The HNF1B gene provides instructions for making a protein called hepatocyte nuclear factor-1 beta (HNF-1β). This protein attaches (binds) to specific regions of DNA and regulates the activity of other genes. Based on this role, the protein is called a transcription factor. The HNF-1β protein is one of a large group of transcription factors called homeodomain proteins. The homeodomain is a region of the protein that allows it to bind to DNA.
The HNF-1β protein is found in many organs and tissues, including the lungs, liver, intestines, pancreas, kidneys, genital tract, and urinary tract and is thought to play a role in their development. The HNF-1β protein is important for development and function of the kidneys and beta cells in the pancreas. Beta cells produce and release (secrete) the hormone insulin. Insulin helps regulate blood sugar levels by controlling how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy.
Health Conditions Related to Genetic Changes
Maturity-onset diabetes of the young
Mutations in the HNF1B gene cause maturity-onset diabetes of the young (MODY). MODY is a group of conditions characterized by abnormally high blood sugar that usually begins before age 30. HNF1B gene mutations cases a type of MODY known as renal cysts and diabetes (RCAD) syndrome (also known as HNF1B-MODY or MODY5). In addition to diabetes, people with RCAD typically also have kidney abnormalities (primarily fluid-filled sacs called cysts). Affected individuals may also have abnormalities of the pancreas, liver, or genital tract; or a condition called gout, which is a form of arthritis.
HNF1B gene mutations involved in RCAD occur in one copy of the gene in each cell. The changes reduce the amount of functional HNF-1β protein. A shortage of this transcription factor disrupts the activity of genes that direct the development and function of certain tissues and organs. In the pancreas, these changes prevent normal beta cell function. The cells are less able than normal to produce insulin in response to sugar in the blood, leading to diabetes. In the kidneys, altered HNF-1β activity results in the formation of cysts or other abnormalities.More About This Health Condition
17q12 deletion syndrome
17q12 deletion syndrome is a condition that results from the deletion of a small piece of chromosome 17 in each cell. Signs and symptoms of 17q12 deletion syndrome can include a type of maturity-onset diabetes of the young (MODY) called renal cysts and diabetes (RCAD) syndrome (described above). Other features of 17q12 deletion syndrome include abnormalities of the urinary tract and reproductive system, delayed development, impaired thinking (cognitive) ability, and behavioral or psychiatric disorders. The health problems associated with 17q12 deletion syndrome vary widely, even among affected members of the same family.
The part of chromosome 17 that is deleted is on the long (q) arm of the chromosome at a position designated q12. This region of the chromosome contains at least 15 genes, including HNF1B. A deletion of this region results in a loss of one copy of the HNF1B gene in each cell, leading to a reduced amount of HNF-1β protein. A shortage of this protein likely disrupts the regulation of genes that are necessary for the normal development of several organs, including the kidneys and pancreas. Studies suggest that a loss of one copy of the HNF1B gene underlies RCAD syndrome in people with 17q12 deletion syndrome.More About This Health Condition
Congenital anomalies of kidney and urinary tract
Mutations within the HNF1B gene are found in people with abnormalities of the kidneys and other structures of the urinary tract but without other features of 17q12 deletion syndrome (described above) or RCAD syndrome (described above). These abnormalities vary in severity and are grouped together as congenital anomalies of kidney and urinary tract (CAKUT). The most severe CAKUT abnormalities can cause kidney damage and life-threatening kidney failure.
Mutations associated with CAKUT occur in one copy of the HNF1B gene in each cell. Many change single protein building blocks (amino acids) in the HNF-1β protein. Others lead to an abnormally shaped protein or prevent the production of any functional protein from one copy of the gene. A shortage of functional HNF-1β protein likely disrupts the regulation of genes that help direct development of the kidneys and urinary tract. It is unclear why only structures of the urinary tract are affected in these individuals.More About This Health Condition
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HNF1B gene mutations can also cause abnormalities of multiple organ systems. Some of the features associated with HNF1B gene mutations are the same as those of 17q12 deletion syndrome (described above), including RCAD syndrome (described above) and abnormalities of the urinary tract, reproductive system, and other organs. Like the signs and symptoms of those syndromes, the health problems associated with HNF1B gene mutations vary widely among affected individuals. However, unlike 17q12 deletions, mutations in the HNF1B gene have not been found to cause delayed development, intellectual disability, or behavioral or psychiatric disorders.
More than 200 mutations in the HNF1B gene have been identified. As in CAKUT (described above), the mutations lead to a shortage of functional HNF-1β protein, which likely disrupts the regulation of genes that are necessary for the normal development of several organs. It is unclear why these mutations can affect different organ systems in different people.
Other Names for This Gene
- hepatocyte nuclear factor 1B
- HNF1 beta A
- homeoprotein LFB3
- transcription factor 2, hepatic
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Bockenhauer D, Jaureguiberry G. HNF1B-associated clinical phenotypes: the kidney and beyond. Pediatr Nephrol. 2016 May;31(5):707-14. doi: 10.1007/s00467-015-3142-2. Epub 2015 Jul 8. Citation on PubMed
- Chen YZ, Gao Q, Zhao XZ, Chen YZ, Bennett CL, Xiong XS, Mei CL, Shi YQ, Chen XM. Systematic review of TCF2 anomalies in renal cysts and diabetes syndrome/maturity onset diabetes of the young type 5. Chin Med J (Engl). 2010 Nov;123(22):3326-33. Citation on PubMed
- Clissold RL, Shaw-Smith C, Turnpenny P, Bunce B, Bockenhauer D, Kerecuk L, Waller S, Bowman P, Ford T, Ellard S, Hattersley AT, Bingham C. Chromosome 17q12 microdeletions but not intragenic HNF1B mutations link developmental kidney disease and psychiatric disorder. Kidney Int. 2016 Jul;90(1):203-11. doi: 10.1016/j.kint.2016.03.027. Epub 2016 May 24. Citation on PubMed or Free article on PubMed Central
- El-Khairi R, Vallier L. The role of hepatocyte nuclear factor 1beta in disease and development. Diabetes Obes Metab. 2016 Sep;18 Suppl 1:23-32. doi: 10.1111/dom.12715. Citation on PubMed
- Ferre S, Igarashi P. New insights into the role of HNF-1beta in kidney (patho)physiology. Pediatr Nephrol. 2019 Aug;34(8):1325-1335. doi: 10.1007/s00467-018-3990-7. Epub 2018 Jul 1. Citation on PubMed
- Heidet L, Decramer S, Pawtowski A, Moriniere V, Bandin F, Knebelmann B, Lebre AS, Faguer S, Guigonis V, Antignac C, Salomon R. Spectrum of HNF1B mutations in a large cohort of patients who harbor renal diseases. Clin J Am Soc Nephrol. 2010 Jun;5(6):1079-90. doi: 10.2215/CJN.06810909. Epub 2010 Apr 8. Citation on PubMed or Free article on PubMed Central
- Laffargue F, Bourthoumieu S, Llanas B, Baudouin V, Lahoche A, Morin D, Bessenay L, De Parscau L, Cloarec S, Delrue MA, Taupiac E, Dizier E, Laroche C, Bahans C, Yardin C, Lacombe D, Guigonis V. Towards a new point of view on the phenotype of patients with a 17q12 microdeletion syndrome. Arch Dis Child. 2015 Mar;100(3):259-64. doi: 10.1136/archdischild-2014-306810. Epub 2014 Oct 16. Citation on PubMed
- Madariaga L, Garcia-Castano A, Ariceta G, Martinez-Salazar R, Aguayo A, Castano L; Spanish group for the study of HNF1B mutations. Variable phenotype in HNF1B mutations: extrarenal manifestations distinguish affected individuals from the population with congenital anomalies of the kidney and urinary tract. Clin Kidney J. 2018 Nov 13;12(3):373-379. doi: 10.1093/ckj/sfy102. eCollection 2019 Jun. Citation on PubMed or Free article on PubMed Central
- Mancusi S, La Manna A, Bellini G, Scianguetta S, Roberti D, Casale M, Rossi F, Della Ragione F, Perrotta S. HNF-1beta mutation affects PKD2 and SOCS3 expression causing renal cysts and diabetes in MODY5 kindred. J Nephrol. 2013 Jan-Feb;26(1):207-12. doi: 10.5301/jn.5000126. Citation on PubMed
- Mefford HC, Clauin S, Sharp AJ, Moller RS, Ullmann R, Kapur R, Pinkel D, Cooper GM, Ventura M, Ropers HH, Tommerup N, Eichler EE, Bellanne-Chantelot C. Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy. Am J Hum Genet. 2007 Nov;81(5):1057-69. doi: 10.1086/522591. Epub 2007 Sep 26. Citation on PubMed or Free article on PubMed Central
- van der Made CI, Hoorn EJ, de la Faille R, Karaaslan H, Knoers NV, Hoenderop JG, Vargas Poussou R, de Baaij JH. Hypomagnesemia as First Clinical Manifestation of ADTKD-HNF1B: A Case Series and Literature Review. Am J Nephrol. 2015;42(1):85-90. doi: 10.1159/000439286. Citation on PubMed
- Verhave JC, Bech AP, Wetzels JF, Nijenhuis T. Hepatocyte Nuclear Factor 1beta-Associated Kidney Disease: More than Renal Cysts and Diabetes. J Am Soc Nephrol. 2016 Feb;27(2):345-53. doi: 10.1681/ASN.2015050544. Epub 2015 Aug 28. Citation on PubMed or Free article on PubMed Central
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