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ABCC8

ATP binding cassette subfamily C member 8

The ABCC8 gene provides instructions for a key component of ATP-sensitive potassium (KATP) channels, which are crucial for regulating insulin secretion in pancreatic beta cells. The ABCC8 gene encodes a subunit of the ATP-sensitive potassium (KATP) channels, found in the beta cells of the pancreas.

Chromosome 11p15.1 Autosomal recessive HGNC:59 Tier C
ABCC8 11p15.1 p arm q arm 11

ABCC8 is located on the short (p) arm of chromosome 11, at band 11p15.1. Arm ratio per GRCh38 - banding schematic.

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Clinical tests that include this

Carrier Screening panel
ABCC8 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions
Newborn Genetic Screening panel
ABCC8 is 1 of 258 genes on this panel
Genomic newborn screening for actionable paediatric conditions

Overview

The ABCC8 gene, also known as ATP binding cassette subfamily C member 8, is fundamental for the proper functioning of pancreatic beta cells. It is responsible for producing a part of the ATP-sensitive potassium (KATP) channels, which are critical for maintaining healthy blood glucose levels. Disruptions in this gene can lead to conditions characterised by either too much or too little insulin secretion.

What the gene does

The ABCC8 gene provides the genetic blueprint for one subunit of the ATP-sensitive potassium (KATP) channels. These channels are embedded within the cell membranes of pancreatic beta cells, which are specialised cells responsible for producing and releasing insulin. KATP channels are composed of eight subunits in total, with four derived from the ABCC8 gene and four from the KCNJ11 gene. They regulate insulin secretion in response to blood glucose levels; when glucose levels are high, the KATP channels close, triggering the release of insulin into the bloodstream. This mechanism is essential for controlling blood glucose levels and maintaining metabolic homeostasis.

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Chromosome location

The ABCC8 gene is located on chromosome 11, specifically at position 11p15.1. This precise genomic address helps in understanding its inheritance patterns and its relationship to other genes in the region.

Protein structure

The ABCC8 protein is 1581 amino acids long and contains several distinct domains. It features an ABC transmembrane type-1 1 domain (amino acids 299-602) and an ABC transporter 1 domain (amino acids 679-929). A disordered region is found between amino acids 935-987, followed by an ABC transmembrane type-1 2 domain (amino acids 1012-1306) and a second ABC transporter 2 domain (amino acids 1344-1578).

Domain map · 1,581 amino acids
ABC transmembrane type-1 1 (299–602)ABC transporter 1 (679–929)ABC transmembrane type-1 2 (1012–1306)ABC transporter 2 (1344–1578)ABC transmembrane type299–602ABC transporter 1679–929ABC transmembrane type1012–13061~7911,581
Domain - independent functional unit
🧬 Explore 3D structure on AlphaFold
UniProt:Q09428Length:1,581 aaStructure:AlphaFold

Key variants

Variants within the ABCC8 gene can alter the function of the ATP-sensitive potassium channels. These genetic changes may affect the protein's structure or its ability to regulate insulin release, leading to various health conditions. The impact of a variant often depends on its specific location and the type of change it causes in the gene sequence.

2,941
Total variants catalogued in ClinVar
View all on ClinVar →
477 Pathogenic / Likely pathogenic 797 Uncertain significance 1,276 Benign / Likely benign 391 Conflicting or other

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1176+2T>C
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Familial hyperinsulinism
c.1254_1284dup
Duplication
 p.Met429Ter Pathogenic ★★☆☆ Hyperinsulinemic hypoglycemia, familial, 1
c.1290G>A
single nucleotide variant
 p.Trp430Ter Pathogenic/Likely pathogenic ★★☆☆ Hyperinsulinemic hypoglycemia, familial, 1
c.1330C>T
single nucleotide variant
 p.Gln444Ter Pathogenic ★★☆☆ Hyperinsulinemic hypoglycemia, familial, 1
c.1332G>T
single nucleotide variant
 p.Gln444His Pathogenic/Likely pathogenic ★★☆☆ not provided
c.1333-1013A>G
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Hyperinsulinemic hypoglycemia, familial, 1
c.1347_1348del
Deletion
 p.Ile450fs Pathogenic ★★☆☆ Hyperinsulinemic hypoglycemia, familial, 1
c.1473T>G
single nucleotide variant
 p.Tyr491Ter Pathogenic ★★☆☆ Hereditary hyperinsulinism
c.148+1G>A
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Hyperinsulinemic hypoglycemia, familial, 1
c.1501G>A
single nucleotide variant
 p.Glu501Lys Pathogenic/Likely pathogenic ★★☆☆ Hyperinsulinemic hypoglycemia, familial, 1

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the ABCC8 gene are primarily associated with conditions affecting insulin secretion. These include congenital hyperinsulinism, which can manifest as either diffuse or focal KATP-related forms, leading to episodes of dangerously low blood glucose. Conversely, certain ABCC8 variants can also cause various forms of diabetes, such as permanent neonatal diabetes mellitus and transient neonatal diabetes mellitus, both characterised by issues with blood glucose regulation.

Inheritance pattern

Conditions caused by pathogenic ABCC8 variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous ABCC8 carrier status across ancestry groups?

UK clinical status

The ABCC8 gene is included in several NHS Genomic Medicine Service national test panels. These panels cover conditions such as Congenital hyperinsulinism (green, R144), Monogenic diabetes (green, R141), Neonatal diabetes (green, R143), and Diabetes with additional phenotypes suggestive of a monogenic aetiology (green). It is also part of the small panel for Neonatal diabetes (green, R143.1), Familial diabetes (green), and Pulmonary arterial hypertension (green, R188).

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Congenital hyperinsulinism · R144 NHS GMS → Monogenic diabetes · R141 NHS GMS → Neonatal diabetes · R143 NHS GMS → Neonatal diabetes - small panel · R143.1 NHS GMS → Pulmonary arterial hypertension · R188 NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the primary role of the ABCC8 gene?

The ABCC8 gene provides instructions for making a crucial part of the ATP-sensitive potassium (KATP) channels in pancreatic beta cells. These channels are essential for regulating the release of insulin, which helps control blood glucose levels.

What conditions are associated with ABCC8 gene variants?

Variants in the ABCC8 gene are linked to conditions affecting insulin secretion, including congenital hyperinsulinism, which causes low blood glucose, and various forms of monogenic diabetes, such as permanent and transient neonatal diabetes mellitus.

How does ABCC8 relate to blood glucose control?

The KATP channels, formed in part by the ABCC8 protein, control when pancreatic beta cells release insulin. When blood glucose is high, these channels close, prompting insulin release to lower glucose levels, thus maintaining metabolic balance.

References

  1. Bennett K, James C, Hussain K. Pancreatic β-cell KATP channels: Hypoglycaemia and hyperglycaemia. Reviews in endocrine & metabolic disorders. 2010. PMID: 20878482
  2. Edghill EL, Flanagan SE, Ellard S. Permanent neonatal diabetes due to activating mutations in ABCC8 and KCNJ11. Reviews in endocrine & metabolic disorders. 2010. PMID: 20922570
  3. Flanagan SE, Clauin S, Bellanné-Chantelot C. 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. Human mutation. 2009. PMID: 18767144
  4. Sandal T, Laborie LB, Brusgaard K. The spectrum of ABCC8 mutations in Norwegian patients with congenital hyperinsulinism of infancy. Clinical genetics. 2009. PMID: 19475716
  5. Pinney SE, MacMullen C, Becker S. Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations. The Journal of clinical investigation. 2008. PMID: 18596924
  6. Flanagan SE, Patch AM, Mackay DJ. Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood. Diabetes. 2007. PMID: 17446535
  7. Ellard S, Flanagan SE, Girard CA. Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects. American journal of human genetics. 2007. PMID: 17668386
  8. 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. Human mutation. 2006. PMID: 16416420
  9. Huopio H, Shyng SL, Otonkoski T. K(ATP) channels and insulin secretion disorders. American journal of physiology. Endocrinology and metabolism. 2002. PMID: 12110524
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 18 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .