Genes Overview <table class="infobox infobox-gene">
Pathway Diagram ...
Genes Overview <table class="infobox infobox-gene">
Pathway Diagram
Mermaid diagram (expand to render)
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 diagnosisPredictive testing : Asymptomatic at-risk individuals (controversial)Carrier testing : Family planning decisionsPharmacogenomic testing : Treatment response predictionTherapeutic Implications Genetic discoveries enable multiple therapeutic approaches:
Gene silencing : ASO therapies (tofersen for SOD1), RNAiGene replacement : AAV-delivered therapeutic genes (under development)Protein targeting : Small molecules and antibodies against encoded proteinsModulation : Modifying expression or function of risk genesPrecision medicine : Genotype-stratified clinical trialsGene 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 sectionLast Updated: This section is actively maintainedA-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)
[See all 3857 genes pages...](/genes/rankings)
References
[Karch CM, Goate AM, Alzheimer's disease risk genes and mechanisms of disease pathogenesis (2015)](https://pubmed.ncbi.nlm.nih.gov/25526224/)
[Cookson MR, LRRK2 pathways to Parkinson's disease (2015)](https://pubmed.ncbi.nlm.nih.gov/25433316/)
[Taylor JP, Brown RH Jr, Cleveland DW, Decoding ALS: from genes to mechanism (2016)](https://pubmed.ncbi.nlm.nih.gov/27820478/)
Pathway Diagram The following diagram shows the key molecular relationships involving Genes Overview discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)
Show full description