Incidental Mutation 'R5170:Psen1'
ID 397520
Institutional Source Beutler Lab
Gene Symbol Psen1
Ensembl Gene ENSMUSG00000019969
Gene Name presenilin 1
Synonyms PS1, presenilin-1, Ad3h, S182, PS-1
MMRRC Submission 042750-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R5170 (G1)
Quality Score 225
Status Not validated
Chromosome 12
Chromosomal Location 83734926-83781869 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 83761636 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Methionine to Lysine at position 146 (M146K)
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: M146K

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000048363
Gene: ENSMUSG00000019969
AA Change: M146K

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: M146K

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000098786
Gene: ENSMUSG00000019969
AA Change: M146K

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: ENSMUST00000221993
Predicted Effect noncoding transcript
Transcript: ENSMUST00000223542
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.3%
  • 20x: 95.4%
Validation Efficiency
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: 40 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acox3 A G 5: 35,745,969 (GRCm39) I51V probably benign Het
Agbl2 A G 2: 90,633,541 (GRCm39) K559R probably benign Het
Arhgap30 A G 1: 171,235,618 (GRCm39) D664G probably benign Het
BC034090 A G 1: 155,089,396 (GRCm39) V798A probably damaging Het
Bdp1 A T 13: 100,167,302 (GRCm39) C2237* probably null Het
C3 C T 17: 57,530,938 (GRCm39) V388M probably damaging Het
Ccdc170 G A 10: 4,464,200 (GRCm39) E60K probably damaging Het
Cdh8 G A 8: 100,006,182 (GRCm39) T135M probably damaging Het
Cep131 G T 11: 119,961,435 (GRCm39) A572E probably damaging Het
Clec16a A G 16: 10,559,655 (GRCm39) Y976C probably benign Het
Cplx3 G A 9: 57,522,902 (GRCm39) R153* probably null Het
Defa41 A T 8: 21,691,696 (GRCm39) D26V probably damaging Het
Dmpk C G 7: 18,821,944 (GRCm39) L301V probably benign Het
Eno3 A G 11: 70,553,040 (GRCm39) I393V probably benign Het
Fbxo47 A G 11: 97,748,520 (GRCm39) V305A probably benign Het
Fry G A 5: 150,353,319 (GRCm39) V1779M probably benign Het
Gtse1 T C 15: 85,748,465 (GRCm39) probably null Het
Gucy2e A T 11: 69,126,396 (GRCm39) L328Q probably damaging Het
Ifi207 T C 1: 173,558,064 (GRCm39) T225A unknown Het
Igkv4-80 A C 6: 68,993,649 (GRCm39) S81A probably benign Het
Lamc3 A T 2: 31,777,356 (GRCm39) M1L probably benign Het
Myo16 A G 8: 10,619,745 (GRCm39) D1432G probably benign Het
Nwd2 A T 5: 63,963,380 (GRCm39) N988I probably damaging Het
Otx1 C A 11: 21,947,037 (GRCm39) A91S probably damaging Het
Parp14 T C 16: 35,677,649 (GRCm39) E773G probably benign Het
Ptx4 G A 17: 25,342,152 (GRCm39) R209Q probably benign Het
Slc13a2 T C 11: 78,291,634 (GRCm39) T340A probably damaging Het
St8sia1 T C 6: 142,909,434 (GRCm39) K21E probably damaging Het
Stxbp1 T C 2: 32,684,686 (GRCm39) D581G probably benign Het
Sumo2 G A 11: 115,425,486 (GRCm39) probably benign Het
Supt5 G A 7: 28,015,508 (GRCm39) P910S probably benign Het
Tbc1d30 T C 10: 121,142,743 (GRCm39) Q158R possibly damaging Het
Tenm2 T A 11: 35,915,633 (GRCm39) H1968L probably damaging Het
Trmt1 T C 8: 85,421,861 (GRCm39) Y220H probably damaging Het
Trp73 C T 4: 154,189,295 (GRCm39) E60K possibly damaging Het
Ttn A G 2: 76,617,413 (GRCm39) Y8026H probably damaging Het
Zar1l A G 5: 150,441,050 (GRCm39) probably null Het
Zfp740 T C 15: 102,117,640 (GRCm39) Y117H probably damaging Het
Zfp941 G A 7: 140,392,870 (GRCm39) probably benign Het
Zp1 C A 19: 10,897,918 (GRCm39) V8F possibly damaging 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
R5077:Psen1 UTSW 12 83,771,439 (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'- GCAGACCTCACAGTGAATTACAG -3'
(R):5'- TCTTTGCTAGACCAAGTCAAGAC -3'

Sequencing Primer
(F):5'- GTGAATTACAGTTTTAAGAGTGTGC -3'
(R):5'- GCTCAGAACGTGACGCTTAC -3'
Posted On 2016-07-06