Mutagenetix > Incidental Mutation

Incidental Mutation 'R8805:Pcsk6'

672001

Institutional Source

Beutler Lab

Gene Symbol

Pcsk6

Ensembl Gene

ENSMUSG00000030513

Gene Name

proprotein convertase subtilisin/kexin type 6

Synonyms

PACE4, SPC4

MMRRC Submission

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.450) question?

Stock #

R8805 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

65861734-66050386 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 65929143 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Asparagine at position 222 (Y222N)

Ref Sequence

ENSEMBL: ENSMUSP00000095992 (fasta)

Gene Model

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

AlphaFold

F6XJP7

Predicted Effect

possibly damaging
Transcript: ENSMUST00000055576
AA Change: Y222N

PolyPhen 2 Score 0.670 (Sensitivity: 0.86; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000053742
Gene: ENSMUSG00000030513
AA Change: Y222N

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: Y222N

PolyPhen 2 Score 0.670 (Sensitivity: 0.86; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000095992
Gene: ENSMUSG00000030513
AA Change: Y222N

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: ENSMUST00000176199
AA Change: Y100N

PolyPhen 2 Score 0.619 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000135851
Gene: ENSMUSG00000030513
AA Change: Y100N

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: Y135N

PolyPhen 2 Score 0.019 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000135033
Gene: ENSMUSG00000030513
AA Change: Y135N

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: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.3%

Validation Efficiency

96% (70/73)

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: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700010I14Rik	G	A	17: 9,007,905	W467*	probably null	Het
4921509C19Rik	A	T	2: 151,471,365		probably benign	Het
Actl6b	G	A	5: 137,554,656	M82I	probably benign	Het
Bmp2	T	A	2: 133,561,334	D268E	probably damaging	Het
C530008M17Rik	T	C	5: 76,858,642	V950A	unknown	Het
Cacng7	T	A	7: 3,366,782	L221H	probably damaging	Het
Ccser2	A	G	14: 36,879,755	V224A	probably damaging	Het
Cdc40	A	G	10: 40,857,580	F125L	probably damaging	Het
Cfap46	C	T	7: 139,632,063	A1669T	unknown	Het
Cfap58	A	T	19: 47,953,096	E301V	probably damaging	Het
Clcn2	C	A	16: 20,713,418	G96C	probably damaging	Het
Cotl1	T	A	8: 119,810,205		probably benign	Het
Cps1	G	A	1: 67,176,951	A812T	probably damaging	Het
Crnkl1	T	C	2: 145,931,430		probably null	Het
Cry1	A	G	10: 85,157,105	V83A	probably benign	Het
Cyp2a5	G	T	7: 26,841,105	R381L	probably damaging	Het
Cyp46a1	T	C	12: 108,361,203	F425L	probably damaging	Het
Dek	A	T	13: 47,099,454	N158K	unknown	Het
Dgcr8	T	A	16: 18,258,297	Q674L	probably damaging	Het
Dlec1	C	A	9: 119,112,582	S345R	probably benign	Het
Dnah7b	T	A	1: 46,234,145	C2478S	possibly damaging	Het
Dstyk	T	A	1: 132,434,225	L131Q	probably damaging	Het
Fbxw7	T	A	3: 84,954,920	L186M		Het
Fn1	T	C	1: 71,605,080	Q1684R	probably benign	Het
Fsip2	C	A	2: 82,983,109	H3257Q	possibly damaging	Het
Gm5773	T	C	3: 93,773,735	V238A	probably damaging	Het
Gm9611	T	C	14: 42,294,700	D131G		Het
Gpatch8	T	C	11: 102,480,192	E840G	unknown	Het
Grm5	G	A	7: 87,803,968	R271Q	probably damaging	Het
Has3	A	T	8: 106,874,503	Y199F	probably damaging	Het
Hmcn2	A	G	2: 31,425,381	N3714S	probably benign	Het
Idh1	CA	CAA	1: 65,165,188		probably null	Het
Il2	T	A	3: 37,123,133	T85S	possibly damaging	Het
Kank4	T	C	4: 98,780,036	H58R	possibly damaging	Het
Kcnk4	T	A	19: 6,928,011	I154F	probably damaging	Het
Krt2	T	C	15: 101,815,944	K295R	possibly damaging	Het
Lipm	A	T	19: 34,112,908	D163V	probably damaging	Het
Lpl	A	G	8: 68,887,563	N70S	probably damaging	Het
Mgme1	A	G	2: 144,272,531		probably benign	Het
Mnd1	T	A	3: 84,088,125	E187D	probably benign	Het
Morn5	A	G	2: 36,079,521	D149G	probably benign	Het
Mrrf	G	A	2: 36,147,953	V79I	probably damaging	Het
Msh4	T	A	3: 153,857,633	Q896L	probably benign	Het
Mtus2	A	C	5: 148,078,493	M699L	possibly damaging	Het
Mycbp	T	A	4: 123,910,087	C130S	unknown	Het
Ntn5	A	T	7: 45,684,475	Y4F	probably benign	Het
Olfr868	T	C	9: 20,101,284	V175A	probably benign	Het
Osm	A	G	11: 4,239,839	S208G	probably benign	Het
Pde6a	A	G	18: 61,257,033	E486G	probably benign	Het
Pdzk1	T	A	3: 96,851,594	L105Q	possibly damaging	Het
Prkd1	C	G	12: 50,388,372	S524T	probably benign	Het
Prkd1	T	A	12: 50,388,373	S524C	probably damaging	Het
Rab4b	T	C	7: 27,174,723	I90V		Het
Rc3h1	T	C	1: 160,967,652	V1083A	probably benign	Het
Rfx7	C	T	9: 72,617,034	T502I	probably benign	Het
Rtn4rl2	T	C	2: 84,872,214	Y332C	probably damaging	Het
Senp2	A	G	16: 22,028,039	T265A	probably benign	Het
Slc38a3	T	C	9: 107,655,146	M396V	probably benign	Het
Sord	G	A	2: 122,264,126	V332I	probably benign	Het
Sprr1b	GTGGCAGGGCTCAGGAGCCTTGGGGTGGCAGGGCTCAGGAGCCTTGGGATGGCAGGGCTCAGGAGCCTTGGGGTGGCAGGGCTCAGGA	GTGGCAGGGCTCAGGAGCCTTGGGGTGGCAGGGCTCAGGA	3: 92,437,346		probably benign	Het
Star	G	A	8: 25,809,549	R53H	probably benign	Het
Stard4	T	G	18: 33,203,696	I189L	possibly damaging	Het
Stk38	G	T	17: 29,000,120	T7K	probably benign	Het
Stxbp5	T	A	10: 9,838,115	K227*	probably null	Het
Taf4b	C	T	18: 14,813,428	P436L	possibly damaging	Het
Tgm3	T	A	2: 130,047,782	V632E	probably damaging	Het
Tmem158	A	G	9: 123,260,244	F101S	probably damaging	Het
Trmt10b	T	C	4: 45,301,281	S77P	probably benign	Het
Ttn	A	T	2: 76,889,963	L6973*	probably null	Het
Tubal3	T	C	13: 3,933,293	F358L	probably damaging	Het
Vmn1r214	C	T	13: 23,035,103	L256F	possibly damaging	Het
Vmn2r86	A	G	10: 130,446,527	V740A	probably benign	Het
Yipf1	A	T	4: 107,336,158	E80D	probably benign	Het
Zcchc11	T	C	4: 108,549,378	V1381A	possibly damaging	Het
Zdhhc2	G	T	8: 40,445,805		probably null	Het
Zfp655	C	T	5: 145,244,480	H383Y	probably damaging	Het
Zfp981	C	T	4: 146,537,953	T445I	possibly 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
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
R8734:Pcsk6	UTSW	7	65931733	missense	probably benign	0.06
R8987:Pcsk6	UTSW	7	65927227	nonsense	probably null
R9276:Pcsk6	UTSW	7	65910202	missense	probably damaging	1.00
R9492:Pcsk6	UTSW	7	66047598	missense	probably benign	0.02
R9747:Pcsk6	UTSW	7	65983722	missense	probably damaging	1.00
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'- TAGGATGGTAGTTACAGTCAGAGTG -3'
(R):5'- AACAATGTTTTGCCCCATTTCTGG -3'

Sequencing Primer
(F):5'- AGTTACAGTCAGAGTGATCCTGG -3'
(R):5'- TAACTCCATGGAAGCCATCTGTG -3'

Posted On

2021-04-30