Mutagenetix > Incidental Mutation

Incidental Mutation 'R4657:Pcsk1'

352552

Institutional Source

Beutler Lab

Gene Symbol

Pcsk1

Ensembl Gene

ENSMUSG00000021587

Gene Name

proprotein convertase subtilisin/kexin type 1

Synonyms

PC3, Nec1, Phpp-1, Nec-1, SPC3, prohormone convertase 1/3, PC1

MMRRC Submission

041917-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4657 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

75237945-75282980 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 75280354 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glutamic Acid at position 726 (D726E)

Ref Sequence

ENSEMBL: ENSMUSP00000022075 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000022075]

AlphaFold

P63239

PDB Structure

Solution Structure of the Mouse Prohormone Convertase 1 Pro-Domain [SOLUTION NMR]
PC1/3 DCSG sorting domain structure in DPC [SOLUTION NMR]
PC1/3 DCSG sorting domain in CHAPS [SOLUTION NMR]

Predicted Effect

probably damaging
Transcript: ENSMUST00000022075
AA Change: D726E

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

SMART Domains

Protein: ENSMUSP00000022075
Gene: ENSMUSG00000021587
AA Change: D726E

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC
Pfam:S8_pro-domain	34	110	6.4e-26	PFAM
Pfam:Peptidase_S8	158	442	2.2e-49	PFAM
Pfam:P_proprotein	504	591	6.1e-30	PFAM
low complexity region	679	694	N/A	INTRINSIC
Pfam:Proho_convert	713	751	4.3e-26	PFAM

Meta Mutation Damage Score

0.2813

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.4%
20x: 95.6%

Validation Efficiency

98% (105/107)

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 subcellular compartments where a second autocatalytic even takes place and the catalytic activity is acquired. The protease is packaged into and activated in dense core secretory granules and expressed in the neuroendocrine system and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It functions in the proteolytic activation of polypeptide hormones and neuropeptides precursors. Mutations in this gene have been associated with susceptibility to obesity and proprotein convertase 1/3 deficiency. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene [provided by RefSeq, Jan 2014]
PHENOTYPE: Homozygotes for a null allele show pre- and postnatal death, low weight, diarrhea, hypoglycemia, low insulin and GHRH levels, and lack mature glucagon and ACTH levels. Homozygotes for another null allele die prior to implantation. ENU mutants show obesity, polyphagia and higher metabolic efficiency. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 102 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aatk	A	T	11: 119,904,304 (GRCm39)	V264E	possibly damaging	Het
Abcg1	T	A	17: 31,327,408 (GRCm39)	W368R	probably benign	Het
Acin1	A	G	14: 54,880,504 (GRCm39)	I476T	possibly damaging	Het
Acsm1	T	A	7: 119,239,917 (GRCm39)	I287N	possibly damaging	Het
Adgrv1	C	T	13: 81,553,483 (GRCm39)	V5464I	probably benign	Het
AI429214	T	A	8: 37,461,545 (GRCm39)	L231Q	probably damaging	Het
Akp3	A	G	1: 87,053,556 (GRCm39)		probably benign	Het
Amy2b	C	T	3: 113,060,793 (GRCm39)		noncoding transcript	Het
Apoa5	A	G	9: 46,181,170 (GRCm39)	Q82R	probably benign	Het
Arhgap44	A	G	11: 64,896,278 (GRCm39)		probably null	Het
Arhgef38	C	A	3: 132,940,442 (GRCm39)	G48V	probably damaging	Het
Bltp3a	T	A	17: 28,109,079 (GRCm39)	F1099L	probably benign	Het
Bod1l	G	T	5: 41,975,955 (GRCm39)	N1786K	probably benign	Het
Cav2	A	T	6: 17,281,409 (GRCm39)	D17V	probably null	Het
Ccdc148	G	T	2: 58,891,900 (GRCm39)	N238K	probably benign	Het
Ccin	A	T	4: 43,984,981 (GRCm39)	I463F	probably damaging	Het
Cd8b1	C	T	6: 71,306,758 (GRCm39)	H162Y	possibly damaging	Het
Cdh16	T	A	8: 105,341,858 (GRCm39)		probably null	Het
Cfap65	T	A	1: 74,964,513 (GRCm39)		probably benign	Het
Clec4n	T	C	6: 123,209,155 (GRCm39)		probably null	Het
Cpne7	T	A	8: 123,861,314 (GRCm39)	*558R	probably null	Het
Cs	A	G	10: 128,189,006 (GRCm39)	I172V	probably benign	Het
Cyp2ab1	A	T	16: 20,131,822 (GRCm39)	L306Q	probably damaging	Het
D16Ertd472e	A	T	16: 78,344,814 (GRCm39)	V98E	probably damaging	Het
Dcaf15	A	C	8: 84,829,467 (GRCm39)	S92A	probably damaging	Het
Dkk3	T	C	7: 111,748,253 (GRCm39)		probably null	Het
Dnah11	A	T	12: 118,156,162 (GRCm39)	C163S	probably benign	Het
Eda2r	T	A	X: 96,385,239 (GRCm39)	Q171L	probably damaging	Het
Eml4	A	T	17: 83,758,377 (GRCm39)	K397*	probably null	Het
Eml6	A	T	11: 29,755,108 (GRCm39)	I889N	possibly damaging	Het
Etaa1	A	T	11: 17,896,964 (GRCm39)	D384E	possibly damaging	Het
Fzr1	T	A	10: 81,203,386 (GRCm39)		probably null	Het
Gm13889	G	T	2: 93,786,921 (GRCm39)	F61L	probably damaging	Het
Gm14149	A	T	2: 151,072,684 (GRCm39)		noncoding transcript	Het
Gm5828	T	A	1: 16,839,642 (GRCm39)		noncoding transcript	Het
Gm5866	G	A	5: 52,740,262 (GRCm39)		noncoding transcript	Het
Gp2	T	C	7: 119,056,391 (GRCm39)	I27M	probably benign	Het
Gpr83	G	A	9: 14,778,279 (GRCm39)		probably null	Het
Gucd1	T	C	10: 75,346,959 (GRCm39)	N97S	probably benign	Het
H2bc27	C	T	11: 58,839,797 (GRCm39)	P11L	probably benign	Het
H2-Q7	T	A	17: 35,661,735 (GRCm39)	V326E	possibly damaging	Het
Haao	A	T	17: 84,139,774 (GRCm39)	D227E	possibly damaging	Het
Hipk3	C	T	2: 104,264,104 (GRCm39)	S819N	probably benign	Het
Hlcs	A	G	16: 94,063,557 (GRCm39)	V501A	probably benign	Het
Hmcn1	A	G	1: 150,500,301 (GRCm39)	Y3964H	probably damaging	Het
Ifi204	C	A	1: 173,587,927 (GRCm39)		probably benign	Het
Ifi211	A	G	1: 173,735,226 (GRCm39)	F68L	probably benign	Het
Ift57	A	G	16: 49,582,957 (GRCm39)		probably null	Het
Ighv5-12-4	A	T	12: 113,725,887 (GRCm39)	L112*	probably null	Het
Il1rl2	CTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTATT	CTTTATTTTATTTTATTTTATTTTATTTTATTTTATT	1: 40,366,470 (GRCm39)		probably benign	Het
Il36a	T	A	2: 24,114,416 (GRCm39)	M97K	possibly damaging	Het
Itsn2	A	G	12: 4,763,197 (GRCm39)	*1686W	probably null	Het
Jkamp	G	T	12: 72,140,823 (GRCm39)	V123F	probably damaging	Het
Kat7	C	A	11: 95,168,424 (GRCm39)	V411L	probably damaging	Het
Kcnj5	A	G	9: 32,233,973 (GRCm39)	V114A	probably benign	Het
Krtap5-4	T	A	7: 141,857,491 (GRCm39)	C54S	unknown	Het
Lats1	T	A	10: 7,581,448 (GRCm39)	N744K	possibly damaging	Het
Lpo	T	C	11: 87,705,173 (GRCm39)	E387G	probably damaging	Het
Lrba	T	G	3: 86,644,471 (GRCm39)	M388R	probably damaging	Het
Lrp2	C	A	2: 69,297,337 (GRCm39)	R3208L	probably damaging	Het
Mterf1b	T	A	5: 4,247,176 (GRCm39)	C272*	probably null	Het
Myh15	A	T	16: 48,992,421 (GRCm39)	R1632*	probably null	Het
Myo3b	T	C	2: 70,069,243 (GRCm39)	V494A	possibly damaging	Het
Myo9a	T	C	9: 59,782,699 (GRCm39)		probably null	Het
Nelfa	T	G	5: 34,059,157 (GRCm39)	S233R	probably benign	Het
Nr4a3	A	T	4: 48,051,522 (GRCm39)	E121V	probably damaging	Het
Obscn	T	A	11: 58,933,116 (GRCm39)	E5406D	probably damaging	Het
Ofcc1	G	A	13: 40,168,864 (GRCm39)	T841I	probably damaging	Het
Or1j18	T	A	2: 36,624,415 (GRCm39)	Y27*	probably null	Het
Or7e177	A	C	9: 20,211,919 (GRCm39)	H142P	probably damaging	Het
Oxct2b	T	C	4: 123,010,926 (GRCm39)	L282P	probably damaging	Het
Pappa	G	A	4: 65,233,033 (GRCm39)		probably null	Het
Pcdhb14	A	G	18: 37,581,900 (GRCm39)	I335M	possibly damaging	Het
Pkhd1	T	A	1: 20,434,391 (GRCm39)	Q2349L	possibly damaging	Het
Pkhd1l1	G	A	15: 44,410,743 (GRCm39)	C2750Y	probably damaging	Het
Ppp2r3d	A	G	9: 124,476,821 (GRCm38)	C26R	unknown	Het
Prex2	T	A	1: 11,136,049 (GRCm39)	I74N	probably benign	Het
Ptgir	A	G	7: 16,641,071 (GRCm39)	D121G	probably benign	Het
Pwwp3a	T	A	10: 80,068,848 (GRCm39)	C331S	probably benign	Het
Ralbp1	T	C	17: 66,159,686 (GRCm39)	S526G	probably null	Het
Ric8b	T	C	10: 84,828,001 (GRCm39)	Y442H	probably damaging	Het
Rpap1	C	T	2: 119,605,487 (GRCm39)	D385N	probably benign	Het
Sash1	T	C	10: 8,601,424 (GRCm39)	Y1177C	probably damaging	Het
Shroom1	T	C	11: 53,356,415 (GRCm39)	I363T	possibly damaging	Het
Slc26a9	T	C	1: 131,680,876 (GRCm39)	L95P	probably damaging	Het
Slc44a5	A	G	3: 153,962,221 (GRCm39)	T385A	possibly damaging	Het
Slc5a9	C	A	4: 111,748,941 (GRCm39)		probably null	Het
Slc7a1	T	A	5: 148,289,209 (GRCm39)	M13L	probably benign	Het
Snrpb2	A	G	2: 142,912,893 (GRCm39)	N172S	possibly damaging	Het
Spns1	G	T	7: 125,973,474 (GRCm39)		probably benign	Het
Srsf6	T	A	2: 162,775,347 (GRCm39)	S86R	probably benign	Het
Stk25	A	T	1: 93,553,378 (GRCm39)		probably benign	Het
Szt2	A	T	4: 118,254,866 (GRCm39)	C275S	probably benign	Het
Tcp10b	T	A	17: 13,292,504 (GRCm39)		probably null	Het
Tmem248	T	A	5: 130,260,615 (GRCm39)	L60H	probably damaging	Het
Trim27	T	C	13: 21,367,930 (GRCm39)	I182T	probably damaging	Het
Tspan10	A	G	11: 120,335,324 (GRCm39)	N145D	probably damaging	Het
Vps13d	A	G	4: 144,801,412 (GRCm39)	F487S	probably damaging	Het
Wdr86	A	T	5: 24,923,229 (GRCm39)	D154E	probably benign	Het
Wfdc18	C	A	11: 83,600,695 (GRCm39)	A32D	possibly damaging	Het
Wrn	A	T	8: 33,826,019 (GRCm39)		probably null	Het
Zfp811	C	A	17: 33,019,897 (GRCm39)	E7*	probably null	Het

Other mutations in Pcsk1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00324:Pcsk1	APN	13	75,280,206 (GRCm39)	missense	probably benign
IGL01554:Pcsk1	APN	13	75,280,426 (GRCm39)	missense	probably benign
IGL01960:Pcsk1	APN	13	75,241,286 (GRCm39)	missense	possibly damaging	0.82
IGL02026:Pcsk1	APN	13	75,260,772 (GRCm39)	missense	probably benign	0.16
IGL02047:Pcsk1	APN	13	75,246,108 (GRCm39)	missense	probably benign	0.33
IGL02264:Pcsk1	APN	13	75,254,078 (GRCm39)	missense	probably damaging	1.00
IGL02441:Pcsk1	APN	13	75,280,282 (GRCm39)	missense	probably benign	0.16
IGL02795:Pcsk1	APN	13	75,260,739 (GRCm39)	missense	probably damaging	1.00
IGL02829:Pcsk1	APN	13	75,274,955 (GRCm39)	missense	probably damaging	1.00
IGL03116:Pcsk1	APN	13	75,280,335 (GRCm39)	missense	probably damaging	0.99
IGL03156:Pcsk1	APN	13	75,280,070 (GRCm39)	missense	probably benign
clipper	UTSW	13	75,278,189 (GRCm39)	missense	probably damaging	1.00
spareribs	UTSW	13	75,263,374 (GRCm39)	missense	possibly damaging	0.88
swivel	UTSW	13	75,274,103 (GRCm39)	missense	probably damaging	1.00
Tweeze	UTSW	13	75,274,958 (GRCm39)	missense	probably benign	0.00
PIT4453001:Pcsk1	UTSW	13	75,260,769 (GRCm39)	missense	probably damaging	1.00
R0771:Pcsk1	UTSW	13	75,280,281 (GRCm39)	missense	probably benign	0.31
R0894:Pcsk1	UTSW	13	75,246,096 (GRCm39)	missense	probably damaging	1.00
R1014:Pcsk1	UTSW	13	75,280,353 (GRCm39)	missense	probably damaging	1.00
R1035:Pcsk1	UTSW	13	75,280,238 (GRCm39)	missense	probably benign
R1199:Pcsk1	UTSW	13	75,244,532 (GRCm39)	splice site	probably benign
R1517:Pcsk1	UTSW	13	75,246,166 (GRCm39)	nonsense	probably null
R1625:Pcsk1	UTSW	13	75,274,971 (GRCm39)	missense	probably benign	0.11
R1691:Pcsk1	UTSW	13	75,280,344 (GRCm39)	missense	possibly damaging	0.65
R1717:Pcsk1	UTSW	13	75,258,947 (GRCm39)	missense	probably damaging	0.99
R2168:Pcsk1	UTSW	13	75,260,653 (GRCm39)	intron	probably benign
R2252:Pcsk1	UTSW	13	75,274,845 (GRCm39)	missense	probably benign	0.00
R2400:Pcsk1	UTSW	13	75,238,245 (GRCm39)	missense	probably benign	0.00
R4110:Pcsk1	UTSW	13	75,244,488 (GRCm39)	missense	probably damaging	0.99
R4358:Pcsk1	UTSW	13	75,260,838 (GRCm39)	missense	possibly damaging	0.58
R4359:Pcsk1	UTSW	13	75,260,838 (GRCm39)	missense	possibly damaging	0.58
R5195:Pcsk1	UTSW	13	75,274,974 (GRCm39)	missense	probably damaging	1.00
R5669:Pcsk1	UTSW	13	75,278,221 (GRCm39)	missense	probably benign	0.01
R5671:Pcsk1	UTSW	13	75,246,026 (GRCm39)	missense	possibly damaging	0.63
R5745:Pcsk1	UTSW	13	75,280,079 (GRCm39)	missense	probably benign	0.03
R6107:Pcsk1	UTSW	13	75,275,967 (GRCm39)	missense	probably benign	0.09
R6200:Pcsk1	UTSW	13	75,263,374 (GRCm39)	missense	possibly damaging	0.88
R6326:Pcsk1	UTSW	13	75,280,298 (GRCm39)	missense	possibly damaging	0.89
R6537:Pcsk1	UTSW	13	75,280,358 (GRCm39)	missense	probably damaging	1.00
R6541:Pcsk1	UTSW	13	75,274,103 (GRCm39)	missense	probably damaging	1.00
R6567:Pcsk1	UTSW	13	75,278,189 (GRCm39)	missense	probably damaging	1.00
R6723:Pcsk1	UTSW	13	75,241,188 (GRCm39)	splice site	probably null
R7258:Pcsk1	UTSW	13	75,241,305 (GRCm39)	missense	probably damaging	1.00
R7357:Pcsk1	UTSW	13	75,274,079 (GRCm39)	missense	probably damaging	0.96
R7487:Pcsk1	UTSW	13	75,259,002 (GRCm39)	missense	probably benign	0.01
R7519:Pcsk1	UTSW	13	75,258,984 (GRCm39)	missense	probably damaging	0.99
R7647:Pcsk1	UTSW	13	75,280,329 (GRCm39)	missense	possibly damaging	0.73
R7787:Pcsk1	UTSW	13	75,280,277 (GRCm39)	missense	possibly damaging	0.88
R7944:Pcsk1	UTSW	13	75,280,211 (GRCm39)	missense	probably benign
R7945:Pcsk1	UTSW	13	75,280,211 (GRCm39)	missense	probably benign
R7961:Pcsk1	UTSW	13	75,274,958 (GRCm39)	missense	probably benign	0.00
R8009:Pcsk1	UTSW	13	75,274,958 (GRCm39)	missense	probably benign	0.00
R8022:Pcsk1	UTSW	13	75,247,412 (GRCm39)	missense	possibly damaging	0.77
R8171:Pcsk1	UTSW	13	75,238,210 (GRCm39)	nonsense	probably null
R8489:Pcsk1	UTSW	13	75,274,121 (GRCm39)	missense	probably damaging	1.00
R9310:Pcsk1	UTSW	13	75,238,191 (GRCm39)	missense	probably benign
R9404:Pcsk1	UTSW	13	75,280,342 (GRCm39)	missense	probably benign	0.11
R9544:Pcsk1	UTSW	13	75,259,039 (GRCm39)	missense	probably damaging	0.99
R9588:Pcsk1	UTSW	13	75,259,039 (GRCm39)	missense	probably damaging	0.99
R9706:Pcsk1	UTSW	13	75,247,473 (GRCm39)	critical splice donor site	probably null
Z1176:Pcsk1	UTSW	13	75,246,161 (GRCm39)	missense	probably damaging	1.00
Z1177:Pcsk1	UTSW	13	75,273,983 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CTGCGACTCCTACAAAGTGC -3'
(R):5'- ACGAATGATGAAGTTGGCTTTC -3'

Sequencing Primer
(F):5'- GCGACTCCTACAAAGTGCTTTTAG -3'
(R):5'- GAAACTCACTCCAAAGTACAGTTTG -3'

Posted On

2015-10-08