Mutations

Search Mutations

Disclaimer: Alzforum does not provide medical advice. The Content is for informational, educational, research and reference purposes only and is not intended to substitute for professional medical advice, diagnosis or treatment. Always seek advice from a qualified physician or health care professional about any medical concern, and do not disregard professional medical advice because of anything you may read on Alzforum.

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 : Unclear Pathogenicity 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 : Unclear Pathogenicity 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