Alzheimer Disease-4 (AD4) malady

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Mental diseases

Aliases & Classifications for Alzheimer Disease-4

Aliases & Descriptions for Alzheimer Disease-4:

Name: Alzheimer Disease-4 54 13
Alzheimer Disease 4 12 50 66 69
Ad4 12 50 24 66
Alzheimer Disease Type 4 50 24 29
Alzheimer's Disease 4 12 14
Alzheimer Disease Familial Type 4 50
Alzheimer Disease, Familial4 12
Ad 4 24



alzheimer disease-4:
Inheritance autosomal dominant inheritance
Onset and clinical course middle age onset


External Ids:

OMIM 54 606889
Disease Ontology 12 DOID:0110040
MedGen 40 C1847200
MeSH 42 D000544

Summaries for Alzheimer Disease-4

UniProtKB/Swiss-Prot : 66 Alzheimer disease 4: A familial early-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.

MalaCards based summary : Alzheimer Disease-4, also known as alzheimer disease 4, is related to early-onset, autosomal dominant alzheimer disease and alzheimer disease, and has symptoms including dementia, cerebral amyloid angiopathy and alzheimer disease. An important gene associated with Alzheimer Disease-4 is PSEN2 (Presenilin 2), and among its related pathways/superpathways are Cytochrome P450 - arranged by substrate type and Presenilin-Mediated Signaling. The drugs Aluminum hydroxide and Vaccines have been mentioned in the context of this disorder. Related phenotypes are behavior/neurological and cardiovascular system

Disease Ontology : 12 An Alzheimer's disease that has material basis in a mutation in the presenilin-2 gene (PSEN2) on chromosome 1q42.

Description from OMIM: 606889

Related Diseases for Alzheimer Disease-4

Diseases in the Alzheimer Disease family:

Alzheimer Disease-4 Alzheimer Disease 17
Alzheimer Disease 12 Alzheimer Disease, Type 3
Alzheimer Disease 18 Alzheimer Disease-2
Alzheimer Disease 19, Late Onset Alzheimer Disease 16
Alzheimer's Disease 7 Alzheimer's Disease 11
Alzheimer's Disease 13 Alzheimer's Disease 14
Alzheimer's Disease 15 Early-Onset Familial Alzheimer Disease
Alzheimer Disease Type 1 Early-Onset, Autosomal Dominant Alzheimer Disease
Alzheimer Disease Risk Factor

Diseases related to Alzheimer Disease-4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 46)
id Related Disease Score Top Affiliating Genes
1 early-onset, autosomal dominant alzheimer disease 10.9
2 alzheimer disease 10.9
3 encephalitozoonosis 10.2 APP PSEN1
4 spastic ataxia 3 10.2 CYP11B1 CYP11B2
5 ectodermal dysplasia mental retardation syndactyly 10.2 APP PSEN1 PSEN2
6 balanoposthitis 10.2 ABCA7 PSEN2
7 foxp2-related speech and language disorders 10.2 APP PSEN1 PSEN2
8 meckel syndrome 10 10.2 APP PSEN1 PSEN2
9 cardiomyopathy, dilated, 1u 10.2 APP PSEN1 PSEN2
10 cytomegalovirus retinitis 10.1 NR0B1 NR5A1
11 combined oxidative phosphorylation deficiency 8 10.1 ABCA7 GPR180 PSEN2
12 centrotemporal epilepsy 10.1 NR0B1 NR5A1
13 intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies 10.1 CYP11B1 CYP11B2
14 abl1 kd-related altered drug metabolism 10.1 NR0B1 NR5A1
15 duchenne muscular dystrophy 10.1 NR0B1 NR5A1
16 alzheimer's disease 14 10.1 ABCA7 APP GPR180
17 benign peritoneal mesothelioma 10.1 CYP11B1 CYP11B2 NR5A1
18 amelogenesis imperfecta, type iia3 10.1 ABCA7 APP GPR180
19 eumycotic mycetoma 10.1 APP PSEN1 PSEN2
20 intracranial structure hemangioma 10.1 APP PSEN1
21 hypoaldosteronism, congenital, due to cmo i deficiency 10.1 CYP11B1 CYP11B2
22 x-linked sideroblastic anemia with ataxia 10.1 CYP11A1 CYP17A1
23 substance-induced psychosis 10.0 APP PSEN1 PSEN2
24 autosomal dominant optic atrophy and late-onset deafness 10.0 NR0B1 NR5A1
25 deafness, autosomal recessive 29 10.0 CYP11A1 CYP17A1
26 esophagus squamous cell papilloma 10.0 CYP11A1 CYP11B1 CYP11B2
27 clear cell adenocarcinoma 10.0 CYP11B1 CYP11B2 CYP17A1
28 clear cell acanthoma 10.0 CYP11A1 CYP11B1 CYP17A1
29 microphthalmia, syndromic 9 10.0 CYP11A1 CYP11B1 CYP17A1
30 malignant otitis externa 9.9 CYP11A1 NR0B1 NR5A1
31 pick disease 9.9 ABCA7 APP CYP11B2 PSEN1 PSEN2
32 borderline personality disorder 9.9 CYP17A1 CYP19A1
33 bent bone dysplasia syndrome 9.9 CYP17A1 CYP19A1
34 ameloblastoma 9.9 CYP11A1 CYP11B1 CYP17A1 NR5A1
35 tardive dyskinesia 9.9
36 epithelial predominant pulmonary blastoma 9.8 CYP11A1 CYP17A1
37 panuveitis 9.8 CYP11A1 CYP11B1 CYP11B2 CYP17A1
38 childhood optic tract astrocytoma 9.8 CYP11A1 CYP11B1 CYP11B2 CYP17A1
39 second-degree atrioventricular block 9.8 CYP11A1 CYP11B1 CYP11B2 CYP17A1
40 liver sarcoma 9.8 CYP11A1 CYP17A1 CYP19A1
41 farmer's lung 9.8 CYP11A1 CYP17A1 NR0B1 NR5A1
42 primary biliary cirrhosis 9.8 CYP11A1 CYP17A1 CYP19A1
43 jackson-weiss syndrome 9.7 CYP11A1 CYP11B1 CYP11B2 CYP17A1 NR5A1
44 loeffler endocarditis 9.6 CYP11A1 CYP11B1 CYP17A1 NR0B1 NR5A1
45 glioma susceptibility 1 9.4 CYP11A1 CYP11B1 CYP11B2 CYP17A1 CYP19A1 NR5A1
46 cardiomyopathy, dilated, 1v 8.4 ABCA7 APP CYP11A1 CYP11B1 CYP11B2 CYP17A1

Graphical network of the top 20 diseases related to Alzheimer Disease-4:

Diseases related to Alzheimer Disease-4

Symptoms & Phenotypes for Alzheimer Disease-4

Symptoms by clinical synopsis from OMIM:


Clinical features from OMIM:


Human phenotypes related to Alzheimer Disease-4:

id Description HPO Frequency HPO Source Accession
1 dementia 32 HP:0000726
2 cerebral amyloid angiopathy 32 HP:0011970
3 alzheimer disease 32 HP:0002511
4 sleep-wake cycle disturbance 32 HP:0006979

MGI Mouse Phenotypes related to Alzheimer Disease-4:

id Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.01 APP CYP11A1 CYP11B1 CYP17A1 CYP19A1 NR5A1
2 cardiovascular system MP:0005385 9.97 PSEN2 CYP11A1 CYP11B1 CYP11B2 CYP19A1 GPR180
3 homeostasis/metabolism MP:0005376 9.93 CYP19A1 GPR180 NR0B1 NR5A1 PSEN1 PSEN2
4 cellular MP:0005384 9.92 APP CYP11A1 CYP11B1 CYP17A1 CYP19A1 NR5A1
5 endocrine/exocrine gland MP:0005379 9.86 CYP11A1 CYP11B1 CYP11B2 CYP19A1 NR0B1 NR5A1
6 renal/urinary system MP:0005367 9.43 ABCA7 CYP11B1 CYP11B2 CYP19A1 PSEN1 PSEN2
7 reproductive system MP:0005389 9.23 APP CYP11A1 CYP11B2 CYP17A1 CYP19A1 NR0B1

Drugs & Therapeutics for Alzheimer Disease-4

Drugs for Alzheimer Disease-4 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

id Name Status Phase Clinical Trials Cas Number PubChem Id
Aluminum hydroxide Approved Phase 1 21645-51-2
2 Vaccines Phase 1
3 Krestin Phase 1

Interventional clinical trials:

id Name Status NCT ID Phase
1 A Phase 1 Ascending Dose Study to Assess the Safety and Immunogenicity of Adenovirus Anthrax Vector Candidate Vaccines Unknown status NCT01979406 Phase 1
2 Safety and Immunogenicity of Replication-Competent Adenovirus 4-vectored Vaccine for Avian Influenza H5N1 Completed NCT01006798 Phase 1
3 Study of Safety and Immunogenicity of HIV Vaccines in Healthy Volunteers Recruiting NCT01989533 Phase 1
4 A Study to Assess the Safety, Pharmacodynamics, and Immunogenicity of PXVX0047 Recruiting NCT03160339 Phase 1
5 Intranasal AD4-H5-VTN as an Adenovirus Vaccine Active, not recruiting NCT01806909 Phase 1
6 Experimental AD4-H5-VTN Vaccine in Healthy Volunteers Active, not recruiting NCT01443936 Phase 1
7 Study to Evaluate the Safety and Immunogenicity of Orally-administered HIV Vaccine in Healthy, HIV-uninfected Adult Participants Active, not recruiting NCT02771730 Phase 1

Search NIH Clinical Center for Alzheimer Disease-4

Genetic Tests for Alzheimer Disease-4

Genetic tests related to Alzheimer Disease-4:

id Genetic test Affiliating Genes
1 Alzheimer Disease, Type 4 29
2 Alzheimer Disease Type 4 24 PSEN2

Anatomical Context for Alzheimer Disease-4

Publications for Alzheimer Disease-4

Variations for Alzheimer Disease-4

UniProtKB/Swiss-Prot genetic disease variations for Alzheimer Disease-4:

id Symbol AA change Variation ID SNP ID
1 PSEN2 p.Asn141Ile VAR_006462 rs63750215
2 PSEN2 p.Met239Val VAR_006463 rs28936379
3 PSEN2 p.Val148Ile VAR_007958 rs63750812
4 PSEN2 p.Thr122Pro VAR_009214 rs63749851
5 PSEN2 p.Met239Ile VAR_009215 rs63749884

ClinVar genetic disease variations for Alzheimer Disease-4:

id Gene Variation Type Significance SNP ID Assembly Location
1 PSEN2 NM_000447.2(PSEN2): c.422A> T (p.Asn141Ile) single nucleotide variant Pathogenic rs63750215 GRCh37 Chromosome 1, 227073304: 227073304
2 PSEN2 NM_000447.2(PSEN2): c.715A> G (p.Met239Val) single nucleotide variant Pathogenic rs28936379 GRCh37 Chromosome 1, 227076678: 227076678
3 PSEN2 NM_000447.2(PSEN2): c.1289C> T (p.Thr430Met) single nucleotide variant Pathogenic rs63750666 GRCh37 Chromosome 1, 227083222: 227083222
4 PSEN2 NM_000447.2(PSEN2): c.364A> C (p.Thr122Pro) single nucleotide variant Pathogenic rs63749851 GRCh37 Chromosome 1, 227073246: 227073246
5 PSEN2 NM_000447.2(PSEN2): c.717G> A (p.Met239Ile) single nucleotide variant Pathogenic rs63749884 GRCh37 Chromosome 1, 227076680: 227076680
6 PSEN2 NM_000447.2(PSEN2): c.365C> G (p.Thr122Arg) single nucleotide variant Pathogenic rs28936380 GRCh37 Chromosome 1, 227073247: 227073247
7 PSEN2 NM_000447.2(PSEN2): c.254C> T (p.Ala85Val) single nucleotide variant Pathogenic rs63750048 GRCh37 Chromosome 1, 227071518: 227071518
8 PSEN1 NG_007386.2: g.73292_77847del4556 deletion Pathogenic GRCh37 Chromosome 14, 73671470: 73676025
9 PSEN1 NM_000021.3(PSEN1): c.806G> A (p.Arg269His) single nucleotide variant Pathogenic rs63750900 GRCh37 Chromosome 14, 73664775: 73664775

Expression for Alzheimer Disease-4

Search GEO for disease gene expression data for Alzheimer Disease-4.

Pathways for Alzheimer Disease-4

Pathways related to Alzheimer Disease-4 according to GeneCards Suite gene sharing:

(show all 13)
id Super pathways Score Top Affiliating Genes
Show member pathways
12.96 CYP11A1 CYP11B1 CYP11B2 CYP17A1 CYP19A1 CYP2B6
2 11.82 APP PSEN1 PSEN2
3 11.4 APP PSEN1 PSEN2
Show member pathways
11.31 CYP11B1 CYP17A1 CYP19A1
Show member pathways
11.3 CYP11A1 CYP11B1 CYP11B2 CYP17A1 CYP19A1
6 11.24 CYP11A1 CYP17A1 CYP19A1
7 11.15 APP PSEN1 PSEN2
8 11.03 CYP19A1 NR5A1
9 10.94 PSEN1 PSEN2
10 10.85 APP PSEN1 PSEN2
Show member pathways
10.83 CYP11A1 CYP11B1 CYP11B2 CYP17A1 CYP19A1
Show member pathways
10.65 CYP11B1 CYP11B2 CYP17A1
13 10.13 PSEN1 PSEN2

GO Terms for Alzheimer Disease-4

Cellular components related to Alzheimer Disease-4 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 9.73 ABCA7 APP CYP11A1 CYP11B1 CYP11B2 CYP17A1
2 endoplasmic reticulum membrane GO:0005789 9.65 CYP17A1 CYP19A1 CYP2B6 PSEN1 PSEN2
3 mitochondrial membrane GO:0031966 9.33 CYP11A1 CYP11B1 CYP11B2
4 smooth endoplasmic reticulum GO:0005790 9.32 APP PSEN1
5 ciliary rootlet GO:0035253 8.62 APP PSEN1

Biological processes related to Alzheimer Disease-4 according to GeneCards Suite gene sharing:

(show all 22)
id Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.93 CYP11A1 CYP11B1 CYP11B2 CYP17A1 CYP19A1 CYP2B6
2 Notch signaling pathway GO:0007219 9.74 APP PSEN1 PSEN2
3 female gonad development GO:0008585 9.61 CYP19A1 NR5A1
4 membrane protein ectodomain proteolysis GO:0006509 9.6 PSEN1 PSEN2
5 regulation of protein binding GO:0043393 9.59 APP PSEN1
6 adrenal gland development GO:0030325 9.58 NR0B1 NR5A1
7 Notch receptor processing GO:0007220 9.58 PSEN1 PSEN2
8 beta-amyloid metabolic process GO:0050435 9.56 PSEN1 PSEN2
9 amyloid precursor protein catabolic process GO:0042987 9.55 PSEN1 PSEN2
10 steroid metabolic process GO:0008202 9.55 CYP11A1 CYP11B1 CYP11B2 CYP17A1 CYP2B6
11 sex determination GO:0007530 9.54 NR0B1 NR5A1
12 glucocorticoid biosynthetic process GO:0006704 9.52 CYP11B1 CYP17A1
13 cellular response to potassium ion GO:0035865 9.51 CYP11B1 CYP11B2
14 cellular response to beta-amyloid GO:1904646 9.49 APP PSEN1
15 regulation of epidermal growth factor-activated receptor activity GO:0007176 9.48 APP PSEN1
16 astrocyte activation involved in immune response GO:0002265 9.43 APP PSEN1
17 C21-steroid hormone biosynthetic process GO:0006700 9.43 CYP11A1 CYP11B1 CYP11B2
18 aldosterone biosynthetic process GO:0032342 9.4 CYP11B1 CYP11B2
19 cortisol biosynthetic process GO:0034651 9.37 CYP11B1 CYP11B2
20 sterol metabolic process GO:0016125 9.35 CYP11A1 CYP11B1 CYP11B2 CYP17A1 CYP19A1
21 smooth endoplasmic reticulum calcium ion homeostasis GO:0051563 9.32 APP PSEN1
22 steroid biosynthetic process GO:0006694 9.1 CYP11A1 CYP11B1 CYP11B2 CYP17A1 CYP19A1 NR0B1

Molecular functions related to Alzheimer Disease-4 according to GeneCards Suite gene sharing:

(show all 11)
id Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.73 CYP11A1 CYP11B1 CYP11B2 CYP17A1 CYP19A1 CYP2B6
2 iron ion binding GO:0005506 9.63 CYP11A1 CYP11B1 CYP11B2 CYP17A1 CYP19A1 CYP2B6
3 monooxygenase activity GO:0004497 9.61 CYP11B2 CYP19A1 CYP2B6
4 oxygen binding GO:0019825 9.58 CYP17A1 CYP19A1 CYP2B6
5 aspartic-type endopeptidase activity GO:0004190 9.49 PSEN1 PSEN2
6 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen GO:0016712 9.48 CYP19A1 CYP2B6
7 steroid hydroxylase activity GO:0008395 9.46 CYP11B2 CYP19A1
8 heme binding GO:0020037 9.43 CYP11A1 CYP11B1 CYP11B2 CYP17A1 CYP19A1 CYP2B6
9 corticosterone 18-monooxygenase activity GO:0047783 9.37 CYP11B1 CYP11B2
10 steroid 11-beta-monooxygenase activity GO:0004507 9.32 CYP11B1 CYP11B2
11 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen GO:0016705 9.1 CYP11A1 CYP11B1 CYP11B2 CYP17A1 CYP19A1 CYP2B6

Sources for Alzheimer Disease-4

9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
32 HPO
33 ICD10
34 ICD10 via Orphanet
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
52 Novoseek
55 OMIM via Orphanet
59 PubMed
65 SNOMED-CT via Orphanet
68 Tocris
70 UMLS via Orphanet
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