Mutations

Search Mutations

Search Results

PSEN2 (48)

The gene PSEN2 encodes presenilin-2, a subunit of γ-secretase, the aspartyl protease responsible for Aβ generation. Missense mutations in PSEN2 are a rare cause of early onset Alzheimer's disease.

Mutation Clinical
Phenotype
Pathogenicity Neuropathology Biological Effect Genomic Position Genomic Region Mutation Type
Codon Change
Research
Models
Primary
Papers
T18M
Parkinson's Disease PD : Unclear Pathogenicity Unknown. Unknown; predicted pathogenic in silico.

rs143061887
Coding
Exon 3
Point, Missense
ACG to ATG
0 Blauwendraat et al., 2016
R29H
None AD : Not Pathogenic Not applicable. Unknown.

Coding
Exon 3
Point
CGC to CAC
0 Guerreiro et al., 2010
G34S
Alzheimer's Disease AD : Unclear Pathogenicity Unknown. Unchanged Aβ42/Aβ40 ratio.

Coding
Exon 3
Point
GGC to AGC
0 Sleegers et al., 2004
R62C
Alzheimer's Disease, None AD : Unclear Pathogenicity Unknown. Unknown; predicted possibly damaging in silico.

rs150400387
Coding
Exon 4
Point
CGC to TGC
0 Sleegers et al., 2004;
Ertekin-Taner et al., 2008;
Brouwers et al., 2008
R62H
Alzheimer's Disease, Frontotemporal Dementia, Parkinson's Disease Dementia AD : Not Pathogenic, FTD : Not Pathogenic Unknown. Unchanged Aβ42/Aβ40 ratio; unchanged Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF.

rs58973334
Coding
Exon 4
Point, Missense
CGC to CAC
0 Cruts et al., 1998;
Gallo et al., 2010
P69A
Alzheimer's Disease AD : Unclear Pathogenicity Unknown. Unknown.

Coding
Exon 4
Point, Missense
CCC to GCC
0 Dobricic et al., 2012
R71W
Alzheimer's Disease, None, Parkinson's Disease Dementia AD : Not Pathogenic Leukoencephalopathy with periventricular white-matter lacunar infarctions. Unchanged Aβ42/Aβ40 ratio; Reduces the stability of the presenilin-2 protein and impairs Notch signaling.

rs140501902
Coding
Exon 4
Point, Missense
CGG to TGG
0 Sleegers et al., 2004
K82R
Alzheimer's Disease AD : Unclear Pathogenicity Unknown; neuroimaging showed diffuse cortical atrophy, especially in the posterior region and mild hippocampal atrophy. FDG-PET showed widespread hypometabolism. PIB-PET showed amyloid deposition in the frontal lobe, lateral temporal lobe, parietal lobe, posterior cingulate cortex, precuneus, and striatum.

 

Unknown.

Coding
Exon 4
Point, Missense
AAA to AGA
0 Shi et al., 2015
A85V
Alzheimer's Disease, Dementia with Lewy Bodies AD : Pathogenic, DLB : Unclear Pathogenicity Amyloid deposition; Neurofibrillary changes; Diffuse Lewy bodies in the neocortex; Bilateral basal ganglia calcifications. Unknown.

rs63750048
Coding
Exon 4
Point, Missense
GCG to GTG
0 Piscopo et al., 2008
V101M
Alzheimer's Disease AD : Unclear Pathogenicity Unknown. Unknown; predicted probably damaging in silico.

Coding
Exon 4
Point, Missense
GTG to ATG
0 Sala Frigerio et al., 2015
K115Efs*
Alzheimer's Disease AD : Pathogenic Unknown; FDG-PET showed hypometabolism in the parietal and temporal lobes. The deletion of two nucleotides from exon 5 leads to a frameshift and ultimately to a premature stop codon in exon 6. This is predicted to result in either a truncated presenilin-2 protein or transcript degradation due to nonsense-mediated decay.

Coding
Exon 4
Deletion
AAG to A--
0 Jayadev et al., 2010
T122P
Alzheimer's Disease AD : Pathogenic Unknown. Increased Aβ42/Aβ40 ratio; increased Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF.

rs63749851
Coding
Exon 5
Point, Missense
ACG to CCG
0 Finckh et al., 2000
T122R
Atypical Dementia Atypical Dementia : Pathogenic Variable cortical and subcortical atrophy. Reduced calcium ion released from intracellular stores.

rs28936380
Coding
Exon 5
Point, Missense
ACG to AGG
0 Binetti et al., 2003
P123L
Alzheimer's Disease AD : Unclear Pathogenicity Unknown; Neuroimaging showed diffuse cortical atrophy, predominantly in the right hemisphere. FDG-PET showed hypoperfusion in the right temporal and parietal regions. Unknown; predicted probably damaging in silico.

Coding
Exon 5
Point, Missense
CCA to CTA
0 Xia et al., 2015
E126fs
Alzheimer's Disease AD : Pathogenic Unknown; neuroimaging showed hippocampal and parahippocampal atrophy. Unknown; the insertion of one nucleotide (A) is predicted to result in a frameshift at codon 126.

Coding
Exon 5
Insertion
GAG.GAC to GAA.GGA
0 El Kadmiri et al., 2014
E126K
Alzheimer's Disease AD : Pathogenic Unknown. Unknown; predicted probably damaging in silico.

Coding
Exon 5
Point, Missense
GAG to AAG
0 Müller et al., 2014
S130L
Alzheimer's Disease, None, Parkinson's Disease Dementia AD : Unclear Pathogenicity Neuropathology consistent with AD at autopsy in at least one case. Unchanged Aβ42/Aβ40 ratio; unchanged Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF.

rs63750197
Coding
Exon 5
Point, Missense
TCG to TTG
0 Sorbi et al., 2002;
Tedde et al., 2003
V139M
Alzheimer's Disease, None AD : Unclear Pathogenicity Bilateral hypoperfusion in the parietal-temporal lobes. Unknown.

Coding
Exon 5
Point, Missense
GTG to ATG
0 Bernardi et al., 2008
N141I
(Volga German)
Alzheimer's Disease AD : Pathogenic Extensive amyloid plaques; Extensive neurofibrillary tangles (typically a Braak score of V or VI); α-synuclein inclusions, especially in the amygdala; Rare TDP-43 pathology; Hippocampal sclerosis. Increased Aβ42/Aβ40 ratio; increased Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF.

rs63750215
Coding
Exon 5
Point, Missense
AAC to ATC
5 Levy-Lahad et al., 1995;
Rogaev et al., 1995
N141Y
Alzheimer's Disease AD : Pathogenic Proband had autopsy-confirmed AD with severe brain atrophy and numerous plaques and neurofibrillary tangles. Unknown; predicted damaging in silico.

rs61761208
Coding
Exon 5
Point, Missense
AAC to TAC
0 Niu et al., 2014
L143H
None AD : Not Pathogenic Not applicable. Unknown.

Coding
Exon 5
Point, Missense
CTC to CAC
0 Guerreiro et al., 2010
V148I
Alzheimer's Disease AD : Pathogenic Unknown. Unchanged Aβ42/Aβ40 ratio; unchanged Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF.

rs63750812
Coding
Exon 5
Point, Missense
GTC to ATC
0 Lao et al., 1998
K161R
Alzheimer's Disease AD : Pathogenic Unknown. Unknown.

Coding
Exon 5
Point, Missense
AAG to AGG
0 Wallon et al., 2012
R163H
None AD : Not Pathogenic Not applicable. Unknown.

Coding
Exon 5
Point, Missense
CGC to CAC
0 Puschmann et al., 2009
H169N
Alzheimer's Disease, Frontotemporal Dementia, Progressive Nonfluent Aphasia AD : Unclear Pathogenicity, FTD : Unclear Pathogenicity Unknown; neuroimaging showed mild atrophy and widespread hypometabolism. PIB-PET showed amyloid deposition in the AD case, but no amyloid deposition in the FTD case. Unknown.

Coding
Exon 6
Point, Missense
CAT to AAT
0 Shi et al., 2015
M174V
Alzheimer's Disease, Frontotemporal Dementia AD : Not Pathogenic Unknown; imaging has shown frontal atrophy and hypoperfusion in temporoparietal regions. Unknown; predicted benign in silico.

rs61757781
Coding
Exon 6
Point, Missense
ATG to GTG
0 Andreoli et al., 2008;
Clarimón et al., 2008;
Guerreiro et al., 2010
S175C
Alzheimer's Disease AD : Pathogenic Unknown; MRI showed focal atrophy in the medial temporal lobe; SPECT showed bilateral hypoperfusion in temporoparietal regions. Unknown.

Coding
Exon 6
Point, Missense
TCT to TGT
0 Piscopo et al., 2010
G212V
Alzheimer's Disease AD : Pathogenic Neuropathology consistent with AD. Unknown; predicted pathogenic in silico.

Coding
Exon 7
Point, Missense
GGG to GTG
0 Marín-Muñoz et al., 2016
V214L
Alzheimer's Disease AD : Pathogenic Unknown; neuroimaging showed diffuse cortical atrophy and widespread hypometabolism. Unknown; structural changes were predicted in silico, especially at amino acids 214, 219, and 220. PolyPhen2 predicted a probably or possibly damaging effect.

Coding
Exon 7
Point, Missense
GTG to TTG
0 Youn et al., 2014
Q228L
Alzheimer's Disease AD : Pathogenic Unknown. Unknown.

rs63750880
Coding
Exon 7
Point, Missense
CAG to CTG
0 Zekanowski et al., 2003
Y231C
Frontotemporal Dementia FTD : Pathogenic Unknown; MRI showed diffuse subcortical and cortical atrophy, particularly in the frontotemporoparietal lobes. Unknown.

Coding
Exon 7
Point, Missense
TAC to TGC
0 Marcon et al., 2009
I235F
Alzheimer's Disease, None AD : Not Pathogenic Not applicable. Unknown.

Coding
Exon 7
Point, Missense
ATC to TTC
0 Lee et al., 2014
A237V
Alzheimer's Disease AD : Unclear Pathogenicity Neuropathology consistent with AD. Unknown; predicted possibly damaging in silico.

rs200670135
Coding
Exon 7
Point, Missense
GCG to GTG
0 Sassi et al., 2014
L238F
Alzheimer's Disease AD : Unclear Pathogenicity Unknown. Unknown; predicted probably damaging in silico.

Coding
Exon 7
Point, Missense
CTC to TTC
0 Sala Frigerio et al., 2015
L238P
Alzheimer's Disease AD : Pathogenic Unknown; MRI showed supratentorial cortical atrophy, particularly atrophy of the parietal cortex. Unknown; predicted damaging in silico.

Coding
Exon 8
Point, Missense
CTC to CCC
0 Blauwendraat et al., 2016
M239I
Alzheimer's Disease AD : Pathogenic Moderate cortical atrophy; Numerous neurofibrillary tangles; Numerous senile plaques, especially in the amygdala. Increased Aβ42/Aβ40 ratio; increased Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF; Reduced calcium release.

rs63749884
Coding
Exon 7
Point, Missense
ATG to ATA
0 Finckh et al., 2000
M239V
Alzheimer's Disease AD : Pathogenic Diffuse cerebral atrophy; Senile plaques; Neurofibrillary tangles (stage VI of Braak and Braak); Ectopic neurons in the subcortical white matter; Extracellular "ghost" neurofibrillary tangles. Increased Aβ42/Aβ40 ratio; increased Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF.

rs28936379
Coding
Exon 7
Point, Missense
ATG to GTG
0 Rogaev et al., 1995
A252T
None AD : Not Pathogenic Not applicable. Unknown.

rs138836272
Coding
Exon 7
Point, Missense
GCG to ACG
0 Guerreiro et al., 2010
A258T
None AD : Not Pathogenic Not applicable. Unknown.

rs148238688
Coding
Exon 7
Point, Missense
GCC to ACC
0 Sala Frigerio et al., 2015
T301M
Alzheimer's Disease AD : Unclear Pathogenicity Unknown. Unchanged Aβ42/Aβ40 ratio.

rs144277432
Coding
Exon 7
Point, Missense
ACG to ATG
0 Croes et al., 2004
K306fs
Alzheimer's Disease AD : Pathogenic Unknown; neuroimaging showed cortical atrophy. Unknown; the deletion of a single nucleotide (A) in exon 9 is predicted to result in a frameshift at codon 306.

Coding
Exon 9
Deletion
AAG.CTG to AGC.TGG
0 El Kadmiri et al., 2014
P334A
Alzheimer's Disease, None AD : Not Pathogenic Not applicable. Unknown.

Coding
Exon 10
Point, Missense
CCT to GCT
0 Lee et al., 2014
P334R
Alzheimer's Disease, None AD : Not Pathogenic Not applicable. Unknown.

rs63750207
Coding
Exon 10
Point, Missense
CCT to CGT
0 Lleó et al., 2002
P348L
Alzheimer's Disease AD : Unclear Pathogenicity Unknown. Unknown.

Coding
Exon 10
Point, Missense
CCA to CTA
0 Blauwendraat et al., 2016
A377V
Alzheimer's Disease, None AD : Not Pathogenic Not applicable. Unknown.

Coding
Exon 11
Point, Missense
GCG to GTG
0 Lee et al., 2014
V393M
Alzheimer's Disease AD : Unclear Pathogenicity Unknown; bilateral hypometabolism in the parieto-occipital regions. Unchanged Aβ42/Aβ40 ratio; unchanged Aβ42.

rs142690225
Coding
Exon 11
Point, Missense
GTG to ATG
0 Lindquist et al., 2008
T430M
Alzheimer's Disease AD : Pathogenic Right frontotemporal hypoperfusion. Unknown.

rs63750666
Coding
Exon 12
Point, Missense
ACG to ATG
0 Ezquerra et al., 2003
D439A
Alzheimer's Disease AD : Unclear Pathogenicity Unknown; imaging showed moderate cortical atrophy in the frontal and parietal regions. Unchanged Aβ42/Aβ40 ratio; unchanged Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF.

rs63750110
Coding
Exon 12
Point, Missense
GAC to GCC
0 Lleó et al., 2001