What Is Haploinsufficiency?
Most people have two copies of most genes, one inherited from each parent. Sometimes one copy is missing or not working. For many genes, one working copy is enough. Haploinsufficiency happens when one working copy is not enough, so the body has too little of an important protein or gene product.
Plain-English explanation
Most people have two copies of most genes, one inherited from each parent. Sometimes one copy is missing or not working. For many genes, one working copy is enough. Haploinsufficiency happens when one working copy is not enough, so the body has too little of an important protein or gene product.
Why it matters
Many neurodevelopmental and rare genetic disorders involve dosage: the problem is not that a toxic protein is being made, but that the body does not have enough of something it needs. That distinction changes treatment strategy. Researchers may ask whether they can add a working copy, increase expression from the remaining copy, or support pathways affected downstream.
How it works
A gene can become haploinsufficient through a deletion, a truncating variant, a damaging missense variant, or another change that reduces function. Clinicians and researchers look at the gene, the variant, inheritance, symptoms, and published evidence to decide whether reduced dosage explains the condition. Treatment research then focuses on restoring enough function or compensating for what the missing dosage disrupts.
Key terms
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