Glossary

Allele

A single copy of a gene. For most genes, humans have two alleles, one inherited from the female and one from the male.

Biallelic

Of or pertaining to both alleles of a single gene (paternal and maternal). For example, biallelic variant carriers have a variant (not necessarily the same variant) in both copies of a particular gene (a paternal and a maternal variant).

Heterozygous

The presence of a genetic variant on only one of the two parental copies of a given gene.

Hyperphagia

This symptom is characterized by an overwhelming, heightened, and relentless hunger, longer time to reach satiety and shorter duration of satiety and potentially extreme food-seeking behaviors, such waking up at night to find food or eating non-food items.

Hypothalamus

A region of the brain, between the pituitary gland and thalamus, that plays a vital role in controlling many physiological processes, including body temperature, hunger, and thirst. A major function is to is to maintain overall energy balance and control body weight.

Leptin receptor (LEPR)

The LEPR gene provides instructions for making a protein called the leptin receptor. The leptin receptor protein is found on the surface of cells in many organs and tissues of the body, including on POMC neurons in the hypothalamus, where it can regulate energy balance.

Melanocyte-stimulating hormone (MSH)

MSH is the endogenous agonist for the MC4R and is important for regulating hunger, food intake, energy expenditure and consequentially, body weight. MSH is generated from cleavage of the larger POMC protein by the enzyme proprotein convertase 1/3, which cleaves POMC into smaller bioactive molecules.

MC4R-pathway

The MC4R is located in the central nervous system and includes key molecules that regulate satiety, energy expenditure and consequently, body weight.

Proopiomelanocortin (POMC)

The POMC Gene provides instructions for making a protein called proopiomelanocortin (POMC), which is cleaved into peptides, such as MSH, that regulate several different physiological processes. These peptides bind to one of several receptors in different regions of the body, including the MC4R pathway, located within the hypothalamus, to control energy balance.

Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1)

The PCSK1 gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein. PCSK1 in POMC neurons of the hypothalamus is required for the processing of MSH from the POMC protein.

Satiety

The feeling or state where one’s appetite has been satisfied.

Syndromic

Occurring as a group of signs and symptoms that characterize a particular abnormality.