Mutagenetix > Incidental Mutation

Incidental Mutation 'R0496:Pcsk6'

43928

Institutional Source

Beutler Lab

Gene Symbol

Pcsk6

Ensembl Gene

ENSMUSG00000030513

Gene Name

proprotein convertase subtilisin/kexin type 6

Synonyms

SPC4, PACE4, b2b2830Clo

MMRRC Submission

038692-MU

Accession Numbers

Essential gene?

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

Stock #

R0496 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

65511884-65700134 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 65576997 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Asparagine at position 58 (S58N)

Ref Sequence

ENSEMBL: ENSMUSP00000135033 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000055576] [ENSMUST00000098391] [ENSMUST00000176199] [ENSMUST00000176209]

AlphaFold

F6XJP7

Predicted Effect

probably benign
Transcript: ENSMUST00000055576
AA Change: S145N

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000053742
Gene: ENSMUSG00000030513
AA Change: S145N

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: S145N

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000095992
Gene: ENSMUSG00000030513
AA Change: S145N

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 benign
Transcript: ENSMUST00000176199
AA Change: S23N

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000135851
Gene: ENSMUSG00000030513
AA Change: S23N

Domain	Start	End	E-Value	Type
low complexity region	9	22	N/A	INTRINSIC
Pfam:Peptidase_S8	68	160	1.3e-21	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000176209
AA Change: S58N

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000135033
Gene: ENSMUSG00000030513
AA Change: S58N

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

Meta Mutation Damage Score

0.1029

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.3%
20x: 92.6%

Validation Efficiency

98% (99/101)

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: 97 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1110002E22Rik	A	G	3: 137,774,005 (GRCm39)	K1065E	probably damaging	Het
4933402N03Rik	T	C	7: 130,747,860 (GRCm39)	N44S	probably benign	Het
Abca13	A	G	11: 9,241,701 (GRCm39)	D1188G	probably benign	Het
Abcb11	C	T	2: 69,108,228 (GRCm39)		probably benign	Het
Abcc8	A	T	7: 45,758,244 (GRCm39)	I1274N	probably damaging	Het
Adamtsl1	G	A	4: 86,259,435 (GRCm39)	C827Y	probably damaging	Het
Agap3	T	A	5: 24,706,241 (GRCm39)	V369E	probably damaging	Het
Ankrd13b	G	A	11: 77,363,867 (GRCm39)	R195C	probably damaging	Het
Ap3b1	A	G	13: 94,609,446 (GRCm39)		probably benign	Het
Arhgef40	A	T	14: 52,242,364 (GRCm39)		probably benign	Het
Atad5	A	G	11: 79,991,182 (GRCm39)	I692V	probably benign	Het
Atp5f1b	G	T	10: 127,922,043 (GRCm39)	R310L	possibly damaging	Het
AY358078	A	T	14: 52,040,989 (GRCm39)	M103L	unknown	Het
Bcl9l	T	G	9: 44,420,815 (GRCm39)	V1370G	probably benign	Het
Bglap3	T	A	3: 88,276,444 (GRCm39)	Q38L	probably damaging	Het
Bltp1	A	G	3: 37,041,784 (GRCm39)	T2721A	probably damaging	Het
Ccn2	G	T	10: 24,473,413 (GRCm39)	M317I	possibly damaging	Het
Cd38	T	C	5: 44,026,233 (GRCm39)	F6L	probably damaging	Het
Cela3a	A	C	4: 137,131,779 (GRCm39)	V138G	probably damaging	Het
Cemip2	A	T	19: 21,774,709 (GRCm39)	N117I	possibly damaging	Het
Clvs1	T	A	4: 9,424,241 (GRCm39)	I229N	probably damaging	Het
Cpne1	G	A	2: 155,921,339 (GRCm39)	H16Y	probably damaging	Het
Ctc1	T	C	11: 68,926,333 (GRCm39)	L1069P	probably damaging	Het
Dgkd	G	A	1: 87,864,622 (GRCm39)	S996N	probably null	Het
Dnah9	A	T	11: 65,965,961 (GRCm39)	M1685K	probably null	Het
Dnajb12	C	T	10: 59,715,623 (GRCm39)	R42*	probably null	Het
Dock5	T	C	14: 68,054,967 (GRCm39)	Q633R	probably damaging	Het
Dync2h1	A	G	9: 7,155,180 (GRCm39)	M868T	probably benign	Het
Enpp1	G	T	10: 24,547,950 (GRCm39)	H208Q	probably benign	Het
Epha7	T	A	4: 28,821,292 (GRCm39)	D152E	probably damaging	Het
Fancd2	T	C	6: 113,532,091 (GRCm39)		probably benign	Het
Gart	G	A	16: 91,419,925 (GRCm39)		probably benign	Het
Gm10964	A	T	3: 103,646,745 (GRCm39)		probably null	Het
Gpbar1	T	C	1: 74,318,140 (GRCm39)	F128L	probably benign	Het
Gsx2	T	A	5: 75,237,726 (GRCm39)	M226K	probably benign	Het
Gucd1	T	C	10: 75,347,100 (GRCm39)	D50G	possibly damaging	Het
Has1	A	G	17: 18,064,008 (GRCm39)	Y544H	probably benign	Het
Hc	A	T	2: 34,903,583 (GRCm39)	Y1024N	probably damaging	Het
Hoxa13	CCG	CCGCG	6: 52,237,618 (GRCm39)		probably null	Het
Ift122	T	A	6: 115,882,863 (GRCm39)	H659Q	probably benign	Het
Itga2	T	C	13: 114,990,435 (GRCm39)	Q902R	probably benign	Het
Itgb2l	T	C	16: 96,235,901 (GRCm39)	K181E	possibly damaging	Het
Jak3	A	T	8: 72,135,041 (GRCm39)	H558L	probably damaging	Het
Kcnh8	A	G	17: 53,032,886 (GRCm39)	T58A	probably benign	Het
Klhl6	GT	G	16: 19,775,716 (GRCm39)	279	probably null	Het
Krt33a	C	T	11: 99,903,155 (GRCm39)		probably benign	Het
Magi2	A	T	5: 20,866,357 (GRCm39)		probably benign	Het
Map4	G	A	9: 109,868,918 (GRCm39)		probably benign	Het
Map4k4	T	A	1: 40,045,982 (GRCm39)	S754T	probably damaging	Het
Mapk8ip3	A	G	17: 25,133,424 (GRCm39)		probably benign	Het
Mib1	A	G	18: 10,804,773 (GRCm39)	S918G	probably benign	Het
Mipol1	T	A	12: 57,503,963 (GRCm39)	V377D	probably damaging	Het
Mlh1	T	C	9: 111,070,624 (GRCm39)	T364A	probably benign	Het
Mta1	C	T	12: 113,094,941 (GRCm39)	Q400*	probably null	Het
Mthfd1l	C	G	10: 4,040,006 (GRCm39)	R806G	probably benign	Het
Myh13	C	A	11: 67,239,641 (GRCm39)	N730K	probably damaging	Het
Myom1	A	G	17: 71,391,301 (GRCm39)	K937E	probably damaging	Het
Naxd	T	C	8: 11,560,224 (GRCm39)		probably benign	Het
Negr1	G	T	3: 156,721,904 (GRCm39)	K159N	probably damaging	Het
Nwd2	G	T	5: 63,963,686 (GRCm39)	W1090L	probably damaging	Het
Or1e1f	T	C	11: 73,855,706 (GRCm39)	S91P	probably benign	Het
Or2j3	A	G	17: 38,615,549 (GRCm39)	S268P	probably damaging	Het
Or51v14	C	T	7: 103,261,204 (GRCm39)	A119T	probably benign	Het
Or52r1c	T	C	7: 102,734,797 (GRCm39)	I19T	probably damaging	Het
Or5d41	A	T	2: 88,054,499 (GRCm39)	Y292*	probably null	Het
Pdzrn3	G	A	6: 101,127,531 (GRCm39)	T1045I	possibly damaging	Het
Pitrm1	T	C	13: 6,618,750 (GRCm39)	L641P	probably damaging	Het
Pkd1l1	G	T	11: 8,879,430 (GRCm39)	H474N	probably damaging	Het
Pltp	A	G	2: 164,694,381 (GRCm39)		probably benign	Het
Qtrt1	C	T	9: 21,330,844 (GRCm39)	T324M	probably benign	Het
Racgap1	A	T	15: 99,537,713 (GRCm39)		probably benign	Het
Rhbg	A	G	3: 88,161,805 (GRCm39)	V50A	probably benign	Het
Rnf135	G	A	11: 80,074,776 (GRCm39)	V12M	probably damaging	Het
Rnf7l	G	T	10: 63,257,381 (GRCm39)	C46*	probably null	Het
Rufy2	T	C	10: 62,828,949 (GRCm39)	V117A	probably damaging	Het
Safb	A	G	17: 56,912,630 (GRCm39)	M866V	probably benign	Het
Slc35c2	G	T	2: 165,122,735 (GRCm39)	T183K	probably damaging	Het
Slc39a7	A	G	17: 34,248,512 (GRCm39)	L377P	probably damaging	Het
Slit1	G	A	19: 41,596,750 (GRCm39)		probably benign	Het
Spaca9	G	A	2: 28,583,022 (GRCm39)	H133Y	probably damaging	Het
Spout1	A	G	2: 30,064,983 (GRCm39)	F339S	probably benign	Het
St6gal2	A	G	17: 55,789,015 (GRCm39)	I16M	probably damaging	Het
Stat2	T	C	10: 128,112,378 (GRCm39)	M6T	probably benign	Het
Swt1	T	A	1: 151,287,021 (GRCm39)	H157L	probably benign	Het
Syne2	A	G	12: 76,085,714 (GRCm39)	N147D	possibly damaging	Het
Tmem222	A	T	4: 133,004,902 (GRCm39)	M45K	possibly damaging	Het
Tmem30a	T	A	9: 79,684,567 (GRCm39)	H95L	probably damaging	Het
Tns3	A	C	11: 8,497,262 (GRCm39)		probably benign	Het
Trpm3	A	G	19: 22,676,142 (GRCm39)	I103V	probably benign	Het
Ube2n	T	C	10: 95,377,206 (GRCm39)	F57S	probably benign	Het
Vil1	T	C	1: 74,460,499 (GRCm39)	S219P	possibly damaging	Het
Wdfy4	A	G	14: 32,862,695 (GRCm39)		probably benign	Het
Wdr7	T	C	18: 63,924,914 (GRCm39)	S966P	probably benign	Het
Wnt8a	A	G	18: 34,677,900 (GRCm39)	N103D	probably damaging	Het
Zfp523	G	A	17: 28,419,419 (GRCm39)	E186K	possibly damaging	Het
Zfp791	A	T	8: 85,836,609 (GRCm39)	D418E	probably benign	Het
Zscan20	A	G	4: 128,485,682 (GRCm39)	V192A	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
R0518:Pcsk6	UTSW	7	65,629,915 (GRCm39)	missense	possibly damaging	0.64
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'- GCTCGCTGTTGCTGCTAGATTACC -3'
(R):5'- TCCATACAGAGCCCTCTCTGAATCC -3'

Sequencing Primer
(F):5'- CTGCTAGATTACCGATAGGAGCTG -3'
(R):5'- ccacaggggtcacatatcag -3'

Posted On

2013-05-29