Alzheimer Disease-4 (AD4) malady

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

Aliases & Classifications for Alzheimer Disease-4

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Aliases & Descriptions for Alzheimer Disease-4:

Name: Alzheimer Disease-4 52 12
Alzheimer Disease 4 11 48 70 68
Ad4 11 48 24 70
Alzheimer Disease Type 4 48 24 27
Alzheimer's Disease 4 11 13
Alzheimer Disease Familial Type 4 48
Alzheimer Disease, Familial4 11
Ad 4 24



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


External Ids:

OMIM52 606889
Disease Ontology11 DOID:0110040
MedGen37 C1847200
MeSH39 D000544

Summaries for Alzheimer Disease-4

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UniProtKB/Swiss-Prot:70 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, alzheimer disease and sleep-wake cycle disturbance. An important gene associated with Alzheimer Disease-4 is PSEN2 (Presenilin 2), and among its related pathways are Canonical and Non-canonical Notch signaling and Notch Pathway. Related mouse phenotypes are renal/urinary system and cardiovascular system.

Disease Ontology:11 An Alzheimer's disease that has material basis in a mutation in the presenilin-2 gene (PSEN2) on chromosome 1q42.

Description from OMIM:52 606889

Related Diseases for Alzheimer Disease-4

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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)
idRelated DiseaseScoreTop Affiliating Genes
1early-onset, autosomal dominant alzheimer disease10.9
2alzheimer disease10.9
3encephalitozoonosis10.2APP, PSEN1
4spastic ataxia 310.2CYP11B1, CYP11B2
5ectodermal dysplasia mental retardation syndactyly10.2APP, PSEN1, PSEN2
6balanoposthitis10.2ABCA7, PSEN2
7foxp2-related speech and language disorders10.2APP, PSEN1, PSEN2
8meckel syndrome 1010.2APP, PSEN1, PSEN2
9cardiomyopathy, dilated, 1u10.2APP, PSEN1, PSEN2
10cytomegalovirus retinitis10.1NR0B1, NR5A1
11combined oxidative phosphorylation deficiency 810.1ABCA7, GPR180, PSEN2
12centrotemporal epilepsy10.1NR0B1, NR5A1
13intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies10.1CYP11B1, CYP11B2
14abl1 kd-related altered drug metabolism10.1NR0B1, NR5A1
15duchenne muscular dystrophy10.1NR0B1, NR5A1
16alzheimer's disease 1410.1ABCA7, APP, GPR180
17benign peritoneal mesothelioma10.1CYP11B1, CYP11B2, NR5A1
18amelogenesis imperfecta, type iia310.1ABCA7, APP, GPR180
19eumycotic mycetoma10.1APP, PSEN1, PSEN2
20intracranial structure hemangioma10.1APP, PSEN1
21hypoaldosteronism, congenital, due to cmo i deficiency10.1CYP11B1, CYP11B2
22x-linked sideroblastic anemia with ataxia10.1CYP11A1, CYP17A1
23substance-induced psychosis10.0APP, PSEN1, PSEN2
24autosomal dominant optic atrophy and late-onset deafness10.0NR0B1, NR5A1
25deafness, autosomal recessive 2910.0CYP11A1, CYP17A1
26esophagus squamous cell papilloma10.0CYP11A1, CYP11B1, CYP11B2
27clear cell adenocarcinoma10.0CYP11B1, CYP11B2, CYP17A1
28clear cell acanthoma10.0CYP11A1, CYP11B1, CYP17A1
29microphthalmia, syndromic 910.0CYP11A1, CYP11B1, CYP17A1
30malignant otitis externa9.9CYP11A1, NR0B1, NR5A1
31pick disease9.9ABCA7, APP, CYP11B2, PSEN1, PSEN2
32borderline personality disorder9.9CYP17A1, CYP19A1
33bent bone dysplasia syndrome9.9CYP17A1, CYP19A1
34ameloblastoma9.9CYP11A1, CYP11B1, CYP17A1, NR5A1
35tardive dyskinesia9.9
36epithelial predominant pulmonary blastoma9.8CYP11A1, CYP17A1
37panuveitis9.8CYP11A1, CYP11B1, CYP11B2, CYP17A1
38childhood optic tract astrocytoma9.8CYP11A1, CYP11B1, CYP11B2, CYP17A1
39second-degree atrioventricular block9.8CYP11A1, CYP11B1, CYP11B2, CYP17A1
40liver sarcoma9.8CYP11A1, CYP17A1, CYP19A1
41farmer's lung9.8CYP11A1, CYP17A1, NR0B1, NR5A1
42primary biliary cirrhosis9.8CYP11A1, CYP17A1, CYP19A1
43jackson-weiss syndrome9.7CYP11A1, CYP11B1, CYP11B2, CYP17A1, NR5A1
44loeffler endocarditis9.6CYP11A1, CYP11B1, CYP17A1, NR0B1, NR5A1
45glioma susceptibility 19.4CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1, NR5A1
46cardiomyopathy, dilated, 1v8.4ABCA7, 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

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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 dementia64 HP:0000726
2 alzheimer disease64 HP:0002511
3 sleep-wake cycle disturbance64 HP:0006979
4 cerebral amyloid angiopathy64 HP:0011970

MGI Mouse Phenotypes related to Alzheimer Disease-4 according to GeneCards Suite gene sharing:

idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053678.8ABCA7, CYP11B1, CYP11B2, CYP19A1, PSEN1, PSEN2
2MP:00053858.0CYP11A1, CYP11B1, CYP11B2, CYP19A1, GPR180, NR5A1
3MP:00053868.0APP, CYP11A1, CYP11B1, CYP17A1, CYP19A1, NR5A1
4MP:00053848.0APP, CYP11A1, CYP11B1, CYP17A1, CYP19A1, NR5A1
5MP:00053797.8CYP11A1, CYP11B1, CYP11B2, CYP19A1, NR0B1, NR5A1
6MP:00053896.8APP, CYP11A1, CYP11B2, CYP17A1, CYP19A1, NR0B1
7MP:00053766.2ABCA7, APP, CYP11A1, CYP11B1, CYP11B2, CYP17A1

Drugs & Therapeutics for Alzheimer Disease-4

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

idNameStatusPhaseClinical TrialsCas NumberPubChem Id
Aluminum hydroxideapprovedPhase 121021645-51-2
Aluminium hydroxide
Aluminium hydroxide gel, dried
Aluminium hydroxide, dried
Aluminum hydroxide gel, dried
Aluminum hydroxide, dried
Dried aluminium hydroxide
Dried aluminum hydroxide gel
2VaccinesPhase 16611
3KrestinPhase 1210

Interventional clinical trials:

idNameStatusNCT IDPhase
1A Phase 1 Ascending Dose Study to Assess the Safety and Immunogenicity of Adenovirus Anthrax Vector Candidate VaccinesUnknown statusNCT01979406Phase 1
2Safety and Immunogenicity of Replication-Competent Adenovirus 4-vectored Vaccine for Avian Influenza H5N1CompletedNCT01006798Phase 1
3Study of Safety and Immunogenicity of HIV Vaccines in Healthy VolunteersRecruitingNCT01989533Phase 1
4A Study to Assess the Safety, Pharmacodynamics, and Immunogenicity of PXVX0047RecruitingNCT03160339Phase 1
5Intranasal AD4-H5-VTN as an Adenovirus VaccineActive, not recruitingNCT01806909Phase 1
6Experimental AD4-H5-VTN Vaccine in Healthy VolunteersActive, not recruitingNCT01443936Phase 1
7Study to Evaluate the Safety and Immunogenicity of Orally-administered HIV Vaccine in Healthy, HIV-uninfected Adult ParticipantsActive, not recruitingNCT02771730Phase 1

Search NIH Clinical Center for Alzheimer Disease-4

Genetic Tests for Alzheimer Disease-4

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Genetic tests related to Alzheimer Disease-4:

id Genetic test Affiliating Genes
1 Alzheimer Disease, Type 427
2 Alzheimer Disease Type 424 PSEN2

Anatomical Context for Alzheimer Disease-4

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Publications for Alzheimer Disease-4

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Variations for Alzheimer Disease-4

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

id Symbol AA change Variation ID SNP ID

Clinvar genetic disease variations for Alzheimer Disease-4:

id Gene Variation Type Significance SNP ID Assembly Location
1PSEN1NG_ 007386.2: g.73292_ 77847del4556deletionPathogenicGRCh37Chr 14, 73671470: 73676025
2PSEN1NM_ 000021.3(PSEN1): c.806G> A (p.Arg269His)SNVPathogenicrs63750900GRCh37Chr 14, 73664775: 73664775
3PSEN2NM_ 000447.2(PSEN2): c.422A> T (p.Asn141Ile)SNVPathogenicrs63750215GRCh37Chr 1, 227073304: 227073304
4PSEN2NM_ 000447.2(PSEN2): c.715A> G (p.Met239Val)SNVPathogenicrs28936379GRCh37Chr 1, 227076678: 227076678
5PSEN2NM_ 000447.2(PSEN2): c.1289C> T (p.Thr430Met)SNVPathogenicrs63750666GRCh37Chr 1, 227083222: 227083222
6PSEN2NM_ 000447.2(PSEN2): c.364A> C (p.Thr122Pro)SNVPathogenicrs63749851GRCh37Chr 1, 227073246: 227073246
7PSEN2NM_ 000447.2(PSEN2): c.717G> A (p.Met239Ile)SNVPathogenicrs63749884GRCh37Chr 1, 227076680: 227076680
8PSEN2NM_ 000447.2(PSEN2): c.365C> G (p.Thr122Arg)SNVPathogenicrs28936380GRCh37Chr 1, 227073247: 227073247
9PSEN2NM_ 000447.2(PSEN2): c.254C> T (p.Ala85Val)SNVPathogenicrs63750048GRCh37Chr 1, 227071518: 227071518

Expression for genes affiliated with Alzheimer Disease-4

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

Pathways for genes affiliated with Alzheimer Disease-4

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

(show all 13)
idSuper pathwaysScoreTop Affiliating Genes
110.0PSEN1, PSEN2
210.0PSEN1, PSEN2
79.4CYP19A1, NR5A1
Show member pathways
9.2CYP11B1, CYP11B2, CYP17A1
Show member pathways
8.8CYP11B1, CYP17A1, CYP19A1
108.6CYP11A1, CYP17A1, CYP19A1
Show member pathways
7.9CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1
Show member pathways
7.9CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1
Show member pathways
7.4CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1, CYP2B6

GO Terms for genes affiliated with Alzheimer Disease-4

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

idNameGO IDScoreTop Affiliating Genes
1ciliary rootletGO:003525310.7APP, PSEN1
2smooth endoplasmic reticulumGO:00057909.9APP, PSEN1
3mitochondrial membraneGO:00319669.6CYP11A1, CYP11B1, CYP11B2
4endoplasmic reticulum membraneGO:00057899.0CYP17A1, CYP19A1, CYP2B6, PSEN1, PSEN2
5membraneGO:00160205.8ABCA7, APP, CYP11A1, CYP11B1, CYP11B2, CYP17A1

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

(show all 22)
idNameGO IDScoreTop Affiliating Genes
1amyloid precursor protein catabolic processGO:004298710.7PSEN1, PSEN2
2beta-amyloid metabolic processGO:005043510.7PSEN1, PSEN2
3membrane protein ectodomain proteolysisGO:000650910.7PSEN1, PSEN2
4Notch receptor processingGO:000722010.7PSEN1, PSEN2
5astrocyte activation involved in immune responseGO:000226510.6APP, PSEN1
6cellular response to beta-amyloidGO:190464610.6APP, PSEN1
7regulation of epidermal growth factor-activated receptor activityGO:000717610.5APP, PSEN1
8regulation of protein bindingGO:004339310.5APP, PSEN1
9smooth endoplasmic reticulum calcium ion homeostasisGO:005156310.5APP, PSEN1
10aldosterone biosynthetic processGO:003234210.5CYP11B1, CYP11B2
11cellular response to potassium ionGO:003586510.5CYP11B1, CYP11B2
12cortisol biosynthetic processGO:003465110.5CYP11B1, CYP11B2
13Notch signaling pathwayGO:000721910.4APP, PSEN1, PSEN2
14glucocorticoid biosynthetic processGO:000670410.3CYP11B1, CYP17A1
15adrenal gland developmentGO:003032510.3NR0B1, NR5A1
16sex determinationGO:000753010.2NR0B1, NR5A1
17female gonad developmentGO:000858510.1CYP19A1, NR5A1
18C21-steroid hormone biosynthetic processGO:00067009.9CYP11A1, CYP11B1, CYP11B2
19steroid metabolic processGO:00082028.6CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP2B6
20oxidation-reduction processGO:00551148.0CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1, CYP2B6
21sterol metabolic processGO:00161257.9CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1
22steroid biosynthetic processGO:00066947.8CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1, NR0B1

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

(show all 11)
idNameGO IDScoreTop Affiliating Genes
1aspartic-type endopeptidase activityGO:000419010.7PSEN1, PSEN2
2corticosterone 18-monooxygenase activityGO:004778310.5CYP11B1, CYP11B2
3steroid 11-beta-monooxygenase activityGO:000450710.0CYP11B1, CYP11B2
4oxidoreductase 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 oxygenGO:00167129.7CYP19A1, CYP2B6
5monooxygenase activityGO:00044979.5CYP11B2, CYP19A1, CYP2B6
6steroid hydroxylase activityGO:00083959.3CYP11B2, CYP19A1
7oxygen bindingGO:00198259.0CYP17A1, CYP19A1, CYP2B6
8heme bindingGO:00200378.1CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1, CYP2B6
9iron ion bindingGO:00055068.1CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1, CYP2B6
10oxidoreductase activityGO:00164918.0CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1, CYP2B6
11oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygenGO:00167057.9CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1, CYP2B6

Sources for Alzheimer Disease-4

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31ICD10 via Orphanet
40MESH via Orphanet
53OMIM via Orphanet
63SNOMED-CT via Orphanet
67Tumor Gene Family of Databases
69UMLS via Orphanet