trim5	T	C	7: 104,265,684	I393V	probably benign	Het
Trpm6	A	G	19: 18,853,587	E1272G	probably benign	Het
Ttc21b	A	T	2: 66,188,326	Y1246N	probably damaging	Het
Ttll3	T	A	6: 113,398,777	L151H	probably damaging	Het
U2surp	C	T	9: 95,484,443	V470I	probably benign	Het
Ubr1	A	T	2: 120,946,657	Y276N	probably benign	Het
Uggt1	A	G	1: 36,179,670	S59P	probably benign	Het
Unc45a	T	C	7: 80,326,344	T796A	probably damaging	Het
Unc5b	C	A	10: 60,778,940	V193F	possibly damaging	Het
Upp1	G	T	11: 9,129,590	M50I	probably benign	Het
Vps18	C	T	2: 119,293,905	R438C	probably damaging	Het
Zfp715	T	C	7: 43,299,336	Y400C	possibly damaging	Het
Zfp955b	T	C	17: 33,302,522	Y322H	probably benign	Het

Other mutations in Pcsk5

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00418:Pcsk5	APN	19	17511421	missense	possibly damaging	0.49
IGL00423:Pcsk5	APN	19	17642559	missense	probably benign	0.23
IGL01315:Pcsk5	APN	19	17451958	missense	probably damaging	1.00
IGL01372:Pcsk5	APN	19	17617744	missense	probably damaging	1.00
IGL01738:Pcsk5	APN	19	17433780	splice site	probably benign
IGL01874:Pcsk5	APN	19	17595677	missense	probably damaging	0.96
IGL02070:Pcsk5	APN	19	17439042	missense	probably benign	0.25
IGL02311:Pcsk5	APN	19	17433420	nonsense	probably null
IGL02436:Pcsk5	APN	19	17564708	critical splice donor site	probably null
IGL02498:Pcsk5	APN	19	17511556	missense	probably damaging	0.99
IGL02504:Pcsk5	APN	19	17477872	critical splice donor site	probably null
IGL02664:Pcsk5	APN	19	17456770	missense	probably damaging	1.00
IGL02735:Pcsk5	APN	19	17675468	missense	probably damaging	1.00
IGL02941:Pcsk5	APN	19	17447501	missense	probably damaging	1.00
PIT4377001:Pcsk5	UTSW	19	17439102	missense	probably damaging	1.00
R0007:Pcsk5	UTSW	19	17654861	missense	probably damaging	1.00
R0007:Pcsk5	UTSW	19	17654861	missense	probably damaging	1.00
R0032:Pcsk5	UTSW	19	17564815	missense	possibly damaging	0.81
R0032:Pcsk5	UTSW	19	17564815	missense	possibly damaging	0.81
R0784:Pcsk5	UTSW	19	17714769	missense	probably benign	0.06
R0843:Pcsk5	UTSW	19	17654818	missense	probably damaging	1.00
R1014:Pcsk5	UTSW	19	17564830	missense	probably damaging	1.00
R1221:Pcsk5	UTSW	19	17837148	missense	possibly damaging	0.85
R1435:Pcsk5	UTSW	19	17563882	nonsense	probably null
R1471:Pcsk5	UTSW	19	17568324	missense	probably damaging	1.00
R1564:Pcsk5	UTSW	19	17654756	missense	probably damaging	1.00
R1597:Pcsk5	UTSW	19	17436600	missense	probably benign	0.00
R1614:Pcsk5	UTSW	19	17515256	missense	probably damaging	1.00
R1661:Pcsk5	UTSW	19	17447574	missense	probably damaging	0.98
R1671:Pcsk5	UTSW	19	17454868	missense	probably damaging	1.00
R1703:Pcsk5	UTSW	19	17752094	missense	probably benign	0.15
R1793:Pcsk5	UTSW	19	17454750	missense	possibly damaging	0.83
R1855:Pcsk5	UTSW	19	17515192	missense	possibly damaging	0.93
R1909:Pcsk5	UTSW	19	17433461	missense	probably benign	0.00
R1959:Pcsk5	UTSW	19	17433418	missense	unknown
R2006:Pcsk5	UTSW	19	17477916	missense	probably benign	0.32
R2045:Pcsk5	UTSW	19	17581144	missense	possibly damaging	0.48
R2061:Pcsk5	UTSW	19	17454872	missense	probably benign	0.03
R2110:Pcsk5	UTSW	19	17473059	missense	probably damaging	1.00
R2402:Pcsk5	UTSW	19	17474834	nonsense	probably null
R2496:Pcsk5	UTSW	19	17466158	nonsense	probably null
R4115:Pcsk5	UTSW	19	17433419	missense	unknown
R4504:Pcsk5	UTSW	19	17451955	missense	probably damaging	1.00
R4616:Pcsk5	UTSW	19	17560750	missense	probably benign	0.00
R4683:Pcsk5	UTSW	19	17473041	missense	probably damaging	1.00
R4717:Pcsk5	UTSW	19	17525267	missense	probably damaging	1.00
R4761:Pcsk5	UTSW	19	17837148	missense	possibly damaging	0.85
R4789:Pcsk5	UTSW	19	17433599	missense	probably benign	0.09
R4880:Pcsk5	UTSW	19	17447690	missense	probably damaging	1.00
R5100:Pcsk5	UTSW	19	17515135	critical splice donor site	probably null
R5114:Pcsk5	UTSW	19	17675585	missense	probably damaging	1.00
R5116:Pcsk5	UTSW	19	17463434	missense	possibly damaging	0.87
R5193:Pcsk5	UTSW	19	17564810	missense	possibly damaging	0.79
R5279:Pcsk5	UTSW	19	17595658	splice site	probably null
R5334:Pcsk5	UTSW	19	17461851	missense	probably benign	0.00
R5369:Pcsk5	UTSW	19	17581255	missense	probably damaging	1.00
R5451:Pcsk5	UTSW	19	17463356	missense	possibly damaging	0.91
R5547:Pcsk5	UTSW	19	17752124	missense	probably benign	0.08
R5630:Pcsk5	UTSW	19	17575831	missense	probably benign	0.04
R5805:Pcsk5	UTSW	19	17456829	missense	probably benign	0.01
R6063:Pcsk5	UTSW	19	17454681	critical splice donor site	probably null
R6130:Pcsk5	UTSW	19	17511556	missense	probably damaging	0.99
R6153:Pcsk5	UTSW	19	17511492	missense	probably damaging	0.98
R6163:Pcsk5	UTSW	19	17473041	missense	probably damaging	1.00
R6164:Pcsk5	UTSW	19	17836953	critical splice donor site	probably null
R6228:Pcsk5	UTSW	19	17581267	missense	possibly damaging	0.91
R6426:Pcsk5	UTSW	19	17617729	missense	probably damaging	1.00
R6601:Pcsk5	UTSW	19	17511380	missense	probably benign	0.00
R6648:Pcsk5	UTSW	19	17575821	missense	probably damaging	0.99
R6789:Pcsk5	UTSW	19	17456786	missense	possibly damaging	0.93
R6807:Pcsk5	UTSW	19	17572622	splice site	probably null
R6837:Pcsk5	UTSW	19	17439084	missense	probably benign	0.01
R6998:Pcsk5	UTSW	19	17473112	missense	probably benign	0.20
R7051:Pcsk5	UTSW	19	17433731	missense	probably benign	0.00
R7164:Pcsk5	UTSW	19	17451985	missense	probably damaging	1.00
R7173:Pcsk5	UTSW	19	17477877	missense	possibly damaging	0.85
R7348:Pcsk5	UTSW	19	17456818	nonsense	probably null
R7360:Pcsk5	UTSW	19	17515213	missense	probably benign	0.00
R7407:Pcsk5	UTSW	19	17675516	missense	probably damaging	1.00
R7447:Pcsk5	UTSW	19	17510236	missense	probably benign	0.31
R7521:Pcsk5	UTSW	19	17454832	missense	probably benign	0.29
R7525:Pcsk5	UTSW	19	17642590	missense	probably damaging	1.00
R7560:Pcsk5	UTSW	19	17836972	missense	probably benign	0.01
R7566:Pcsk5	UTSW	19	17572457	missense	probably benign
R7631:Pcsk5	UTSW	19	17564780	missense	probably damaging	1.00
R7654:Pcsk5	UTSW	19	17456804	missense	possibly damaging	0.46
R7677:Pcsk5	UTSW	19	17581229	missense	possibly damaging	0.59
R7711:Pcsk5	UTSW	19	17439080	missense	possibly damaging	0.82
R7903:Pcsk5	UTSW	19	17572483	missense	probably damaging	0.98
R7938:Pcsk5	UTSW	19	17466185	critical splice acceptor site	probably null
R8025:Pcsk5	UTSW	19	17561051	intron	probably benign
R8032:Pcsk5	UTSW	19	17714787	missense	probably damaging	0.98
R8064:Pcsk5	UTSW	19	17714861	missense	probably damaging	1.00
R8115:Pcsk5	UTSW	19	17510166	critical splice donor site	probably null
R8193:Pcsk5	UTSW	19	17586051	missense	possibly damaging	0.64
R8408:Pcsk5	UTSW	19	17433445	missense	probably benign	0.00
R8466:Pcsk5	UTSW	19	17572500	nonsense	probably null
R8739:Pcsk5	UTSW	19	17454774	missense	probably benign	0.00
R8753:Pcsk5	UTSW	19	17469044	missense	probably benign	0.00
R8797:Pcsk5	UTSW	19	17466108	missense	probably benign	0.00
R8944:Pcsk5	UTSW	19	17474911	missense	probably damaging	0.96
R9041:Pcsk5	UTSW	19	17560768	nonsense	probably null
R9135:Pcsk5	UTSW	19	17586108	missense
R9288:Pcsk5	UTSW	19	17836981	missense	probably benign	0.10
R9406:Pcsk5	UTSW	19	17793733	missense	probably benign	0.14
X0023:Pcsk5	UTSW	19	17474872	missense	possibly damaging	0.66
X0063:Pcsk5	UTSW	19	17447604	missense	probably damaging	1.00
Z1088:Pcsk5	UTSW	19	17463374	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- ACTGCTGTTGCCGTATGATACTCAC -3'
(R):5'- CCCCATTTGCATCATGGGAACAGAG -3'

Sequencing Primer
(F):5'- CGTATGATACTCACACTCATGTTC -3'
(R):5'- tgggaacagagattgtgttgg -3'

Posted On

2013-04-24