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SCN9A

sodium voltage-gated channel alpha subunit 9

The SCN9A gene provides instructions for a key component of the NaV1.7 sodium channel, vital for transmitting electrical signals in nerve cells, particularly those involved in pain sensation. SCN9A encodes the alpha subunit of the NaV1.7 sodium channel, primarily found in nociceptors and olfactory sensory neurons.

Chromosome 2q24.3 AD/AR HGNC:10597 Tier C
SCN9A 2q24.3 p arm q arm 2

SCN9A is located on the long (q) arm of chromosome 2, at band 2q24.3. Arm ratio per GRCh38 - banding schematic.

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Clinical tests that include this

Carrier Screening panel
SCN9A is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The SCN9A gene, formally known as sodium voltage-gated channel alpha subunit 9, is integral to the proper functioning of the nervous system. It provides the genetic blueprint for a crucial part of a sodium channel, NaV1.7. This channel is predominantly found in nerve cells responsible for detecting sensations like pain and smell. Understanding SCN9A is important for comprehending conditions that affect pain sensitivity and for pharmacogenomics, which explores how genes influence an individual's response to medications.

What the gene does

The SCN9A gene directs the synthesis of the alpha subunit of the NaV1.7 sodium channel. Sodium channels are pore-forming proteins embedded in cell membranes that control the flow of positively charged sodium ions into cells. This ion movement is fundamental to a cell's ability to create and propagate electrical signals. The NaV1.7 channel is particularly abundant in nociceptors, which are specialised nerve cells within the peripheral nervous system responsible for transmitting pain signals to the brain. These channels also contribute to the function of olfactory sensory neurons, which are involved in the sense of smell. By regulating sodium ion influx, the NaV1.7 channel dictates nerve excitability and the relay of sensory information.

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Chromosome location

The SCN9A gene is situated on the long arm of chromosome 2, specifically at position 2q24.3. This genomic location places it within a region that has been linked to various neurological conditions. The gene's position is consistent across the human population.

Protein structure

The SCN9A gene encodes a protein consisting of 1988 amino acids, known as NaV1.7. This protein features several key structural elements. It includes multiple disordered regions, such as those spanning amino acids 26-55, 461-543, 565-611, 1102-1148, and 1934-1988. The protein also contains four main repeat domains: I (amino acids 112-410), II (amino acids 726-989), III (amino acids 1180-1488), and IV (amino acids 1497-1795). Additionally, an IQ domain is present from amino acids 1889-1918.

Domain map · 1,988 amino acids
I (112–410)II (726–989)III (1180–1488)IV (1497–1795)IQ (1889–1918)I112–410III1180–1488IV1497–17951~9941,988
Repeat - repeating structural motif
Domain - independent functional unit
🧬 Explore 3D structure on AlphaFold
UniProt:Q15858Length:1,988 aaStructure:AlphaFold

Key variants

Genetic variations within the SCN9A gene can lead to alterations in the structure or function of the NaV1.7 sodium channel. These changes can impact how nerve cells transmit electrical signals, thereby influencing pain perception and other sensory functions. The inheritance pattern for conditions associated with SCN9A can be autosomal dominant or autosomal recessive.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for SCN9A.
View all on ClinVar →

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.258+1G>A
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Generalized epilepsy with febrile seizures plus, type 7
c.611_612dup
Duplication
 p.Val205fs Pathogenic/Likely pathogenic ★★☆☆ Neuropathy, hereditary sensory and autonomic, type 2A
c.829C>T
single nucleotide variant
 p.Arg277Ter Pathogenic/Likely pathogenic ★★☆☆ SCN9A-related disorder
g.(?_167085181)_(167168266_?)del
Deletion
 - Pathogenic ★☆☆☆ Generalized epilepsy with febrile seizures plus, type 7
c.102del
Deletion
 p.Glu34fs Pathogenic ★☆☆☆ Neuropathy, hereditary sensory and autonomic, type 2A
c.420C>A
single nucleotide variant
 p.Cys140Ter Pathogenic ★☆☆☆ Neuropathy, hereditary sensory and autonomic, type 2A
c.52C>T
single nucleotide variant
 p.Gln18Ter Pathogenic ★☆☆☆ Neuropathy, hereditary sensory and autonomic, type 2A
c.531T>A
single nucleotide variant
 p.Cys177Ter Pathogenic ★☆☆☆ Neuropathy, hereditary sensory and autonomic, type 2A
c.722C>A
single nucleotide variant
 p.Ser241Ter Pathogenic ★☆☆☆ Neuropathy, hereditary sensory and autonomic, type 2A
c.900delA
Deletion
 p.Lys301fs Pathogenic ★☆☆☆ Neuropathy, hereditary sensory and autonomic, type 2A

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

Variations in the SCN9A gene are linked to a spectrum of conditions primarily affecting pain sensation. These include congenital insensitivity to pain (SCN9A), a rare autosomal recessive disorder where individuals cannot feel physical pain. Autosomal dominant conditions associated with SCN9A variants include erythromelalgia (primary), characterised by intense burning pain in the extremities, paroxysmal extreme pain disorder, involving severe pain attacks, and small fibre neuropathy (SCN9A/SCN10A/SCN11A), which impacts nerve fibres responsible for pain and temperature sensation.

Inheritance pattern

Conditions caused by pathogenic SCN9A variants typically follow ad/ar inheritance.

♀ Affected parent 1 altered copy ♂ Unaffected parent 2 typical copies Affected Unaffected Unaffected Affected Affected Carrier Unaffected Circles = females · Squares = males

Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.

Carrier frequency by population How common is heterozygous SCN9A carrier status across ancestry groups?

UK clinical status

The SCN9A gene is included in several Green RAG (Red Amber Green) rated panels within the NHS Genomic Medicine Service's PanelApp, indicating its established clinical utility in the UK. It is relevant for hereditary neuropathy, hereditary neuropathy or pain disorder (R78), pain syndromes, familial dysautonomia, and vascular skin disorders (R326).

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Hereditary neuropathy or pain disorder · R78 NHS GMS → Vascular skin disorders · R326 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 SCN9A gene?

The SCN9A gene provides instructions for the alpha subunit of the NaV1.7 sodium channel. This channel is crucial for transmitting electrical signals in nerve cells, particularly nociceptors, which are involved in pain sensation.

Which conditions are linked to variations in SCN9A?

Variations in the SCN9A gene are associated with several pain-related conditions, including congenital insensitivity to pain, erythromelalgia (primary), paroxysmal extreme pain disorder, and small fibre neuropathy.

Is SCN9A relevant for pharmacogenomics?

Yes, SCN9A is classified under pharmacogenomics, meaning that genetic variations in this gene can influence an individual's response to certain medications, especially those targeting pain pathways.

References

  1. Faber CG, Hoeijmakers JG, Ahn HS. Gain of function Naν1.7 mutations in idiopathic small fiber neuropathy. Annals of neurology. 2012. PMID: 21698661
  2. Houlden H. Extending the clinical spectrum of pain channelopathies. Brain : a journal of neurology. 2012. PMID: 22345085
  3. Hoeijmakers JG, Merkies IS, Gerrits MM. Genetic aspects of sodium channelopathy in small fiber neuropathy. Clinical genetics. 2012. PMID: 22803682
  4. Waxman SG. Neuroscience: Channelopathies have many faces. Nature. 2011. PMID: 21490662
  5. Doty CN. SCN9A: another sodium channel excited to play a role in human epilepsies. Clinical genetics. 2010. PMID: 20095983
  6. Lampert A, O'Reilly AO, Reeh P. Sodium channelopathies and pain. Pflugers Archiv : European journal of physiology. 2010. PMID: 20101409
  7. Fischer TZ, Waxman SG. Familial pain syndromes from mutations of the NaV1.7 sodium channel. Annals of the New York Academy of Sciences. 2010. PMID: 20146699
  8. Meisler MH, O'Brien JE, Sharkey LM. Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects. The Journal of physiology. 2010. PMID: 20351042
  9. Singh NA, Pappas C, Dahle EJ. A role of SCN9A in human epilepsies, as a cause of febrile seizures and as a potential modifier of Dravet syndrome. PLoS genetics. 2009. PMID: 19763161
  10. Young FB. When adaptive processes go awry: gain-of-function in SCN9A. Clinical genetics. 2008. PMID: 18070139
  11. Dib-Hajj SD, Yang Y, Waxman SG. Genetics and molecular pathophysiology of Na(v)1.7-related pain syndromes. Advances in genetics. 2008. PMID: 19185186
  12. Goldberg YP, MacFarlane J, MacDonald ML. Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations. Clinical genetics. 2007. PMID: 17470132
  13. Fertleman CR, Ferrie CD, Aicardi J. Paroxysmal extreme pain disorder (previously familial rectal pain syndrome). Neurology. 2007. PMID: 17679678
  14. Dib-Hajj SD, Cummins TR, Black JA. From genes to pain: Na v 1.7 and human pain disorders. Trends in neurosciences. 2007. PMID: 17950472
  15. Drenth JP, Waxman SG. Mutations in sodium-channel gene SCN9A cause a spectrum of human genetic pain disorders. The Journal of clinical investigation. 2007. PMID: 18060017
  16. Waxman SG. Neurobiology: a channel sets the gain on pain. Nature. 2006. PMID: 17167466
  17. Cox JJ, Reimann F, Nicholas AK. An SCN9A channelopathy causes congenital inability to experience pain. Nature. 2006. PMID: 17167479
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 4 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .