Mutagenetix > Incidental Mutation

Incidental Mutation 'R0032:Pcsk5'

18616

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

038326-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0032 (G1) of strain 731

Quality Score

Status

Validated

Chromosome

Chromosomal Location

17409683-17814996 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 17542179 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Asparagine to Serine at position 804 (N804S)

Ref Sequence

ENSEMBL: ENSMUSP00000050272 (fasta)

Gene Model

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

AlphaFold

Q04592

Predicted Effect

possibly damaging
Transcript: ENSMUST00000025618
AA Change: N804S

PolyPhen 2 Score 0.806 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000025618
Gene: ENSMUSG00000024713
AA Change: N804S

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

possibly damaging
Transcript: ENSMUST00000050715
AA Change: N804S

PolyPhen 2 Score 0.806 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000050272
Gene: ENSMUSG00000024713
AA Change: N804S

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

0.1495

Coding Region Coverage

1x: 80.9%
3x: 73.4%
10x: 52.4%
20x: 32.5%

Validation Efficiency

94% (87/93)

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: 40 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acss3	T	A	10: 106,959,156 (GRCm39)	T97S	probably benign	Het
Adcy1	T	C	11: 7,094,729 (GRCm39)	S552P	possibly damaging	Het
C2cd3	T	A	7: 100,093,652 (GRCm39)		probably benign	Het
Cd86	A	T	16: 36,441,235 (GRCm39)	S77R	probably damaging	Het
Cfap54	C	T	10: 92,768,559 (GRCm39)	R188H	probably benign	Het
Cpne8	T	A	15: 90,453,771 (GRCm39)		probably benign	Het
Ctsg	T	A	14: 56,339,196 (GRCm39)	I21F	probably damaging	Het
Cyp2j9	T	G	4: 96,457,043 (GRCm39)	N476T	possibly damaging	Het
Dcaf4	G	A	12: 83,582,762 (GRCm39)		probably benign	Het
Dennd4c	T	C	4: 86,746,387 (GRCm39)		probably null	Het
Dicer1	A	T	12: 104,671,057 (GRCm39)	L995*	probably null	Het
Dnah10	A	G	5: 124,877,955 (GRCm39)	K2623R	possibly damaging	Het
Dnajc21	G	T	15: 10,461,963 (GRCm39)	T146K	probably benign	Het
Dnmbp	A	C	19: 43,891,158 (GRCm39)	L203R	probably damaging	Het
Eif4g1	C	T	16: 20,504,648 (GRCm39)	S829F	probably damaging	Het
Enkur	T	C	2: 21,194,115 (GRCm39)	I153V	probably benign	Het
Erf	T	C	7: 24,944,500 (GRCm39)	Y277C	possibly damaging	Het
Fcsk	G	A	8: 111,618,735 (GRCm39)	T341M	possibly damaging	Het
Fstl5	T	A	3: 76,555,742 (GRCm39)		probably benign	Het
Grm3	A	G	5: 9,561,452 (GRCm39)		probably null	Het
Il11ra1	A	G	4: 41,768,187 (GRCm39)	E366G	probably damaging	Het
Ipo8	A	G	6: 148,712,209 (GRCm39)	C261R	probably damaging	Het
Itga11	T	C	9: 62,681,377 (GRCm39)	F998L	probably benign	Het
Krt74	T	A	15: 101,669,887 (GRCm39)		noncoding transcript	Het
Me2	T	G	18: 73,927,596 (GRCm39)	M219L	probably benign	Het
Mlh3	A	G	12: 85,292,523 (GRCm39)		probably benign	Het
Nfx1	T	A	4: 41,015,321 (GRCm39)	V842E	probably benign	Het
Oma1	T	A	4: 103,223,209 (GRCm39)	S465T	possibly damaging	Het
Opa1	A	T	16: 29,433,887 (GRCm39)	H574L	probably damaging	Het
Pde4a	C	A	9: 21,112,728 (GRCm39)		probably benign	Het
Pilra	T	A	5: 137,829,527 (GRCm39)	D179V	probably damaging	Het
Piwil1	G	A	5: 128,820,344 (GRCm39)	S247N	probably benign	Het
Prss58	T	G	6: 40,872,633 (GRCm39)	T158P	probably benign	Het
Slc35e3	T	C	10: 117,580,837 (GRCm39)	M156V	probably benign	Het
Slit2	G	A	5: 48,414,198 (GRCm39)	R938Q	probably damaging	Het
Syt8	T	C	7: 141,992,926 (GRCm39)	V152A	probably benign	Het
Tppp2	G	T	14: 52,156,866 (GRCm39)	R81L	possibly damaging	Het
Trpc3	A	G	3: 36,698,405 (GRCm39)	I618T	probably damaging	Het
Zc3h4	T	A	7: 16,168,565 (GRCm39)	D891E	unknown	Het
Zfp120	A	T	2: 149,959,512 (GRCm39)	V270E	possibly damaging	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
R0373:Pcsk5	UTSW	19	17,632,213 (GRCm39)	missense	probably damaging	1.00
R0784:Pcsk5	UTSW	19	17,692,133 (GRCm39)	missense	probably benign	0.06
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

Posted On

2013-03-25