SCN11A Gene: Structure, Function, and Clinical Significance
A comprehensive guide to the sodium voltage-gated channel alpha subunit 11, its role in pain perception, and associated disorders.
Gene Information Card
| Symbol | SCN11A |
|---|---|
| Full Name | sodium voltage-gated channel alpha subunit 11 |
| Gene Type | protein coding |
| Chromosomal Location | 3p22.2 |
| NCBI Gene ID | 11280 ncbi.nlm.nih.gov/gene/11280 |
| Ensembl ID | ENSG00000168356 |
| UniProt ID | Q9UI33 |
| OMIM ID | 604385 |
| HGNC ID | 10583 |
| Aliases | Nav1.9, SCN12A, SNS2, NaN |
Description
The SCN11A gene encodes the alpha subunit of the voltage-gated sodium channel Nav1.9, which is primarily expressed in nociceptive sensory neurons. This channel plays a critical role in the generation and propagation of action potentials in pain pathways, particularly in the setting of inflammation. Mutations in SCN11A are associated with various pain disorders, including hereditary sensory and autonomic neuropathies and episodic pain syndromes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary sensory and autonomic neuropathy type VII (HSAN7) | Gain-of-function mutations lead to increased channel activity, causing hyperexcitability of nociceptors and impaired development of pain sensation. | OMIM #615548; PMID: 23817550 |
| Familial episodic pain syndrome (FEPS) | Gain-of-function mutations enhance channel activity, leading to episodic severe pain episodes. | OMIM #615552; PMID: 23817549 |
| Congenital insensitivity to pain (CIP) | Loss-of-function mutations reduce channel function, resulting in diminished pain perception. | OMIM #243000; PMID: 23817550 |
| Small fiber neuropathy | Gain-of-function mutations may contribute to peripheral nerve hyperexcitability and neuropathic pain. | PMID: 25316600 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Dorsal root ganglion | High | Predominant expression in nociceptive neurons |
| Trigeminal ganglion | High | Expression in sensory neurons |
| Spinal cord | Low | Minimal expression |
| Brain | Low | Very low expression |
| Testis | Low | Low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | Low | Low expression; not a primary model for Nav1.9 |
| PC-12 (pheochromocytoma) | Low | Low expression; neuronal differentiation may increase |
| HEK293 (embryonic kidney) | Not detected | Used for heterologous expression studies |
| ND7/23 (DRG-derived hybrid) | Moderate | Often used for electrophysiological studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg225Cys | Missense | Rare | Gain-of-function; associated with HSAN7 |
| p.Arg225Ser | Missense | Rare | Gain-of-function; associated with HSAN7 |
| p.Leu811Pro | Missense | Rare | Gain-of-function; associated with FEPS |
| p.Ile381Thr | Missense | Rare | Gain-of-function; associated with small fiber neuropathy |
| p.Val1185Leu | Missense | Rare | Loss-of-function; associated with CIP |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations reduce or abolish Nav1.9 channel activity, leading to impaired pain signaling and congenital insensitivity to pain.
Gain of Function (GOF)
Gain-of-function mutations increase channel activity, causing hyperexcitability of nociceptors and resulting in pain syndromes such as HSAN7 and FEPS.
Dominant Negative (DN)
No dominant-negative mutations have been reported for SCN11A.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated sodium channel activity | • sodium ion binding |
| • ion channel activity | • plasma membrane |
| • integral component of plasma membrane | • action potential propagation |
| • sensory perception of pain | • response to pain |
Pathways
• Voltage-gated sodium channel complex
• Nociception
• Pain signaling
• Inflammatory response
Protein Summary
The Nav1.9 protein is a large, multi-domain alpha subunit that forms a functional sodium channel when associated with auxiliary beta subunits. It is characterized by a tetrodotoxin-resistant (TTX-R) sodium current with slow kinetics and a hyperpolarized activation threshold, making it crucial for setting the resting membrane potential and amplifying subthreshold stimuli in nociceptors. Nav1.9 is involved in inflammatory pain sensitization and is a potential target for analgesic drugs.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SCN11A Knockout HEK293 Cell Line | EDJ-KQ7360 | Human | 11280 | Details Get a Quote |
| SCN11A Knockout HeLa Cell Line | EDJ-KQ55624 | Human | 11280 | Details Get a Quote |
| SCN11A Knockout A-549 Cell Line | EDJ-KQ64123 | Human | 11280 | Details Get a Quote |
| SCN11A Knockout HCT 116 Cell Line | EDJ-KQ72567 | Human | 11280 | Details Get a Quote |
| Scn11a Overexpression CHO-K1 Stable Cell Line | EDC90621 | Chinese hamster | 100755682 | Details Get a Quote |
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