Mutagenetix > Incidental Mutation

Incidental Mutation 'R9276:Pcsk6'

703295

Institutional Source

Beutler Lab

Gene Symbol

Pcsk6

Ensembl Gene

ENSMUSG00000030513

Gene Name

proprotein convertase subtilisin/kexin type 6

Synonyms

SPC4, PACE4, b2b2830Clo

MMRRC Submission

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.483) question?

Stock #

R9276 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

65511884-65700134 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 65559950 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Phenylalanine at position 92 (I92F)

Ref Sequence

ENSEMBL: ENSMUSP00000095992 (fasta)

Gene Model

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

AlphaFold

F6XJP7

Predicted Effect

probably damaging
Transcript: ENSMUST00000055576
AA Change: I92F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000053742
Gene: ENSMUSG00000030513
AA Change: I92F

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 damaging
Transcript: ENSMUST00000098391
AA Change: I92F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000095992
Gene: ENSMUSG00000030513
AA Change: I92F

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

possibly damaging
Transcript: ENSMUST00000176209
AA Change: I5F

PolyPhen 2 Score 0.951 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000135033
Gene: ENSMUSG00000030513
AA Change: I5F

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: 98.7%

Validation Efficiency

99% (83/84)

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
9630041A04Rik	A	T	9: 101,819,887 (GRCm39)	R102S	probably benign	Het
Abitram	A	T	4: 56,806,141 (GRCm39)	K184N	probably benign	Het
Acvr2b	C	T	9: 119,231,616 (GRCm39)	T2M	probably benign	Het
Adamtsl3	A	G	7: 82,206,710 (GRCm39)		probably benign	Het
Adcy7	A	G	8: 89,052,014 (GRCm39)	Y894C	probably damaging	Het
Afdn	T	A	17: 14,024,270 (GRCm39)	C59S	probably damaging	Het
Amt	C	A	9: 108,178,410 (GRCm39)	T339K	probably benign	Het
Ankrd27	G	T	7: 35,319,995 (GRCm39)	V639L	probably benign	Het
Anxa10	G	T	8: 62,549,753 (GRCm39)	Q31K	probably damaging	Het
Ap1g2	T	C	14: 55,339,818 (GRCm39)	T454A	probably benign	Het
Boll	A	T	1: 55,399,812 (GRCm39)	I43N	possibly damaging	Het
Cacna1c	T	C	6: 118,601,394 (GRCm39)	D1472G		Het
Calcrl	T	C	2: 84,205,643 (GRCm39)	N16S	probably benign	Het
Ccdc191	C	T	16: 43,764,041 (GRCm39)	Q501*	probably null	Het
Cchcr1	T	C	17: 35,841,105 (GRCm39)	L658P	probably damaging	Het
Cfap46	A	T	7: 139,201,207 (GRCm39)	C1919S	unknown	Het
Col6a3	G	A	1: 90,735,403 (GRCm39)	L1356F	possibly damaging	Het
Dlc1	A	G	8: 37,046,558 (GRCm39)	S680P	possibly damaging	Het
Dock4	T	G	12: 40,699,404 (GRCm39)	M206R	possibly damaging	Het
Eml5	T	C	12: 98,765,060 (GRCm39)	K1630E	probably damaging	Het
Fat1	A	G	8: 45,488,514 (GRCm39)	T3432A	probably damaging	Het
Fcrl5	G	T	3: 87,343,138 (GRCm39)		probably benign	Het
Fcrla	A	G	1: 170,755,135 (GRCm39)		probably benign	Het
Fut4	C	A	9: 14,662,572 (GRCm39)	D241Y	probably benign	Het
Fzd6	A	G	15: 38,870,962 (GRCm39)		probably benign	Het
Gjc2	T	C	11: 59,068,453 (GRCm39)	T10A	probably damaging	Het
Gle1	C	T	2: 29,829,514 (GRCm39)	H203Y	possibly damaging	Het
Gm5565	A	T	5: 146,096,917 (GRCm39)	I74N	probably damaging	Het
Gnl2	T	A	4: 124,947,250 (GRCm39)	I624K	possibly damaging	Het
Gnpat	C	A	8: 125,614,524 (GRCm39)	N653K	probably benign	Het
Gstcd	A	G	3: 132,777,665 (GRCm39)	L382S	probably damaging	Het
Ipcef1	A	G	10: 6,857,936 (GRCm39)		probably benign	Het
Jmjd7	T	C	2: 119,860,895 (GRCm39)	V115A	possibly damaging	Het
Ltbp2	G	A	12: 84,837,864 (GRCm39)	P1192L	probably benign	Het
Ltbp2	T	G	12: 84,876,885 (GRCm39)	D440A	possibly damaging	Het
Macf1	T	G	4: 123,328,501 (GRCm39)	D4744A	probably damaging	Het
Mapk11	T	C	15: 89,029,372 (GRCm39)	D230G	probably damaging	Het
Mfsd6	A	C	1: 52,747,514 (GRCm39)	Y450*	probably null	Het
Mtmr9	A	G	14: 63,781,001 (GRCm39)	C30R	probably damaging	Het
Ncf1	G	A	5: 134,250,693 (GRCm39)	Q376*	probably null	Het
Ncor2	C	A	5: 125,113,150 (GRCm39)	R296M		Het
Or51ah3	A	T	7: 103,210,004 (GRCm39)	T107S	probably damaging	Het
Or5d37	A	G	2: 87,923,806 (GRCm39)	V158A	probably benign	Het
Or5k8	A	G	16: 58,644,734 (GRCm39)	F113L	probably benign	Het
Or8b57	A	T	9: 40,003,632 (GRCm39)	I210K	possibly damaging	Het
Or8b8	C	A	9: 37,809,415 (GRCm39)	S238R	probably benign	Het
Or8k31-ps1	A	T	2: 86,356,392 (GRCm39)	L43*	probably null	Het
Pate9	A	T	9: 36,445,727 (GRCm39)	C75S	probably damaging	Het
Plec	A	G	15: 76,060,445 (GRCm39)	V3164A	probably benign	Het
Prss16	A	G	13: 22,190,175 (GRCm39)		probably benign	Het
Ptch2	T	A	4: 116,967,505 (GRCm39)	H724Q	probably damaging	Het
Pzp	A	T	6: 128,499,077 (GRCm39)	F190Y	probably damaging	Het
Rab6a	A	G	7: 100,275,809 (GRCm39)	T41A	probably benign	Het
Rbm6	A	G	9: 107,660,926 (GRCm39)	L879P	probably damaging	Het
Rem1	T	A	2: 152,469,969 (GRCm39)		probably benign	Het
Rnf17	T	C	14: 56,719,554 (GRCm39)	S935P	probably damaging	Het
Ryr1	C	A	7: 28,802,254 (GRCm39)	V789L	probably damaging	Het
Scgb2b3	A	T	7: 31,059,528 (GRCm39)	M82K	possibly damaging	Het
Sgce	T	A	6: 4,674,585 (GRCm39)	L451F	probably damaging	Het
Slc25a17	A	C	15: 81,207,814 (GRCm39)	V258G	probably benign	Het
Spidr	G	A	16: 15,784,712 (GRCm39)	T452I	probably benign	Het
Tas2r129	A	G	6: 132,928,576 (GRCm39)	N171S	probably benign	Het
Tbc1d24	A	T	17: 24,405,114 (GRCm39)	V10E	probably damaging	Het
Tdo2	T	G	3: 81,876,885 (GRCm39)	M115L	probably benign	Het
Tdrd9	T	C	12: 111,980,935 (GRCm39)		probably null	Het
Tead1	T	A	7: 112,493,601 (GRCm39)	I376N	probably damaging	Het
Tmem26	A	G	10: 68,614,488 (GRCm39)	H301R	possibly damaging	Het
Tnxb	A	G	17: 34,929,134 (GRCm39)	T2726A	possibly damaging	Het
Trim43c	T	C	9: 88,723,966 (GRCm39)	M164T	probably benign	Het
Trpc1	G	A	9: 95,590,288 (GRCm39)	S723L	probably benign	Het
Txndc15	A	G	13: 55,865,914 (GRCm39)	D126G	probably benign	Het
Urb1	C	T	16: 90,569,463 (GRCm39)		probably benign	Het
Usp25	C	T	16: 76,910,721 (GRCm39)	H926Y	probably benign	Het
Uvssa	T	A	5: 33,572,180 (GRCm39)	M700K	possibly damaging	Het
Vdac1	T	A	11: 52,274,789 (GRCm39)	Y146N	probably damaging	Het
Vmn1r231	A	T	17: 21,110,560 (GRCm39)	S118R	probably benign	Het
Vmn1r41	A	G	6: 89,724,080 (GRCm39)	Y207C	probably damaging	Het
Vmn2r79	A	G	7: 86,687,045 (GRCm39)	I809V	probably damaging	Het
Vnn1	G	A	10: 23,776,794 (GRCm39)	G382R	probably damaging	Het
Xcr1	A	T	9: 123,685,680 (GRCm39)	H27Q	probably benign	Het
Yeats2	T	A	16: 19,975,786 (GRCm39)	N94K	probably benign	Het
Zfp28	C	T	7: 6,397,440 (GRCm39)	T625M	probably damaging	Het
Zfp521	T	C	18: 13,977,698 (GRCm39)	Q905R	probably benign	Het
Zfp804b	T	C	5: 6,821,398 (GRCm39)	D555G	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
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
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'- TGTGTATGCTTCCTCAGAAACAC -3'
(R):5'- ACCCATTATGGTCTCCTTTGAG -3'

Sequencing Primer
(F):5'- TGCTTCCTCAGAAACACTACATTGAG -3'
(R):5'- TCCTTTGAGGAGGGCAAAAC -3'

Posted On

2022-03-25