Mutagenetix > Incidental Mutations

Incidental Mutation 'R4991:Pcsk4'

386203

Institutional Source

Beutler Lab

Gene Symbol

Pcsk4

Ensembl Gene

ENSMUSG00000020131

Gene Name

proprotein convertase subtilisin/kexin type 4

Synonyms

PC4, SPC5

MMRRC Submission

042585-MU

Accession Numbers

Is this an essential gene?

Non essential (E-score: 0.000) question?

Stock #

R4991 (G1)

Quality Score

208

Status

Validated

Chromosome

Chromosomal Location

80321283-80329498 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 80325381 bp

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Threonine at position 233 (I233T)

Ref Sequence

ENSEMBL: ENSMUSP00000020340 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000020340] [ENSMUST00000020341] [ENSMUST00000040081] [ENSMUST00000105354] [ENSMUST00000105355] [ENSMUST00000105357] [ENSMUST00000105358] [ENSMUST00000128653] [ENSMUST00000135071] [ENSMUST00000186864]

Predicted Effect

possibly damaging
Transcript: ENSMUST00000020340
AA Change: I233T

PolyPhen 2 Score 0.741 (Sensitivity: 0.85; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000020340
Gene: ENSMUSG00000020131
AA Change: I233T

Domain	Start	End	E-Value	Type
signal peptide	1	26	N/A	INTRINSIC
Pfam:S8_pro-domain	34	110	1.2e-24	PFAM
Pfam:Peptidase_S8	146	429	3.1e-50	PFAM
Pfam:P_proprotein	488	574	5e-25	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000020341

SMART Domains

Protein: ENSMUSP00000020341
Gene: ENSMUSG00000020133

Domain	Start	End	E-Value	Type
Pfam:UPF0449	6	103	7.5e-40	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000040081

SMART Domains

Protein: ENSMUSP00000043722
Gene: ENSMUSG00000035504

Domain	Start	End	E-Value	Type
Pfam:TB2_DP1_HVA22	50	118	8e-28	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000105354

SMART Domains

Protein: ENSMUSP00000100991
Gene: ENSMUSG00000035504

Domain	Start	End	E-Value	Type
Pfam:TB2_DP1_HVA22	50	144	5e-36	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000105355

SMART Domains

Protein: ENSMUSP00000100992
Gene: ENSMUSG00000035504

Domain	Start	End	E-Value	Type
Pfam:TB2_DP1_HVA22	50	144	3.4e-36	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000105357

SMART Domains

Protein: ENSMUSP00000100994
Gene: ENSMUSG00000035504

Domain	Start	End	E-Value	Type
low complexity region	22	61	N/A	INTRINSIC
low complexity region	108	129	N/A	INTRINSIC
low complexity region	297	319	N/A	INTRINSIC
low complexity region	340	352	N/A	INTRINSIC
low complexity region	411	428	N/A	INTRINSIC
SCOP:d1gkub1	434	465	1e-3	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000105358

SMART Domains

Protein: ENSMUSP00000100995
Gene: ENSMUSG00000035504

Domain	Start	End	E-Value	Type
low complexity region	22	61	N/A	INTRINSIC
low complexity region	108	129	N/A	INTRINSIC
low complexity region	324	346	N/A	INTRINSIC
low complexity region	367	379	N/A	INTRINSIC
low complexity region	438	455	N/A	INTRINSIC
SCOP:d1gkub1	461	492	8e-4	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000128653

SMART Domains

Protein: ENSMUSP00000137809
Gene: ENSMUSG00000020131

Domain	Start	End	E-Value	Type
signal peptide	1	26	N/A	INTRINSIC
SCOP:d1kn6a_	31	102	8e-29	SMART
Pfam:Peptidase_S8	150	242	6.4e-18	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000130521

Predicted Effect

silent
Transcript: ENSMUST00000135071

SMART Domains

Protein: ENSMUSP00000137719
Gene: ENSMUSG00000020131

Domain	Start	End	E-Value	Type
SCOP:d1kn6a_	14	85	3e-27	SMART
Pfam:Peptidase_S8	133	187	1.7e-7	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000137177

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000147132

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000153167

Predicted Effect

probably benign
Transcript: ENSMUST00000186864

SMART Domains

Protein: ENSMUSP00000140840
Gene: ENSMUSG00000035504

Domain	Start	End	E-Value	Type
Pfam:TB2_DP1_HVA22	50	144	5e-36	PFAM

Meta Mutation Damage Score

0.4674

Coding Region Coverage

1x: 99.0%
3x: 98.2%
10x: 95.7%
20x: 90.0%

Validation Efficiency

95% (73/77)

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. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. The protease is expressed only in the testis, placenta, and ovary. It plays a critical role in fertilization, fetoplacental growth, and embryonic development and processes multiple prohormones including pro-pituitary adenylate cyclase-activating protein and pro-insulin-like growth factor II. [provided by RefSeq, Jan 2014]
PHENOTYPE: Inactivation of this locus results in significantly reduced male fertility, putatively due to impaired fertilization. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 62 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adcy4	G	T	14: 55,773,465	T665K	probably benign	Het
Adgrf3	C	T	5: 30,199,148	V369M	probably benign	Het
Als2	T	C	1: 59,207,768	K571E	probably benign	Het
Amer3	A	C	1: 34,588,741	D687A	probably benign	Het
Asb14	T	C	14: 26,915,058	S586P	probably damaging	Het
Chmp4b	A	G	2: 154,692,625	E187G	probably benign	Het
Cox6b2	T	C	7: 4,752,161	D38G	probably damaging	Het
Cpm	G	A	10: 117,668,103	C138Y	probably damaging	Het
Csmd3	G	T	15: 48,001,478	P785Q	probably damaging	Het
Cstf1	A	G	2: 172,377,800	Y277C	probably damaging	Het
Cstf2t	T	A	19: 31,084,583	N506K	probably damaging	Het
Dmpk	C	G	7: 19,088,019	L301V	probably benign	Het
Ebf2	A	T	14: 67,389,657	T265S	possibly damaging	Het
Elmo1	T	C	13: 20,342,519	F413S	probably damaging	Het
Fbp1	C	T	13: 62,865,074	V102I	probably benign	Het
Gm13212	C	A	4: 145,622,334	Q114K	probably benign	Het
Gm14548	T	G	7: 3,895,572	Q292H	probably benign	Het
Gm16432	A	C	1: 178,098,421	I218L	probably benign	Het
Gm19684	A	G	17: 36,127,472		probably benign	Het
Gm29106	T	C	1: 118,178,391	M37T	probably benign	Het
Grem2	A	G	1: 174,836,813	C157R	probably damaging	Het
Hdac5	T	A	11: 102,205,624	E252D	probably damaging	Het
Ifitm3	A	T	7: 141,010,459	F63I	probably damaging	Het
Igkv4-80	A	C	6: 69,016,665	S81A	probably benign	Het
Irx4	G	T	13: 73,265,507	R32L	probably benign	Het
Itgb1bp1	C	T	12: 21,274,848	G69D	probably damaging	Het
Kcnh3	A	G	15: 99,232,756	D418G	probably benign	Het
Kif1a	T	C	1: 93,078,808	T46A	probably benign	Het
Klk1b26	T	A	7: 44,016,249		probably null	Het
Lca5l	T	C	16: 96,159,732	E510G	possibly damaging	Het
Lrriq1	A	G	10: 103,200,559	I911T	probably damaging	Het
Mios	T	G	6: 8,215,847	S348A	probably benign	Het
Mog	T	C	17: 37,017,489		probably null	Het
Mtmr7	A	G	8: 40,554,345	S516P	probably damaging	Het
Nat8f4	T	C	6: 85,901,140	K134E	probably benign	Het
Nbeal2	C	T	9: 110,638,767	C451Y	probably damaging	Het
Nkx2-1	T	C	12: 56,534,939	Y41C	possibly damaging	Het
Nmnat1	G	A	4: 149,469,127	T176M	possibly damaging	Het
Nrxn3	T	A	12: 89,260,474	I293N	probably damaging	Het
Olfr1031	A	G	2: 85,992,287	M157V	probably damaging	Het
Olfr1447	T	G	19: 12,901,451	T110P	probably damaging	Het
Olfr313	T	C	11: 58,817,718	S237P	probably damaging	Het
Osgin1	A	G	8: 119,445,289	E274G	probably damaging	Het
Otof	G	A	5: 30,394,181	R343W	probably damaging	Het
Pcdha9	A	T	18: 36,998,345	I156F	probably damaging	Het
Samd4	A	T	14: 47,074,010	S262C	probably damaging	Het
Snap91	T	C	9: 86,790,154		probably null	Het
Spata31d1a	T	C	13: 59,703,151	N388D	probably benign	Het
St3gal4	A	G	9: 35,053,136	V190A	possibly damaging	Het
Sv2b	T	C	7: 75,117,722	N642S	possibly damaging	Het
Svil	T	A	18: 5,056,810	I561K	probably benign	Het
Tmem201	A	T	4: 149,728,155	Y235N	possibly damaging	Het
Tpx2	T	C	2: 152,869,724	S60P	probably benign	Het
Trpa1	T	C	1: 14,910,746	Y144C	probably benign	Het
U90926	G	A	5: 92,210,020	P91S	probably benign	Het
Utp20	G	T	10: 88,746,934	H2780Q	probably benign	Het
Vmn1r215	T	G	13: 23,076,527	F246V	probably damaging	Het
Vmn2r72	A	G	7: 85,751,130	L237S	probably damaging	Het
Washc5	A	G	15: 59,344,080	S817P	probably damaging	Het
Zbtb24	A	G	10: 41,456,618		probably null	Het
Zfp212	G	A	6: 47,926,862	R127H	probably damaging	Het
Zfp740	G	T	15: 102,208,279		probably null	Het

Other mutations in Pcsk4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00161:Pcsk4	APN	10	80322823	missense	probably damaging	1.00
IGL02818:Pcsk4	APN	10	80322792	missense	probably damaging	0.98
IGL03115:Pcsk4	APN	10	80329049	missense	probably damaging	1.00
IGL03354:Pcsk4	APN	10	80326059	missense	probably damaging	0.99
R0538:Pcsk4	UTSW	10	80325334	missense	probably damaging	1.00
R0760:Pcsk4	UTSW	10	80325941	unclassified	probably benign
R1462:Pcsk4	UTSW	10	80325981	missense	probably damaging	1.00
R1462:Pcsk4	UTSW	10	80325981	missense	probably damaging	1.00
R1554:Pcsk4	UTSW	10	80321951	missense	probably benign	0.01
R1728:Pcsk4	UTSW	10	80323570	missense	probably damaging	0.99
R1784:Pcsk4	UTSW	10	80323570	missense	probably damaging	0.99
R1886:Pcsk4	UTSW	10	80328960	missense	probably benign	0.32
R1981:Pcsk4	UTSW	10	80325779	missense	probably damaging	1.00
R2090:Pcsk4	UTSW	10	80325821	missense	probably benign	0.02
R2125:Pcsk4	UTSW	10	80323879	missense	probably benign	0.32
R2283:Pcsk4	UTSW	10	80322750	missense	probably damaging	1.00
R4183:Pcsk4	UTSW	10	80325011	missense	probably benign	0.12
R4283:Pcsk4	UTSW	10	80329453	unclassified	probably benign
R4798:Pcsk4	UTSW	10	80323104	missense	probably damaging	1.00
R4857:Pcsk4	UTSW	10	80325039	missense	probably damaging	1.00
R4990:Pcsk4	UTSW	10	80325381	missense	possibly damaging	0.74
R5020:Pcsk4	UTSW	10	80326035	missense	probably benign	0.00
R5123:Pcsk4	UTSW	10	80322145	missense	probably null	0.56
R5354:Pcsk4	UTSW	10	80323689	missense	probably damaging	0.98
R6077:Pcsk4	UTSW	10	80326239	missense	probably damaging	0.99
R6102:Pcsk4	UTSW	10	80325817	nonsense	probably null
R6250:Pcsk4	UTSW	10	80325592	missense	probably benign	0.04
R6378:Pcsk4	UTSW	10	80328975	missense	probably benign	0.34
R6729:Pcsk4	UTSW	10	80325101	missense	probably damaging	0.99
R7308:Pcsk4	UTSW	10	80323173	missense	probably benign	0.41
R7595:Pcsk4	UTSW	10	80322101	missense	possibly damaging	0.84
R8004:Pcsk4	UTSW	10	80322840	missense	probably damaging	1.00
Z1176:Pcsk4	UTSW	10	80322726	missense	possibly damaging	0.94

Predicted Primers

PCR Primer
(F):5'- GATGAACAGTGTACCCAGCC -3'
(R):5'- AGGTTAAGCTTGGCTAGTGCAG -3'

Sequencing Primer
(F):5'- CGAGAGAACAGAGTCAGTCCTC -3'
(R):5'- TAGTGCAGGGACCTCCGTTC -3'

Posted On

2016-05-10