Human Gene HFE (ENST00000352392.8) from GENCODE V44
Description: Homo sapiens homeostatic iron regulator (HFE), transcript variant 11, mRNA. (from RefSeq NM_139011) RefSeq Summary (NM_139011): 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]. Gencode Transcript: ENST00000352392.8 Gencode Gene: ENSG00000010704.19 Transcript (Including UTRs) Position: hg38 chr6:26,087,281-26,094,488 Size: 7,208 Total Exon Count: 3 Strand: + Coding Region Position: hg38 chr6:26,087,441-26,094,226 Size: 6,786 Coding Exon Count: 3
ID:HFE_HUMAN DESCRIPTION: RecName: Full=Hereditary hemochromatosis protein; AltName: Full=HLA-H; Flags: Precursor; FUNCTION: Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin. SUBUNIT: Binds TFR through the extracellular domain in a pH- dependent manner. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. TISSUE SPECIFICITY: Expressed in all tissues tested except brain. POLYMORPHISM: Genetic variations in HFE define the transferrin serum level quantitative trait locus 2 (TFQTL2) [MIM:614193]. Iron is essential for biochemical functions such as oxygen transport and oxidative phosphorylation. Excessive iron can cause iron- overload-related liver diseases, whereas iron deficiency can lead to anemia. Iron status can be assessed by measuring the levels of serum iron, serum transferrin, transferrin saturation with iron, and serum ferritin. DISEASE: Defects in HFE are a cause of hemochromatosis (HFE) [MIM:235200]. 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. DISEASE: Defects in HFE are associated with variegate porphyria (VP) [MIM:176200]. 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. Note=Iron overload due to HFE mutations is a precipitating or exacerbating factor in variegate porphyria. DISEASE: Defects in HFE are associated with susceptibility to microvascular complications of diabetes type 7 (MVCD7) [MIM:612635]. 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. SIMILARITY: Belongs to the MHC class I family. SIMILARITY: Contains 1 Ig-like C1-type (immunoglobulin-like) domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/HFEID44099ch6p22.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/HFE"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/hfe/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q30201
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Mouse
Rat
Zebrafish
D. melanogaster
C. elegans
S. cerevisiae
No ortholog
No ortholog
No ortholog
No ortholog
No ortholog
No ortholog
Gene Ontology (GO) Annotations with Structured Vocabulary
Biological Process: GO:0002626 negative regulation of T cell antigen processing and presentation GO:0002725 negative regulation of T cell cytokine production GO:0006811 ion transport GO:0006879 cellular iron ion homeostasis GO:0006953 acute-phase response GO:0007565 female pregnancy GO:0010039 response to iron ion GO:0010106 cellular response to iron ion starvation GO:0010628 positive regulation of gene expression GO:0010862 positive regulation of pathway-restricted SMAD protein phosphorylation GO:0030509 BMP signaling pathway GO:0032092 positive regulation of protein binding GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process GO:0033572 transferrin transport GO:0042446 hormone biosynthetic process GO:0048260 positive regulation of receptor-mediated endocytosis GO:0055072 iron ion homeostasis GO:0060586 multicellular organismal iron ion homeostasis GO:0065003 macromolecular complex assembly GO:0071281 cellular response to iron ion GO:0090277 positive regulation of peptide hormone secretion GO:0097421 liver regeneration GO:0098711 iron ion import across plasma membrane GO:1900121 negative regulation of receptor binding GO:1900122 positive regulation of receptor binding GO:1900390 regulation of iron ion import GO:1904283 negative regulation of antigen processing and presentation of endogenous peptide antigen via MHC class I GO:1904434 positive regulation of ferrous iron binding GO:1904437 positive regulation of transferrin receptor binding GO:1990641 response to iron ion starvation GO:2000008 regulation of protein localization to cell surface GO:2000059 negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:2000272 negative regulation of receptor activity GO:2000273 positive regulation of receptor activity GO:2001186 negative regulation of CD8-positive, alpha-beta T cell activation GO:0002474 antigen processing and presentation of peptide antigen via MHC class I GO:0019882 antigen processing and presentation
US Server
