Mutagenetix > Incidental Mutation

Incidental Mutation 'R9404:Pcsk1'

711431

Institutional Source

Beutler Lab

Gene Symbol

Pcsk1

Ensembl Gene

ENSMUSG00000021587

Gene Name

proprotein convertase subtilisin/kexin type 1

Synonyms

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

MMRRC Submission

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R9404 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

75089826-75134861 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 75132223 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Serine to Arginine at position 722 (S722R)

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 benign
Transcript: ENSMUST00000022075
AA Change: S722R

PolyPhen 2 Score 0.109 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000022075
Gene: ENSMUSG00000021587
AA Change: S722R

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.0%

Validation Efficiency

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: 74 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acot11	T	C	4: 106,758,312	K314R	possibly damaging	Het
Armt1	AC	A	10: 4,450,848		probably null	Het
Atad5	T	C	11: 80,114,238	V1167A	probably damaging	Het
Bbs12	T	C	3: 37,319,408	S2P	probably damaging	Het
Cdh11	A	T	8: 102,679,622	L73Q	probably damaging	Het
Cdk15	A	G	1: 59,289,755	E274G	possibly damaging	Het
Col27a1	T	C	4: 63,275,941	V845A	possibly damaging	Het
Cyp3a11	T	C	5: 145,862,448	T310A	probably benign	Het
Efcab5	G	A	11: 77,132,108	T593I	probably damaging	Het
Ewsr1	A	G	11: 5,072,940	M388T	unknown	Het
Fat2	A	G	11: 55,253,522		probably null	Het
Gm8225	T	A	17: 26,543,060	I75N	probably damaging	Het
Gsap	A	G	5: 21,269,921	Y526C	probably damaging	Het
Hk1	T	A	10: 62,296,080	I203F	possibly damaging	Het
Insl5	T	C	4: 103,018,338	R72G	probably benign	Het
Iqcb1	T	C	16: 36,851,270	V321A	probably damaging	Het
Iqcd	A	C	5: 120,600,536	T140P		Het
Kcnt2	T	A	1: 140,425,369	I272K	probably damaging	Het
Klhl25	A	C	7: 75,865,405	I20L	probably benign	Het
Krt1	AAGCTGCCACCCCCAAAGCCACCACCGCCGTAGCTGCCACCCCCAAAGCCACCACCGCCGTAGCTGCCACCCCCAAAGCCACCAC	AAGCTGCCACCCCCAAAGCCACCACCGCCGTAGCTGCCACCCCCAAAGCCACCAC	15: 101,850,378		probably benign	Het
Lrba	T	C	3: 86,297,917	V356A	probably damaging	Het
Mast4	A	G	13: 102,751,425	Y1159H	probably damaging	Het
Mavs	T	A	2: 131,241,898	L105Q	probably damaging	Het
Megf6	T	A	4: 154,263,768	C902S		Het
Mgea5	CTCGGGTC	CTC	19: 45,754,657		probably null	Het
Mmp17	A	G	5: 129,605,677	D460G	possibly damaging	Het
Myh2	G	T	11: 67,179,628	A466S	probably damaging	Het
Neb	T	C	2: 52,257,776	N2744D	probably damaging	Het
Olfr1197	T	A	2: 88,729,207	M131L	probably benign	Het
Olfr169	C	T	16: 19,565,981	V301M	probably benign	Het
Olfr213	T	G	6: 116,540,747	I98S	probably damaging	Het
Olfr446	T	C	6: 42,927,816	V195A	probably benign	Het
Olfr541	T	A	7: 140,704,809	L186H	probably damaging	Het
Olfr972	A	T	9: 39,873,412	I46F	possibly damaging	Het
Parpbp	A	G	10: 88,114,549	V323A	possibly damaging	Het
Pax5	G	A	4: 44,645,565	P255S	possibly damaging	Het
Pcdhga2	A	G	18: 37,670,014	T304A	probably benign	Het
Pcsk9	C	A	4: 106,454,526	R218L	probably damaging	Het
Pds5a	T	A	5: 65,618,964	I96F	probably damaging	Het
Pkdrej	C	A	15: 85,819,069	V889L	probably benign	Het
Plekhh2	A	T	17: 84,571,040		probably null	Het
Pnn	A	G	12: 59,071,972	E447G	probably damaging	Het
Ppp2r3a	A	G	9: 101,148,641	L289P	probably damaging	Het
Ppp6r2	A	G	15: 89,268,550	H298R	probably benign	Het
Ptpn23	T	C	9: 110,386,957	N1277S		Het
Pus10	T	A	11: 23,711,202	F263L	possibly damaging	Het
Rexo5	A	G	7: 119,801,319	Y109C	probably damaging	Het
Rnf185	A	T	11: 3,432,615	C23*	probably null	Het
Runx1	T	C	16: 92,689,027	N140D	probably benign	Het
Sbf2	T	C	7: 110,441,495	Q375R	possibly damaging	Het
Scn9a	G	A	2: 66,526,696	T1087I	probably benign	Het
Sh2b1	TGGGGACCAGCTCAGCCACGGGGACCAGCTC	TGGGGACCAGCTCAGCCACGGGGACCAGCTCAGCCACGGGGACCAGCTC	7: 126,467,570		probably benign	Het
Sh2b1	TC	TCAGCCACGGGGACCAGCCC	7: 126,467,599		probably benign	Het
Slc7a11	T	C	3: 50,381,039	H350R	possibly damaging	Het
Spaca6	T	C	17: 17,837,538	C155R	probably damaging	Het
Spire2	C	T	8: 123,363,338	R580*	probably null	Het
Srgap3	A	T	6: 112,729,655	M851K	probably benign	Het
Themis	A	G	10: 28,789,747	D602G	probably benign	Het
Tmem56	T	C	3: 121,235,082	N52S	probably benign	Het
Trak2	T	C	1: 58,921,137	T236A	possibly damaging	Het
Trrap	T	C	5: 144,815,415	C1709R	possibly damaging	Het
Ttn	A	T	2: 76,754,156	S22203T	probably damaging	Het
Ube3a	A	G	7: 59,287,015	T701A	probably damaging	Het
Ufl1	T	C	4: 25,275,912	I164V	probably benign	Het
Vcpip1	T	C	1: 9,747,631	T176A	probably damaging	Het
Virma	T	A	4: 11,513,626	D493E	probably benign	Het
Vmn2r77	T	A	7: 86,802,039	W378R	probably benign	Het
Vps13b	A	T	15: 35,876,419	T2799S	probably damaging	Het
Vps8	T	C	16: 21,608,177	S1337P	probably benign	Het
Zcchc6	A	T	13: 59,799,887	N873K	probably benign	Het
Zfp235	A	T	7: 24,140,437	I94F	possibly damaging	Het
Zfp3	A	G	11: 70,772,540	K442E	probably damaging	Het
Zfp418	A	T	7: 7,182,105	I356F	possibly damaging	Het
Zfp790	G	A	7: 29,825,760	G68S	probably benign	Het

Other mutations in Pcsk1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00324:Pcsk1	APN	13	75132087	missense	probably benign
IGL01554:Pcsk1	APN	13	75132307	missense	probably benign
IGL01960:Pcsk1	APN	13	75093167	missense	possibly damaging	0.82
IGL02026:Pcsk1	APN	13	75112653	missense	probably benign	0.16
IGL02047:Pcsk1	APN	13	75097989	missense	probably benign	0.33
IGL02264:Pcsk1	APN	13	75105959	missense	probably damaging	1.00
IGL02441:Pcsk1	APN	13	75132163	missense	probably benign	0.16
IGL02795:Pcsk1	APN	13	75112620	missense	probably damaging	1.00
IGL02829:Pcsk1	APN	13	75126836	missense	probably damaging	1.00
IGL03116:Pcsk1	APN	13	75132216	missense	probably damaging	0.99
IGL03156:Pcsk1	APN	13	75131951	missense	probably benign
clipper	UTSW	13	75130070	missense	probably damaging	1.00
spareribs	UTSW	13	75115255	missense	possibly damaging	0.88
swivel	UTSW	13	75125984	missense	probably damaging	1.00
Tweeze	UTSW	13	75126839	missense	probably benign	0.00
PIT4453001:Pcsk1	UTSW	13	75112650	missense	probably damaging	1.00
R0771:Pcsk1	UTSW	13	75132162	missense	probably benign	0.31
R0894:Pcsk1	UTSW	13	75097977	missense	probably damaging	1.00
R1014:Pcsk1	UTSW	13	75132234	missense	probably damaging	1.00
R1035:Pcsk1	UTSW	13	75132119	missense	probably benign
R1199:Pcsk1	UTSW	13	75096413	splice site	probably benign
R1517:Pcsk1	UTSW	13	75098047	nonsense	probably null
R1625:Pcsk1	UTSW	13	75126852	missense	probably benign	0.11
R1691:Pcsk1	UTSW	13	75132225	missense	possibly damaging	0.65
R1717:Pcsk1	UTSW	13	75110828	missense	probably damaging	0.99
R2168:Pcsk1	UTSW	13	75112534	intron	probably benign
R2252:Pcsk1	UTSW	13	75126726	missense	probably benign	0.00
R2400:Pcsk1	UTSW	13	75090126	missense	probably benign	0.00
R4110:Pcsk1	UTSW	13	75096369	missense	probably damaging	0.99
R4358:Pcsk1	UTSW	13	75112719	missense	possibly damaging	0.58
R4359:Pcsk1	UTSW	13	75112719	missense	possibly damaging	0.58
R4657:Pcsk1	UTSW	13	75132235	missense	probably damaging	1.00
R5195:Pcsk1	UTSW	13	75126855	missense	probably damaging	1.00
R5669:Pcsk1	UTSW	13	75130102	missense	probably benign	0.01
R5671:Pcsk1	UTSW	13	75097907	missense	possibly damaging	0.63
R5745:Pcsk1	UTSW	13	75131960	missense	probably benign	0.03
R6107:Pcsk1	UTSW	13	75127848	missense	probably benign	0.09
R6200:Pcsk1	UTSW	13	75115255	missense	possibly damaging	0.88
R6326:Pcsk1	UTSW	13	75132179	missense	possibly damaging	0.89
R6537:Pcsk1	UTSW	13	75132239	missense	probably damaging	1.00
R6541:Pcsk1	UTSW	13	75125984	missense	probably damaging	1.00
R6567:Pcsk1	UTSW	13	75130070	missense	probably damaging	1.00
R6723:Pcsk1	UTSW	13	75093069	splice site	probably null
R7258:Pcsk1	UTSW	13	75093186	missense	probably damaging	1.00
R7357:Pcsk1	UTSW	13	75125960	missense	probably damaging	0.96
R7487:Pcsk1	UTSW	13	75110883	missense	probably benign	0.01
R7519:Pcsk1	UTSW	13	75110865	missense	probably damaging	0.99
R7647:Pcsk1	UTSW	13	75132210	missense	possibly damaging	0.73
R7787:Pcsk1	UTSW	13	75132158	missense	possibly damaging	0.88
R7944:Pcsk1	UTSW	13	75132092	missense	probably benign
R7945:Pcsk1	UTSW	13	75132092	missense	probably benign
R7961:Pcsk1	UTSW	13	75126839	missense	probably benign	0.00
R8009:Pcsk1	UTSW	13	75126839	missense	probably benign	0.00
R8022:Pcsk1	UTSW	13	75099293	missense	possibly damaging	0.77
R8171:Pcsk1	UTSW	13	75090091	nonsense	probably null
R8489:Pcsk1	UTSW	13	75126002	missense	probably damaging	1.00
R9310:Pcsk1	UTSW	13	75090072	missense	probably benign
R9544:Pcsk1	UTSW	13	75110920	missense	probably damaging	0.99
R9588:Pcsk1	UTSW	13	75110920	missense	probably damaging	0.99
R9706:Pcsk1	UTSW	13	75099354	critical splice donor site	probably null
Z1176:Pcsk1	UTSW	13	75098042	missense	probably damaging	1.00
Z1177:Pcsk1	UTSW	13	75125864	missense	probably damaging	1.00

Predicted Primers

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

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

Posted On

2022-05-16