Maturity-onset diabetes of the young (MODY) is a group of several conditions characterized by abnormally high levels of blood glucose, also called blood sugar. These forms of diabetes typically begin before age 30, although they can occur later in life. In MODY, elevated blood glucose arises from reduced production of insulin, which is a hormone produced in the pancreas that helps regulate blood glucose levels. Specifically, insulin controls how much glucose (a type of sugar) is passed from the blood into cells, where it is used as an energy source.

The different types of MODY are distinguished by their genetic causes. The most common types are HNF1A-MODY (also known as MODY3), accounting for 50 to 70 percent of cases, and GCK-MODY (MODY2), accounting for 30 to 50 percent of cases. Less frequent types include HNF4A-MODY (MODY1) and renal cysts and diabetes (RCAD) syndrome (also known as HNF1B-MODY or MODY5), which each account for 5 to 10 percent of cases. At least ten other types have been identified, and these are very rare.

HNF1A-MODY and HNF4A-MODY have similar signs and symptoms that develop slowly over time. Early signs and symptoms in these types are caused by high blood glucose and may include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, weight loss, and recurrent skin infections. Over time uncontrolled high blood glucose can damage small blood vessels in the eyes and kidneys. Damage to the light-sensitive tissue at the back of the eye (the retina) causes a condition known as diabetic retinopathy that can lead to vision loss and eventual blindness. Kidney damage (diabetic nephropathy) can lead to kidney failure and end-stage renal disease (ESRD). While these two types of MODY are very similar, certain features are particular to each type. For example, babies with HNF4A-MODY tend to weigh more than average or have abnormally low blood glucose at birth, even though other signs of the condition do not occur until childhood or young adulthood. People with HNF1A-MODY have a higher-than-average risk of developing noncancerous (benign) liver tumors known as hepatocellular adenomas.

GCK-MODY is a very mild type of the condition. People with this type have slightly elevated blood glucose levels, particularly in the morning before eating (fasting blood glucose). However, affected individuals often have no symptoms related to the disorder, and diabetes-related complications are extremely rare.

RCAD is associated with a combination of diabetes and kidney or urinary tract abnormalities (unrelated to the elevated blood glucose), most commonly fluid-filled sacs (cysts) in the kidneys. However, the signs and symptoms are variable, even within families, and not everyone with RCAD has both features. Affected individuals may have other features unrelated to diabetes, such as abnormalities of the pancreas or liver or a form of arthritis called gout.

MODY can be caused by a mutation in one of several genes. HNF1A-MODY, GCK-MODY, HNF4A-MODY, and RCAD, are caused by mutations in the HNF1A, GCK, HNF4A, and HNF1B gene, respectively. All of these genes provide instructions for making proteins involved in the production of insulin to control blood glucose levels in the body. In particular, the proteins are important in specialized cells in the pancreas called beta cells, which secrete insulin.

The proteins produced from the HNF1A, HNF4A, and HNF1B genes all act as transcription factors, which means they control the activity of other genes. In particular, these proteins regulate genes that direct the development and function of beta cells. HNF1A, HNF4A, or HNF1B gene mutations result in production of an altered transcription factor that is unable to function normally. These changes alter gene activity in cells, impairing normal beta cell development and function. As a result, beta cells are less able than normal to produce insulin in response to glucose in the blood, which means the body cannot control blood glucose. Elevated blood glucose results in the signs and symptoms of MODY. Some of these MODY-related genes play roles in the development of other body systems, in addition to beta cells. Disrupted development of these systems underlies additional signs and symptoms in particular forms of MODY. For example, the HNF1B gene is involved in kidney development, which helps explain the kidney abnormalities in people with RCAD.

The protein produced from the GCK gene acts as a sensor that recognizes when the amount of glucose in the blood rises. In response, the protein helps stimulate the release of insulin from beta cells so glucose can be taken up and used by cells for energy. This protein also helps determine when excess glucose should be taken into liver cells and stored. Mutations in the GCK gene limit the protein's ability to sense a rise in blood glucose, so levels remain elevated.

Other genes involved in controlling blood glucose cause rare types of MODY. It is likely that additional genes that have not been identified are also involved in the condition.

Normal Function

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 glucose levels. The closing of the channels results in a process that triggers insulin secretion by beta cells.

Health Conditions Related to Genetic Changes

Congenital hyperinsulinism

More than 300 mutations in the ABCC8 gene have been found to cause congenital hyperinsulinism. This condition causes frequent episodes of low blood glucose (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

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.

Maturity-onset diabetes of the young

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Other disorders

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, the most common form of diabetes. Other studies, however, have not found an association between ABCC8 gene variants and type 2 diabetes. 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, a combination of lifestyle, genetic, and environmental factors all play a part in determining the risk of this complex disorder.

Other Names for This Gene

• ABC36
• ABCC8_HUMAN
• ATP-binding cassette, sub-family C (CFTR/MRP), member 8
• ATP-binding cassette, sub-family C, member 8
• MRP8
• SUR
• SUR1
• TNDM2

Genomic Location

Normal Function

The GCK gene provides instructions for making a protein called glucokinase. This protein plays an important role in the breakdown of sugars (particularly glucose) in the body. Glucokinase is primarily found in the liver and in beta cells in the pancreas. Beta cells produce and release (secrete) the hormone insulin, which helps regulate blood glucose levels by controlling how much glucose is passed from the bloodstream into cells to be used as energy. Glucokinase acts as a sensor, recognizing when the level of glucose in the blood rises and helping stimulate the release of insulin from beta cells to control it. In the liver, glucokinase helps determine when excess glucose should be taken in and converted to glycogen, which is a major source of stored energy in the body.

Health Conditions Related to Genetic Changes

Maturity-onset diabetes of the young

Mutations in the GCK gene cause maturity-onset diabetes of the young (MODY), which is a group of conditions characterized by abnormally high blood glucose levels. This form of diabetes usually begins before age 30. GCK gene mutations cause a type known as GCK-MODY (also called MODY2). Affected individuals usually have mildly elevated blood glucose levels from birth, although they typically have no symptoms associated with the condition, and diabetes-related complications are extremely rare.

Most GCK gene mutations involved in GCK-MODY change single protein building blocks in the glucokinase protein or result in an abnormally short version of the protein. The altered protein may be broken down, or the function may be impaired, reducing glucokinase activity in cells. As a result, beta cells are less able to detect changes in blood glucose and release insulin to control it, so blood glucose remains elevated.

Congenital hyperinsulinism

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Gestational diabetes

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Permanent neonatal diabetes mellitus

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Other Names for This Gene

• ATP:D-glucose 6-phosphotransferase
• HEXOKINASE 4
• Hexokinase type IV
• HK4

Genomic Location

Normal Function

The HNF1A gene provides instructions for making a protein called hepatocyte nuclear factor-1 alpha (HNF-1α). The HNF-1α protein acts as a transcription factor, which means it attaches (binds) to specific regions of DNA and helps control the activity of certain genes. While this protein is found in several tissues and organs, it seems to be especially important in the pancreas and liver.

Regulation of gene activity by the HNF-1α protein is critical for the growth and development of 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. The HNF-1α protein also controls genes involved in liver development. By controlling genes that regulate cell growth and survival, the HNF-1α protein is thought to act as a tumor suppressor, which means that it helps prevent cells from growing and dividing too rapidly or in an uncontrolled way.

The structure of HNF-1α includes several important regions that help it carry out its functions. One of the regions, called the dimerization domain, is critical for protein interactions. This region allows HNF-1α proteins to interact with each other or with other proteins that have a similar structure, creating a two-protein unit (dimer) that functions as a transcription factor. Another region, known as the DNA binding domain, binds to specific areas of DNA, allowing the dimer to control gene activity.

Health Conditions Related to Genetic Changes

Maturity-onset diabetes of the young

Mutations in the HNF1A gene cause maturity-onset diabetes of the young (MODY), which is a group of conditions characterized by abnormally high blood glucose levels. This form of diabetes usually begins before age 30. HNF1A gene mutations cause the most common type of MODY, called HNF1A-MODY (also known as MODY3). Early symptoms are caused by high blood glucose and include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, weight loss, and recurrent skin infections. Over time, uncontrolled high blood glucose can lead to eye and kidney problems.

HNF1A gene mutations that cause HNF1A-MODY occur in one of the two copies of the gene in each cell. These mutations result in production of an altered HNF-1α protein that is unable to function normally. Some changes prevent the HNF-1α protein from forming dimers; others prevent the protein from entering the nucleus where it interacts with DNA; still others prevent the transcription factor from attaching to DNA to control gene activity. These changes interrupt transcription, altering gene activity in cells. As a result, beta cell development and function are impaired. The cells are less able than normal to produce insulin in response to glucose in the blood, which means blood glucose cannot be controlled. Elevated blood glucose results in the signs and symptoms of MODY.

Rarely, individuals with HNF1A-MODY develop one or more noncancerous (benign) liver tumors called hepatocellular adenomas. In these individuals, a mutation occurs in the second copy of the HNF1A gene in liver cells. This second mutation, called a somatic mutation, is not inherited. It is unclear how the mutations cause liver cells to grow uncontrollably and form tumors.

Congenital hyperinsulinism

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Type 1 diabetes

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Other disorders

Hepatocellular adenomas also occur in people without HNF1A-MODY (described above). In these individuals, the tumors are associated with somatic mutations in both copies of the HNF1A gene. While rare, hepatocellular adenomas occur in women more frequently than in men, and most affected individuals develop a single tumor. HNF1A-mutated hepatocellular adenomas (also known as H-HCA) account for about 30 to 40 percent of this type of liver tumor. The HNF1A gene mutations that cause these tumors severely reduce or eliminate the function of the HNF-1α protein in affected liver cells. It is unclear how loss of HNF-1α function causes cells to grow uncontrollably and form tumors.

Other Names for This Gene

• HNF1 Homeobox A Gene
• LFB1
• TCF1

Genomic Location

Normal Function

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 glucose 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 glucose in the blood, leading to diabetes. In the kidneys, altered HNF-1β activity results in the formation of cysts or other abnormalities.

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.

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.

Prostate cancer

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Other disorders

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

• FJHN
• hepatocyte nuclear factor 1B
• HNF-1-beta
• HNF-1B
• HNF1 beta A
• HNF1beta
• HNF2
• homeoprotein LFB3
• HPC11
• LF-B3
• LFB3
• TCF-2
• TCF2
• transcription factor 2, hepatic
• VHNF1

Genomic Location

Normal Function

The INS gene provides instructions for producing the hormone insulin, which is necessary for the control of glucose levels in the blood. Glucose is a simple sugar and the primary energy source for most cells in the body.

Insulin is produced in a precursor form called proinsulin, which consists of a single chain of protein building blocks (amino acids). The proinsulin chain is cut (cleaved) to form individual pieces called the A and B chains, which are joined together by connections called disulfide bonds to form insulin.

Health Conditions Related to Genetic Changes

Permanent neonatal diabetes mellitus

At least 10 mutations in the INS 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 glucose (hyperglycemia) within the first 6 months of life.

INS gene mutations that cause permanent neonatal diabetes mellitus change single protein building blocks (amino acids) in the protein sequence. These mutations are believed to disrupt the cleavage of the proinsulin chain or the binding of the A and B chains to form insulin, leading to impaired blood glucose control.

Maturity-onset diabetes of the young

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Type 1 diabetes

MedlinePlus Genetics provides information about Type 1 diabetes

Other disorders

Mutations in the INS gene can also cause other disorders involving insulin production and blood glucose control. Some individuals with INS gene mutations have increased levels of proinsulin in their blood (hyperproinsulinemia) and may also have impaired blood glucose control. INS gene mutations are also associated with a disorder called maturity-onset diabetes of the young (MODY). This term refers to hereditary forms of relatively mild diabetes mellitus caused by changes in single genes.

Other Names for This Gene

• IDDM2
• ILPR
• INS_HUMAN
• insulin preproprotein
• IRDN
• MODY10
• proinsulin

Genomic Location

Normal Function

The HNF4A gene provides instructions for making a protein called hepatocyte nuclear factor-4 alpha (HNF-4α). This protein plays an important role in the function of certain tissues and organs in the body. The HNF-4α protein acts as a transcription factor, which means it attaches (binds) to specific regions of DNA and helps control the activity of particular genes.

The HNF-4α protein controls genes that are especially important for development and function of 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. The HNF-4α protein also controls genes involved in normal liver functions.

The structure of the HNF-4α protein includes several important regions. One of the regions, called the dimerization domain, is critical for protein interactions. This region allows molecules of HNF-4α to interact with each other, creating a two-protein unit (dimer) that functions as a transcription factor. Another region, known as the DNA binding domain, binds to specific areas of DNA, allowing the dimer to control gene activity.

Health Conditions Related to Genetic Changes

Maturity-onset diabetes of the young

Mutations in the HNF4A gene cause maturity-onset diabetes of the young (MODY), which is a group of conditions characterized by abnormally high blood sugar levels. MODY usually begins before age 30. HNF4A gene mutations cause a type called HNF4A-MODY (also known as MODY1). Often babies with this condition are heavier than average when they are born, and they may have unusually low blood sugar levels. Symptoms of high blood sugar, which usually begin in childhood or early adulthood, include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, weight loss, and recurrent skin infections. Over time, uncontrolled high blood sugar can lead to eye and kidney problems.

HNF4A gene mutations result in production of an altered HNF-4α protein that is unable to function normally. Some changes prevent the HNF-4α protein from forming dimers; others prevent the attachment of additional proteins that aid in transcription; still others prevent the transcription factor from attaching to DNA to control gene activity. These changes interrupt transcription, altering gene activity in cells. As a result, beta cell development and function are impaired. The cells are less able than normal to produce insulin in response to sugar in the blood, which means blood sugar cannot be controlled. Elevated blood sugar results in the signs and symptoms of MODY.

Congenital hyperinsulinism

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Other Names for This Gene

• HEPATOCYTE NUCLEAR FACTOR 4-ALPHA
• HNF4-ALPHA
• HNF4A gene
• NR2A1
• Nuclear Receptor Subfamily 2, Group A, Member 1
• TCF14
• TRANSCRIPTION FACTOR 14, HEPATIC NUCLEAR FACTOR

Genomic Location

Normal Function

The KCNJ11 gene provides instructions for making parts (subunits) of the ATP-sensitive potassium (K-ATP) channel. Each K-ATP channel consists of eight subunits. Four subunits are produced from the KCNJ11 gene, and four are produced from another gene called ABCC8.

K-ATP channels are found in beta cells, which are cells in the pancreas that secrete the hormone insulin. The K-ATP channels are embedded in cell membranes, where they open and close in response to the amount of glucose in the bloodstream. Glucose is a simple sugar and the primary energy source for most cells in the body. Closure of the K-ATP channels in response to increased glucose triggers the release of insulin out of beta cells and into the bloodstream, which helps control blood glucose levels.

Health Conditions Related to Genetic Changes

Congenital hyperinsulinism

More than 30 mutations in the KCNJ11 gene have been found to cause congenital hyperinsulinism. This condition causes frequent episodes of low blood glucose (hypoglycemia), decreased energy, and irritability. Most of these mutations change single protein building blocks (amino acids) in the protein sequence, reducing or preventing activity of the K-ATP channels. Loss of K-ATP channel function leads 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

At least 30 mutations in the KCNJ11 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 glucose (hyperglycemia) within the first 6 months of life.

KCNJ11 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 glucose control.

Gestational diabetes

MedlinePlus Genetics provides information about Gestational diabetes

Maturity-onset diabetes of the young

MedlinePlus Genetics provides information about Maturity-onset diabetes of the young

Other disorders

Other KCNJ11 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 glucose 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, KCNJ11 gene mutations that cause transient neonatal diabetes mellitus also interfere with K-ATP channel closure and lead to a reduction in insulin secretion.

A normal variation (polymorphism) in the KCNJ11 gene is associated with an increased risk of type 2 diabetes, the most common form of diabetes. This variant leads to a change in the K-ATP channel, replacing the amino acid glutamic acid with the amino acid lysine at position 23, written as Glu23Lys or E23K. People with type 2 diabetes have hyperglycemia because the body does not respond correctly to the insulin secreted from beta cells. The same variant has also been associated with changes in the heart's response to stress, leading to an increased risk of heart failure. Although changes in the KCNJ11 gene can be associated with type 2 diabetes and heart failure, a combination of lifestyle, genetic, and environmental factors all play a part in determining the risk of these complex disorders.

Other Names for This Gene

• ATP-sensitive inward rectifier potassium channel 11
• beta-cell inward rectifier subunit
• BIR
• HHF2
• IKATP
• inward rectifier K(+) channel Kir6.2
• inwardly rectifying potassium channel KIR6.2
• KIR6.2
• MGC133230
• potassium channel, inwardly rectifying subfamily J member 11
• potassium channel, inwardly rectifying subfamily J, member 11
• potassium inwardly-rectifying channel, subfamily J, member 11
• TNDM3

Genomic Location

MODY is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Testing for monogenic diabetes involves providing a blood sample from which DNA is isolated. The DNA is analyzed for changes in the genes that cause monogenic diabetes. Abnormal results can determine the gene responsible for diabetes in a particular individual or show whether someone is likely to develop a monogenic form of diabetes in the future. Genetic testing can also be helpful in selecting the most appropriate treatment for individuals with monogenic diabetes. Prenatal testing can diagnose these conditions in unborn children. Most forms of monogenic diabetes are caused by dominant mutations, meaning that the condition can be passed on to children when only one parent is affected. In contrast, if the mutation is a recessive mutation, a disease gene must be inherited from both parents for diabetes to occur. For recessive forms of monogenic diabetes, testing can indicate whether parents or siblings without disease are carriers for recessive genetic conditions that could be inherited by their children.

If you suspect that you or a member of your family may have a monogenic form of diabetes, you should seek help from your health care professional or a genetic counselor. These healthcare professionals, who are familiar with your medical and family history, can determine whether genetic testing is appropriate, select the genetic tests that should be performed, and provide information about the basic principles of genetics, genetic testing options, and confidentiality issues. They also can review the test results and management options with you.

MODY is estimated to account for 1 to 3 percent of all cases of diabetes.