HFE cDNA Clone – Hemochromatosis (Human)

The protein encoded by this gene is a membrane protein that is similar to MHC class I-type proteins and associates with beta2-microglobulin (beta2M). It is thought that this protein functions to regulate iron absorption by regulating the interaction of the transferrin receptor with transferrin. The iron storage disorder, hereditary haemochromatosis, is a recessive genetic disorder that results from defects in this gene. At least nine alternatively spliced variants have been described for this gene. Additional variants have been found but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

HFE: Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin. Defects in HFE are a cause of hemochromatosis (HFE). A disorder of iron metabolism characterized by iron overload. Excess iron is deposited in a variety of organs leading to their failure, and resulting in serious illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis, and hypogonadotropic hypogonadism. Severe effects of the disease usually do not appear until after decades of progressive iron loading. Defects in HFE are associated with variegate porphyria (VP). Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. VP is the most common form of porphyria in South Africa. It is characterized by skin hyperpigmentation and hypertrichosis, abdominal pain, tachycardia, hypertension and neuromuscular disturbances. High fecal levels of protoporphyrin and coproporphyrin, increased urine uroporphyrins and iron overload are typical markers of the disease. Iron overload due to HFE mutations is a precipitating or exacerbating factor in variegate porphyria. Defects in HFE are associated with susceptibility to microvascular complications of diabetes type 7 (MVCD7). These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Belongs to the MHC class I family. 11 isoforms of the human protein are produced by alternative splicing.

Protein type: Membrane protein, integral

Chromosomal Location of Human Ortholog: 6p21.3

Cellular Component: apical part of cell; cytoplasmic vesicle; early endosome; external side of plasma membrane; extracellular space; integral to plasma membrane; MHC class I protein complex; perinuclear region of cytoplasm; plasma membrane; recycling endosome

Molecular Function: antigen binding; beta-2-microglobulin binding; peptide antigen binding; protein binding; receptor binding

Biological Process: antigen processing and presentation; antigen processing and presentation of peptide antigen via MHC class I; BMP signaling pathway; iron ion homeostasis; negative regulation of proteasomal ubiquitin-dependent protein catabolic process; negative regulation of T cell cytokine production; positive regulation of protein binding; positive regulation of receptor-mediated endocytosis; protein complex assembly; response to iron ion

Disease: Alzheimer Disease; Hemochromatosis, Type 1; Microvascular Complications Of Diabetes, Susceptibility To, 7; Porphyria Cutanea Tarda; Porphyria Variegata; Transferrin Serum Level Quantitative Trait Locus 2