Most inherited diseases are due to mutations in genes in the nuclear chromosomes, though mitochondrial gene mutations can also cause them to happen. A single gene mutation can result in the absence or modification of a particular protein, such as the abnormal haemoglobin found in sickle cell anaemia. In some instances, the inherited disorder may lead to defective carrier proteins, such as in cystinuria, where renal reabsorption of cystine (formed by the oxidation of two cysteines) is impaired or defective receptor synthesis, such as in familial hypercholesterolemia where there is a defect in low density lipoprotein (LDL) receptors.

If the missing or damaged protein is an enzyme, a metabolic disorder will result. The majority of hereditary metabolic diseases are autosomal recessive conditions, meaning that heterozygotes have normal phenotypes because enough of the protein is produced and only homozygotes exhibit symptoms. However, some of these diseases have an autosomal dominant mode of inheritance, which makes heterozygotes susceptible. Porphyrias and familial hypercholesterolemia are two examples of these.