Genes Overview

Genes Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">Genes Overview</th>
</tr>
<tr>
<td class="label">Gene Category</td>
<td>Examples</td>
</tr>
<tr>
<td class="label">Protein Aggregation</td>
<td>SNCA, [MAPT](/proteins/tau), APP</td>
</tr>
<tr>
<td class="label">RNA Processing</td>
<td>[C9orf72](/entities/c9orf72), FUS, TARDBP</td>
</tr>
<tr>
<td class="label">Mitochondrial Function</td>
<td>PARK2, PINK1, SOD1</td>
</tr>
<tr>
<td class="label">Lipid Metabolism</td>
<td>APOE, GBA</td>
</tr>
<tr>
<td class="label">Inflammation</td>
<td>[TREM2](/proteins/trem2), CD33</td>
</tr>
<tr>
<td class="label">Protein Quality Control</td>
<td>UBQLN2, VCP</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer-disease" style="color:#ef9a9a">ALZHEIMER DISEASE</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1715 edges</a></td>
</tr>
</table>

Pathway Diagram

Genes Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">Genes Overview</th>
</tr>
<tr>
<td class="label">Gene Category</td>
<td>Examples</td>
</tr>
<tr>
<td class="label">Protein Aggregation</td>
<td>SNCA, [MAPT](/proteins/tau), APP</td>
</tr>
<tr>
<td class="label">RNA Processing</td>
<td>[C9orf72](/entities/c9orf72), FUS, TARDBP</td>
</tr>
<tr>
<td class="label">Mitochondrial Function</td>
<td>PARK2, PINK1, SOD1</td>
</tr>
<tr>
<td class="label">Lipid Metabolism</td>
<td>APOE, GBA</td>
</tr>
<tr>
<td class="label">Inflammation</td>
<td>[TREM2](/proteins/trem2), CD33</td>
</tr>
<tr>
<td class="label">Protein Quality Control</td>
<td>UBQLN2, VCP</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer-disease" style="color:#ef9a9a">ALZHEIMER DISEASE</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1715 edges</a></td>
</tr>
</table>

Pathway Diagram

Overview

APP is a human gene. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration. [@karch2015]

This section covers genes associated with neurodegenerative diseases, including risk genes, causal mutations, and therapeutic targets. Genetic discoveries have illuminated disease mechanisms and enabled precision medicine approaches. [@cookson2015]

Major Alzheimer's Disease Genes

Causal Genes (Autosomal Dominant)

• [APP](/genes/app) — [Amyloid precursor protein](/entities/app-protein). APP mutations cause early-onset AD through increased [Aβ](/proteins/amyloid-beta) production or aggregation tendency.
• [PSEN1](/genes/psen1) — [Presenilin 1](/entities/psen1). Catalytic component of [gamma-secretase](/entities/gamma-secretase). Over 300 mutations cause early-onset AD.
• [PSEN2](/genes/psen2) — [Presenilin 2](/entities/psen2). Similar to PSEN1 but with later onset. About 40 known mutations.

Risk Genes (GWAS)

• [APOE](/genes/apoe) — [Apolipoprotein E](/proteins/apoe). ε4 allele increases risk 3-4x heterozygous, 12-15x homozygous.
• [TREM2](/genes/trem2) — Triggering receptor on myeloid cells 2. R47H variant similar risk to one APOE ε4 allele.
• [CLU](/genes/clusterin) — Clusterin. [Complement system](/entities/complement-system) protein involved in Aβ clearance.
• [PICALM](/genes/picalm) — Phosphatidylinositol binding clathrin assembly protein. Affects APP processing.
• [BIN1](/genes/bin1) — Bridging integrator 1. Modulates tau pathology.

Major Parkinson's Disease Genes

Causal Genes

• [SNCA](/genes/snca) — [Alpha-synuclein](/proteins/alpha-synuclein). First PD gene discovered. Point mutations and gene multiplications cause disease.
• [LRRK2](/genes/lrrk2) — Leucine-rich repeat kinase 2. Most common genetic cause (~5% of PD).
• [PARK2](/genes/park2) — Parkin. Autosomal recessive juvenile PD.
• [PARK6](/genes/park6) — PINK1. Autosomal recessive PD, functions in mitophagy.
• [DJ1](/genes/park7) — DJ-1. Autosomal recessive PD, oxidative stress response.
• [ATP13A2](/genes/atp13a2) — ATPase 13A2. Kufor-Rakek syndrome, atypical parkinsonism.

Risk Genes

• [GBA](/genes/gba) — Glucocerebrosidase. Most significant risk factor after LRRK2/SNCA.
• [MAPT](/genes/mapt) — Microtubule-associated protein tau. H1 haplotype increases PD risk.

ALS/FTD Genes

Causal Genes

• [C9orf72](/genes/c9orf72) — Hexanucleotide repeat expansion. Most common cause of familial ALS/FTD.
• [SOD1](/genes/sod1) — Superoxide dismutase 1. First ALS gene discovered (1993). Over 180 mutations.
• [FUS](/genes/fus) — Fused in sarcoma. RNA-binding protein with aggregation propensity.
• [TARDBP](/genes/tardbp) — TAR DNA-binding protein 43. Aggregates in most ALS/FTD cases.
• [ANG](/genes/ang) — Angiogenin. Secreted RNase with neurotrophic activity.
• [OPTN](/genes/optn) — Optineurin. [Autophagy](/entities/autophagy) receptor, mutations cause glaucoma and ALS.
• [UBQLN2](/genes/ubqln2) — Ubiquilin 2. Protein degradation, X-linked dominant.
• [TBK1](/genes/tbk1) — TANK-binding kinase 1. Autophagy and inflammation.

FTD-Specific Genes

• [GRN](/genes/grn) — Progranulin. Haploinsufficiency causes FTD. [TDP-43](/mechanisms/tdp-43-proteinopathy) pathology.
• [MAPT](/genes/mapt) — Microtubule-associated protein tau. Tauopathy without Aβ.

Huntington's Disease Genes

• [HTT](/genes/htt) — [Huntingtin](/proteins/huntingtin). CAG repeat expansion (>36) causes HD. Polyglutamine toxicity.

Gene Function Categories

Genetic Testing

Clinical genetic testing is available for many neurodegenerative disease genes:

• Diagnostic testing: Confirming clinical diagnosis
• Predictive testing: Asymptomatic at-risk individuals (controversial)
• Carrier testing: Family planning decisions
• Pharmacogenomic testing: Treatment response prediction

Therapeutic Implications

Genetic discoveries enable multiple therapeutic approaches:

• Gene silencing: ASO therapies (tofersen for SOD1), RNAi
• Gene replacement: AAV-delivered therapeutic genes (under development)
• Protein targeting: Small molecules and antibodies against encoded proteins
• Modulation: Modifying expression or function of risk genes
• Precision medicine: Genotype-stratified clinical trials

Gene Discovery Methods

Linkage Analysis

• Family-based studies identifying causal variants
• Successful for early-onset familial disease

GWAS (Genome-Wide Association Studies)

• Population-based identification of risk loci
• Focus on common variants with small effect sizes

Whole Exome/Genome Sequencing

• Rare variant discovery
• Rapid gene discovery in recent years

Expression Quantitative Trait Loci (eQTL)

• Functional interpretation of GWAS variants
• Tissue-specific gene regulation

Research Resources

• [Gene Rankings](/genes/rankings) — genes by research activity
• [Gene-Disease Associations](/genes/gene-disease-associations) — comprehensive mapping
• [Genetic Testing Centers](/institutions/) — clinical testing facilities

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [NCBI Gene: APP](https://www.ncbi.nlm.nih.gov/gene/?term=APP)
• [GeneCards: APP](https://www.genecards.org/cgi-bin/carddisp.pl?gene=APP)
• [OMIM: APP](https://omim.org/search?search=APP)
• [Ensembl: APP](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=APP)
• [Allen Brain Atlas: APP](https://human.brain-map.org/microarray/search/show?search_term=APP)

Topics

• [Genes Overview](/genes/overview) — This page
• [Genes Rankings](/genes/rankings) — Ranked list by research activity
• [Genes Dashboard](/genes/dashboard) — Data visualizations and metrics

Summary Statistics

• Total Pages: 3857 Genes pages in this section
• Last Updated: This section is actively maintained

A-Z All Pages

• [5-Hydroxytryptamine Receptor 1F](/genes/htr1f)
• [A2M Gene](/genes/a2m)
• [ABCA1 Gene](/genes/abcab1)
• [ABCA1 Gene](/genes/abca1)
• [ABCA2 — ATP Binding Cassette Subfamily A Member 2](/genes/abca2)
• [ABCA7 Gene](/genes/abca7)
• [ABCB1 (MDR1) - ATP Binding Cassette Subfamily B Member 1](/genes/abcb1)
• [ABCB1 — ATP-Binding Cassette Subfamily B Member 1](/genes/abcbl)
• [ABCD1 Gene](/genes/abcd1)
• [ABCD2](/genes/abcd2)
• [ABCD3 Gene](/genes/abcd3)
• [ABCG1 Gene](/genes/abcg1)
• [ABCG2 (BCRP) - ATP Binding Cassette Subfamily G Member 2](/genes/abcg2)
• [ABCG4 Gene — ATP-Binding Cassette Subfamily G Member 4](/genes/abcg4)
• [ABHD12](/genes/abhd12)
• [ABI3 Gene](/genes/abi3)
• [ABIN1 Gene](/genes/abin1)
• [ACAD9 Gene](/genes/acad9)
• [ACE Gene](/genes/ace)
• [ACO2 — Aconitase 2](/genes/aco2)
• [ACSL4 Gene - Acyl-CoA Synthetase Long Chain Family Member 4](/genes/acsl4)
• [ACTB Gene](/genes/actb)
• [ACTG1 Gene](/genes/actg1)
• [ACTN2 — Actinin Alpha 2](/genes/actn2)
• [ACVR1](/genes/acvr1)
• [ACVR2A Gene](/genes/acvr2a)
• [ACVR2B Gene](/genes/acvr2b)
• [ADAM10 (Alpha-Secretase)](/genes/adam10)
• [ADAM12 Gene](/genes/adam12)
• [ADAM15 Gene](/genes/adam15)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving Genes Overview discovered through SciDEX knowledge graph analysis: