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SCN9A

SCN9A

Reviewed November 2012

What is the official name of the SCN9A gene?

The official name of this gene is “sodium channel, voltage gated, type IX alpha subunit.”

SCN9A is the gene's official symbol. The SCN9A gene is also known by other names, listed below.

Read more about gene names and symbols on the About page.

What is the normal function of the SCN9A gene?

The SCN9A gene belongs to a family of genes that provide instructions for making sodium channels. These channels, which transport positively charged sodium atoms (sodium ions) into cells, play a key role in a cell's ability to generate and transmit electrical signals.

The SCN9A gene provides instructions for making one part (the alpha subunit) of a sodium channel called NaV1.7. NaV1.7 sodium channels are found in nerve cells called nociceptors that transmit pain signals. Nociceptors are part of the peripheral nervous system, which connects the brain and spinal cord to cells that detect sensations such as touch, smell, and pain. Nociceptors are primarily involved in transmitting pain signals. The centers of nociceptors, known as the cell bodies, are located in a part of the spinal cord called the dorsal root ganglion. Fibers called axons extend from the cell bodies, reaching throughout the body to receive sensory information. Axons transmit the information back to the dorsal root ganglion, which then sends it to the brain. NaV1.7 sodium channels are also found in olfactory sensory neurons, which are nerve cells in the nasal cavity that transmit smell-related signals to the brain.

Does the SCN9A gene share characteristics with other genes?

The SCN9A gene belongs to a family of genes called SC (sodium channels).

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? in the Handbook.

How are changes in the SCN9A gene related to health conditions?

congenital insensitivity to pain - caused by mutations in the SCN9A gene

At least 13 mutations in the SCN9A gene have been found to cause congenital insensitivity to pain, a condition that inhibits the ability to perceive physical pain. The SCN9A gene mutations that cause congenital insensitivity to pain create a premature stop signal in the instructions for making the alpha subunit of the NaV1.7 sodium channel. As a result, a shortened, nonfunctional subunit is produced which cannot be incorporated into the channel, leading to a loss of functional NaV1.7 sodium channels. The loss of these channels impairs the transmission of pain signals from the site of injury to the brain, causing those affected to be insensitive to pain. Loss of this channel in olfactory sensory neurons likely impairs the transmission of smell-related signals to the brain, leading to a complete loss of the sense of smell (anosmia).

erythromelalgia - caused by mutations in the SCN9A gene

More than 10 mutations in the SCN9A gene have been found to cause erythromelalgia, a condition characterized by episodes of pain, redness, and swelling in various parts of the body, particularly the hands and feet. All identified mutations change one protein building block (amino acid) in the NaV1.7 sodium channel. These mutations result in a NaV1.7 sodium channel that opens more easily than usual and stays open longer than normal, increasing the flow of sodium ions that produce nerve impulses within nociceptors. This increase in sodium ions enhances transmission of pain signals, leading to the signs and symptoms of erythromelalgia.

paroxysmal extreme pain disorder - caused by mutations in the SCN9A gene

Approximately 10 mutations in the SCN9A gene have been found to cause paroxysmal extreme pain disorder. This condition is characterized by severe pain attacks accompanied by skin redness and warmth (flushing) and, sometimes, seizures and changes in breathing and heart rate. The mutations that cause this condition change single amino acids in the alpha subunit of the NaV1.7 sodium channel. As a result, the sodium channel does not completely close when it is turned off, allowing sodium ions to flow abnormally into nociceptors. This increase in sodium ions enhances transmission of pain signals, leading to the pain attacks experienced by people with paroxysmal extreme pain disorder.

small fiber neuropathy - caused by mutations in the SCN9A gene

Mutations in the SCN9A gene account for approximately 30 percent of cases of small fiber neuropathy, a condition characterized by severe pain attacks and a reduced ability to differentiate between hot and cold. The mutations that cause this condition change single amino acids in the alpha subunit of the NaV1.7 sodium channel. As a result of the altered alpha subunit, the sodium channel does not completely close when it is turned off, allowing sodium ions to flow abnormally into nociceptors. This increase in sodium ions enhances transmission of pain signals. In this condition, the small fibers that extend from the nociceptors and transmit pain signals (axons) degenerate over time. The cause of this degeneration is unknown, but it likely accounts for signs and symptoms such as the loss of temperature differentiation.

other disorders - caused by mutations in the SCN9A gene

At least three mutations in the SCN9A gene have been found in a group of people affected with febrile seizures, which are seizures that are triggered by a high fever. Febrile seizures are the most common type of seizures in young children, affecting 2 to 5 percent of children in Europe and North America. Children who have febrile seizures have a 2 to 9 percent chance of developing non-fever-related seizures later in life. When febrile seizures are associated with mutations in the SCN9A gene, the condition is known as familial febrile seizures 3B. If these individuals go on to develop seizures without fevers, the condition is then known as generalized epilepsy with febrile seizures plus, type 7. The mutations that cause these conditions change single amino acids in the alpha subunit of the NaV1.7 sodium channel. It is unknown how a change in the sodium channel leads to febrile seizures.

Variants in the SCN9A gene, when coupled with mutations in another gene called SCN1A, alter the progression of a seizure disorder called Dravet syndrome in some individuals. Dravet syndrome is characterized by convulsive seizures in infancy, followed in childhood by absence seizures, which cause loss of consciousness for short periods. In mid-childhood, the seizures change to the generalized tonic-clonic type, which involve muscle rigidity, convulsions, and loss of consciousness. Generalized tonic-clonic seizures are also associated with prolonged episodes of seizure activity known as nonconvulsive status epilepticus. These episodes can cause confusion and a loss of alertness lasting from hours to weeks. SCN1A gene mutations are the most common cause of Dravet syndrome, but when an affected individual also has a SCN9A gene change, which might not otherwise cause health problems, the signs and symptoms of Dravet syndrome are more severe. For example, individuals with both SCN1A and SCN9A gene changes may have status epilepticus in infancy and experience a variety of seizures at any time. It is unknown how SCN9A gene changes contribute to the signs and symptoms of Dravet syndrome.

Where is the SCN9A gene located?

Cytogenetic Location: 2q24

Molecular Location on chromosome 2: base pairs 166,195,184 to 166,375,986

The SCN9A gene is located on the long (q) arm of chromosome 2 at position 24.

The SCN9A gene is located on the long (q) arm of chromosome 2 at position 24.

More precisely, the SCN9A gene is located from base pair 166,195,184 to base pair 166,375,986 on chromosome 2.

See How do geneticists indicate the location of a gene? in the Handbook.

Where can I find additional information about SCN9A?

You and your healthcare professional may find the following resources about SCN9A 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 SCN9A gene or gene products?

  • hNE
  • Nav1.7
  • NENA
  • NE-NA
  • PN1
  • SCN9A_HUMAN
  • sodium channel, voltage-gated, type IX, alpha
  • sodium channel, voltage-gated, type IX, alpha polypeptide
  • sodium channel, voltage-gated, type IX, alpha subunit
  • voltage-gated sodium channel alpha subunit Nav1.7

Where can I find general information about genes?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding SCN9A?

acids ; action potential ; amino acid ; anosmia ; axons ; cell ; channel ; congenital ; differentiation ; epilepsy ; familial ; fever ; gene ; injury ; ions ; Na ; nervous system ; neuropathy ; nociceptors ; peripheral ; peripheral nervous system ; progression ; protein ; seizure ; sodium ; sodium channel ; status epilepticus ; subunit ; syndrome ; voltage

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

See also Understanding Medical Terminology.

References (19 links)

 

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? in the Handbook.

 
Reviewed: November 2012
Published: May 4, 2015