Incidental Mutation 'R5077:Psen1'
ID 401952
Institutional Source Beutler Lab
Gene Symbol Psen1
Ensembl Gene ENSMUSG00000019969
Gene Name presenilin 1
Synonyms PS1, presenilin-1, Ad3h, S182, PS-1
MMRRC Submission 042666-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R5077 (G1)
Quality Score 225
Status Validated
Chromosome 12
Chromosomal Location 83734926-83781869 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 83771439 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Histidine at position 240 (Y240H)
Ref Sequence ENSEMBL: ENSMUSP00000098786 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000041806] [ENSMUST00000101225]
AlphaFold P49769
Predicted Effect probably damaging
Transcript: ENSMUST00000041806
AA Change: Y240H

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000048363
Gene: ENSMUSG00000019969
AA Change: Y240H

DomainStartEndE-ValueType
low complexity region 61 72 N/A INTRINSIC
Blast:PSN 75 113 1e-12 BLAST
PSN 130 453 2.03e-150 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000101225
AA Change: Y240H

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000098786
Gene: ENSMUSG00000019969
AA Change: Y240H

DomainStartEndE-ValueType
low complexity region 61 72 N/A INTRINSIC
Blast:PSN 75 113 1e-12 BLAST
PSN 130 453 2.03e-150 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000221072
Predicted Effect noncoding transcript
Transcript: ENSMUST00000221993
Meta Mutation Damage Score 0.8913 question?
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.7%
  • 10x: 97.4%
  • 20x: 95.7%
Validation Efficiency 93% (51/55)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1; PSEN2) or in the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that they either directly regulate gamma-secretase activity or themselves are protease enzymes. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene, the full-length nature of only some have been determined. [provided by RefSeq, Aug 2008]
PHENOTYPE: Homozygotes for targeted null mutations exhibit deformed axial skeletons, reduced Notch signaling, impaired brain growth with a deficiency of neural stem cells, cerebral hemorrhages, inhibited cleavage of amyloid precursor protein, and perinatal death. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 52 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adam34l A G 8: 44,080,200 (GRCm39) V8A possibly damaging Het
Agbl4 A T 4: 111,423,939 (GRCm39) M322L probably benign Het
Ankrd55 A G 13: 112,492,522 (GRCm39) K231R probably benign Het
Asap1 A C 15: 63,999,272 (GRCm39) M534R probably damaging Het
B4galnt2 T A 11: 95,767,140 (GRCm39) probably benign Het
Cacna1e A T 1: 154,437,475 (GRCm39) probably null Het
Cacna1h T C 17: 25,594,224 (GRCm39) I2311M probably benign Het
Capn2 G T 1: 182,300,138 (GRCm39) D617E possibly damaging Het
Catsper1 A G 19: 5,385,998 (GRCm39) D77G probably damaging Het
Cdc42bpa A T 1: 179,922,098 (GRCm39) probably benign Het
Cdca8 T C 4: 124,820,470 (GRCm39) K109E probably damaging Het
Dbx1 A G 7: 49,283,242 (GRCm39) S223P probably damaging Het
Dlg4 A G 11: 69,917,852 (GRCm39) N45S possibly damaging Het
Dlgap2 T G 8: 14,872,691 (GRCm39) V723G probably benign Het
Efl1 C A 7: 82,307,295 (GRCm39) Q64K probably damaging Het
Eml1 T A 12: 108,472,871 (GRCm39) probably benign Het
Fbxw16 A G 9: 109,270,117 (GRCm39) probably null Het
Gm10800 A T 2: 98,497,379 (GRCm39) L80M probably benign Het
H4c16 A G 6: 136,781,113 (GRCm39) Y89H probably benign Het
Insig2 A T 1: 121,239,964 (GRCm39) V112E probably damaging Het
Kcnip3 A G 2: 127,307,797 (GRCm39) S123P probably damaging Het
Map3k9 T C 12: 81,780,851 (GRCm39) probably null Het
Myo16 T C 8: 10,372,658 (GRCm39) V119A probably damaging Het
Naa25 G A 5: 121,562,639 (GRCm39) V474M probably benign Het
Nckap1 A T 2: 80,379,277 (GRCm39) V219E probably damaging Het
Niban1 A G 1: 151,590,274 (GRCm39) I523V probably benign Het
Nrp1 G T 8: 129,227,154 (GRCm39) probably null Het
Nsun4 A T 4: 115,905,781 (GRCm39) D58E probably benign Het
Obscn G T 11: 58,934,883 (GRCm39) A5249D probably damaging Het
Or8k53 A T 2: 86,177,683 (GRCm39) H142Q probably benign Het
Osmr A T 15: 6,873,874 (GRCm39) Y174* probably null Het
Pi4k2a T C 19: 42,108,275 (GRCm39) probably null Het
Pram1 C T 17: 33,863,878 (GRCm39) Q572* probably null Het
Prdm5 C A 6: 65,756,158 (GRCm39) T25K probably damaging Het
Pygl C T 12: 70,248,666 (GRCm39) G318S probably benign Het
Rbck1 A C 2: 152,160,371 (GRCm39) M436R probably benign Het
Resf1 T G 6: 149,227,528 (GRCm39) S191R probably benign Het
Rmnd1 T C 10: 4,377,488 (GRCm39) N64D possibly damaging Het
Rsph4a A G 10: 33,784,275 (GRCm39) D299G probably damaging Het
Sema4c T C 1: 36,590,812 (GRCm39) S480G probably benign Het
Srp68 T C 11: 116,136,638 (GRCm39) D552G probably damaging Het
Syde2 G T 3: 145,707,764 (GRCm39) A568S probably damaging Het
Szrd1 G T 4: 140,867,092 (GRCm39) probably null Het
Szt2 A T 4: 118,226,813 (GRCm39) probably null Het
Tbc1d31 A G 15: 57,818,797 (GRCm39) E800G probably benign Het
Tmprss11d C A 5: 86,457,122 (GRCm39) probably null Het
Usp37 A G 1: 74,480,720 (GRCm39) V895A probably damaging Het
Vmn1r19 T C 6: 57,382,026 (GRCm39) I193T probably benign Het
Vmn2r102 T C 17: 19,897,834 (GRCm39) V283A probably benign Het
Vps13d C T 4: 144,814,811 (GRCm39) G3180D probably damaging Het
Xirp2 A C 2: 67,344,821 (GRCm39) D2354A probably benign Het
Zc3h14 T A 12: 98,723,465 (GRCm39) probably null Het
Other mutations in Psen1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00580:Psen1 APN 12 83,777,343 (GRCm39) missense probably benign 0.01
IGL00793:Psen1 APN 12 83,769,792 (GRCm39) missense probably damaging 0.98
IGL03171:Psen1 APN 12 83,761,638 (GRCm39) missense probably damaging 1.00
hiortron UTSW 12 83,771,439 (GRCm39) missense probably damaging 1.00
R0685:Psen1 UTSW 12 83,761,594 (GRCm39) nonsense probably null
R1394:Psen1 UTSW 12 83,771,346 (GRCm39) missense probably damaging 1.00
R1395:Psen1 UTSW 12 83,771,346 (GRCm39) missense probably damaging 1.00
R1681:Psen1 UTSW 12 83,771,394 (GRCm39) missense probably damaging 1.00
R2257:Psen1 UTSW 12 83,761,594 (GRCm39) missense probably damaging 1.00
R4833:Psen1 UTSW 12 83,778,552 (GRCm39) missense probably benign 0.23
R5170:Psen1 UTSW 12 83,761,636 (GRCm39) missense probably damaging 1.00
R5782:Psen1 UTSW 12 83,759,233 (GRCm39) missense possibly damaging 0.54
R5804:Psen1 UTSW 12 83,778,474 (GRCm39) missense probably damaging 1.00
R7458:Psen1 UTSW 12 83,761,540 (GRCm39) missense probably damaging 1.00
R7494:Psen1 UTSW 12 83,775,017 (GRCm39) missense probably benign 0.19
R7797:Psen1 UTSW 12 83,746,396 (GRCm39) missense probably benign 0.02
R8547:Psen1 UTSW 12 83,761,630 (GRCm39) missense possibly damaging 0.68
R9286:Psen1 UTSW 12 83,775,549 (GRCm39) missense probably benign
Predicted Primers PCR Primer
(F):5'- CACTTCAAATCCTTGCGTGATTG -3'
(R):5'- TTGCAATCCTTAGCAGTGTAACAG -3'

Sequencing Primer
(F):5'- CAAATCCTTGCGTGATTGTTTTCAG -3'
(R):5'- TCCTTAGCAGTGTAACAGGAAAAC -3'
Posted On 2016-07-22