Mutagenetix > Incidental Mutation

Incidental Mutation 'R1013:Psenen'

95870

Institutional Source

Beutler Lab

Gene Symbol

Psenen

Ensembl Gene

ENSMUSG00000036835

Gene Name

presenilin enhancer gamma secretase subunit

Synonyms

Pen2, 1700023M09Rik

MMRRC Submission

039117-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1013 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

30261290-30263052 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 30261802 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Phenylalanine to Serine at position 38 (F38S)

Ref Sequence

ENSEMBL: ENSMUSP00000146469 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000043273] [ENSMUST00000043850] [ENSMUST00000043898] [ENSMUST00000043975] [ENSMUST00000108161] [ENSMUST00000108164] [ENSMUST00000163482] [ENSMUST00000163848] [ENSMUST00000156241] [ENSMUST00000163464] [ENSMUST00000164365] [ENSMUST00000163276] [ENSMUST00000163330] [ENSMUST00000163654] [ENSMUST00000207797] [ENSMUST00000207747] [ENSMUST00000167361] [ENSMUST00000166960] [ENSMUST00000167202] [ENSMUST00000207031] [ENSMUST00000168931] [ENSMUST00000166510] [ENSMUST00000167042] [ENSMUST00000171850] [ENSMUST00000168555] [ENSMUST00000166257] [ENSMUST00000172251] [ENSMUST00000167501] [ENSMUST00000168229] [ENSMUST00000168333] [ENSMUST00000171912] [ENSMUST00000208628]

AlphaFold

Q9CQR7

Predicted Effect

probably benign
Transcript: ENSMUST00000043273

SMART Domains

Protein: ENSMUSP00000039406
Gene: ENSMUSG00000078765

Domain	Start	End	E-Value	Type
ZnF_C3H1	13	39	4.79e-3	SMART
RRM	66	143	5.99e-4	SMART
ZnF_C3H1	149	175	2.49e-1	SMART
low complexity region	187	219	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000043850

SMART Domains

Protein: ENSMUSP00000042312
Gene: ENSMUSG00000036826

Domain	Start	End	E-Value	Type
signal peptide	1	20	N/A	INTRINSIC
transmembrane domain	166	188	N/A	INTRINSIC
low complexity region	247	264	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000043898
AA Change: F38S

PolyPhen 2 Score 0.541 (Sensitivity: 0.88; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000044682
Gene: ENSMUSG00000036835
AA Change: F38S

Domain	Start	End	E-Value	Type
Pfam:PEN-2	7	99	2.9e-43	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000043975

SMART Domains

Protein: ENSMUSP00000048557
Gene: ENSMUSG00000036845

Domain	Start	End	E-Value	Type
Pfam:LIN37	84	240	5e-51	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000108161

SMART Domains

Protein: ENSMUSP00000103796
Gene: ENSMUSG00000109378

Domain	Start	End	E-Value	Type
Pfam:zf-CCCH	13	39	8.8e-10	PFAM
SCOP:d1jmta_	43	115	2e-17	SMART
PDB:1JMT\|A	43	116	3e-40	PDB
Blast:RRM	45	116	2e-36	BLAST

Predicted Effect

probably benign
Transcript: ENSMUST00000108164

SMART Domains

Protein: ENSMUSP00000103799
Gene: ENSMUSG00000036845

Domain	Start	End	E-Value	Type
Pfam:LIN37	58	229	1.4e-45	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000149400

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000163994

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000165524

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000165543

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000164438

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000165009

Predicted Effect

probably benign
Transcript: ENSMUST00000163482

SMART Domains

Protein: ENSMUSP00000130649
Gene: ENSMUSG00000078765

Domain	Start	End	E-Value	Type
low complexity region	34	54	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000163848

Predicted Effect

probably benign
Transcript: ENSMUST00000156241

SMART Domains

Protein: ENSMUSP00000122248
Gene: ENSMUSG00000036845

Domain	Start	End	E-Value	Type
Pfam:LIN37	80	202	7.5e-29	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000165722

SMART Domains

Protein: ENSMUSP00000125790
Gene: ENSMUSG00000078765

Domain	Start	End	E-Value	Type
Pfam:zf-CCCH	1	26	4.7e-10	PFAM
PDB:1JMT\|A	30	51	2e-6	PDB
SCOP:d1jmta_	30	51	5e-3	SMART
Blast:RRM	32	53	7e-8	BLAST

Predicted Effect

probably benign
Transcript: ENSMUST00000163464

SMART Domains

Protein: ENSMUSP00000125959
Gene: ENSMUSG00000078765

Domain	Start	End	E-Value	Type
ZnF_C3H1	13	39	4.79e-3	SMART
RRM	66	143	5.99e-4	SMART
ZnF_C3H1	149	171	3.95e1	SMART
low complexity region	183	215	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000164365

Predicted Effect

probably benign
Transcript: ENSMUST00000163276

Predicted Effect

probably benign
Transcript: ENSMUST00000163330

SMART Domains

Protein: ENSMUSP00000129385
Gene: ENSMUSG00000078765

Domain	Start	End	E-Value	Type
RRM	39	116	5.99e-4	SMART
Pfam:zf-CCCH	122	148	4.9e-8	PFAM
low complexity region	160	192	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000163654

SMART Domains

Protein: ENSMUSP00000131048
Gene: ENSMUSG00000078765

Domain	Start	End	E-Value	Type
Pfam:zf-CCCH	13	39	1.3e-9	PFAM
RRM	66	143	5.99e-4	SMART
low complexity region	167	187	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000207797
AA Change: F38S

PolyPhen 2 Score 0.261 (Sensitivity: 0.91; Specificity: 0.88)

Predicted Effect

possibly damaging
Transcript: ENSMUST00000207747
AA Change: F38S

PolyPhen 2 Score 0.541 (Sensitivity: 0.88; Specificity: 0.91)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000169962

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000166864

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000169283

Predicted Effect

probably benign
Transcript: ENSMUST00000167361

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000165773

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000169071

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000171364

Predicted Effect

probably benign
Transcript: ENSMUST00000166960

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000167024

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000170453

Predicted Effect

probably benign
Transcript: ENSMUST00000167202

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000207972

Predicted Effect

probably benign
Transcript: ENSMUST00000207031

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000169911

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000168222

Predicted Effect

probably benign
Transcript: ENSMUST00000168931

SMART Domains

Protein: ENSMUSP00000129697
Gene: ENSMUSG00000078765

Domain	Start	End	E-Value	Type
RRM	44	119	4.14e-2	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000166510

SMART Domains

Protein: ENSMUSP00000132316
Gene: ENSMUSG00000078765

Domain	Start	End	E-Value	Type
ZnF_C3H1	13	39	4.79e-3	SMART
RRM	45	133	2.51e-6	SMART
ZnF_C3H1	139	165	2.49e-1	SMART
low complexity region	177	209	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000167042

SMART Domains

Protein: ENSMUSP00000128886
Gene: ENSMUSG00000109378

Domain	Start	End	E-Value	Type
ZnF_C3H1	13	39	4.79e-3	SMART
RRM	66	143	5.99e-4	SMART
ZnF_C3H1	149	175	2.49e-1	SMART
low complexity region	187	219	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000171850

SMART Domains

Protein: ENSMUSP00000131781
Gene: ENSMUSG00000078765

Domain	Start	End	E-Value	Type
ZnF_C3H1	13	39	4.79e-3	SMART
PDB:1JMT\|A	43	113	1e-16	PDB
SCOP:d1jmta_	43	113	1e-9	SMART
Blast:RRM	45	110	3e-17	BLAST
ZnF_C3H1	116	142	2.49e-1	SMART
low complexity region	154	186	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000168555

Predicted Effect

probably benign
Transcript: ENSMUST00000166257

SMART Domains

Protein: ENSMUSP00000125838
Gene: ENSMUSG00000078765

Domain	Start	End	E-Value	Type
ZnF_C3H1	13	39	4.79e-3	SMART
RRM	33	104	2.35e-2	SMART
ZnF_C3H1	110	136	2.49e-1	SMART
low complexity region	148	180	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000172251

SMART Domains

Protein: ENSMUSP00000132400
Gene: ENSMUSG00000036826

Domain	Start	End	E-Value	Type
signal peptide	1	41	N/A	INTRINSIC
transmembrane domain	186	208	N/A	INTRINSIC
low complexity region	267	284	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000167501

Predicted Effect

probably benign
Transcript: ENSMUST00000168229

Predicted Effect

probably benign
Transcript: ENSMUST00000168333

SMART Domains

Protein: ENSMUSP00000128950
Gene: ENSMUSG00000078765

Domain	Start	End	E-Value	Type
Pfam:zf-CCCH	13	39	4.8e-10	PFAM
PDB:1JMT\|A	43	94	5e-21	PDB
SCOP:d1jmta_	43	94	2e-9	SMART
Blast:RRM	45	94	5e-17	BLAST

Predicted Effect

probably benign
Transcript: ENSMUST00000171912

SMART Domains

Protein: ENSMUSP00000130983
Gene: ENSMUSG00000109378

Domain	Start	End	E-Value	Type
ZnF_C3H1	13	39	4.79e-3	SMART
RRM	66	143	5.99e-4	SMART
ZnF_C3H1	149	175	2.49e-1	SMART
low complexity region	187	219	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000208628
AA Change: F38S

PolyPhen 2 Score 0.789 (Sensitivity: 0.85; Specificity: 0.93)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000209110

Meta Mutation Damage Score

0.4565

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.1%
20x: 91.4%

Validation Efficiency

98% (39/40)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Presenilins, which are components of the gamma-secretase protein complex, are required for intramembranous processing of some type I transmembrane proteins, such as the Notch proteins and the beta-amyloid precursor protein. Signaling by Notch receptors mediates a wide range of developmental cell fates. Processing of the beta-amyloid precursor protein generates neurotoxic amyloid beta peptides, the major component of senile plaques associated with Alzheimer's disease. This gene encodes a protein that is required for Notch pathway signaling, and for the activity and accumulation of gamma-secretase. Mutations resulting in haploinsufficiency for this gene cause familial acne inversa-2 (ACNINV2). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
PHENOTYPE: Homozygous mutation of this gene results in lethality before weaning. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 34 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700056E22Rik	C	T	1: 183,765,702 (GRCm39)	S119N	probably benign	Het
4930527J03Rik	ACCC	ACC	1: 178,276,503 (GRCm38)		noncoding transcript	Het
Bclaf1	T	A	10: 20,207,822 (GRCm39)		probably benign	Het
Bicdl2	A	G	17: 23,884,377 (GRCm39)		probably benign	Het
C8a	T	C	4: 104,685,236 (GRCm39)	I336V	probably benign	Het
Calcr	A	T	6: 3,692,621 (GRCm39)	V374D	probably damaging	Het
Col28a1	A	G	6: 7,999,452 (GRCm39)		probably benign	Het
Cuedc1	C	T	11: 88,078,853 (GRCm39)	A327V	possibly damaging	Het
Cul2	C	A	18: 3,425,535 (GRCm39)	Y378*	probably null	Het
Dnaaf10	A	G	11: 17,178,183 (GRCm39)	K226E	probably damaging	Het
Flt4	C	T	11: 49,527,166 (GRCm39)		probably benign	Het
Gm8369	TG	TGNG	19: 11,489,147 (GRCm39)		probably null	Het
Hivep1	A	G	13: 42,310,438 (GRCm39)	R893G	probably damaging	Het
Il10rb	A	G	16: 91,211,581 (GRCm39)	N140D	probably benign	Het
Itga4	A	G	2: 79,150,847 (GRCm39)	M818V	probably benign	Het
Kyat3	T	C	3: 142,432,007 (GRCm39)	I245T	probably damaging	Het
Lck	C	T	4: 129,451,920 (GRCm39)	C20Y	probably damaging	Het
Mcm6	T	G	1: 128,276,778 (GRCm39)	S271R	probably benign	Het
Megf10	A	G	18: 57,394,291 (GRCm39)	I472V	probably benign	Het
Mroh2a	T	C	1: 88,162,334 (GRCm39)		probably null	Het
Mrpl11	T	C	19: 5,013,651 (GRCm39)	I144T	possibly damaging	Het
Or2t26	G	A	11: 49,039,977 (GRCm39)	V298M	probably damaging	Het
Or8k25	G	A	2: 86,244,319 (GRCm39)	P26S	possibly damaging	Het
Pcdhb17	A	G	18: 37,619,020 (GRCm39)	D270G	probably damaging	Het
Plg	G	A	17: 12,597,608 (GRCm39)		probably benign	Het
Ppp3cb	T	A	14: 20,574,072 (GRCm39)	E255D	probably benign	Het
Rims4	C	T	2: 163,705,849 (GRCm39)	V262M	possibly damaging	Het
Sorl1	T	C	9: 41,913,855 (GRCm39)	N1358S	probably benign	Het
Trim3	G	A	7: 105,267,102 (GRCm39)	P426S	probably benign	Het
Ttc28	T	C	5: 111,424,831 (GRCm39)	M1552T	probably benign	Het
Unc13c	T	C	9: 73,840,614 (GRCm39)	D79G	probably benign	Het
Zcchc14	A	G	8: 122,333,664 (GRCm39)		probably benign	Het
Zfp354a	T	C	11: 50,951,677 (GRCm39)		probably benign	Het
Zfp729a	T	C	13: 67,767,626 (GRCm39)	I868V	probably benign	Het

Other mutations in Psenen

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
R1430:Psenen	UTSW	7	30,261,815 (GRCm39)	missense	probably benign
R6572:Psenen	UTSW	7	30,261,773 (GRCm39)	missense	probably benign	0.00
R6994:Psenen	UTSW	7	30,262,932 (GRCm39)	critical splice donor site	probably null
R7985:Psenen	UTSW	7	30,261,503 (GRCm39)	missense	probably benign	0.00
X0065:Psenen	UTSW	7	30,262,272 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TGAGCGCCAAACATCTAGAGTGAAG -3'
(R):5'- TCCAGTTAAACGTGGGAGAGGACC -3'

Sequencing Primer
(F):5'- GGTGAGAGAGTTGGCCTCC -3'
(R):5'- CCTTCCAAATAGGTTTTCTAAGGTGG -3'

Posted On

2014-01-05