Mutagenetix > Incidental Mutation

Incidental Mutation 'R0103:Pcsk6'

34474

Institutional Source

Beutler Lab

Gene Symbol

Pcsk6

Ensembl Gene

ENSMUSG00000030513

Gene Name

proprotein convertase subtilisin/kexin type 6

Synonyms

SPC4, PACE4, b2b2830Clo

MMRRC Submission

038389-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.420) question?

Stock #

R0103 (G1)

Quality Score

225

Status

Validated (trace)

Chromosome

Chromosomal Location

65511884-65700134 bp(+) (GRCm39)

Type of Mutation

splice site

DNA Base Change (assembly)

T to C at 65578845 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

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

SMART Domains

Protein: ENSMUSP00000053742
Gene: ENSMUSG00000030513

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

SMART Domains

Protein: ENSMUSP00000095992
Gene: ENSMUSG00000030513

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

SMART Domains

Protein: ENSMUSP00000135851
Gene: ENSMUSG00000030513

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

SMART Domains

Protein: ENSMUSP00000135033
Gene: ENSMUSG00000030513

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: 99.3%
3x: 98.6%
10x: 97.0%
20x: 94.8%

Validation Efficiency

99% (84/85)

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: 84 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca13	A	C	11: 9,223,951 (GRCm39)	R443S	probably damaging	Het
Anapc1	T	C	2: 128,522,372 (GRCm39)		probably benign	Het
Aqr	T	A	2: 113,979,497 (GRCm39)	I313F	probably damaging	Het
Arfgap3	A	T	15: 83,206,922 (GRCm39)		probably benign	Het
Asah2	G	T	19: 31,996,377 (GRCm39)	H374N	probably benign	Het
Avl9	G	T	6: 56,713,468 (GRCm39)	R242L	probably benign	Het
Ccdc106	C	A	7: 5,060,544 (GRCm39)	Q35K	probably benign	Het
Ccm2l	G	T	2: 152,909,839 (GRCm39)	E64*	probably null	Het
Cep85l	A	T	10: 53,154,270 (GRCm39)	D776E	possibly damaging	Het
Cfap52	T	A	11: 67,815,951 (GRCm39)	I611F	possibly damaging	Het
Cldn22	C	T	8: 48,277,589 (GRCm39)	T9M	probably benign	Het
Coa7	T	C	4: 108,195,338 (GRCm39)	L89P	possibly damaging	Het
Cox7a2l	A	T	17: 83,821,701 (GRCm39)	Y2N	probably damaging	Het
Ctns	A	C	11: 73,076,137 (GRCm39)	I299M	probably damaging	Het
Cyp27a1	A	C	1: 74,775,074 (GRCm39)	E301A	probably benign	Het
Cyp2b13	A	T	7: 25,788,135 (GRCm39)	K421M	probably damaging	Het
Cyp4f40	G	T	17: 32,895,282 (GRCm39)	C468F	probably damaging	Het
Cyp4f40	C	A	17: 32,895,283 (GRCm39)	C468*	probably null	Het
Dcun1d5	G	A	9: 7,188,788 (GRCm39)	C74Y	probably damaging	Het
Dennd4c	A	G	4: 86,730,683 (GRCm39)	Y860C	probably benign	Het
Dgkz	T	C	2: 91,764,550 (GRCm39)	T1028A	probably benign	Het
Dhx58	T	C	11: 100,586,096 (GRCm39)	T642A	probably damaging	Het
Dlg4	A	G	11: 69,922,019 (GRCm39)	Y87C	probably damaging	Het
Dnah6	C	T	6: 73,069,155 (GRCm39)	E2511K	probably damaging	Het
Entpd5	C	A	12: 84,443,717 (GRCm39)	E9*	probably null	Het
Fbln2	A	C	6: 91,248,532 (GRCm39)	I1066L	probably benign	Het
Fhl2	C	T	1: 43,192,381 (GRCm39)	R4H	probably benign	Het
Frmpd1	T	A	4: 45,229,884 (GRCm39)	I17K	probably damaging	Het
Galnt2l	A	G	8: 122,996,472 (GRCm39)		probably benign	Het
Gbp7	T	A	3: 142,252,299 (GRCm39)	N627K	probably benign	Het
Gnptab	A	G	10: 88,265,381 (GRCm39)	Y331C	probably damaging	Het
Hdac4	T	C	1: 91,903,366 (GRCm39)	E521G	possibly damaging	Het
Hibadh	T	A	6: 52,534,862 (GRCm39)	M173L	probably benign	Het
Iba57	C	T	11: 59,054,439 (GRCm39)	A27T	probably benign	Het
Itga1	T	C	13: 115,152,790 (GRCm39)	I211V	probably benign	Het
Keg1	A	T	19: 12,696,280 (GRCm39)	I155F	possibly damaging	Het
Krt84	T	C	15: 101,438,671 (GRCm39)	E272G	probably damaging	Het
Lrp2	C	A	2: 69,307,384 (GRCm39)	V2892L	probably benign	Het
Ltb	A	G	17: 35,414,016 (GRCm39)		probably benign	Het
Masp1	G	A	16: 23,276,768 (GRCm39)	P579L	probably damaging	Het
Mtor	T	A	4: 148,618,359 (GRCm39)	M1724K	probably benign	Het
Myo3a	T	G	2: 22,436,360 (GRCm39)		probably benign	Het
Myo9b	C	T	8: 71,776,493 (GRCm39)		probably benign	Het
Ncor1	G	T	11: 62,233,871 (GRCm39)	Q444K	possibly damaging	Het
Nek7	A	T	1: 138,471,980 (GRCm39)	C53*	probably null	Het
Obscn	G	T	11: 58,953,522 (GRCm39)	Y4044*	probably null	Het
Or5b105	G	A	19: 13,080,642 (GRCm39)	R3C	possibly damaging	Het
Pcdh15	A	T	10: 74,046,257 (GRCm39)	D178V	probably damaging	Het
Phxr4	T	C	9: 13,343,087 (GRCm39)		probably benign	Het
Pkhd1	T	A	1: 20,593,583 (GRCm39)	D1510V	probably benign	Het
Pkhd1l1	T	C	15: 44,460,537 (GRCm39)	C4249R	probably benign	Het
Plxnb2	A	G	15: 89,045,972 (GRCm39)	Y968H	possibly damaging	Het
Prpf39	T	C	12: 65,102,057 (GRCm39)	V378A	possibly damaging	Het
Psd2	A	G	18: 36,137,770 (GRCm39)	N455S	probably damaging	Het
Ptch2	C	A	4: 116,966,622 (GRCm39)		probably benign	Het
Rab4b	A	G	7: 26,873,927 (GRCm39)	I117T	probably benign	Het
Rad9b	A	T	5: 122,469,590 (GRCm39)	V348E	probably damaging	Het
Rcor1	T	C	12: 111,076,212 (GRCm39)		probably benign	Het
Rhoc	A	T	3: 104,699,307 (GRCm39)	E32V	possibly damaging	Het
Rnf40	T	G	7: 127,199,743 (GRCm39)	V925G	probably damaging	Het
Rptor	G	T	11: 119,775,793 (GRCm39)	R988L	probably benign	Het
Slc25a32	A	T	15: 38,963,292 (GRCm39)	Y176*	probably null	Het
Slc7a1	T	A	5: 148,289,236 (GRCm39)	K4*	probably null	Het
Ss18	A	C	18: 14,812,478 (GRCm39)	Y38D	probably damaging	Het
Syt4	T	A	18: 31,580,273 (GRCm39)		probably benign	Het
Taar4	A	T	10: 23,837,304 (GRCm39)	N305Y	probably damaging	Het
Taar7b	A	T	10: 23,876,192 (GRCm39)	Y119F	probably benign	Het
Tcaf1	G	T	6: 42,663,324 (GRCm39)	D185E	probably benign	Het
Tmem138	T	C	19: 10,552,316 (GRCm39)	N62S	possibly damaging	Het
Tnfaip2	C	T	12: 111,412,244 (GRCm39)	T215M	probably benign	Het
Tnfrsf21	C	T	17: 43,349,104 (GRCm39)	H239Y	probably benign	Het
Tnfrsf25	C	T	4: 152,201,405 (GRCm39)	P65S	possibly damaging	Het
Trp53bp1	A	T	2: 121,067,240 (GRCm39)	S495R	possibly damaging	Het
Trpv3	T	C	11: 73,184,805 (GRCm39)	F597S	probably damaging	Het
Tsc22d4	A	C	5: 137,745,378 (GRCm39)	M1L	possibly damaging	Het
Ttc39a	A	G	4: 109,278,650 (GRCm39)		probably null	Het
Ttn	T	G	2: 76,591,570 (GRCm39)	H21033P	probably damaging	Het
Ugt2a3	A	G	5: 87,484,577 (GRCm39)	V149A	possibly damaging	Het
Ush2a	T	G	1: 188,051,267 (GRCm39)	I251R	possibly damaging	Het
Vamp4	T	C	1: 162,417,108 (GRCm39)	C114R	possibly damaging	Het
Wdr33	T	C	18: 31,966,388 (GRCm39)	V135A	probably damaging	Het
Zc3h13	T	A	14: 75,567,908 (GRCm39)	V1067E	probably damaging	Het
Zcwpw1	G	A	5: 137,808,375 (GRCm39)	W274*	probably null	Het
Zfp219	T	A	14: 52,244,163 (GRCm39)	H627L	probably damaging	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
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
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'- GGGACGAGTTGTGAAGACTGCATTA -3'
(R):5'- GGTGAAGCACCCAGAGCCTAGA -3'

Sequencing Primer
(F):5'- gaggggtgggtggggag -3'
(R):5'- CCAGAGCCTAGAACTTCTGC -3'

Posted On

2013-05-09