SCN9A Gene: Sodium Voltage-Gated Channel Alpha Subunit 9
Genetic insights into pain perception and sensory neuron function
Gene Information Card
| Symbol | SCN9A |
|---|---|
| Full Name | Sodium voltage-gated channel alpha subunit 9 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q24.3 |
| NCBI Gene ID | 6335 ncbi.nlm.nih.gov/gene/6335 |
| Ensembl ID | ENSG00000169432 |
| UniProt ID | Q15858 |
| OMIM ID | 603415 |
| HGNC ID | 10597 |
| Aliases | Nav1.7, NE-NA, ETHA, PN1, SFNP |
Description
The SCN9A gene encodes the alpha subunit of the voltage-gated sodium channel Nav1.7, which is highly expressed in nociceptive neurons of the dorsal root ganglia and sympathetic ganglia. This channel plays a critical role in the initiation and propagation of action potentials in pain pathways. Mutations in SCN9A are associated with several pain disorders, including congenital insensitivity to pain (loss-of-function) and inherited erythromelalgia (gain-of-function).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital insensitivity to pain (CIP) | Loss-of-function mutations result in non-functional Nav1.7 channels, abolishing pain signaling. | OMIM 243000; ClinVar |
| Paroxysmal extreme pain disorder (PEPD) | Gain-of-function mutations cause hyperexcitability of nociceptors, leading to episodic pain. | OMIM 167400; ClinVar |
| Inherited erythromelalgia (IEM) | Gain-of-function mutations lower the activation threshold of Nav1.7, causing burning pain and redness. | OMIM 133020; ClinVar |
| Small fiber neuropathy (SFN) | Some gain-of-function mutations are associated with SFN, presenting with burning pain and autonomic symptoms. | ClinVar; PMID 22961002 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Dorsal root ganglia | High | nTPM not available; high expression in nociceptors |
| Sympathetic ganglia | High | nTPM not available; high expression in sympathetic neurons |
| Brain | Low | nTPM not available; low expression in CNS |
| Testis | Low | nTPM not available; low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | Not specified | Endogenous expression; used in pain research |
| PC12 (pheochromocytoma) | Not specified | Endogenous expression; neuronal differentiation model |
| HEK293 (transfected) | Not specified | Commonly used for heterologous expression of Nav1.7 |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R896Q | Missense | Rare | Gain-of-function; associated with IEM |
| I228M | Missense | Rare | Gain-of-function; associated with IEM |
| W153R | Missense | Rare | Loss-of-function; associated with CIP |
| R185H | Missense | Rare | Gain-of-function; associated with PEPD |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in SCN9A typically result in truncated or non-functional Nav1.7 channels, leading to congenital insensitivity to pain (CIP). These mutations are often nonsense, frameshift, or splice-site variants that abolish channel function.
Gain of Function (GOF)
Gain-of-function mutations enhance channel activity by shifting activation to more negative potentials, slowing inactivation, or increasing ramp currents. This leads to hyperexcitability of nociceptors and conditions like inherited erythromelalgia and paroxysmal extreme pain disorder.
Dominant Negative (DN)
Dominant-negative effects are less common but have been reported for some SCN9A mutations, where the mutant subunit interferes with the function of the wild-type channel, potentially contributing to pain disorders.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated sodium channel activity | • sodium ion transmembrane transport |
| • ion channel activity | • plasma membrane |
| • response to pain |
Pathways
• Voltage-gated sodium channel complex
• Nociception pathway
• Pain signaling pathway
Protein Summary
The Nav1.7 protein is a large, pore-forming alpha subunit that forms a functional sodium channel with auxiliary beta subunits. It is composed of four homologous domains (I-IV), each with six transmembrane segments. The channel is responsible for the rapid depolarization phase of action potentials in peripheral sensory neurons. Nav1.7 is a key target for analgesic drug development due to its selective expression in pain pathways.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SCN9A Knockout HEK293 Cell Line | EDJ-KQ3932 | Human | 6335 | Details Get a Quote |
| SCN9A Knockout A-549 Cell Line | EDJ-KQ26170 | Human | 6335 | Details Get a Quote |
| SCN9A Knockout HeLa Cell Line | EDJ-KQ24825 | Human | 6335 | Details Get a Quote |
| SCN9A Knockout HCT 116 Cell Line | EDJ-KQ71361 | Human | 6335 | Details Get a Quote |
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