HEPATOCYTE NUCLEAR FACTOR 1A BOUND TO DNA : MODY3 GENE PRODUCT
[HNF1A_HUMAN] Defects in HNF1A are a cause of hepatic adenomas familial (HEPAF) [MIM:142330]. Hepatic adenomas are rare benign liver tumors of presumable epithelial origin that develop in an otherwise normal liver. Hepatic adenomas may be single or multiple. They consist of sheets of well-differentiated hepatocytes that contain fat and glycogen and can produce bile. Bile ducts or portal areas are absent. Kupffer cells, if present, are reduced in number and are non-functional. Conditions associated with adenomas are insulin-dependent diabetes mellitus and glycogen storage diseases (types 1 and 3). Note=Bi-allelic inactivation of HNF1A, whether sporadic or associated with MODY3, may be an early step in the developmant of some hepatocellular carcinomas. Defects in HNF1A are the cause of maturity-onset diabetes of the young type 3 (MODY3) [MIM:600496]; also symbolized MODY-3. MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.                Defects in HNF1A are the cause of susceptibility to diabetes mellitus insulin-dependent type 20 (IDDM20) [MIM:612520]. IDDM20 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These features can result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.  
[HNF1A_HUMAN] Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver. Required for the expression of several liver specific genes. Binds to the inverted palindrome 5'-GTTAATNATTAAC-3'. 
Publication Abstract from PubMed
Mutations in Hnf-1alpha are the most common Mendelian cause of diabetes mellitus. To elucidate the molecular function of a mutational hotspot, we cocrystallized human HNF-1alpha 83-279 with a high-affinity promoter and solved the structure of the complex. Two identical protein molecules are bound to the promoter. Each contains a homeodomain and a second domain structurally similar to POU-specific domains that was not predicted on the basis of amino acid sequence. Atypical elements in both domains create a stable interface that further distinguishes HNF-1alpha from other flexible POU-homeodomain proteins. The numerous diabetes-causing mutations in HNF-1alpha thus identified a previously unrecognized POU domain which was used as a search model to identify additional POU domain proteins in sequence databases.
Diabetes mutations delineate an atypical POU domain in HNF-1alpha.,Chi YI, Frantz JD, Oh BC, Hansen L, Dhe-Paganon S, Shoelson SE Mol Cell. 2002 Nov;10(5):1129-37. PMID:12453420
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.