Provide a comprehensive cross-database identifier and functional mapping reference for human APP. This should serve as a definitive lookup resource for researchers. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 1: GENE IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Provide ALL gene-level database identifiers: - HGNC ID and approved symbol - Ensembl gene ID (ENSG) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 2: TRANSCRIPT IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ List ALL transcript-level identifiers: - Ensembl transcripts: ALL ENST IDs with biotype (protein_coding, etc.) How many total transcripts? - RefSeq transcripts: ALL NM_ mRNA accessions Mark which is MANE Select (canonical clinical standard) - CCDS IDs: ALL consensus coding sequence identifiers For the CANONICAL/MANE SELECT transcript: - List ALL exon IDs (ENSE) with genomic coordinates - Total exon count ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 3: PROTEIN IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ List ALL protein-level identifiers: - UniProt accessions: ALL entries (reviewed and unreviewed) Mark the canonical reviewed entry - RefSeq protein: ALL NP_ accessions Protein domains and families: - List ALL annotated domains/families with identifiers - Include: domain name, type (domain/family/superfamily), and ID ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 4: STRUCTURE IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Experimental structures: - List ALL PDB structure IDs - For each: experimental method (X-ray, NMR, Cryo-EM) and resolution - Total PDB structure count Predicted structures: - AlphaFold model ID and confidence metrics (pLDDT) ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 5: CROSS-SPECIES ORTHOLOGS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ List orthologous genes in key model organisms (where available): - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 6: CLINICAL VARIANTS & AI PREDICTIONS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Clinical variant annotations: - Total variant count in clinical databases - Breakdown by classification: Pathogenic, Likely Pathogenic, Uncertain Significance (VUS), Likely Benign, Benign - List TOP 50 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: Total count List TOP 50 predicted splice-altering variants with delta scores - Missense pathogenicity predictions: Total count List TOP 50 predicted pathogenic missense variants with scores ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 7: BIOLOGICAL PATHWAYS & GENE ONTOLOGY ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Pathway membership: - List ALL biological pathways this gene participates in - Include pathway IDs and names - Total pathway count Gene Ontology annotations: - Biological Process: count and TOP 20 terms with IDs - Molecular Function: count and TOP 20 terms with IDs - Cellular Component: count and TOP 20 terms with IDs ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 8: PROTEIN INTERACTIONS & MOLECULAR NETWORKS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Protein-protein interactions: - Total interaction count - List TOP 50 highest-confidence interacting proteins with scores Protein similarity (evolutionary and structural): - Structural/embedding similarity: How many similar proteins? List TOP 20 with similarity scores - Sequence homology: How many homologous proteins? List TOP 20 with identity/similarity scores ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 9: TRANSCRIPTION FACTOR REGULATORY DATA ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ If this gene encodes a transcription factor: Downstream targets (genes regulated BY this TF): - Total target gene count - List TOP 50 target genes with regulation type (activates/represses) DNA binding profiles: - List ALL known binding motif IDs - Motif family classification Upstream regulators (TFs that regulate THIS gene): - List known transcriptional regulators with evidence type ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 10: DRUG & PHARMACOLOGY DATA ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ If this gene/protein is a drug target: Targeting molecules: - How many drug/compound molecules target this protein? - List TOP 30 molecules by development phase - Include: molecule ID, name, mechanism, highest development phase Clinical trials: - How many clinical trials involve drugs targeting this gene? - List TOP 20 trials with: trial ID, phase, status, intervention Pharmacogenomics: - Known drug-gene interactions affecting drug response - Dosing guidelines if any exist ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 11: EXPRESSION PROFILES ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Tissue expression: - Which tissues express this gene most highly? - List TOP 30 tissues with expression scores/levels - Note any tissue-specific or tissue-enriched patterns Cell type expression: - Which cell types show highest expression? - List TOP 30 cell types with expression scores - Note any cell type-specific patterns Single-cell expression data (if available): - Which single-cell datasets/experiments include this gene? - Notable cell population patterns ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 12: DISEASE ASSOCIATIONS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Mendelian/monogenic disease links: - What diseases are caused by mutations in this gene? - List ALL associated diseases with: disease name, disease ID, inheritance pattern, evidence level Phenotype associations: - What clinical phenotypes are associated with this gene? - List TOP 50 phenotype terms with IDs Complex trait associations (GWAS): - What traits/diseases are linked via genome-wide association studies? - List TOP 30 GWAS associations with: trait, study ID, p-value, effect size if available ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ FORMATTING REQUIREMENTS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ - Present each section with clear headers - Use tables for listing multiple items - Always include COUNTS for every category - For lists with 50 items: show total count + TOP 50 - For lists with

Question

Provide a comprehensive cross-database identifier and functional mapping
reference for human APP. This should serve as a definitive
lookup resource for researchers.

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 1: GENE IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Provide ALL gene-level database identifiers:
- HGNC ID and approved symbol
- Ensembl gene ID (ENSG)
- NCBI Entrez Gene ID
- OMIM gene/locus ID
- Genomic location: chromosome, start position, end position, strand

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 2: TRANSCRIPT IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
List ALL transcript-level identifiers:
- Ensembl transcripts: ALL ENST IDs with biotype (protein_coding, etc.)
  How many total transcripts?
- RefSeq transcripts: ALL NM_ mRNA accessions
  Mark which is MANE Select (canonical clinical standard)
- CCDS IDs: ALL consensus coding sequence identifiers

For the CANONICAL/MANE SELECT transcript:
- List ALL exon IDs (ENSE) with genomic coordinates
- Total exon count

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 3: PROTEIN IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
List ALL protein-level identifiers:
- UniProt accessions: ALL entries (reviewed and unreviewed)
  Mark the canonical reviewed entry
- RefSeq protein: ALL NP_ accessions

Protein domains and families:
- List ALL annotated domains/families with identifiers
- Include: domain name, type (domain/family/superfamily), and ID

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 4: STRUCTURE IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Experimental structures:
- List ALL PDB structure IDs
- For each: experimental method (X-ray, NMR, Cryo-EM) and resolution
- Total PDB structure count

Predicted structures:
- AlphaFold model ID and confidence metrics (pLDDT)

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 5: CROSS-SPECIES ORTHOLOGS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
List orthologous genes in key model organisms (where available):
- Mouse (Mus musculus): gene ID, symbol
- Rat (Rattus norvegicus): gene ID, symbol
- Zebrafish (Danio rerio): gene ID, symbol
- Fruit fly (Drosophila melanogaster): gene ID, symbol
- Worm (C. elegans): gene ID, symbol
- Yeast (S. cerevisiae): gene ID, symbol

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 6: CLINICAL VARIANTS & AI PREDICTIONS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Clinical variant annotations:
- Total variant count in clinical databases
- Breakdown by classification: Pathogenic, Likely Pathogenic,
  Uncertain Significance (VUS), Likely Benign, Benign
- List TOP 50 pathogenic/likely pathogenic variants with:
  variant ID, HGVS notation, associated condition

AI-based variant effect predictions:
- Splice effect predictions: Total count
  List TOP 50 predicted splice-altering variants with delta scores
- Missense pathogenicity predictions: Total count
  List TOP 50 predicted pathogenic missense variants with scores

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 7: BIOLOGICAL PATHWAYS & GENE ONTOLOGY
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Pathway membership:
- List ALL biological pathways this gene participates in
- Include pathway IDs and names
- Total pathway count

Gene Ontology annotations:
- Biological Process: count and TOP 20 terms with IDs
- Molecular Function: count and TOP 20 terms with IDs
- Cellular Component: count and TOP 20 terms with IDs

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 8: PROTEIN INTERACTIONS & MOLECULAR NETWORKS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Protein-protein interactions:
- Total interaction count
- List TOP 50 highest-confidence interacting proteins with scores

Protein similarity (evolutionary and structural):
- Structural/embedding similarity: How many similar proteins?
  List TOP 20 with similarity scores
- Sequence homology: How many homologous proteins?
  List TOP 20 with identity/similarity scores

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 9: TRANSCRIPTION FACTOR REGULATORY DATA
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
If this gene encodes a transcription factor:

Downstream targets (genes regulated BY this TF):
- Total target gene count
- List TOP 50 target genes with regulation type (activates/represses)

DNA binding profiles:
- List ALL known binding motif IDs
- Motif family classification

Upstream regulators (TFs that regulate THIS gene):
- List known transcriptional regulators with evidence type

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 10: DRUG & PHARMACOLOGY DATA
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
If this gene/protein is a drug target:

Targeting molecules:
- How many drug/compound molecules target this protein?
- List TOP 30 molecules by development phase
- Include: molecule ID, name, mechanism, highest development phase

Clinical trials:
- How many clinical trials involve drugs targeting this gene?
- List TOP 20 trials with: trial ID, phase, status, intervention

Pharmacogenomics:
- Known drug-gene interactions affecting drug response
- Dosing guidelines if any exist

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 11: EXPRESSION PROFILES
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Tissue expression:
- Which tissues express this gene most highly?
- List TOP 30 tissues with expression scores/levels
- Note any tissue-specific or tissue-enriched patterns

Cell type expression:
- Which cell types show highest expression?
- List TOP 30 cell types with expression scores
- Note any cell type-specific patterns

Single-cell expression data (if available):
- Which single-cell datasets/experiments include this gene?
- Notable cell population patterns

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 12: DISEASE ASSOCIATIONS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Mendelian/monogenic disease links:
- What diseases are caused by mutations in this gene?
- List ALL associated diseases with: disease name, disease ID,
  inheritance pattern, evidence level

Phenotype associations:
- What clinical phenotypes are associated with this gene?
- List TOP 50 phenotype terms with IDs

Complex trait associations (GWAS):
- What traits/diseases are linked via genome-wide association studies?
- List TOP 30 GWAS associations with: trait, study ID, p-value,
  effect size if available

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
FORMATTING REQUIREMENTS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
- Present each section with clear headers
- Use tables for listing multiple items
- Always include COUNTS for every category
- For lists with >50 items: show total count + TOP 50
- For lists with <50 items: show ALL items
- Always include database identifiers (IDs), not just names
- Mark canonical/primary/reviewed entries where applicable
- If a section has no data available, state "No data available"
  rather than omitting the section

Accepted Answer

Section 1: Gene Identifiers
DatabaseIdentifierNotes HGNC IDHGNC:620Approved HGNC SymbolAPPCurrent approved symbol Full NameAmyloid beta precursor protein Previous SymbolsAD1 Previous NamesAlzheimer disease; amyloid beta (A4) precursor protein Aliasesalpha-sAPP Ensembl Gene IDENSG00000142192 NCBI Entrez Gene ID351 OMIM Gene ID104760 Locus Typeprotein-coding genegene with protein product Gene GroupReceptor ligands Genomic Location AttributeValue Chromosome21 Cytogenetic Band21q21.3 Start …

Attribute	Value
Chromosome	21
Cytogenetic Band	21q21.3
Start Position	25,880,535
End Position	26,171,128
Strand	Minus (-)
Gene Length	290,593 bp
Genome Assembly	GRCh38

Transcript ID	Biotype	Start	End	Status
ENST00000346798	protein_coding	25880550	26170770	Canonical
ENST00000348990	protein_coding	25880550	26170767
ENST00000354192	protein_coding	25880550	26170747
ENST00000357903	protein_coding	25880550	26170787
ENST00000358918	protein_coding	25881610	26170667
ENST00000359726	protein_coding	25880551	26171128
ENST00000415997	protein_coding	25975190	26051032
ENST00000439274	protein_coding	25881332	26170654
ENST00000440126	protein_coding	25881331	26140460
ENST00000448850	protein_coding	25945524	26090061
ENST00000462267	retained_intron	26089511	26112083
ENST00000463070	protein_coding_CDS_not_defined	26021922	26053502
ENST00000464867	retained_intron	25881514	25897983
ENST00000466453	protein_coding_CDS_not_defined	26111985	26169429
ENST00000474136	protein_coding_CDS_not_defined	26009596	26170746
ENST00000491395	protein_coding_CDS_not_defined	25997188	26051018
ENST00000548570	protein_coding_CDS_not_defined	26051160	26068338
ENST00000707132	protein_coding_CDS_not_defined	25880535	26170743
ENST00000707133	protein_coding_CDS_not_defined	25880550	25925142
ENST00000707134	protein_coding_CDS_not_defined	25880559	25970517
ENST00000872524	protein_coding	25880550	26170830
ENST00000872525	protein_coding	25880550	26170770
ENST00000872526	protein_coding	25880550	26170770
ENST00000872527	protein_coding	25880550	26170770
ENST00000872528	protein_coding	25880550	26170770
ENST00000872529	protein_coding	25880553	26170770
ENST00000872530	protein_coding	25880553	26170770
ENST00000872531	protein_coding	25880553	26170767
ENST00000872532	protein_coding	25880553	26170767
ENST00000872533	protein_coding	25880553	26170767
ENST00000872534	protein_coding	25880550	26170712
ENST00000872535	protein_coding	25880809	26170770
ENST00000872536	protein_coding	25880809	26170767
ENST00000872537	protein_coding	25880809	26170767
ENST00000872538	protein_coding	25880809	26170767
ENST00000932837	protein_coding	25880806	26170765
ENST00000932838	protein_coding	25880826	26170757
ENST00000965079	protein_coding	25880826	26170767
ENST00000965080	protein_coding	25880826	26170647
ENST00000965081	protein_coding	25881514	26170755

Accession	Type	Status	MANE Select
NM_000484	mRNA	REVIEWED	Yes (Canonical)
NM_001136016	mRNA	REVIEWED	No
NM_001136129	mRNA	REVIEWED	No
NM_001136130	mRNA	REVIEWED	No
NM_001136131	mRNA	REVIEWED	No
NM_001204301	mRNA	REVIEWED	No
NM_001204302	mRNA	REVIEWED	No
NM_001204303	mRNA	REVIEWED	No
NM_001385253	mRNA	REVIEWED	No
NM_201413	mRNA	REVIEWED	No
NM_201414	mRNA	REVIEWED	No

Exon ID	Start	End	Length
ENSE00003845466	26170564	26170770	207 bp
ENSE00003998291	26111979	26112146	168 bp
ENSE00003998299	26089943	26090072	130 bp
ENSE00003998282	26053236	26053348	113 bp
ENSE00003998285	26051000	26051193	194 bp
ENSE00003998298	26021840	26022042	203 bp
ENSE00001309322	25997360	25997416	57 bp
ENSE00003998293	25975954	25976028	75 bp
ENSE00003998290	25975070	25975228	159 bp
ENSE00003998279	25955627	25955755	129 bp
ENSE00003998288	25954590	25954689	100 bp
ENSE00003998294	25982344	25982477	134 bp
ENSE00003998287	25911741	25911962	222 bp
ENSE00003998292	25905024	25905077	54 bp
ENSE00003998296	25897573	25897673	101 bp
ENSE00003998286	25891722	25891868	147 bp
ENSE00003998297	25880550	25881771	1,222 bp

Accession	Status	Notes
P05067	Reviewed (Swiss-Prot)	Canonical entry
A0A0A0MRG2	Unreviewed
A0A140VJC8	Unreviewed
E9PG40	Unreviewed
H7C0V9	Unreviewed
H7C2L2	Unreviewed

APP Gene Complete Identifier and Functional Mapping Reference

Structured Data Sources

Database	Identifier	Notes
HGNC ID	HGNC:620	Approved
HGNC Symbol	APP	Current approved symbol
Full Name	Amyloid beta precursor protein
Previous Symbols	AD1
Previous Names	Alzheimer disease; amyloid beta (A4) precursor protein
Aliases	alpha-sAPP
Ensembl Gene ID	ENSG00000142192
NCBI Entrez Gene ID	351
OMIM Gene ID	104760
Locus Type	protein-coding gene	gene with protein product
Gene Group	Receptor ligands

Property	Value
Name	Amyloid-beta precursor protein
Length	770 amino acids
Mass	86,943 Da
Alternative Names	ABPP, APPI, Alzheimer disease amyloid A4 protein homolog, Amyloid-beta A4 protein, Cerebral vascular amyloid peptide, PreA4, Protease nexin-II

Accession	Type	MANE Select
NP_000475	protein	Yes (Canonical)
NP_001129488	protein	No
NP_001129601	protein	No
NP_001129602	protein	No
NP_001129603	protein	No
NP_001191230	protein	No
NP_001191231	protein	No
NP_001191232	protein	No
NP_001372182	protein	No
NP_958816	protein	No
NP_958817	protein	No

ID	Name	Type
IPR002223	Kunitz_BPTI	Domain
IPR008154	Amyloid_glyco_extra	Domain
IPR008155	Amyloid_glyco	Family
IPR011178	Amyloid_glyco_Cu-bd	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR013803	Amyloid_glyco_Abeta	Domain
IPR015849	Amyloid_glyco_heparin-bd	Domain
IPR019543	APP_amyloid_C	Domain
IPR019744	APP_CUBD_CS	Conserved_site
IPR019745	Amyloid_glyco_intracell_CS	Conserved_site
IPR020901	Prtase_inh_Kunz-CS	Conserved_site
IPR024329	Amyloid_glyco_E2_domain	Domain
IPR036176	E2_sf	Homologous_superfamily
IPR036454	Amyloid_glyco_heparin-bd_sf	Homologous_superfamily
IPR036669	Amyloid_Cu-bd_sf	Homologous_superfamily
IPR036880	Kunitz_BPTI_sf	Homologous_superfamily
IPR037071	Amyloid_glyco_Abeta_sf	Homologous_superfamily

Pfam ID	Description
PF00014	Kunitz/BPTI domain
PF02177	APP copper-binding domain
PF03494	Beta-amyloid peptide (Abeta)
PF10515	APP E2 domain
PF12924	APP N-terminal heparin binding
PF12925	APP extracellular domain

PDB ID	Method	Resolution	Description
2FMA	X-RAY	0.85 Å	APP Copper Binding Domain, atomic resolution
1AAP	X-RAY	1.5 Å	Protease inhibitor domain (Kunitz)
2FJZ	X-RAY	1.61 Å	Copper binding domain, metal-free
2FK1	X-RAY	1.6 Å	Copper binding domain, Cu(II)-bound
2FK2	X-RAY	1.65 Å	Copper binding domain, Cu(I)-bound
2IPU	X-RAY	1.65 Å	Fab-Abeta 1-8 complex
4PWQ	X-RAY	1.4 Å	E1-domain high resolution
4PQD	X-RAY	1.332 Å	Growth factor like domain
3BAE	X-RAY	1.593 Å	Fab WO2 bound to Abeta 1-28
1MWP	X-RAY	1.8 Å	N-terminal domain
1TAW	X-RAY	1.8 Å	Trypsin-APPI complex
5CSZ	X-RAY	1.8 Å	Gantenerumab Fab-Abeta 1-11
6IYC	CRYO-EM	2.6 Å	APP-gamma-secretase complex
8X54	CRYO-EM	2.9 Å	gamma-secretase with APP-C99
8X52	CRYO-EM	2.9 Å	gamma-secretase with Abeta49
2NAO	NMR	-	Abeta(1-42) amyloid fibril, atomic resolution
5KK3	SOLID-STATE NMR	-	Monomorphic Abeta42 fibrils
7Q4B	CRYO-EM	2.5 Å	Type I Abeta42 from human brain
6W0O	CRYO-EM	2.77 Å	Abeta(1-40) from AD cortex
8BG0	CRYO-EM	1.99 Å	Arctic mutation Abeta40 tetrameric filaments
8QN6	CRYO-EM	2.4 Å	Abeta40 type 2 from leptomeninges
8OT1	CRYO-EM	2.59 Å	Unseeded Abeta(1-40) fibril
9JB1	CRYO-EM	2.5 Å	Abeta42 with D-Asp at positions 7,23
9K0D	CRYO-EM	2.6 Å	Abeta42-4b polymorph 1
9CZN	CRYO-EM	2.6 Å	Type Ic Abeta42 from familial AD
3DXC	X-RAY	2.1 Å	APP intracellular domain with Fe65-PTB2
6CO3	X-RAY	2.384 Å	Aducanumab-Abeta complex
5VZY	X-RAY	2.32 Å	Crenezumab Fab-Abeta complex
4HIX	X-RAY	2.204 Å	3D6 Fab-Abeta complex
1X11	X-RAY	2.5 Å	X11 PTB domain with APP peptide
3KTM	X-RAY	2.7 Å	Heparin-induced E1-Dimer
3NYL	X-RAY	2.8 Å	E2 domain antiparallel dimer
7WVY	CRYO-EM	3.0 Å	FPR2 receptor with Abeta42
1IYT	NMR	-	Abeta(1-42) solution structure
2LP1	NMR	-	C99 transmembrane domain
2LLM	NMR	-	APP transmembrane domain
1OWT	NMR	-	Copper binding domain solution structure
1TKN	NMR	-	CAPPD extracellular domain
6SZF	NMR	-	Abeta(1-42) solution structure
6RHY	NMR	-	Pore-forming Abeta tetramers
2BEG	NMR	-	Abeta(1-42) fibrils 3D structure
2M4J	SOLID-STATE NMR	-	Abeta40 from AD brain
2LMN	SOLID-STATE NMR	-	Abeta40 2-fold symmetry model
2MVX	SOLID-STATE NMR	-	Osaka mutation Abeta fibrils
8SEJ	CRYO-EM	3.17 Å	Type I Abeta42 from Down syndrome
8AZS	CRYO-EM	2.9 Å	Type I Abeta42 from AD brain
8BFA	CRYO-EM	3.0 Å	Abeta42 from AppNL-G-F mice
8EZD	CRYO-EM	2.83 Å	Brain-derived Abeta42 type A
8FF2	CRYO-EM	2.87 Å	Abeta(1-40) from CAA patient
9WAP	CRYO-EM	3.22 Å	Type II Abeta from mouse model

Property	Value
AlphaFold ID	AF-P05067-F1
Global pLDDT	68.11
Sequence Length	6,091 (includes isoforms)
Fraction Very High Confidence (pLDDT >90)	30%

Organism	Gene ID	Symbol	Notes
Mouse (Mus musculus)	ENSMUSG00000022892	App	protein_coding
Rat (Rattus norvegicus)	ENSRNOG00000006997	App	protein_coding
Zebrafish (Danio rerio)	ENSDARG00000055543	appb	protein_coding
Zebrafish (Danio rerio)	ENSDARG00000104279	appa	protein_coding (paralog)
Fruit fly (Drosophila melanogaster)	FBGN0000108	Appl	protein_coding
Worm (C. elegans)	WBGENE00000149	apl-1
Yeast (S. cerevisiae)	-	No ortholog	APP has no yeast ortholog

Classification	Count
Pathogenic	23
Likely pathogenic	8
Uncertain significance (VUS)	~150
Likely benign	~150
Benign	~200
Conflicting classifications	~50

ClinVar ID	HGVS Notation	Type	Condition
18088	c.2149G>A (p.Val717Ile)	SNV	Alzheimer disease type 1
18089	c.2149G>T (p.Val717Phe)	SNV	Alzheimer disease type 1
18090	c.2150T>G (p.Val717Gly)	SNV	Alzheimer disease
18105	c.2149G>C (p.Val717Leu)	SNV	Alzheimer disease
18087	c.2077G>C (p.Glu693Gln)	SNV	Dutch-type cerebral amyloid angiopathy
18093	c.2010_2011inv (p.Lys670_Met671delinsAsnLeu)	Inversion	Swedish mutation - AD
18091	c.2075C>G (p.Ala692Gly)	SNV	Flemish mutation
18098	c.2078A>G (p.Glu693Gly)	SNV	Arctic mutation
18099	c.2077G>A (p.Glu693Lys)	SNV	Italian mutation
18100	c.2141C>T (p.Thr714Ile)	SNV	Austrian mutation
18101	c.2080G>A (p.Asp694Asn)	SNV	Iowa mutation
18102	c.2140A>G (p.Thr714Ala)	SNV	Iranian mutation
18096	c.2146A>G (p.Ile716Val)	SNV	Florida mutation
18106	c.2018C>T (p.Ala673Val)	SNV	AD
98238	c.2144T>C (p.Val715Ala)	SNV	German mutation
98240	c.2147T>C (p.Ile716Thr)	SNV	AD
1457308	c.2145_2146delinsTG (p.Ile716Val)	Indel	AD
2498894	c.2146A>T (p.Ile716Phe)	SNV	AD
1353302	g.(?27251861)(27544138_?)dup	Duplication	APP duplication - AD
1526702	21q11.2-21.3 dup	CNV gain	AD
1807236	Single allele duplication	Duplication	AD
2423147	g.(?27113910)(27542938_?)dup	Duplication	AD
3338917	g.(?27252860)(27543089_?)dup	Duplication	AD

CCDS ID
CCDS13576
CCDS13577
CCDS33523
CCDS46638
CCDS46639
CCDS56211
CCDS56212
CCDS56213

ClinVar ID	HGVS Notation	Type
18094	c.2137G>A (p.Ala713Thr)	SNV
18103	c.2113C>G (p.Leu705Val)	SNV
1298879	c.2148C>G (p.Ile716Met)	SNV
1342870	c.2155A>C (p.Thr719Pro)	SNV
2628367	c.2061A>C (p.Lys687Asn)	SNV
3382968	c.2059A>C (p.Lys687Gln)	SNV
3690355	c.2138C>A (p.Ala713Glu)	SNV
446855	c.2032G>C (p.Asp678His)	SNV

Variant	Effect	Delta Score
21:25881767:TCAAC:T	acceptor_gain	1.0000
21:25881768:CAAC:C	acceptor_gain	1.0000
21:25881768:CAACC:C	acceptor_gain	1.0000
21:25881769:AAC:A	acceptor_gain	1.0000
21:25881769:AACCT:A	acceptor_loss	1.0000
21:25881770:AC:A	acceptor_gain	1.0000
21:25881770:ACCTG:A	acceptor_loss	1.0000
21:25881771:CC:C	acceptor_gain	1.0000
21:25881773:T:A	acceptor_loss	1.0000
21:25881772:C:CC	acceptor_gain	1.0000
21:25881772:C:T	acceptor_gain	0.9900
21:25881780:C:CT	acceptor_gain	0.9800
21:25881781:A:T	acceptor_gain	0.9400
21:25881769:AACC:A	acceptor_gain	0.9100
21:25881770:ACC:A	acceptor_gain	0.9100
21:25881771:CCTGA:C	acceptor_gain	0.9200
21:25881772:CTGAA:C	acceptor_gain	0.9300
21:25881772:C:A	acceptor_gain	0.9000
21:25881773:T:C	acceptor_gain	0.8900
21:25881769:A:T	acceptor_gain	0.8500
21:25881863:CT:C	donor_gain	0.9300
21:25881863:CTCTT:C	donor_gain	0.9200
21:25881945:G:C	donor_gain	0.9100
21:25881942:CCAG:C	donor_gain	0.9100
21:25881862:A:AC	donor_gain	0.9000
21:25881863:C:CC	donor_gain	0.9000
21:25881911:TTG:T	donor_gain	0.8600
21:25881867:T:TA	donor_gain	0.7500
21:25881939:C:T	donor_gain	0.7300
21:25881858:CAGTA:C	donor_gain	0.7200
21:25881937:G:A	donor_gain	0.6900
21:25881858:CA:C	donor_gain	0.6900
21:25881944:A:T	donor_gain	0.6800
21:25881854:A:AC	donor_gain	0.6400
21:25881943:CAG:C	donor_gain	0.6400
21:25881859:AG:A	donor_gain	0.6200
21:25881903:C:CA	donor_gain	0.6100
21:25881904:C:A	donor_gain	0.5300
21:25881908:A:AC	donor_gain	0.5300
21:25881909:C:CC	donor_gain	0.5300

Variant	AA Change	AM Score	Classification
21:25881704:G:T	P760Q	1.000	likely_pathogenic
21:25881706:A:C	N759K	1.000	likely_pathogenic
21:25881706:A:T	N759K	1.000	likely_pathogenic
21:25881691:G:C	F764L	0.999	likely_pathogenic
21:25881691:G:T	F764L	0.999	likely_pathogenic
21:25881692:A:C	F764C	0.999	likely_pathogenic
21:25881699:A:G	Y762H	0.999	likely_pathogenic
21:25881704:G:A	P760L	0.999	likely_pathogenic
21:25881704:G:C	P760R	0.999	likely_pathogenic
21:25881705:G:A	P760S	0.999	likely_pathogenic
21:25881705:G:T	P760T	0.999	likely_pathogenic
21:25881708:T:C	N759D	0.999	likely_pathogenic
21:25881698:T:C	Y762C	0.998	likely_pathogenic
21:25881692:A:G	F764S	0.998	likely_pathogenic
21:25881699:A:C	Y762D	0.998	likely_pathogenic
21:25881707:T:A	N759I	0.998	likely_pathogenic
21:25881707:T:G	N759T	0.998	likely_pathogenic
21:25881710:T:A	E758V	0.998	likely_pathogenic
21:25881713:T:C	Y757C	0.998	likely_pathogenic
21:25881714:A:C	Y757D	0.998	likely_pathogenic
21:25881694:C:A	K763N	0.998	likely_pathogenic
21:25881694:C:G	K763N	0.998	likely_pathogenic
21:25881689:A:G	F765S	0.997	likely_pathogenic
21:25881697:A:T	Y762N	0.997	likely_pathogenic
21:25881708:T:G	N759H	0.997	likely_pathogenic
21:25881711:C:T	E758K	0.996	likely_pathogenic
21:25881701:G:A	T761I	0.996	likely_pathogenic
21:25881708:T:A	N759Y	0.996	likely_pathogenic
21:25881713:T:G	Y757S	0.996	likely_pathogenic
21:25881696:T:C	K763E	0.997	likely_pathogenic
21:25881696:T:G	K763Q	0.956	likely_pathogenic
21:25881710:T:G	E758A	0.995	likely_pathogenic
21:25881707:T:C	N759S	0.995	likely_pathogenic
21:25881686:T:A	E766V	0.995	likely_pathogenic
21:25881714:A:T	Y757N	0.995	likely_pathogenic
21:25881714:A:G	Y757H	0.999	likely_pathogenic
21:25881709:T:A	E758D	0.994	likely_pathogenic
21:25881709:T:G	E758D	0.994	likely_pathogenic
21:25881701:G:T	T761N	0.994	likely_pathogenic
21:25881698:T:G	Y762S	0.994	likely_pathogenic

Pathway ID	Name	Disease Pathway
R-HSA-977225	Amyloid fiber formation	No
R-HSA-8862803	Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models	Yes
R-HSA-114608	Platelet degranulation	No
R-HSA-3000178	ECM proteoglycans	No
R-HSA-381426	Regulation of IGF transport and uptake by IGFBPs	No
R-HSA-416476	G alpha (q) signalling events	No
R-HSA-418594	G alpha (i) signalling events	No
R-HSA-432720	Lysosome Vesicle Biogenesis	No
R-HSA-444473	Formyl peptide receptors bind formyl peptides	No
R-HSA-445989	TAK1-dependent IKK and NF-kappa-B activation	No
R-HSA-844456	The NLRP3 inflammasome	No
R-HSA-879415	Advanced glycosylation endproduct receptor signaling	No
R-HSA-8957275	Post-translational protein phosphorylation	No
R-HSA-933542	TRAF6 mediated NF-kB activation	No
R-HSA-9609523	Insertion of tail-anchored proteins into ER membrane	No
R-HSA-9660826	Purinergic signaling in leishmaniasis infection	Yes
R-HSA-9837999	Mitochondrial protein degradation	No

GO ID	Term
GO:0002511	Alzheimer disease
GO:1990000	amyloid fibril formation
GO:1905908	positive regulation of amyloid fibril formation
GO:0007219	Notch signaling pathway
GO:0006878	intracellular copper ion homeostasis
GO:0007409	axonogenesis
GO:0007417	central nervous system development
GO:0007611	learning or memory
GO:0007612	learning
GO:0016358	dendrite development
GO:0031175	neuron projection development
GO:0048169	regulation of long-term neuronal synaptic plasticity
GO:0050803	regulation of synapse structure or activity
GO:0050808	synapse organization
GO:0043523	regulation of neuron apoptotic process
GO:0110088	hippocampal neuron apoptotic process
GO:0006897	endocytosis
GO:0008285	negative regulation of cell population proliferation
GO:0045944	positive regulation of transcription by RNA polymerase II
GO:0046330	positive regulation of JNK cascade

GO ID	Term
GO:0003677	DNA binding
GO:0004867	serine-type endopeptidase inhibitor activity
GO:0005102	signaling receptor binding
GO:0008201	heparin binding
GO:0016504	peptidase activator activity
GO:0019899	enzyme binding
GO:0030546	signaling receptor activator activity
GO:0042802	identical protein binding
GO:0046914	transition metal ion binding
GO:0048018	receptor ligand activity
GO:0051425	PTB domain binding
GO:0070851	growth factor receptor binding
GO:0120283	protein serine/threonine kinase binding

GO ID	Term
GO:0005886	plasma membrane
GO:0016020	membrane
GO:0009986	cell surface
GO:0005576	extracellular region
GO:0005615	extracellular space
GO:0070062	extracellular exosome
GO:0005783	endoplasmic reticulum
GO:0005794	Golgi apparatus
GO:0005768	endosome
GO:0005769	early endosome
GO:0030424	axon
GO:0030425	dendrite
GO:0043197	dendritic spine
GO:0045202	synapse
GO:0045121	membrane raft
GO:0005743	mitochondrial inner membrane
GO:0005829	cytosol
GO:0005737	cytoplasm
GO:0106003	amyloid-beta complex
GO:0098992	neuronal dense core vesicle

UniProt	Gene	Score	Description
P05067	APP	999	Self-interaction
P02649	APOE	999	Apolipoprotein E
P56817	BACE1	999	Beta-secretase 1
O00213	APBB1	998	APP binding family B member 1 (Fe65)
Q92673	SORL1	994	Sortilin-related receptor
O75509	TNFRSF21	993	Death receptor 6
P49768	PSEN1	992	Presenilin-1
Q99767	NAE1	988	NEDD8-activating enzyme E1
P10636	MAPT	986	Microtubule-associated protein tau
Q13564	APBB2	986	APP binding family B member 2
P04233	CD74	985	HLA class II histocompatibility antigen
P04156	PRNP	984	Prion protein
Q9HCB6	SPON1	980	Spondin-1
Q92993	KAT5	973	Histone acetyltransferase KAT5
Q92870	ARF6	966	ADP-ribosylation factor 6
P10909	CLU	964	Clusterin
Q07954	LRP1	963	LDL receptor-related protein 1
Q09472	EP300	958	Histone acetyltransferase p300
P49810	PSEN2	955	Presenilin-2
P37840	SNCA	954	Alpha-synuclein
Q92542	NCSTN	941	Nicastrin
P29354	SRC	926	Proto-oncogene tyrosine-protein kinase Src
O95704	APBB3	922	APP binding family B member 3
P08247	SYP	916	Synaptophysin
Q02410	APBA1	914	APP binding family A member 1 (X11)
P14735	IDE	912	Insulin-degrading enzyme
P02766	TTR	907	Transthyretin
P10997	IGFBP3	902	IGF-binding protein 3
O96008	TOMM40	898	Mitochondrial import receptor
P07858	CTSB	897	Cathepsin B
Q9H0B6	KLC1	896	Kinesin light chain 1
Q9NZ42	PSENEN	896	Gamma-secretase subunit PEN-2
P78432	PDLIM5	894	PDZ and LIM domain protein 5
O96018	ADAM10	892	Disintegrin and metalloproteinase 10
Q6P597	KLC2	890	Kinesin light chain 2
Q96BI3	APH1A	890	Gamma-secretase subunit APH-1A
Q495T6	APH1B	889	Gamma-secretase subunit APH-1B
P10809	HSPD1	883	Heat shock protein 60
Q13148	TARDBP	880	TAR DNA-binding protein 43
O14672	ADAM9	879	Disintegrin and metalloproteinase 9
Q07866	KLC1	875	Kinesin light chain 1
Q9NRI5	UBQLN1	873	Ubiquilin-1
P01034	CST3	868	Cystatin-C
P01023	A2M	863	Alpha-2-macroglobulin
P29353	SHC1	863	SHC-transforming protein 1
Q92624	APPBP2	861	APP binding protein 2
Q00535	CDK5	860	Cyclin-dependent kinase 5
P23560	BDNF	855	Brain-derived neurotrophic factor
Q9NZC2	TREM2	853	Triggering receptor expressed on myeloid cells 2
P02647	APOA1	849	Apolipoprotein A-I

Interaction ID	Partner A	Partner B	Directionality
CPI-SC0E89A4EF0	APP	TREM2/TYROBP	Ligand-Receptor
CPI-SS07ACDDCD6	APP	SORL1	Ligand-Receptor
CPI-SS080C81D37	APP	CD74	Ligand-Receptor
CPI-SS097A84265	APP	TNFRSF21	Ligand-Receptor
CPI-SS0CB6F5575	APP	PLXNA4	Ligand-Receptor
CPI-SS0F66EA6BE	APP	FPR2	Ligand-Receptor

UniProt	Similarity Score	Avg Similarity
P05067	1.0000 (self)	0.9835
Q5IS80	1.0000	0.9835
P53601	1.0000	0.9835
A2WNF5	1.0000	0.9744
P08592	0.9999	0.9832
P12023	0.9999	0.9832
P51654	0.9999	0.9743
P79307	0.9999	0.9833
Q02818	0.9999	0.9718
Q5NBP9	1.0000	0.9746
Q5RE54	1.0000	0.9759
Q60495	0.9998	0.9838
Q95241	0.9999	0.9831
O70367	0.9995	0.9818
O75829	0.9995	0.9808
Q06481	0.9995	0.9845
O77770	0.9990	0.9813
P15943	0.9995	0.9842
Q06335	0.9986	0.9844
A6QLD2	0.9988	0.9814

UniProt	% Identity	Bit Score	Description
P05067	100.0	1402	Human APP (self)
Q5IS80	100.0	1402	Human APP isoform
P53601	100.0	1397	Human APP
P79307	100.0	1367	Macaque APP
Q60495	100.0	1365	Mouse APP
Q95241	100.0	1353	Bovine APP
P08592	99.0	1395	Rat APP
P12023	99.0	1399	Mouse APP
Q06481	91.4	1277	Pig APP
P15943	91.4	1276	Zebrafish APP
Q06335	87.6	1203	Chicken APP
Q03157	88.1	1056	APLP1
P51693	87.8	1053	APLP2
O73683	83.9	985	Xenopus APP
O93279	80.4	999	Teleost APP
O43278	76.3	842	APLP1
Q9R097	76.3	839	Mouse APLP1
Q2UY09	86.7	819	Zebrafish APP
P00978	88.6	610	Kunitz inhibitor
P04366	85.4	607	Kunitz inhibitor

TF	Regulation	Confidence
SP1	Activation	High
CTCF	Activation	High
SMAD2	Activation	High
AP1	Unknown	High
JUN	Unknown	High
MYC	Unknown	High
NFKB	Unknown	High
TBP	Unknown	High
TFAP2A	Unknown	High
TFAP4	Unknown	High
TFCP2	Unknown	High
TP53	Unknown	High
TP73	Unknown	High
TTF1	Unknown	High
USF1	Unknown	High
MBD2	Unknown	High
NCOR2	Unknown	High
NR1I2	Unknown	High
PURA	Unknown	High
ETS2	Unknown	High
SMAD3	Repression	High
SMAD4	Unknown	High
FOXO3	Repression
CTNNB1	Repression	Low
LEF1	Repression	Low
PPARG	Repression
RARA	Repression

Target Gene	Regulation	Notes
AGER	Activation	Receptor for AGEs
ARG1	Activation	Arginase 1
CCL5	Activation	Chemokine
CCND1	Activation	Cyclin D1
DKK1	Activation	Wnt inhibitor
EGR1	Activation	Early growth response 1
FCGR2B	Activation	Fc gamma receptor
FOS	Activation	Proto-oncogene
IL10	Activation	Interleukin 10
IL1B	Activation	Interleukin 1 beta
KLF10	Activation	Kruppel-like factor 10
NAB2	Activation	EGR1-binding protein
NEDD4	Activation	E3 ubiquitin ligase
PFKFB3	Activation	Glycolytic enzyme
PTEN	Activation	Tumor suppressor
ROCK1	Activation	Rho kinase
ABCB1	Repression	P-glycoprotein
ABCC1	Unknown	MRP1
AXIN2	Repression	Wnt pathway
BECN1	Repression	Autophagy
CCL2	Repression	Monocyte chemotaxis
CLU	Repression	Clusterin
LEF1	Repression	Wnt pathway TF
LRP1	Repression	LDL receptor
SLC40A1	Repression	Iron transporter
TNF	Repression	TNF-alpha
FZD5	Unknown	Frizzled receptor
MME	Unknown	Neprilysin
SLC8A2	Unknown	Sodium/calcium exchanger
WNT5A	Unknown	Wnt ligand

Property	Value
ChEMBL Target ID	CHEMBL2487
Target Name	Amyloid-beta precursor protein
Target Type	SINGLE PROTEIN
Mechanism	Amyloid-beta A4 protein binding agent
Action	BINDING AGENT
Total Molecules	1,865
Total Bioactivities	2,398

ChEMBL ID	Name	Type	Highest Phase
CHEMBL1774461	FLORBETAPIR F-18	Small molecule	4 (Approved)
CHEMBL1908919	FLORBETAPIR	Small molecule	4 (Approved)
CHEMBL2042122	FLUTEMETAMOL F-18	Small molecule	4 (Approved)
CHEMBL579205	FLUTEMETAMOL	Small molecule	4 (Approved)
CHEMBL566752	FLORBETABEN F-18	Small molecule	4 (Approved)
CHEMBL191083	METHYLENE BLUE	Small molecule	4 (Approved)
CHEMBL405110	METHYLENE BLUE ANHYDROUS	Small molecule	4 (Approved)
CHEMBL64894	GENTIAN VIOLET	Small molecule	4 (Approved)
CHEMBL502	DONEPEZIL	Small molecule	4 (Approved)
CHEMBL95	TACRINE	Small molecule	4 (Approved)
CHEMBL497	CLIOQUINOL	Small molecule	4 (Approved)
CHEMBL573	NIACIN	Small molecule	4 (Approved)
CHEMBL723	CARVEDILOL	Small molecule	4 (Approved)
CHEMBL76	CHLOROQUINE	Small molecule	4 (Approved)
CHEMBL682	AMODIAQUINE	Small molecule	4 (Approved)
CHEMBL38	TRETINOIN	Small molecule	4 (Approved)
CHEMBL986	RETINOL	Small molecule	4 (Approved)
CHEMBL140	CURCUMIN	Small molecule	3
CHEMBL145	CAFFEIC ACID	Small molecule	3
CHEMBL149082	TRAMIPROSATE	Small molecule	3
CHEMBL165	RESVERATROL	Small molecule	3
CHEMBL297453	EPIGALLOCATECHIN GALLATE	Small molecule	3
CHEMBL50	QUERCETIN	Small molecule	3
CHEMBL3989948	LANABECESTAT	Small molecule	3
CHEMBL2048308	FLUTAFURANOL	Small molecule	3
CHEMBL858	EDETIC ACID	Small molecule	3

Property	Value
PharmGKB ID	PA24910
Symbol	APP
VIP Gene	Yes (Very Important Pharmacogene)
CPIC Guideline	No
Chromosome	chr21

Property	Value
Expression Breadth	Ubiquitous
Total Present Calls	295
Max Expression Score	99.79
Species	Homo sapiens

Experiment ID	Description	Cells
E-MTAB-8142	Breast skin cells	809,675
E-MTAB-10287	Endometrial biopsies	340,047
E-MTAB-9543	Human gastrointestinal tract	319,479
E-HCAD-15	Pulmonary fibrosis epithelial/mesenchymal	372,319
E-GEOD-139324	Head and neck cancer immune landscape	204,315
E-GEOD-180759	Multiple sclerosis - lymphocyte-microglia-astrocyte	421,220
E-MTAB-6701	First trimester fetal-maternal interface	135,071
E-MTAB-6308	Lung tumor endothelial heterogeneity	113,132
E-MTAB-8322	Synovial macrophages in rheumatoid arthritis	99,512
E-MTAB-10855	Mammary gland lactation	74,404
E-HCAD-9	Human liver cellular landscape	79,612
E-MTAB-9841	Mammary epithelial cells	92,071
E-CURD-114	Airway epithelium smoking effects	81,801
E-MTAB-9435	Glioblastoma single-cell	62,867
E-GEOD-135922	Retinal pigment epithelium in macular degeneration	55,571
E-MTAB-6653	Lung carcinomas	55,719
E-MTAB-8381	Adult human ovary cortex	46,428
E-GEOD-131882	Early human diabetic nephropathy	43,748
E-MTAB-8205	hPSC endothelial-to-haematopoietic transition	25,764
E-MTAB-10553	Human liver cells	24,355
E-MTAB-10042	Fetal bone marrow haematopoiesis	21,485
E-GEOD-137537	Human retina age-related macular degeneration	12,881
E-MTAB-8530	Lung adenocarcinoma disseminated tumor cells	9,812
E-CURD-135	Kidney organoid vs adult kidney	6,192
E-MTAB-6108	Stem cell-derived retinal ganglion cells	1,742
E-MTAB-6819	Naive and primed hESCs	1,344

Disease	Classification	Inheritance	Source
Alzheimer disease type 1 (OMIM:104300)	Strong	Autosomal dominant	Genomics England PanelApp
Alzheimer disease type 1 (OMIM:104300)	Strong	Autosomal dominant	Labcorp Genetics
Cerebral amyloid angiopathy, APP-related (OMIM:605714)	Strong	Autosomal dominant	Genomics England PanelApp
Cerebral amyloid angiopathy, APP-related (OMIM:605714)	Strong	Autosomal dominant	Labcorp Genetics
Early-onset autosomal dominant Alzheimer disease (Orphanet:1020)	Supportive	Autosomal dominant	Orphanet
ABeta amyloidosis, Dutch type (Orphanet:100006)	Supportive	Autosomal dominant	Orphanet
ABetaL34V amyloidosis (Orphanet:324703)	Supportive	Autosomal dominant	Orphanet
ABeta amyloidosis, Iowa type (Orphanet:324708)	Supportive	Autosomal dominant	Orphanet
ABeta amyloidosis, Italian type (Orphanet:324713)	Supportive	Autosomal dominant	Orphanet
ABetaA21G amyloidosis (Orphanet:324718)	Supportive	Autosomal dominant	Orphanet
ABeta amyloidosis, Arctic type (Orphanet:324723)	Supportive	Autosomal dominant	Orphanet

Orphanet ID	Disease Name	Type	Genes	Phenotypes
ORPHA:1020	Early-onset autosomal dominant Alzheimer disease	Disease	6	26
ORPHA:100006	ABeta amyloidosis, Dutch type	Clinical subtype	1	10
ORPHA:324703	ABetaL34V amyloidosis	Clinical subtype	1	11
ORPHA:324708	ABeta amyloidosis, Iowa type	Clinical subtype	1	9
ORPHA:324713	ABeta amyloidosis, Italian type	Clinical subtype	1	7
ORPHA:324718	ABetaA21G amyloidosis	Clinical subtype	1	0
ORPHA:324723	ABeta amyloidosis, Arctic type	Clinical subtype	1	2

HPO ID	Phenotype
HP:0002511	Alzheimer disease
HP:0000726	Dementia
HP:0001268	Mental deterioration
HP:0002354	Memory impairment
HP:0000708	Atypical behavior
HP:0001289	Confusion
HP:0000713	Agitation
HP:0000734	Disinhibition
HP:0000738	Hallucinations
HP:0002463	Language impairment
HP:0002381	Aphasia
HP:0002186	Apraxia
HP:0001250	Seizure
HP:0001336	Myoclonus
HP:0001251	Ataxia
HP:0001300	Parkinsonism
HP:0001288	Gait disturbance
HP:0001276	Hypertonia
HP:0002076	Migraine
HP:0002315	Headache
HP:0011970	Cerebral amyloid angiopathy
HP:0001342	Cerebral hemorrhage
HP:0004968	Recurrent cerebral hemorrhage
HP:0002138	Subarachnoid hemorrhage
HP:0011695	Cerebellar hemorrhage
HP:0002637	Cerebral ischemia
HP:0001297	Stroke
HP:0002120	Cerebral cortical atrophy
HP:0002185	Neurofibrillary tangles
HP:0003791	Deposits immunoreactive to beta-amyloid protein
HP:0004938	Tortuous cerebral arteries
HP:0100659	Abnormal cerebral vascular morphology
HP:0002514	Cerebral calcification
HP:0000504	Abnormality of vision
HP:0000657	Oculomotor apraxia
HP:0002015	Dysphagia
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0012759	Neurodevelopmental abnormality
HP:0001259	Coma
HP:0003401	Paresthesia
HP:0003474	Somatic sensory dysfunction
HP:0010525	Finger agnosia
HP:0010526	Dysgraphia
HP:0030219	Semantic dementia
HP:0002373	Febrile seizure
HP:0012433	Abnormal social behavior
HP:0011446	Abnormality of mental function
HP:0000006	Autosomal dominant inheritance
HP:0003581	Adult onset
HP:0003584	Late onset
HP:0003596	Middle age onset
HP:0100613	Death in early adulthood
HP:0002423	Long-tract sign
HP:0410054	Decreased circulating GABA concentration

Study ID	Trait	P-value	Mapped Gene
GCST012182	Alzheimer's disease	1.0 × 10⁻¹¹	APP
GCST006279	Cerebrospinal fluid α-synuclein levels	2.0 × 10⁻⁷	GABPA - APP
GCST90011770	Glaucoma (primary open-angle)	3.0 × 10⁻⁷	GABPA - APP
GCST003082	Longitudinal change in brain amyloid plaque burden	3.0 × 10⁻⁶	JAM2
GCST009306	Spatial processing	2.0 × 10⁻⁶	APP
GCST90011768	Glaucoma (primary open-angle)	7.0 × 10⁻⁶	GABPA - APP
GCST011743	HDL cholesterol levels in HIV infection	8.0 × 10⁻⁶	-

Category	Count
Gene Identifiers	6 databases
Ensembl Transcripts	40
RefSeq Transcripts (Human)	11
CCDS IDs	8
Canonical Transcript Exons	18
UniProt Entries	6
InterPro Domains	17
Pfam Domains	6
PDB Structures	248+
Cross-Species Orthologs	6 species
ClinVar Variants	593
Pathogenic Variants	23
Likely Pathogenic Variants	8
SpliceAI Predictions	4,341
AlphaMissense Predictions	5,117
Reactome Pathways	17
GO Annotations	123
STRING Interactions	7,062
BioGRID Interactions	2,961
ESM2 Similar Proteins	81
DIAMOND Homologs	77
TF Regulators of APP	50
Downstream Targets of APP	30
ChEMBL Targeting Molecules	1,865
Phase 4 (Approved) Drugs	17
Phase 3 Molecules	9
Single-Cell Datasets	26
HPO Phenotypes	55
GWAS Associations	7
Mendelian Disease Links	11
Orphanet Diseases	7