ADNP (Activity-Dependent Neuroprotective Protein) is a homeobox-containing transcription factor essential for brain development and neuronal survival. ADNP is one of the most frequently mutated genes in autism spectrum disorder (Helsmoortel-Van der Aa syndrome) and has emerged as a critical player in Alzheimer's disease through its direct interaction with tau. The ADNP-derived peptide NAP (davunetide) represents a promising neuroprotective therapeutic strategy that stabilizes microtubules and prevents tau pathology.
| Full Name | Activity-Dependent Neuroprotective Protein |
| Gene Symbol | ADNP |
| Chromosomal Location | 20q13.13 |
| NCBI Gene ID | [23394](https://www.ncbi.nlm.nih.gov/gene/23394) |
| OMIM | [611386](https://omim.org/entry/611386) |
| Ensembl ID | [ENSG00000101126](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000101126) |
| UniProt ID | [Q9H2P0](https://www.uniprot.org/uniprot/Q9H2P0) |
| Protein | [ADNP Protein](/proteins/adnp-protein) |
| Associated Diseases | [Alzheimer's disease](/diseases/alzheimers-disease), [Autism (Helsmoortel-Van der Aa)](/diseases/autism), [FTD](/diseases/frontotemporal-dementia), [Parkinson's disease](/diseases/parkinsons-disease) |
ADNP encodes a 1,102 amino acid protein containing a homeobox domain, nine zinc fingers, and a PxVxL motif that mediates interaction with the SWI/SNF chromatin remodeling complex through HP1. ADNP functions at multiple levels in the nervous system:
ADNP acts as a transcription factor that regulates the expression of hundreds of genes critical for neuronal development and maintenance. ADNP binds chromatin through its homeobox domain and recruits the BAF (BRG1/BRM-associated factor) chromatin remodeling complex via its PxVxL motif. Target genes include those involved in:
The ADNP-derived octapeptide NAP (NAPVSIPQ) binds the microtubule end-binding proteins EB1 and EB3, promoting microtubule dynamics and stability. This interaction is critical for:
ADNP directly interacts with tau protein through the SH3-binding domain. Notably:
De novo mutations in ADNP are one of the most common single-gene causes of autism, accounting for approximately 0.17% of ASD cases. Over 50 pathogenic mutations have been identified, predominantly truncating variants in exon 5. Clinical features include:
ADNP has a multifaceted relationship with Alzheimer's disease:
ADNP mutations produce a specific pattern of tau pathology:
Reduced ADNP expression has been reported in the substantia nigra of PD patients. The NAP peptide protects dopaminergic neurons against MPTP-induced toxicity in animal models.
ADNP is broadly expressed throughout the brain with highest levels in:
Expression pattern via Allen Brain Atlas.
The NAP peptide (NAPVSIPQ), derived from the ADNP active site, is the most advanced ADNP-based therapeutic:
Gene therapy approaches using AAV-ADNP are being developed for ADNP syndrome, showing restoration of social behavior and cognitive function in Adnp-haploinsufficient mice.