Mutagenetix > Incidental Mutation

Incidental Mutation 'R7570:Pcsk6'

585713

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 #

R7570 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

65861734-66050386 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 66033898 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 754 (T754A)

Ref Sequence

ENSEMBL: ENSMUSP00000095992 (fasta)

Gene Model

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

AlphaFold

F6XJP7

Predicted Effect

probably benign
Transcript: ENSMUST00000055576
AA Change: T767A

PolyPhen 2 Score 0.031 (Sensitivity: 0.95; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000053742
Gene: ENSMUSG00000030513
AA Change: T767A

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: T754A

PolyPhen 2 Score 0.031 (Sensitivity: 0.95; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000095992
Gene: ENSMUSG00000030513
AA Change: T754A

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: ENSMUST00000176209
AA Change: T606A

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)

SMART Domains

Protein: ENSMUSP00000135033
Gene: ENSMUSG00000030513
AA Change: T606A

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: 99.9%
10x: 99.7%
20x: 99.1%

Validation Efficiency

98% (104/106)

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: 106 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930590J08Rik	C	T	6: 91,934,610	T613I	probably benign	Het
9130019O22Rik	T	A	7: 127,385,283	S216C	probably benign	Het
Ajuba	T	C	14: 54,576,402	E288G	probably damaging	Het
Ankrd12	C	T	17: 65,985,360	R1026K	probably benign	Het
Apol7b	T	C	15: 77,423,474	T274A	probably benign	Het
Arid4a	A	T	12: 71,063,142	R86*	probably null	Het
Asnsd1	C	T	1: 53,348,258	G70D	probably damaging	Het
Atg4c	T	A	4: 99,228,560	V313D	possibly damaging	Het
Atp13a5	A	C	16: 29,266,963	C885G	probably damaging	Het
Bpifb9a	A	T	2: 154,262,263	I209F	possibly damaging	Het
Bsn	T	C	9: 108,113,543	D1670G	probably damaging	Het
Cct8	T	A	16: 87,491,322	I121F	probably benign	Het
Cd209a	T	G	8: 3,744,151	D217A	probably damaging	Het
Cdk19	C	T	10: 40,477,958	S456L	possibly damaging	Het
Chd9	C	T	8: 90,994,580	H999Y	unknown	Het
Col5a1	G	A	2: 27,951,383	V339M	unknown	Het
Cr2	G	A	1: 195,169,340	R115*	probably null	Het
Cyb561	A	T	11: 105,937,644	F62I	probably damaging	Het
Cyp2c38	A	T	19: 39,404,743	N293K	possibly damaging	Het
Cyp2c69	A	T	19: 39,859,898	D293E	probably damaging	Het
Dcbld2	T	A	16: 58,424,569	C69S	possibly damaging	Het
Dcdc2a	T	C	13: 25,119,373	S296P	probably benign	Het
Dmxl1	T	A	18: 49,893,957	I2044K	possibly damaging	Het
Dnah5	A	G	15: 28,346,952	D2527G	probably damaging	Het
Dnah6	T	C	6: 73,149,430	T1305A	probably benign	Het
Dnajc9	A	G	14: 20,388,644	V47A	probably benign	Het
Dnmt3b	A	G	2: 153,676,699	Y594C	probably damaging	Het
Dph7	A	G	2: 24,965,630	D147G	probably damaging	Het
Drap1	T	C	19: 5,423,352	H164R	possibly damaging	Het
Dsg3	T	A	18: 20,527,780	V392E	possibly damaging	Het
Dxo	A	G	17: 34,837,640	D81G	probably benign	Het
E230025N22Rik	G	T	18: 36,695,592	T11K	probably benign	Het
Esyt1	A	G	10: 128,518,932	V533A	possibly damaging	Het
Etv3	T	A	3: 87,536,031	C307*	probably null	Het
Fam114a1	T	A	5: 65,030,059		probably null	Het
Fam208b	A	G	13: 3,573,621	Y2110H	probably damaging	Het
Fam3c	T	A	6: 22,326,405		probably benign	Het
Fbn1	G	T	2: 125,397,852	T305K	probably benign	Het
Ggt1	A	T	10: 75,585,594	I484F	probably damaging	Het
Gm10639	A	T	9: 78,304,469	D171V	possibly damaging	Het
Gpatch1	T	C	7: 35,293,812	D536G	probably damaging	Het
Gpx4	T	C	10: 80,055,041	I189T	probably damaging	Het
Gsr	T	A	8: 33,669,165	C85S	probably damaging	Het
Havcr1	T	A	11: 46,770,542		probably null	Het
Heatr4	T	C	12: 83,979,644	T280A	probably benign	Het
Hmcn2	A	T	2: 31,423,911	E3532D	probably benign	Het
Hnrnpc	T	C	14: 52,075,099	N308S	possibly damaging	Het
Ighv8-9	A	G	12: 115,468,738	V13A	probably benign	Het
Itgb2l	A	T	16: 96,426,239	F535I	probably benign	Het
Kdm5a	T	G	6: 120,427,842	D1348E	probably damaging	Het
Kndc1	CT	C	7: 139,923,775		probably null	Het
Ky	A	G	9: 102,542,329	I512V	probably benign	Het
Lamc1	A	T	1: 153,243,275	F866Y	possibly damaging	Het
Lbx1	C	A	19: 45,235,248		probably benign	Het
Magel2	A	G	7: 62,378,910	T521A	possibly damaging	Het
Mgam	A	T	6: 40,746,433	I491L	probably benign	Het
Mitd1	T	C	1: 37,890,192	E40G	probably damaging	Het
Mpzl3	A	G	9: 45,070,687	T218A	probably benign	Het
Mrpl42	A	G	10: 95,480,965	S77P	probably benign	Het
Mup5	C	T	4: 61,834,674	W37*	probably null	Het
Myh14	T	C	7: 44,632,426	I803V	probably benign	Het
Ncor2	T	A	5: 125,030,089	T744S		Het
Ndufv3	A	G	17: 31,527,622	D162G	probably damaging	Het
Nostrin	A	G	2: 69,175,806	E278G	probably damaging	Het
Nrxn1	T	G	17: 90,162,379	E1288A	probably benign	Het
Olfr1205	A	G	2: 88,831,128	N4D	possibly damaging	Het
Olfr623	C	A	7: 103,660,881	R123L	probably damaging	Het
Olfr648	T	A	7: 104,179,748	Y220F	probably damaging	Het
Olfr972	A	T	9: 39,873,455	Y60F	possibly damaging	Het
Patj	T	A	4: 98,424,500		probably null	Het
Pcm1	T	G	8: 41,267,344	I314R	possibly damaging	Het
Pde2a	A	T	7: 101,502,834	N326I	probably benign	Het
Plekhg4	T	C	8: 105,378,684	S594P	possibly damaging	Het
Plekhm3	T	C	1: 64,937,906	D135G	probably damaging	Het
Plin4	A	T	17: 56,106,776	M283K	probably benign	Het
Ppfia3	T	C	7: 45,340,748		probably null	Het
Prdm9	T	C	17: 15,555,652	N179S	probably benign	Het
Prrt3	T	C	6: 113,494,488	S908G	probably damaging	Het
Psg22	C	A	7: 18,722,735	S181Y	possibly damaging	Het
Rcor3	C	A	1: 192,137,876	G8V	probably damaging	Het
Rp1l1	T	A	14: 64,031,574	C1536*	probably null	Het
Rpp25l	T	C	4: 41,712,529	H82R	probably damaging	Het
Rps3a1	T	A	3: 86,139,089	M172L	probably benign	Het
Rtbdn	T	C	8: 84,952,927	L110P	probably damaging	Het
Ryr1	T	A	7: 29,078,585	Q2169L	probably damaging	Het
Scn4a	A	T	11: 106,320,473	C1573S	possibly damaging	Het
Sec16b	A	T	1: 157,531,395		probably null	Het
Serpina1a	A	T	12: 103,853,837	D383E	possibly damaging	Het
Sh3gl3	T	C	7: 82,285,077	M262T	probably benign	Het
Sos2	G	A	12: 69,590,880	T1052M	probably damaging	Het
Spag16	G	A	1: 69,996,841	V343I	probably benign	Het
Spocd1	T	G	4: 129,930,164	D251E		Het
Stc2	G	T	11: 31,367,798	N74K	probably damaging	Het
Thbs3	C	T	3: 89,219,052	Q227*	probably null	Het
Tmem92	A	C	11: 94,778,990	I105R	probably benign	Het
Tmod1	T	A	4: 46,083,632	N20K	probably benign	Het
Tns1	T	C	1: 73,953,479	D53G	probably damaging	Het
Tspan33	T	A	6: 29,717,338	L246Q	probably damaging	Het
Ttc16	A	G	2: 32,768,968	L392P	probably damaging	Het
Uggt1	T	A	1: 36,185,838	T572S	probably benign	Het
Usp17la	A	T	7: 104,860,397	T70S	probably damaging	Het
Usp31	C	T	7: 121,674,963	R370H	probably damaging	Het
Wdr83	C	T	8: 85,079,834	V112M	probably damaging	Het
Zbtb25	T	A	12: 76,369,592		probably benign	Het
Zfp110	T	A	7: 12,849,340	N638K	possibly damaging	Het
Zfp820	T	C	17: 21,819,013	T445A	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
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
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
R8805:Pcsk6	UTSW	7	65929143	missense	possibly damaging	0.67
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'- AAACAAGATCCTTACCTGCCCTTG -3'
(R):5'- CTGCTGAGTGCTGTGACTTC -3'

Sequencing Primer
(F):5'- CTTGCTCCCACAGGAAGTG -3'
(R):5'- CCTGGTGCAAGGTTCCACAAAAG -3'

Posted On

2019-10-17