Mutagenetix > Incidental Mutations

Incidental Mutation 'R0103:Pcsk6'

34474

Institutional Source

Beutler Lab

Gene Symbol

Pcsk6

Ensembl Gene

ENSMUSG00000030513

Gene Name

proprotein convertase subtilisin/kexin type 6

Synonyms

PACE4, SPC4

MMRRC Submission

038389-MU

Accession Numbers

Is this an essential gene?

Possibly non essential (E-score: 0.356) question?

Stock #

R0103 (G1)

Quality Score

225

Status

Validated (trace)

Chromosome

Chromosomal Location

65861734-66050386 bp(+) (GRCm38)

Type of Mutation

splice site

DNA Base Change (assembly)

T to C at 65929097 bp

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000135033 (fasta)

Gene Model

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

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: 9,273,951	R443S	probably damaging	Het
Anapc1	T	C	2: 128,680,452		probably benign	Het
Aqr	T	A	2: 114,149,016	I313F	probably damaging	Het
Arfgap3	A	T	15: 83,322,721		probably benign	Het
Asah2	G	T	19: 32,018,977	H374N	probably benign	Het
Avl9	G	T	6: 56,736,483	R242L	probably benign	Het
Ccdc106	C	A	7: 5,057,545	Q35K	probably benign	Het
Ccm2l	G	T	2: 153,067,919	E64*	probably null	Het
Cep85l	A	T	10: 53,278,174	D776E	possibly damaging	Het
Cfap52	T	A	11: 67,925,125	I611F	possibly damaging	Het
Cldn22	C	T	8: 47,824,554	T9M	probably benign	Het
Coa7	T	C	4: 108,338,141	L89P	possibly damaging	Het
Cox7a2l	A	T	17: 83,514,272	Y2N	probably damaging	Het
Ctns	A	C	11: 73,185,311	I299M	probably damaging	Het
Cyp27a1	A	C	1: 74,735,915	E301A	probably benign	Het
Cyp2b13	A	T	7: 26,088,710	K421M	probably damaging	Het
Cyp4f40	C	A	17: 32,676,309	C468*	probably null	Het
Cyp4f40	G	T	17: 32,676,308	C468F	probably damaging	Het
Dcun1d5	G	A	9: 7,188,788	C74Y	probably damaging	Het
Dennd4c	A	G	4: 86,812,446	Y860C	probably benign	Het
Dgkz	T	C	2: 91,934,205	T1028A	probably benign	Het
Dhx58	T	C	11: 100,695,270	T642A	probably damaging	Het
Dlg4	A	G	11: 70,031,193	Y87C	probably damaging	Het
Dnah6	C	T	6: 73,092,172	E2511K	probably damaging	Het
Entpd5	C	A	12: 84,396,943	E9*	probably null	Het
Fbln2	A	C	6: 91,271,550	I1066L	probably benign	Het
Fhl2	C	T	1: 43,153,221	R4H	probably benign	Het
Frmpd1	T	A	4: 45,229,884	I17K	probably damaging	Het
Gbp7	T	A	3: 142,546,538	N627K	probably benign	Het
Gm20388	A	G	8: 122,269,733		probably benign	Het
Gnptab	A	G	10: 88,429,519	Y331C	probably damaging	Het
Hdac4	T	C	1: 91,975,644	E521G	possibly damaging	Het
Hibadh	T	A	6: 52,557,877	M173L	probably benign	Het
Iba57	C	T	11: 59,163,613	A27T	probably benign	Het
Itga1	T	C	13: 115,016,254	I211V	probably benign	Het
Keg1	A	T	19: 12,718,916	I155F	possibly damaging	Het
Krt84	T	C	15: 101,530,236	E272G	probably damaging	Het
Lrp2	C	A	2: 69,477,040	V2892L	probably benign	Het
Ltb	A	G	17: 35,195,040		probably benign	Het
Masp1	G	A	16: 23,458,018	P579L	probably damaging	Het
Mtor	T	A	4: 148,533,902	M1724K	probably benign	Het
Myo3a	T	G	2: 22,544,322		probably benign	Het
Myo9b	C	T	8: 71,323,849		probably benign	Het
Ncor1	G	T	11: 62,343,045	Q444K	possibly damaging	Het
Nek7	A	T	1: 138,544,242	C53*	probably null	Het
Obscn	G	T	11: 59,062,696	Y4044*	probably null	Het
Olfr1458	G	A	19: 13,103,278	R3C	possibly damaging	Het
Pcdh15	A	T	10: 74,210,425	D178V	probably damaging	Het
Phxr4	T	C	9: 13,431,791		probably benign	Het
Pkhd1	T	A	1: 20,523,359	D1510V	probably benign	Het
Pkhd1l1	T	C	15: 44,597,141	C4249R	probably benign	Het
Plxnb2	A	G	15: 89,161,769	Y968H	possibly damaging	Het
Prpf39	T	C	12: 65,055,283	V378A	possibly damaging	Het
Psd2	A	G	18: 36,004,717	N455S	probably damaging	Het
Ptch2	C	A	4: 117,109,425		probably benign	Het
Rab4b	A	G	7: 27,174,502	I117T	probably benign	Het
Rad9b	A	T	5: 122,331,527	V348E	probably damaging	Het
Rcor1	T	C	12: 111,109,778		probably benign	Het
Rhoc	A	T	3: 104,791,991	E32V	possibly damaging	Het
Rnf40	T	G	7: 127,600,571	V925G	probably damaging	Het
Rptor	G	T	11: 119,884,967	R988L	probably benign	Het
Slc25a32	A	T	15: 39,099,897	Y176*	probably null	Het
Slc7a1	T	A	5: 148,352,426	K4*	probably null	Het
Ss18	A	C	18: 14,679,421	Y38D	probably damaging	Het
Syt4	T	A	18: 31,447,220		probably benign	Het
Taar4	A	T	10: 23,961,406	N305Y	probably damaging	Het
Taar7b	A	T	10: 24,000,294	Y119F	probably benign	Het
Tcaf1	G	T	6: 42,686,390	D185E	probably benign	Het
Tmem138	T	C	19: 10,574,952	N62S	possibly damaging	Het
Tnfaip2	C	T	12: 111,445,810	T215M	probably benign	Het
Tnfrsf21	C	T	17: 43,038,213	H239Y	probably benign	Het
Tnfrsf25	C	T	4: 152,116,948	P65S	possibly damaging	Het
Trp53bp1	A	T	2: 121,236,759	S495R	possibly damaging	Het
Trpv3	T	C	11: 73,293,979	F597S	probably damaging	Het
Tsc22d4	A	C	5: 137,747,116	M1L	possibly damaging	Het
Ttc39a	A	G	4: 109,421,453		probably null	Het
Ttn	T	G	2: 76,761,226	H21033P	probably damaging	Het
Ugt2a3	A	G	5: 87,336,718	V149A	possibly damaging	Het
Ush2a	T	G	1: 188,319,070	I251R	possibly damaging	Het
Vamp4	T	C	1: 162,589,539	C114R	possibly damaging	Het
Wdr33	T	C	18: 31,833,335	V135A	probably damaging	Het
Zc3h13	T	A	14: 75,330,468	V1067E	probably damaging	Het
Zcwpw1	G	A	5: 137,810,113	W274*	probably null	Het
Zfp219	T	A	14: 52,006,706	H627L	probably damaging	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
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
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
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'- GGGACGAGTTGTGAAGACTGCATTA -3'
(R):5'- GGTGAAGCACCCAGAGCCTAGA -3'

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

Posted On

2013-05-09