NLRP2 gene

The NLRP2 gene (NLRP2 stands for: NLR Family Pyrin Domain Containing 2) is a protein-coding gene located on chromosome 19q13.42. An allelic variant (rs147585490) was found that is unable to block the transcriptional activity of NF-kB. Alternative splicing leads to multiple transcript variants encoding different isoforms.

The NLRP2 gene belongs to the nucleotide-binding and leucine-rich repeat (NLR) receptor family and is thought to contain an N-terminal pyrin effector domain (PYD), a centrally localized nucleotide-binding and oligomerization domain (NACHT) and C-terminal leucine-rich repeats (LRR). Members of this gene family are considered important regulators of the immune response.

The encoded gene product(NLRP2 protein) interacts with components of the IkB kinase complex (IKK) and can regulate the activity of both caspase-1 and NF-kB (nuclear factor kappa light chain enhancer of activated B cells). The pyrin domain is necessary and sufficient for the suppression of NF-kB activity. It is possibly a component of the inflammasome, a protein complex that also includes PYCARD, CARD8 and CASP1 and whose function is to activate pro-inflammatory caspases.

Diseases associated with NLRP2 includeMultisystem Inflammatory Syndrome in Children (MIC), an inflammatory multisystem inflammatory syndrome in children (All affected children have persistent fever. Other clinical features vary. Initial symptoms often include acute abdominal pain with diarrhea or vomiting. Muscle aches and general fatigue are common, and low blood pressure is also common. Symptoms may also include exanthema, enlarged lymph nodes, swollen hands and feet and a "strawberry tongue". Various psychological disorders are possible. A cytokine storm may occur, in which the child's innate immune system triggers an excessive and uncontrolled inflammatory response. Heart failure is common. Clinical complications may include damage to the heart muscle, shortness of breath, acute kidney damage and increased blood clotting. Anomalies of the coronary arteries can occur (from dilation to aneurysm).

1. Ahmed M et al (2020) Multisystem inflammatory syndrome in children: a systematic review. EClinicalMedicine 26: 100527.
2. Patel JM (2022) . Multisystem Inflammatory Syndrome in Children (MIS-C). Curr Allergy Asthma Rep. 2022 May;22(5):53-60.