**Abstract**

This chapter sheds light on hepcidin, historical view of hepcidin, and the time of its discovery in the first section. Then this chapter gives information about the genetic aspect and the importance of gene knowledge of hepcidin in explaining many disorders in human beings, supported by illustration figures. The regulation of iron in the human body as an essential function of hepcidin is discussed in this chapter. Examples of the genes of hepcidin (HAMP and HFE) are highlighted in detail as they are essential in regulating iron as well as discussing the genetic mutations that occur in these genes and their medical and clinical impacts for many diseases such as thalassemia. Finally, the inherited disorders related to hepcidin that lead to genetic diseases are discussed.

**Keywords:** iron, gene mutation, HAMP gene, HFE gene, hemochromatosis

### **1. Introduction**

Hepcidin is presently regarded as the key to the iron balance regulator. The balance of intracellular iron is preserved by proteins that regulate iron. Hepcidin, encoded by the HAMP gene is a 25 amino acid peptide that has been lately found [1]. Several mutations in the HAMP gene have been reported. The G71D mutation is probable to be linked to reduced hepcidin activity [2]. Mutations in iron-regulating proteins cause the disorder (HFE, TfR2, and HAMP) genes. Fekri et al. showed that H63D mutation of the HFE gene could play some role in disease evolution. In iron homeostasis, the HFE gene plays a very significant role by regulating iron absorption [3]. HFE mutations are currently referred to as the reason for decreased absorption of iron, iron overload, and hereditary hemochromatosis [4]. Many types of research have shown that patients with HFE mutations in beta-thalassemia are likely to create hemochromatosis that will require early chelation of iron even in heterozygous conditions [5]. Among the mutations discovered most frequently are the three missense mutations (SNPs), which are found in the HFE gene. The most prevalent mutation within the HFE gene exon 4, leading in a shift of cysteine-totyrosine amino acid at position 282 (C282Y), 60% of hereditary hemochromatosis instances in Mediterranean populations accounted for this mutation. H63D is also a mutation leading to the replacement of histidine with aspartic acid during a C-G shift at nucleotide 187 of exon 2 of the HFE gene. In combination with the C282Y allele (C282Y/H63D), hemochromatosis is most pronounced. The HFE gene's third mutation is a substitute for 193AT in exon a pair of with an ensuing serine to cysteine replacement in amino acid position 65 (S65C) [6]. The interaction concerning

the mutations over genes influencing blood homeostasis including thalassemia may want to hold a synergistic result, increasing the iron storage [7].
