NAIP Gene: NLR Family Apoptosis Inhibitory Protein - Function, Mutations, and Disease

The NAIP (NLR Family Apoptosis Inhibitory Protein) gene encodes a member of the NLR (nucleotide-binding oligomerization domain-like receptor) family and the inhibitor of apoptosis protein (IAP) family. The protein inhibits apoptosis by binding to caspases and also functions in innate immunity by recognizing bacterial flagellin and activating the inflammasome. NAIP is located in a region of chromosome 5 that is duplicated and polymorphic; copy number variations are associated with spinal muscular atrophy (SMA) and other neurological disorders.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Apoptosis - multiple species (KEGG: hsa04215)

• NOD-like receptor signaling pathway (KEGG: hsa04621)

• Salmonella infection (KEGG: hsa05132)

• Legionellosis (KEGG: hsa05134)

The NAIP protein (Q13075) is a 1403-amino acid multi-domain protein containing an N-terminal baculovirus IAP repeat (BIR) domain, a nucleotide-binding oligomerization domain (NOD), and C-terminal leucine-rich repeats (LRRs). It functions as a cytoplasmic pattern recognition receptor that detects bacterial flagellin and activates the NLRC4 inflammasome, leading to caspase-1 activation and pyroptosis. Additionally, NAIP inhibits apoptosis by directly binding and inhibiting caspases 3 and 7. The protein is predominantly expressed in testis, spinal cord, and brain, and its deficiency is linked to spinal muscular atrophy.