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Genetics Home Reference: your guide to understanding genetic conditions
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ABCC8

Reviewed January 2014

What is the official name of the ABCC8 gene?

The official name of this gene is “ATP-binding cassette, sub-family C (CFTR/MRP), member 8.”

ABCC8 is the gene's official symbol. The ABCC8 gene is also known by other names, listed below.

What is the normal function of the ABCC8 gene?

The ABCC8 gene provides instructions for making the sulfonylurea receptor 1 (SUR1) protein. The SUR1 protein is one part (subunit) of the ATP-sensitive potassium (K-ATP) channel that is found across cell membranes in the beta cells of the pancreas. Beta cells secrete insulin, which is a hormone that helps control blood sugar levels. Insulin controls how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy. The K-ATP channel controls the secretion of insulin out of beta cells and into the bloodstream. These channels open and close in response to the amount of glucose in the bloodstream, which helps regulate insulin secretion and control blood sugar levels. The closing of the channels results in a process that triggers insulin secretion by beta cells.

Does the ABCC8 gene share characteristics with other genes?

The ABCC8 gene belongs to a family of genes called ABC (ATP-binding cassette transporters).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the ABCC8 gene related to health conditions?

congenital hyperinsulinism - caused by mutations in the ABCC8 gene

More than 300 mutations in the ABCC8 gene have been found to cause congenital hyperinsulinism. This condition causes frequent episodes of low blood sugar (hypoglycemia), decreased energy, and irritability. Most of these mutations change single protein building blocks (amino acids) in the SUR1 protein.

Some ABCC8 mutations prevent the SUR1 protein from reaching the cell membrane, interfering with the proper formation of the K-ATP channel. Other mutations interfere with the K-ATP channel's function or its responses to outside molecules. Defective K-ATP channels lead to the constant release of insulin from beta cells. As a result, glucose is rapidly removed from the bloodstream. Without treatment, the hypoglycemia caused by congenital hyperinsulinism may result in serious complications such as intellectual disability and seizures.

permanent neonatal diabetes mellitus - caused by mutations in the ABCC8 gene

At least 14 mutations in the ABCC8 gene have been identified in people with permanent neonatal diabetes mellitus. Individuals with this condition often have a low birth weight and develop increased blood sugar (hyperglycemia) within the first 6 months of life.

ABCC8 gene mutations that cause permanent neonatal diabetes mellitus change single amino acids in the protein sequence. These mutations result in K-ATP channels that do not close, leading to reduced insulin secretion from beta cells and impaired blood sugar control.

other disorders - associated with the ABCC8 gene

Other ABCC8 gene mutations that have a relatively mild effect on K-ATP channel function as compared to that seen in permanent neonatal diabetes mellitus (see above) cause a condition called transient neonatal diabetes mellitus. Infants with this condition have hyperglycemia during the first 6 months of life, but their blood sugar returns to normal by age 18 months. However, affected individuals usually develop hyperglycemia again during adolescence or early adulthood. As in permanent neonatal diabetes mellitus, ABCC8 gene mutations that cause transient neonatal diabetes mellitus interfere with K-ATP channel closure and lead to a reduction in insulin secretion.

Some studies suggest that normal variations (polymorphisms) in the ABCC8 gene are associated with an increased risk of type 2 diabetes mellitus, the most common form of diabetes. Other studies, however, have not found an association between ABCC8 gene variants and type 2 diabetes mellitus. People with this disease have hyperglycemia because the body does not respond correctly to the insulin secreted from beta cells. Although changes in the ABCC8 gene may be associated with type 2 diabetes mellitus, a combination of lifestyle, genetic, and environmental factors all play a part in determining the risk of this complex disorder.

Where is the ABCC8 gene located?

Cytogenetic Location: 11p15.1

Molecular Location on chromosome 11: base pairs 17,392,884 to 17,476,844

The ABCC8 gene is located on the short (p) arm of chromosome 11 at position 15.1.

The ABCC8 gene is located on the short (p) arm of chromosome 11 at position 15.1.

More precisely, the ABCC8 gene is located from base pair 17,392,884 to base pair 17,476,844 on chromosome 11.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about ABCC8?

You and your healthcare professional may find the following resources about ABCC8 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the ABCC8 gene or gene products?

  • ABC36
  • ABCC8_HUMAN
  • ATP-binding cassette, sub-family C, member 8
  • MRP8
  • SUR
  • SUR1
  • TNDM2

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding ABCC8?

acids ; ATP ; cell ; cell membrane ; channel ; congenital ; diabetes ; diabetes mellitus ; disability ; gene ; glucose ; hormone ; hyperglycemia ; hyperinsulinism ; hypoglycemia ; insulin ; neonatal ; pancreas ; potassium ; protein ; protein sequence ; receptor ; secretion ; subunit ; transient

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Bennett K, James C, Hussain K. Pancreatic β-cell KATP channels: Hypoglycaemia and hyperglycaemia. Rev Endocr Metab Disord. 2010 Sep;11(3):157-63. doi: 10.1007/s11154-010-9144-2. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20878482?dopt=Abstract)
  • Edghill EL, Flanagan SE, Ellard S. Permanent neonatal diabetes due to activating mutations in ABCC8 and KCNJ11. Rev Endocr Metab Disord. 2010 Sep;11(3):193-8. doi: 10.1007/s11154-010-9149-x. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20922570?dopt=Abstract)
  • Ellard S, Flanagan SE, Girard CA, Patch AM, Harries LW, Parrish A, Edghill EL, Mackay DJ, Proks P, Shimomura K, Haberland H, Carson DJ, Shield JP, Hattersley AT, Ashcroft FM. Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects. Am J Hum Genet. 2007 Aug;81(2):375-82. Epub 2007 Jun 29. (http://www.ncbi.nlm.nih.gov/pubmed/17668386?dopt=Abstract)
  • Flanagan SE, Clauin S, Bellanné-Chantelot C, de Lonlay P, Harries LW, Gloyn AL, Ellard S. Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism. Hum Mutat. 2009 Feb;30(2):170-80. doi: 10.1002/humu.20838. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18767144?dopt=Abstract)
  • Flanagan SE, Patch AM, Mackay DJ, Edghill EL, Gloyn AL, Robinson D, Shield JP, Temple K, Ellard S, Hattersley AT. Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood. Diabetes. 2007 Jul;56(7):1930-7. Epub 2007 Apr 19. Erratum in: Diabetes. 2008 Feb;57(2):523. (http://www.ncbi.nlm.nih.gov/pubmed/17446535?dopt=Abstract)
  • Gloyn AL, Siddiqui J, Ellard S. Mutations in the genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) in diabetes mellitus and hyperinsulinism. Hum Mutat. 2006 Mar;27(3):220-31. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16416420?dopt=Abstract)
  • Huopio H, Shyng SL, Otonkoski T, Nichols CG. K(ATP) channels and insulin secretion disorders. Am J Physiol Endocrinol Metab. 2002 Aug;283(2):E207-16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12110524?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/6833)
  • OMIM: ATP-BINDING CASSETTE, SUBFAMILY C, MEMBER 8 (http://omim.org/entry/600509)
  • Pinney SE, MacMullen C, Becker S, Lin YW, Hanna C, Thornton P, Ganguly A, Shyng SL, Stanley CA. Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations. J Clin Invest. 2008 Aug;118(8):2877-86. doi: 10.1172/JCI35414. (http://www.ncbi.nlm.nih.gov/pubmed/18596924?dopt=Abstract)
  • Sandal T, Laborie LB, Brusgaard K, Eide SA, Christesen HB, Søvik O, Njølstad PR, Molven A. The spectrum of ABCC8 mutations in Norwegian patients with congenital hyperinsulinism of infancy. Clin Genet. 2009 May;75(5):440-8. (http://www.ncbi.nlm.nih.gov/pubmed/19475716?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: January 2014
Published: July 28, 2014