Mutagenetix > Incidental Mutation

Incidental Mutation 'R6191:Pcsk6'

502558

Institutional Source

Beutler Lab

Gene Symbol

Pcsk6

Ensembl Gene

ENSMUSG00000030513

Gene Name

proprotein convertase subtilisin/kexin type 6

Synonyms

SPC4, PACE4, b2b2830Clo

MMRRC Submission

044331-MU

Accession Numbers

Essential gene?

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

Stock #

R6191 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

65511884-65700134 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 65578875 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glutamic Acid at position 129 (D129E)

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: D216E

PolyPhen 2 Score 0.071 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000053742
Gene: ENSMUSG00000030513
AA Change: D216E

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: D216E

PolyPhen 2 Score 0.071 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000095992
Gene: ENSMUSG00000030513
AA Change: D216E

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: D94E

PolyPhen 2 Score 0.049 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000135851
Gene: ENSMUSG00000030513
AA Change: D94E

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: D129E

PolyPhen 2 Score 0.191 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000135033
Gene: ENSMUSG00000030513
AA Change: D129E

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: 99.6%
20x: 98.8%

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
4930563M21Rik	A	C	9: 55,909,807 (GRCm39)	D144E	possibly damaging	Het
Amigo2	T	A	15: 97,143,419 (GRCm39)	K334N	probably benign	Het
Ano6	T	C	15: 95,846,380 (GRCm39)		probably null	Het
Ap1m2	C	A	9: 21,210,601 (GRCm39)	V343F	probably benign	Het
Apol6	T	C	15: 76,940,098 (GRCm39)	V307A	probably benign	Het
Arsi	C	A	18: 61,045,544 (GRCm39)	A78E	probably damaging	Het
B2m	A	T	2: 121,981,396 (GRCm39)	N37I	possibly damaging	Het
Bltp3b	G	T	10: 89,641,180 (GRCm39)	G784C	possibly damaging	Het
C8a	T	C	4: 104,703,100 (GRCm39)	K363R	probably benign	Het
Ccdc117	C	A	11: 5,484,242 (GRCm39)		probably null	Het
Ccdc154	C	A	17: 25,386,945 (GRCm39)	Q325K	probably damaging	Het
Cd300e	A	T	11: 114,945,359 (GRCm39)	V145E	possibly damaging	Het
Col19a1	G	T	1: 24,356,474 (GRCm39)	P673Q	probably damaging	Het
Csn2	A	G	5: 87,843,885 (GRCm39)		probably null	Het
Ctnna1	T	C	18: 35,307,408 (GRCm39)	V135A	probably damaging	Het
Dnah11	T	A	12: 118,154,632 (GRCm39)	D216V	probably benign	Het
Dnah12	A	G	14: 26,431,412 (GRCm39)	H410R	probably benign	Het
Dock2	C	T	11: 34,181,652 (GRCm39)	R1637H	possibly damaging	Het
Dspp	A	G	5: 104,325,214 (GRCm39)	N526D	unknown	Het
Frem2	T	C	3: 53,562,701 (GRCm39)	H602R	probably benign	Het
Galc	A	T	12: 98,218,293 (GRCm39)	H186Q	probably damaging	Het
Grina	T	C	15: 76,133,218 (GRCm39)	V262A	probably damaging	Het
Gse1	G	A	8: 121,280,542 (GRCm39)		probably null	Het
H2-Oa	C	A	17: 34,312,842 (GRCm39)	Q40K	probably damaging	Het
Hfm1	C	A	5: 107,034,419 (GRCm39)	D763Y	possibly damaging	Het
Hmcn2	T	A	2: 31,348,758 (GRCm39)	Y4925N	probably damaging	Het
Hs3st3b1	C	A	11: 63,780,029 (GRCm39)	R366L	probably benign	Het
Idh2	TCCCAGG	T	7: 79,748,079 (GRCm39)		probably benign	Het
Iqank1	T	C	15: 75,918,218 (GRCm39)		probably null	Het
Itpr2	A	G	6: 146,229,833 (GRCm39)	V1221A	probably benign	Het
Kdm6b	T	C	11: 69,297,584 (GRCm39)	N285S	probably benign	Het
Klk1b1	T	A	7: 43,620,081 (GRCm39)	N181K	probably damaging	Het
Kmt2a	C	A	9: 44,738,125 (GRCm39)		probably benign	Het
Lama5	T	C	2: 179,827,752 (GRCm39)	D2170G	probably damaging	Het
Lama5	T	A	2: 179,822,404 (GRCm39)	T2890S	probably damaging	Het
Lsm2	T	A	17: 35,201,131 (GRCm39)		probably benign	Het
Map3k5	G	T	10: 19,899,415 (GRCm39)	C232F	probably damaging	Het
Mapk9	T	G	11: 49,754,383 (GRCm39)	D45E	probably damaging	Het
Mpnd	T	C	17: 56,319,482 (GRCm39)	V315A	possibly damaging	Het
Msh2	A	G	17: 88,030,900 (GRCm39)	I926V	probably benign	Het
Mtcl1	C	T	17: 66,650,521 (GRCm39)	R1345H	probably damaging	Het
Nbeal2	A	G	9: 110,457,058 (GRCm39)		probably null	Het
Neo1	T	C	9: 58,796,312 (GRCm39)	D1205G	probably damaging	Het
Nhlrc2	A	G	19: 56,559,291 (GRCm39)	S259G	probably benign	Het
Nkain4	G	A	2: 180,577,796 (GRCm39)	P186L	probably damaging	Het
Nkain4	G	A	2: 180,577,797 (GRCm39)	P186S	probably damaging	Het
Nlrp1b	T	A	11: 71,109,283 (GRCm39)	R73*	probably null	Het
Nr5a2	T	C	1: 136,818,536 (GRCm39)	D330G	probably damaging	Het
Nup54	A	G	5: 92,572,153 (GRCm39)	L299P	probably damaging	Het
Or2v1	T	C	11: 49,025,877 (GRCm39)	L286P	probably damaging	Het
Or5aq7	A	G	2: 86,938,296 (GRCm39)	V145A	probably damaging	Het
Pcdhb8	T	A	18: 37,489,279 (GRCm39)	V319E	probably benign	Het
Pld5	G	A	1: 175,798,100 (GRCm39)	T433I	probably benign	Het
Plin1	A	T	7: 79,371,347 (GRCm39)	L459H	probably benign	Het
Psd4	T	C	2: 24,284,499 (GRCm39)	V121A	probably damaging	Het
Pxdn	A	T	12: 30,032,716 (GRCm39)	I167F	possibly damaging	Het
R3hdm2	T	C	10: 127,320,384 (GRCm39)	S569P	probably damaging	Het
Rfng	T	A	11: 120,673,516 (GRCm39)	T202S	probably damaging	Het
Robo1	T	C	16: 72,730,696 (GRCm39)	S266P	probably benign	Het
Sema3c	G	T	5: 17,858,804 (GRCm39)	V68L	probably damaging	Het
Slco6c1	C	T	1: 96,993,808 (GRCm39)	R645H	possibly damaging	Het
Slfn8	A	G	11: 82,907,626 (GRCm39)	Y306H	possibly damaging	Het
Snap91	T	C	9: 86,720,105 (GRCm39)	D144G	probably damaging	Het
St7l	T	G	3: 104,775,349 (GRCm39)	F75C	probably damaging	Het
Stard10	A	G	7: 100,992,468 (GRCm39)	I145V	probably damaging	Het
Tekt3	C	T	11: 62,968,999 (GRCm39)	A242V	probably damaging	Het
Tex44	A	G	1: 86,354,306 (GRCm39)		probably benign	Het
Thg1l	T	C	11: 45,844,988 (GRCm39)	Q88R	probably benign	Het
Trav8n-2	T	A	14: 53,583,744 (GRCm39)	I67N	probably damaging	Het
Ttn	G	A	2: 76,677,770 (GRCm39)		probably benign	Het
Ube4a	A	T	9: 44,861,051 (GRCm39)	L253*	probably null	Het
Uggt1	A	T	1: 36,201,289 (GRCm39)	N1150K	probably damaging	Het
Ush2a	T	A	1: 187,995,298 (GRCm39)	L23*	probably null	Het
Usp22	T	A	11: 61,065,602 (GRCm39)	N37I	probably benign	Het
Usp53	T	A	3: 122,743,390 (GRCm39)	K515N	probably damaging	Het
Vmn2r4	T	C	3: 64,322,702 (GRCm39)	K6E	probably benign	Het
Vps13d	C	T	4: 144,875,918 (GRCm39)	V1530M	probably damaging	Het
Vwa3b	A	G	1: 37,153,612 (GRCm39)	I485V	possibly damaging	Het
Wnk4	T	C	11: 101,155,156 (GRCm39)	Y356H	probably damaging	Het
Zcchc2	A	G	1: 105,917,900 (GRCm39)		probably benign	Het
Zfp345	A	C	2: 150,315,010 (GRCm39)	Y176D	probably benign	Het
Zfp598	T	C	17: 24,896,850 (GRCm39)	F238S	possibly damaging	Het
Zkscan17	T	C	11: 59,393,820 (GRCm39)	D10G	probably damaging	Het
Zmat4	T	G	8: 24,392,083 (GRCm39)	M13R	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
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
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'- GCATTAACACTGGAAAACTTGGTG -3'
(R):5'- TCTGAGACCTAGGTATGCCC -3'

Sequencing Primer
(F):5'- AGCACAAATACTGGGTGGTTCCTC -3'
(R):5'- CCAGGCAGCACCCAGACAG -3'

Posted On

2018-02-27