SCN1A

Key takeaways

SCN1A belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect SCN1A to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of SCN1A from memory before moving on to harder problems.

Reference excerpt

Sodium channel protein type 1 subunit alpha (SCN1A), is a protein which in humans is encoded by the SCN1A gene.

Gene location The SCN1A gene is located on chromosome 2 of humans, and is made up of 26 exons spanning a total length of 6030 nucleotide base pairs. Alternative splicing of exon 5 gives rise to two alternate exons. SCN1A contains a poison exon within intron 20. The promoter has been identified 2.5 kilobase pairs upstream of the transcription start site, and the 5'- untranslated exons may enhance expression of the SCN1A gene in SH-SY5Y cells, a human cell line derived from a neuroblastoma.

Function The vertebrate sodium channel is a voltage-gated ion channel essential for the generation and propagation of action potentials, chiefly in nerve and muscle. Voltage-sensitive sodium channels are heteromeric complexes consisting of a large central pore-forming glycosylated alpha subunit and 2 smaller auxiliary beta subunits. Functional studies have indicated that the transmembrane alpha subunit of the brain sodium channels is sufficient for expression of functional sodium channels. Brain sodium channel alpha subunits form a gene subfamily with several structurally distinct isoforms clustering on chromosome 2q24, types I, II (Nav1.2), and III (Nav1.3). There are also several distinct sodium channel alpha subunit isoforms in skeletal and cardiac muscle (Nav1.4 and Nav1.5, respectively). The SCN1A gene codes for the alpha subunit of the voltage-gated sodium ion channel making it a member of ten paralogous gene families which code for the voltage-gated sodium transmembrane proteins NaV1.1. Within the family of genes which code for other portions of voltage-gated sodium channels, the SCN1A mutations were the first identified, since mutations to this gene caused epilepsy and febrile seizures. Indeed, the SCN1A gene is one of the most commonly mutated genes in the human genome associated with epilepsy, which has given it the title of a 'super culprit gene'. There are 900 distinct mutations reported for the SCN1A gene, approximately half of the reported mutations are truncations which result in no protein. The remaining half of mutations are missense mutations, which are predicted to either cause loss-of-function or gain-of-function, though very few have been tested for functionality in the lab. Subtle differences in voltage-gated sodium ion channels can have devastating physiological effects and underlie abnormal neurological functioning. Mutations to the SCN1A gene most often result in different forms of seizure disorders, the most common forms of seizure disorders are Dravet Syndrome (DS), Intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC), and severe myoclonic epilepsy borderline (SMEB). Clinically, 70-80% of patients with DS have identified mutations specific to the SCN1A gene, which are caused by de novo heterozygous mutations of the SCN1A gene. There are currently two databases on SCN1A mutations. Mice with knock-in SCN1A mutations, who are model organisms for DS quickly develop seizures, indicative of a significant reduction in the function of NaV1.1. It has been hypothesized that reduced sodium currents due to NaV1.1 mutations may cause hypoexcitability in GABAergic inhibitory interneurons leading to epilepsy. Mice in both the homozygous and heterozygous states develop the seizure phenotype and ataxia. Though homozygous mice die on average during the second to third week of life and approximately 50% of heterozygous null mice survive into adulthood.

Clinical significance Mutations in the SCN1A gene cause inherited febrile seizures, GEFS+, type 2, and Dravet syndrome.

Patent controversy On 29 November 2008, The Sydney Morning Herald reported the first evidence of private intellectual property rights over human DNA having adversely affected medical care. The Melbourne company Genetic Technologies (GTG) controls rights to the gene, and requires royalties for tests on the gene, which can help identify Dravet syndrome. Doctors on the Children's Hospital in Westmead, Australia have told journalists that they would test 50% more infants for the gene, if they could conduct the test on site.

Interactions Nav1.1 has been shown to interact with syntrophin, alpha 1.

Illustrations

Worked examples

Example 1 — a first encounter with SCN1A

Start with the simplest possible case. Write down what SCN1A claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to SCN1A before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about SCN1A ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of SCN1A

In research: SCN1A appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses SCN1A in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: SCN1A is common in secondary-school and first-year university syllabi. It links to neighbouring topics Genes on human chromosome 2, Sodium channels, so understanding it makes those chapters shorter.
In everyday life: Look for SCN1A outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study SCN1A in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what SCN1A means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain SCN1A out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is SCN1A in simple terms?

Sodium channel protein type 1 subunit alpha (SCN1A), is a protein which in humans is encoded by the SCN1A gene. Gene location The SCN1A gene is located on chromosome 2 of humans, and is made up of 26 exons spanning a total length of 6030 nucleotide base pairs.

Why does SCN1A matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study SCN1A?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on SCN1A.