Mutagenetix > Incidental Mutations

Incidental Mutation 'R0415:Pcsk6'

40239

Institutional Source

Beutler Lab

Gene Symbol

Pcsk6

Ensembl Gene

ENSMUSG00000030513

Gene Name

proprotein convertase subtilisin/kexin type 6

Synonyms

PACE4, SPC4

MMRRC Submission

038617-MU

Accession Numbers

Is this an essential gene?

Possibly non essential (E-score: 0.347) question?

Stock #

R0415 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

65861734-66050386 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 66033874 bp

Zygosity

Heterozygous

Amino Acid Change

Arginine to Cysteine at position 746 (R746C)

Ref Sequence

ENSEMBL: ENSMUSP00000095992 (fasta)

Gene Model

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000055576
AA Change: R759C

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000053742
Gene: ENSMUSG00000030513
AA Change: R759C

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 damaging
Transcript: ENSMUST00000098391
AA Change: R746C

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000095992
Gene: ENSMUSG00000030513
AA Change: R746C

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

probably damaging
Transcript: ENSMUST00000176209
AA Change: R598C

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000135033
Gene: ENSMUSG00000030513
AA Change: R598C

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

Meta Mutation Damage Score

0.2479

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.7%
20x: 93.6%

Validation Efficiency

97% (99/102)

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: 98 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4933427G23Rik	A	T	5: 23,831,050		noncoding transcript	Het
Acox2	A	G	14: 8,243,835		probably benign	Het
Adgb	T	C	10: 10,431,067		probably null	Het
Adgra3	C	A	5: 49,961,757		probably benign	Het
Adgre4	G	A	17: 55,852,288	V658I	probably benign	Het
Ahnak	A	G	19: 9,012,871		probably benign	Het
Anapc2	A	G	2: 25,278,325	T159A	probably damaging	Het
Arfgef3	A	G	10: 18,613,127		probably benign	Het
Atf7ip	C	T	6: 136,560,012	S81L	possibly damaging	Het
Cacna1i	A	G	15: 80,368,830		probably benign	Het
Camk1	A	T	6: 113,341,891	Y20*	probably null	Het
Ccdc40	T	C	11: 119,232,118	Y249H	possibly damaging	Het
Cd109	T	A	9: 78,712,615	S1380T	probably benign	Het
Cfap57	A	T	4: 118,569,431	L1107Q	possibly damaging	Het
Col6a4	C	T	9: 106,075,080	V540I	probably damaging	Het
Cst9	T	A	2: 148,838,442		probably benign	Het
Cul5	C	T	9: 53,667,070	V73I	probably benign	Het
Cxcl16	T	A	11: 70,458,748	K84*	probably null	Het
Cyp2c29	T	C	19: 39,329,095		probably benign	Het
D6Ertd527e	C	G	6: 87,111,524	T223S	unknown	Het
Dip2c	C	T	13: 9,568,289		probably benign	Het
Dis3	A	T	14: 99,087,456	I513N	probably damaging	Het
Dnajc16	A	T	4: 141,789,048	L3*	probably null	Het
Dopey1	T	A	9: 86,506,502	L480M	probably damaging	Het
Eml6	A	G	11: 29,749,392	V1787A	possibly damaging	Het
Etnk1	A	G	6: 143,180,774	N115S	probably damaging	Het
Fryl	T	C	5: 73,098,414	Y758C	probably damaging	Het
Gbp4	G	A	5: 105,121,106	R394C	possibly damaging	Het
Ggnbp2	A	C	11: 84,833,225		probably benign	Het
Gm7137	A	G	10: 77,788,173		probably benign	Het
Gstm2	T	A	3: 107,984,006	Q132L	probably benign	Het
Habp2	T	C	19: 56,317,717		probably benign	Het
Hectd2	T	C	19: 36,584,884		probably benign	Het
Htr6	A	G	4: 139,062,081	I291T	possibly damaging	Het
Ighg2c	T	C	12: 113,287,910	D199G	unknown	Het
Itih2	A	G	2: 10,105,615		probably benign	Het
Kcnab2	A	G	4: 152,395,136	F248S	probably benign	Het
Kcnc4	T	C	3: 107,445,433	K610E	probably damaging	Het
Kcnk16	T	A	14: 20,262,975		probably null	Het
Kndc1	C	T	7: 139,930,124	T1293I	probably damaging	Het
Lcp1	A	T	14: 75,227,006	I556F	possibly damaging	Het
Lrrc8d	T	C	5: 105,811,865	L47P	probably damaging	Het
Lyst	T	C	13: 13,711,610		probably benign	Het
Macrod2	G	A	2: 142,210,145		probably null	Het
Micalcl	C	T	7: 112,381,028	R70C	probably damaging	Het
Mllt3	ACTGCTGCTGCTGCTGCTGCT	ACTGCTGCTGCTGCTGCT	4: 87,841,339		probably benign	Het
Msh3	A	G	13: 92,346,786	V283A	possibly damaging	Het
Nup205	T	C	6: 35,214,634		probably benign	Het
Nxpe2	T	C	9: 48,326,614	T114A	probably damaging	Het
Olfr1023	A	T	2: 85,887,438	I213F	possibly damaging	Het
Olfr1034	A	T	2: 86,047,055	H191L	probably benign	Het
Olfr229	A	G	9: 39,909,983	Y60C	probably damaging	Het
Olfr78	C	T	7: 102,742,087	M305I	probably benign	Het
Olfr893	A	T	9: 38,209,973	M305L	probably benign	Het
Pard3	G	A	8: 127,610,566	G1221D	probably damaging	Het
Pax5	G	A	4: 44,691,886	A120V	probably damaging	Het
Pif1	G	A	9: 65,588,051	C81Y	probably benign	Het
Plcb1	A	G	2: 135,337,499	Y609C	probably damaging	Het
Plcd4	C	A	1: 74,552,097	S217Y	probably damaging	Het
Plxna1	G	A	6: 89,357,336	H104Y	probably benign	Het
Polr2k	A	G	15: 36,175,456	Y45C	probably damaging	Het
Pqlc3	C	A	12: 16,997,710		probably benign	Het
Prex1	A	G	2: 166,586,699		probably benign	Het
Pth2r	A	G	1: 65,388,439	M424V	probably benign	Het
Pygm	A	G	19: 6,391,366	R464G	probably benign	Het
Rad51c	A	G	11: 87,397,655	L234P	probably damaging	Het
Rnf145	A	G	11: 44,525,138	Y60C	probably damaging	Het
Rnf167	T	C	11: 70,649,699	I135T	probably damaging	Het
Rnf213	A	T	11: 119,414,469	I509F	probably damaging	Het
Ryr2	T	C	13: 11,869,156	S213G	probably damaging	Het
Selenbp1	T	C	3: 94,936,913	V27A	possibly damaging	Het
Selenof	T	G	3: 144,577,692	L14R	probably damaging	Het
Sfswap	A	T	5: 129,504,126	D121V	probably damaging	Het
Slc25a34	C	A	4: 141,620,469	M300I	possibly damaging	Het
Slc34a3	T	G	2: 25,229,110	T583P	probably benign	Het
Smg1	C	A	7: 118,182,468	A1199S	probably benign	Het
Spint1	A	G	2: 119,245,615	T231A	probably damaging	Het
Sptbn1	A	C	11: 30,149,576	N229K	probably damaging	Het
Sult2b1	A	G	7: 45,730,092		probably benign	Het
Tas2r123	A	T	6: 132,847,838	M233L	probably damaging	Het
Tbcel	C	A	9: 42,444,500	C139F	probably benign	Het
Thbs2	A	C	17: 14,679,973	S573A	probably benign	Het
Tmem132c	A	G	5: 127,563,705	E980G	probably damaging	Het
Tmem247	G	T	17: 86,922,322	C197F	probably damaging	Het
Tmem251	T	A	12: 102,744,876	Y119*	probably null	Het
Tmem43	C	A	6: 91,482,318	P257Q	probably benign	Het
Tmprss13	A	G	9: 45,337,132		probably null	Het
Trove2	G	T	1: 143,760,075	N444K	probably benign	Het
Ubr5	T	C	15: 37,972,980	T2626A	probably damaging	Het
Vmn1r196	T	A	13: 22,293,836	V215D	probably damaging	Het
Vmn1r22	G	T	6: 57,900,332	T220K	probably benign	Het
Vmn2r116	G	A	17: 23,387,279	M388I	possibly damaging	Het
Vmn2r74	A	C	7: 85,961,410	C25G	probably damaging	Het
Xndc1	T	C	7: 102,080,616		probably benign	Het
Zfp282	A	G	6: 47,897,881	D340G	probably damaging	Het
Zfp282	T	A	6: 47,905,053	I558N	possibly damaging	Het
Zfp316	T	A	5: 143,264,491	T56S	unknown	Het
Zfp345	A	G	2: 150,474,559		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
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
R1456:Pcsk6	UTSW	7	66043535	missense	possibly damaging	0.87
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
R8734:Pcsk6	UTSW	7	65931733	missense	probably benign	0.06
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'- AAACAAGATCCTTACCTGCCCTTGC -3'
(R):5'- TGCTGAGTGCTGTGACTTCACATCC -3'

Sequencing Primer
(F):5'- TTGCTCCCACAGGAAGTG -3'
(R):5'- CTGGTGCAAGGTTCCACAAAAG -3'

Posted On

2013-05-23