FERM and PDZ domain containing 2B (FRMPD2B)

FERM and PDZ domain containing 2B (FRMPD2B) is a truncated human-specific paralog of FERM and PDZ domain containing 2 (FRMPD2), emerging through a partial duplication event ~2.3 million years ago on chromosome 10q. Although annotated as a pseudogene in many databases, new evidence reveals that FRMPD2B produces a 320-amino-acid protein retaining key PDZ domains that mediate interactions with postsynaptic receptors, notably NMDA receptor subunits. FRMPD2B is expressed postnatally in the human brain and functions as a dominant negative modulator of full-length FRMPD2, affecting synaptic transmission, synaptic plasticity, and susceptibility to induced seizures. Variants affecting this locus, such as deletions or duplications, are associated with intellectual disability, autism, and epilepsy, suggesting a previously unappreciated role in human-specific neurodevelopment and disease. Key points: - FRMPD2B is not a classic receptor, enzyme, or transporter but rather a protein product of a human-specific gene duplication event, functioning in postsynaptic signaling in the brain by antagonizing the full-length FRMPD2 scaffold protein. - It is generally not considered a direct or druggable target, but new functional evidence may warrant re-evaluation of its classification and disease relevance.

Other names

FRMPD2BFRMPD2FRMPD2L1FRMPD2L2FRMPD2P1FRMPD2P2FRMPDP2PDZD5APDZD5BPDZD5CPDZK4PDZK5APDZK5BPDZK5CbA556L1.2yX59F3.2FERM and PDZ domain containing 2 like 1FERM and PDZ domain containing 2 like 2FERM and PDZ domain containing 2 pseudogene 1FERM and PDZ domain containing 2 pseudogene 2FERM and PDZ domain-containing protein 2FRMPD2 related 1FRMPD2 related 2PDZ domain containing 5APDZ domain containing 5BPDZ domain-containing protein 4PDZ domain-containing protein 5C

No clinically targeted mechanism; but antagonism (dominant negative effect) of the endogenous full-length FRMPD2, likely through interaction with NMDA receptor subunits (GluN2A)