Mutagenetix > Incidental Mutations

Incidental Mutation 'R1456:Pcsk6'

161784

Institutional Source

Beutler Lab

Gene Symbol

Pcsk6

Ensembl Gene

ENSMUSG00000030513

Gene Name

proprotein convertase subtilisin/kexin type 6

Synonyms

PACE4, SPC4

MMRRC Submission

039511-MU

Accession Numbers

Is this an essential gene?

Possibly non essential (E-score: 0.250) question?

Stock #

R1456 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

65861734-66050386 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 66043535 bp

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Phenylalanine at position 693 (I693F)

Ref Sequence

ENSEMBL: ENSMUSP00000135033 (fasta)

Gene Model

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

Predicted Effect

possibly damaging
Transcript: ENSMUST00000055576
AA Change: I854F

PolyPhen 2 Score 0.691 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000053742
Gene: ENSMUSG00000030513
AA Change: I854F

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

possibly damaging
Transcript: ENSMUST00000098391
AA Change: I841F

PolyPhen 2 Score 0.691 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000095992
Gene: ENSMUSG00000030513
AA Change: I841F

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: I693F

PolyPhen 2 Score 0.869 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000135033
Gene: ENSMUSG00000030513
AA Change: I693F

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000177272

Predicted Effect

probably benign
Transcript: ENSMUST00000206065

Meta Mutation Damage Score

0.0777

Coding Region Coverage

1x: 98.9%
3x: 97.9%
10x: 95.1%
20x: 88.9%

Validation Efficiency

98% (90/92)

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: 88 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4921504E06Rik	C	T	2: 19,480,920		probably null	Het
4930563D23Rik	T	A	16: 92,320,665	Y245F	probably damaging	Het
4932414N04Rik	A	T	2: 68,716,214	E80V	possibly damaging	Het
Alkbh3	A	G	2: 94,001,419		probably null	Het
Ankar	A	T	1: 72,665,118	Y664N	probably benign	Het
Arhgap18	T	C	10: 26,916,440	I629T	probably benign	Het
Arhgef28	C	T	13: 98,075,002	E158K	probably benign	Het
Asxl2	C	T	12: 3,501,872	H1205Y	possibly damaging	Het
Birc6	A	G	17: 74,609,290	I427V	probably benign	Het
Camk4	A	G	18: 33,129,843		probably benign	Het
Ccdc178	A	T	18: 22,150,424	D16E	possibly damaging	Het
Cct6b	G	T	11: 82,753,620		probably benign	Het
Ccz1	A	G	5: 144,011,018		probably benign	Het
Cdh23	T	C	10: 60,487,120	N335S	possibly damaging	Het
Cemip	T	A	7: 83,998,510	S121C	possibly damaging	Het
Cers1	A	G	8: 70,331,188	E262G	probably damaging	Het
Clec11a	G	T	7: 44,306,450	P58T	possibly damaging	Het
Clec16a	T	C	16: 10,691,555	I797T	probably damaging	Het
Col4a1	A	C	8: 11,242,829		probably benign	Het
Colgalt2	G	A	1: 152,484,904	V231I	probably damaging	Het
D430041D05Rik	G	T	2: 104,208,083	N1580K	probably damaging	Het
Dcdc5	A	G	2: 106,351,565		noncoding transcript	Het
Ddx17	T	C	15: 79,530,376	D530G	probably benign	Het
Dhx9	A	T	1: 153,465,695	D601E	probably benign	Het
Dnah3	A	G	7: 120,047,630	Y1059H	probably damaging	Het
Dtx1	C	A	5: 120,710,504		probably benign	Het
Egfr	A	G	11: 16,863,065	S182G	probably benign	Het
Fads1	A	G	19: 10,185,752	N131S	probably benign	Het
Fancm	C	T	12: 65,118,351	A1490V	possibly damaging	Het
Fsd2	C	A	7: 81,559,591	E168*	probably null	Het
Gm20388	T	C	8: 122,841,948		probably benign	Het
Gm9772	A	T	17: 22,007,118	C62S	probably damaging	Het
H60c	C	T	10: 3,260,307	A81T	possibly damaging	Het
Hira	T	G	16: 18,925,663	S377A	probably benign	Het
Iffo1	T	C	6: 125,145,914	S220P	possibly damaging	Het
Itih4	A	G	14: 30,892,653	M491V	probably benign	Het
Khdrbs2	T	C	1: 32,520,696	R102G	possibly damaging	Het
Klhdc7a	T	G	4: 139,965,524	Y704S	possibly damaging	Het
Klk1b21	G	A	7: 44,105,499	V73I	probably benign	Het
Krt42	G	A	11: 100,269,609	A88V	probably benign	Het
Krt42	C	T	11: 100,269,610	A88T	probably benign	Het
Limk1	G	T	5: 134,657,510	D580E	probably benign	Het
Lipk	C	T	19: 34,046,785	P323S	probably damaging	Het
Lipo5	T	A	19: 33,465,873		probably benign	Het
Llgl2	A	G	11: 115,845,499	D166G	probably benign	Het
Mapk8ip3	A	T	17: 24,906,949	N439K	probably damaging	Het
Mapkbp1	C	T	2: 119,973,145	R32W	probably damaging	Het
Med23	T	A	10: 24,903,652		probably benign	Het
Mrgprb1	A	T	7: 48,448,029	M45K	probably damaging	Het
Mroh7	G	A	4: 106,695,141		probably benign	Het
Mrpl27	G	A	11: 94,653,833		probably benign	Het
Ms4a10	T	A	19: 10,964,733	T175S	possibly damaging	Het
Muc3	T	C	5: 137,137,951	H330R	probably benign	Het
Myo15	A	T	11: 60,508,202	I2787F	probably damaging	Het
Ndst1	A	G	18: 60,713,205	C11R	possibly damaging	Het
Obsl1	C	A	1: 75,487,656	G1669*	probably null	Het
Olfr477	A	G	7: 107,990,398	E11G	probably benign	Het
Olfr784	A	T	10: 129,387,783	D50V	probably damaging	Het
Olfr873	T	C	9: 20,300,838	Y214H	probably benign	Het
Pafah2	T	A	4: 134,404,157	I52N	probably damaging	Het
Pde4c	G	T	8: 70,746,613	R228L	probably benign	Het
Pdzd8	T	C	19: 59,300,472	N832S	probably benign	Het
Plbd1	T	A	6: 136,613,816	M451L	probably benign	Het
Pramef17	G	T	4: 143,993,281	D171E	probably benign	Het
Prom1	T	C	5: 44,037,623	D260G	probably damaging	Het
Ranbp17	A	G	11: 33,266,310	S813P	probably damaging	Het
Scn10a	T	C	9: 119,691,478	I119V	probably benign	Het
Sh3pxd2b	A	G	11: 32,415,967	T353A	probably damaging	Het
Shq1	A	T	6: 100,669,698		probably null	Het
Slc22a28	T	A	19: 8,071,858	H342L	possibly damaging	Het
Slco2b1	C	T	7: 99,664,907	E9K	probably null	Het
Specc1l	T	C	10: 75,246,284	F505L	probably damaging	Het
Sptan1	G	T	2: 29,980,203		probably null	Het
St6gal2	A	G	17: 55,490,931		probably benign	Het
Taok2	T	C	7: 126,880,141	I73V	probably benign	Het
Tax1bp1	C	T	6: 52,744,244	T478I	probably benign	Het
Tbc1d4	A	T	14: 101,507,106	N361K	probably damaging	Het
Tph1	A	T	7: 46,647,483	Y429*	probably null	Het
Tprkb	A	T	6: 85,924,421	R14W	probably damaging	Het
Trio	A	T	15: 27,753,804		probably benign	Het
Ttc23	T	C	7: 67,667,154		probably benign	Het
Vmn1r211	T	C	13: 22,852,245	Y84C	probably damaging	Het
Vmn2r22	C	G	6: 123,637,665	G322A	possibly damaging	Het
Wdr74	A	G	19: 8,740,412	Q330R	probably benign	Het
Wdtc1	C	A	4: 133,297,428	S486I	possibly damaging	Het
Zbtb24	T	C	10: 41,464,993	V673A	possibly damaging	Het
Zfpm2	A	T	15: 41,102,481	R655S	probably damaging	Het
Zkscan5	A	G	5: 145,220,988	N694D	probably benign	Het

Other mutations in Pcsk6

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00234:Pcsk6	APN	7	65927820	missense	probably damaging	1.00
IGL01609:Pcsk6	APN	7	66035273	splice site	probably null
IGL01986:Pcsk6	APN	7	65927877	missense	probably damaging	1.00
IGL02592:Pcsk6	APN	7	65969028	missense	probably damaging	1.00
IGL02720:Pcsk6	APN	7	65980247	nonsense	probably null
R0045:Pcsk6	UTSW	7	65962928	missense	probably damaging	1.00
R0045:Pcsk6	UTSW	7	65962928	missense	probably damaging	1.00
R0053:Pcsk6	UTSW	7	65983703	splice site	probably benign
R0053:Pcsk6	UTSW	7	65983703	splice site	probably benign
R0103:Pcsk6	UTSW	7	65929097	splice site	probably benign
R0103:Pcsk6	UTSW	7	65929097	splice site	probably benign
R0119:Pcsk6	UTSW	7	66039043	missense	probably benign	0.10
R0299:Pcsk6	UTSW	7	66039043	missense	probably benign	0.10
R0415:Pcsk6	UTSW	7	66033874	missense	probably damaging	1.00
R0496:Pcsk6	UTSW	7	65927249	missense	probably benign	0.00
R0518:Pcsk6	UTSW	7	65980167	missense	possibly damaging	0.64
R0748:Pcsk6	UTSW	7	66038968	unclassified	probably benign
R1613:Pcsk6	UTSW	7	65910311	splice site	probably benign
R1680:Pcsk6	UTSW	7	66035250	missense	probably benign	0.14
R1682:Pcsk6	UTSW	7	65910228	missense	probably damaging	1.00
R1987:Pcsk6	UTSW	7	65927287	missense	possibly damaging	0.60
R4191:Pcsk6	UTSW	7	66025308	missense	probably damaging	0.98
R4193:Pcsk6	UTSW	7	66025308	missense	probably damaging	0.98
R4577:Pcsk6	UTSW	7	65959266	nonsense	probably null
R4592:Pcsk6	UTSW	7	65931732	missense	possibly damaging	0.54
R4687:Pcsk6	UTSW	7	65983753	missense	probably damaging	1.00
R4697:Pcsk6	UTSW	7	65959241	missense	probably damaging	1.00
R4778:Pcsk6	UTSW	7	65959145	missense	probably damaging	1.00
R5065:Pcsk6	UTSW	7	65910299	missense	possibly damaging	0.84
R5218:Pcsk6	UTSW	7	66025288	missense	probably benign	0.01
R5356:Pcsk6	UTSW	7	65970592	missense	probably damaging	1.00
R5427:Pcsk6	UTSW	7	66033899	missense	probably benign	0.01
R5589:Pcsk6	UTSW	7	65929185	critical splice donor site	probably null
R5637:Pcsk6	UTSW	7	65968997	missense	probably damaging	1.00
R5888:Pcsk6	UTSW	7	66043624	missense	probably null
R5958:Pcsk6	UTSW	7	66043611	missense	probably damaging	1.00
R5997:Pcsk6	UTSW	7	65959293	missense	probably damaging	1.00
R6191:Pcsk6	UTSW	7	65929127	missense	probably benign	0.19
R6274:Pcsk6	UTSW	7	66033844	missense	probably damaging	1.00
R6374:Pcsk6	UTSW	7	65980155	missense	possibly damaging	0.80
R6393:Pcsk6	UTSW	7	65969014	missense	probably damaging	1.00
R6730:Pcsk6	UTSW	7	65980248	missense	probably damaging	1.00
R7205:Pcsk6	UTSW	7	66025408	critical splice donor site	probably null
R7493:Pcsk6	UTSW	7	66043566	missense	possibly damaging	0.53
R7570:Pcsk6	UTSW	7	66033898	missense	probably benign	0.03
R7731:Pcsk6	UTSW	7	66033893	missense	probably benign	0.00
R7779:Pcsk6	UTSW	7	66025404	missense	probably benign	0.03
R8042:Pcsk6	UTSW	7	65927935	missense	possibly damaging	0.87
Z1177:Pcsk6	UTSW	7	65959113	missense	probably damaging	1.00
Z1177:Pcsk6	UTSW	7	66033811	missense	probably damaging	0.99

Predicted Primers

PCR Primer
(F):5'- GTGTTCTACCCTCACAGCACAACTC -3'
(R):5'- AGCTGCTCTTTCTACAGTGCCCAG -3'

Sequencing Primer
(F):5'- TTGAAGTCAGTCACCAAGGC -3'
(R):5'- TTTCTACAGTGCCCAGATAACC -3'

Posted On

2014-03-14