Mutagenetix > Incidental Mutation

Incidental Mutation 'R0518:Pcsk6'

48296

Institutional Source

Beutler Lab

Gene Symbol

Pcsk6

Ensembl Gene

ENSMUSG00000030513

Gene Name

proprotein convertase subtilisin/kexin type 6

Synonyms

SPC4, PACE4, b2b2830Clo

MMRRC Submission

038711-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.483) question?

Stock #

R0518 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

65511884-65700134 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 65629915 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Glutamic Acid at position 347 (V347E)

Ref Sequence

ENSEMBL: ENSMUSP00000135033 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000055576] [ENSMUST00000098391] [ENSMUST00000176209]

AlphaFold

F6XJP7

Predicted Effect

probably benign
Transcript: ENSMUST00000055576
AA Change: V508E

PolyPhen 2 Score 0.064 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000053742
Gene: ENSMUSG00000030513
AA Change: V508E

Domain	Start	End	E-Value	Type
signal peptide	1	54	N/A	INTRINSIC
Pfam:S8_pro-domain	65	141	3.1e-29	PFAM
Pfam:Peptidase_S8	186	469	5.2e-49	PFAM
Pfam:P_proprotein	529	619	9.7e-37	PFAM
FU	682	729	5.87e-11	SMART
EGF_like	688	737	5.03e1	SMART
FU	733	780	4.35e-14	SMART
EGF_like	738	771	3.57e1	SMART
FU	784	828	2.08e-11	SMART
EGF	789	819	2.48e1	SMART
FU	832	877	9.4e-10	SMART
EGF_like	837	868	6.28e1	SMART
FU	885	933	8.58e-4	SMART
EGF	890	920	1.69e1	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000098391
AA Change: V508E

PolyPhen 2 Score 0.064 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000095992
Gene: ENSMUSG00000030513
AA Change: V508E

Domain	Start	End	E-Value	Type
signal peptide	1	54	N/A	INTRINSIC
PDB:1KN6\|A	62	129	2e-6	PDB
low complexity region	131	144	N/A	INTRINSIC
Pfam:Peptidase_S8	190	478	1.1e-58	PFAM
Pfam:P_proprotein	529	619	4.5e-37	PFAM
FU	669	716	3.87e-11	SMART
EGF_like	675	724	5.03e1	SMART
FU	720	767	4.35e-14	SMART
EGF_like	725	758	3.57e1	SMART
FU	771	815	2.08e-11	SMART
EGF	776	806	2.48e1	SMART
FU	819	864	9.4e-10	SMART
EGF_like	824	855	6.28e1	SMART
FU	872	920	8.58e-4	SMART
EGF	877	907	1.69e1	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000176209
AA Change: V347E

PolyPhen 2 Score 0.645 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000135033
Gene: ENSMUSG00000030513
AA Change: V347E

Domain	Start	End	E-Value	Type
low complexity region	44	57	N/A	INTRINSIC
Pfam:Peptidase_S8	103	372	6.5e-50	PFAM
Pfam:P_proprotein	368	458	6.2e-37	PFAM
FU	521	568	5.87e-11	SMART
EGF_like	527	576	5.03e1	SMART
FU	572	619	4.35e-14	SMART
EGF_like	577	610	3.57e1	SMART
FU	623	667	2.08e-11	SMART
EGF	628	658	2.48e1	SMART
FU	671	716	9.4e-10	SMART
EGF_like	676	707	6.28e1	SMART
FU	724	772	8.58e-4	SMART
EGF	729	759	1.69e1	SMART

Coding Region Coverage

1x: 99.2%
3x: 98.4%
10x: 96.6%
20x: 93.5%

Validation Efficiency

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 the trans-Golgi network where a second autocatalytic event takes place and the catalytic activity is acquired. The encoded protease is constitutively secreted into the extracellular matrix and expressed in many tissues, including neuroendocrine, liver, gut, and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. Some of its substrates include transforming growth factor beta related proteins, proalbumin, and von Willebrand factor. This gene is thought to play a role in tumor progression and left-right patterning. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Feb 2014]
PHENOTYPE: Homozygous mutation of this gene results in partial lethality by E15.5. Embryos develop situs ambiguus with left pulmonary isomerism or craniofacial malformations including cyclopia, or both. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 82 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acaca	A	G	11: 84,181,112 (GRCm39)		probably null	Het
Acsbg3	T	A	17: 57,192,169 (GRCm39)	Y577*	probably null	Het
Acsm5	T	C	7: 119,135,023 (GRCm39)	V327A	possibly damaging	Het
Agt	C	A	8: 125,283,839 (GRCm39)	E427*	probably null	Het
Akr1c14	T	C	13: 4,131,016 (GRCm39)	L236S	probably damaging	Het
Ammecr1l	C	T	18: 31,904,954 (GRCm39)	S65L	probably benign	Het
Ankrd33b	T	C	15: 31,367,432 (GRCm39)	D36G	probably damaging	Het
Ano8	A	T	8: 71,931,902 (GRCm39)	C766S	probably benign	Het
Arhgef16	G	T	4: 154,375,491 (GRCm39)	P168T	probably damaging	Het
Asic1	C	T	15: 99,596,700 (GRCm39)	R499C	probably damaging	Het
Atpsckmt	T	G	15: 31,606,103 (GRCm39)	S20R	probably benign	Het
Bank1	C	T	3: 135,919,703 (GRCm39)	C364Y	probably damaging	Het
Bmerb1	T	A	16: 13,804,676 (GRCm39)	S8T	possibly damaging	Het
Cacna1s	C	A	1: 136,004,597 (GRCm39)	D132E	probably benign	Het
Capn5	C	T	7: 97,782,089 (GRCm39)	R217Q	probably damaging	Het
Clasrp	A	G	7: 19,322,528 (GRCm39)	I284T	probably benign	Het
Coa3	T	A	11: 101,169,716 (GRCm39)	K13M	probably damaging	Het
Col13a1	A	T	10: 61,698,525 (GRCm39)	M512K	unknown	Het
Colgalt2	G	T	1: 152,384,312 (GRCm39)	A551S	possibly damaging	Het
Crhbp	C	A	13: 95,580,403 (GRCm39)		probably null	Het
Cryba2	T	C	1: 74,929,284 (GRCm39)	Y153C	possibly damaging	Het
Cryzl2	T	C	1: 157,292,000 (GRCm39)	V93A	probably damaging	Het
Ctsl	G	A	13: 64,513,032 (GRCm39)	L297F	possibly damaging	Het
Cyp2r1	T	G	7: 114,152,135 (GRCm39)	H274P	probably benign	Het
Ddx4	A	T	13: 112,761,313 (GRCm39)		probably null	Het
Dnai4	A	C	4: 102,921,727 (GRCm39)	Y464*	probably null	Het
Dnd1	A	G	18: 36,897,096 (GRCm39)	V350A	possibly damaging	Het
Dsg1b	A	T	18: 20,521,221 (GRCm39)	Q26L	probably benign	Het
Fam20b	C	A	1: 156,515,026 (GRCm39)	V280F	possibly damaging	Het
Foxb2	G	T	19: 16,849,820 (GRCm39)	C395*	probably null	Het
Glb1	ACCC	ACC	9: 114,250,812 (GRCm39)		probably null	Het
Gm9930	A	T	10: 9,410,547 (GRCm39)		noncoding transcript	Het
Hdac7	G	A	15: 97,704,380 (GRCm39)	Q497*	probably null	Het
Hk3	C	T	13: 55,162,239 (GRCm39)		probably null	Het
Hsd3b7	A	G	7: 127,402,251 (GRCm39)	T330A	probably benign	Het
Il20ra	A	T	10: 19,635,388 (GRCm39)	Q543L	probably damaging	Het
Itk	T	A	11: 46,251,115 (GRCm39)	D163V	probably damaging	Het
Kcnu1	T	G	8: 26,400,916 (GRCm39)	L688R	probably damaging	Het
Kng1	G	A	16: 22,879,232 (GRCm39)	A45T	possibly damaging	Het
Kti12	T	A	4: 108,705,776 (GRCm39)	V230E	possibly damaging	Het
Lhfpl7	T	A	5: 113,383,873 (GRCm39)	L97*	probably null	Het
Mgat5	T	A	1: 127,312,584 (GRCm39)	I241N	probably damaging	Het
Mkln1	A	G	6: 31,445,067 (GRCm39)	N321S	probably benign	Het
Mllt10	T	G	2: 18,076,017 (GRCm39)		probably null	Het
Ms4a1	C	A	19: 11,236,043 (GRCm39)		probably null	Het
Ngly1	C	T	14: 16,290,774 (GRCm38)	Q419*	probably null	Het
Nipsnap3b	T	A	4: 53,021,343 (GRCm39)	F243I	probably damaging	Het
Ogfod1	T	A	8: 94,781,876 (GRCm39)		probably null	Het
Or10a2	T	A	7: 106,673,965 (GRCm39)	L310Q	possibly damaging	Het
Or2y11	C	T	11: 49,443,291 (GRCm39)	T239M	probably damaging	Het
Or51v8	T	A	7: 103,319,696 (GRCm39)	I181F	possibly damaging	Het
Or8c20	A	C	9: 38,260,499 (GRCm39)	N40T	probably damaging	Het
P2ry14	T	A	3: 59,022,625 (GRCm39)	E287D	probably damaging	Het
Pank4	A	T	4: 155,061,082 (GRCm39)	R510S	possibly damaging	Het
Peg3	T	C	7: 6,714,427 (GRCm39)	E265G	probably damaging	Het
Pik3c2b	C	A	1: 133,033,730 (GRCm39)	P1578H	probably damaging	Het
Pkd1	A	G	17: 24,814,193 (GRCm39)	S4188G	probably benign	Het
Ppp1r26	A	G	2: 28,342,314 (GRCm39)	D648G	probably damaging	Het
Ptprs	A	G	17: 56,726,621 (GRCm39)		probably null	Het
Rab24	A	T	13: 55,468,738 (GRCm39)		probably null	Het
Rap1gap2	A	T	11: 74,332,592 (GRCm39)	M71K	probably damaging	Het
Rergl	T	G	6: 139,473,524 (GRCm39)	K42T	probably damaging	Het
Rigi	C	T	4: 40,216,354 (GRCm39)		probably null	Het
Septin5	T	C	16: 18,443,647 (GRCm39)	T92A	probably benign	Het
Ski	A	G	4: 155,243,743 (GRCm39)		probably null	Het
Slc17a8	A	G	10: 89,412,192 (GRCm39)	S414P	probably benign	Het
Slc25a36	A	T	9: 96,979,228 (GRCm39)	I71N	probably damaging	Het
Syne2	A	C	12: 76,155,636 (GRCm39)		probably null	Het
Tdrd5	C	A	1: 156,090,511 (GRCm39)	W845L	probably damaging	Het
Tfb2m	T	C	1: 179,365,389 (GRCm39)	I192V	possibly damaging	Het
Tll1	T	G	8: 64,551,505 (GRCm39)	D292A	probably damaging	Het
Trank1	A	C	9: 111,162,876 (GRCm39)	D45A	probably damaging	Het
Trim17	T	A	11: 58,859,320 (GRCm39)	V178E	probably damaging	Het
Trim9	A	T	12: 70,393,359 (GRCm39)	L195Q	probably damaging	Het
Ttc27	A	T	17: 75,163,544 (GRCm39)	R717S	possibly damaging	Het
Upk2	G	T	9: 44,365,418 (GRCm39)	P50Q	probably damaging	Het
Usp9y	A	T	Y: 1,307,880 (GRCm39)	C2319S	probably benign	Het
Vmn1r4	G	T	6: 56,933,883 (GRCm39)	C129F	probably benign	Het
Vmn2r100	A	T	17: 19,742,178 (GRCm39)	D184V	probably damaging	Het
Xpnpep3	T	G	15: 81,311,693 (GRCm39)	I133S	possibly damaging	Het
Zfp628	A	T	7: 4,922,939 (GRCm39)	Q387L	probably damaging	Het
Zic2	CCCACCACCACCATCACCACCACCACC	CCCACCATCACCACCACCACC	14: 122,713,776 (GRCm39)		probably benign	Het

Other mutations in Pcsk6

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00234:Pcsk6	APN	7	65,577,568 (GRCm39)	missense	probably damaging	1.00
IGL01609:Pcsk6	APN	7	65,685,021 (GRCm39)	splice site	probably null
IGL01986:Pcsk6	APN	7	65,577,625 (GRCm39)	missense	probably damaging	1.00
IGL02592:Pcsk6	APN	7	65,618,776 (GRCm39)	missense	probably damaging	1.00
IGL02720:Pcsk6	APN	7	65,629,995 (GRCm39)	nonsense	probably null
R0045:Pcsk6	UTSW	7	65,612,676 (GRCm39)	missense	probably damaging	1.00
R0045:Pcsk6	UTSW	7	65,612,676 (GRCm39)	missense	probably damaging	1.00
R0053:Pcsk6	UTSW	7	65,633,451 (GRCm39)	splice site	probably benign
R0053:Pcsk6	UTSW	7	65,633,451 (GRCm39)	splice site	probably benign
R0103:Pcsk6	UTSW	7	65,578,845 (GRCm39)	splice site	probably benign
R0103:Pcsk6	UTSW	7	65,578,845 (GRCm39)	splice site	probably benign
R0119:Pcsk6	UTSW	7	65,688,791 (GRCm39)	missense	probably benign	0.10
R0299:Pcsk6	UTSW	7	65,688,791 (GRCm39)	missense	probably benign	0.10
R0415:Pcsk6	UTSW	7	65,683,622 (GRCm39)	missense	probably damaging	1.00
R0496:Pcsk6	UTSW	7	65,576,997 (GRCm39)	missense	probably benign	0.00
R0748:Pcsk6	UTSW	7	65,688,716 (GRCm39)	unclassified	probably benign
R1456:Pcsk6	UTSW	7	65,693,283 (GRCm39)	missense	possibly damaging	0.87
R1613:Pcsk6	UTSW	7	65,560,059 (GRCm39)	splice site	probably benign
R1680:Pcsk6	UTSW	7	65,684,998 (GRCm39)	missense	probably benign	0.14
R1682:Pcsk6	UTSW	7	65,559,976 (GRCm39)	missense	probably damaging	1.00
R1987:Pcsk6	UTSW	7	65,577,035 (GRCm39)	missense	possibly damaging	0.60
R4191:Pcsk6	UTSW	7	65,675,056 (GRCm39)	missense	probably damaging	0.98
R4193:Pcsk6	UTSW	7	65,675,056 (GRCm39)	missense	probably damaging	0.98
R4577:Pcsk6	UTSW	7	65,609,014 (GRCm39)	nonsense	probably null
R4592:Pcsk6	UTSW	7	65,581,480 (GRCm39)	missense	possibly damaging	0.54
R4687:Pcsk6	UTSW	7	65,633,501 (GRCm39)	missense	probably damaging	1.00
R4697:Pcsk6	UTSW	7	65,608,989 (GRCm39)	missense	probably damaging	1.00
R4778:Pcsk6	UTSW	7	65,608,893 (GRCm39)	missense	probably damaging	1.00
R5065:Pcsk6	UTSW	7	65,560,047 (GRCm39)	missense	possibly damaging	0.84
R5218:Pcsk6	UTSW	7	65,675,036 (GRCm39)	missense	probably benign	0.01
R5356:Pcsk6	UTSW	7	65,620,340 (GRCm39)	missense	probably damaging	1.00
R5427:Pcsk6	UTSW	7	65,683,647 (GRCm39)	missense	probably benign	0.01
R5589:Pcsk6	UTSW	7	65,578,933 (GRCm39)	critical splice donor site	probably null
R5637:Pcsk6	UTSW	7	65,618,745 (GRCm39)	missense	probably damaging	1.00
R5888:Pcsk6	UTSW	7	65,693,372 (GRCm39)	missense	probably null
R5958:Pcsk6	UTSW	7	65,693,359 (GRCm39)	missense	probably damaging	1.00
R5997:Pcsk6	UTSW	7	65,609,041 (GRCm39)	missense	probably damaging	1.00
R6191:Pcsk6	UTSW	7	65,578,875 (GRCm39)	missense	probably benign	0.19
R6274:Pcsk6	UTSW	7	65,683,592 (GRCm39)	missense	probably damaging	1.00
R6374:Pcsk6	UTSW	7	65,629,903 (GRCm39)	missense	possibly damaging	0.80
R6393:Pcsk6	UTSW	7	65,618,762 (GRCm39)	missense	probably damaging	1.00
R6730:Pcsk6	UTSW	7	65,629,996 (GRCm39)	missense	probably damaging	1.00
R7205:Pcsk6	UTSW	7	65,675,156 (GRCm39)	critical splice donor site	probably null
R7493:Pcsk6	UTSW	7	65,693,314 (GRCm39)	missense	possibly damaging	0.53
R7570:Pcsk6	UTSW	7	65,683,646 (GRCm39)	missense	probably benign	0.03
R7731:Pcsk6	UTSW	7	65,683,641 (GRCm39)	missense	probably benign	0.00
R7779:Pcsk6	UTSW	7	65,675,152 (GRCm39)	missense	probably benign	0.03
R8042:Pcsk6	UTSW	7	65,577,683 (GRCm39)	missense	possibly damaging	0.87
R8734:Pcsk6	UTSW	7	65,581,481 (GRCm39)	missense	probably benign	0.06
R8805:Pcsk6	UTSW	7	65,578,891 (GRCm39)	missense	possibly damaging	0.67
R8987:Pcsk6	UTSW	7	65,576,975 (GRCm39)	nonsense	probably null
R9276:Pcsk6	UTSW	7	65,559,950 (GRCm39)	missense	probably damaging	1.00
R9492:Pcsk6	UTSW	7	65,697,346 (GRCm39)	missense	probably benign	0.02
R9747:Pcsk6	UTSW	7	65,633,470 (GRCm39)	missense	probably damaging	1.00
Z1177:Pcsk6	UTSW	7	65,683,559 (GRCm39)	missense	probably damaging	0.99
Z1177:Pcsk6	UTSW	7	65,608,861 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- GTGTGTCACTGATGCAGTCCTTCC -3'
(R):5'- AGAGAGTAGCCTCACCTCTTTGCC -3'

Sequencing Primer
(F):5'- AAAGTTTCCCAGCAGTGGTC -3'
(R):5'- GCCAAAAGTTGAGACTTGGTTCC -3'

Posted On

2013-06-12