Infantile spasms: genes and variants

Genes linked to Infantile spasms

• SCN2A: Sodium channel protein type 2 subunit alpha

  The protein forms Nav1.2, a voltage-gated sodium channel that carries sodium current during neuronal action potentials. By shaping neuronal excitability and signal propagation, it supports brain circuits involved in development, learning, and seizure susceptibility.

  14 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in SCN2A have source records linked to Infantile spasms. Association strength is not clinical gene validity.

• KCNQ2: Potassium voltage-gated channel subfamily KQT member 2

  Together with KCNQ3, its slowly activating potassium current provides much of the neuronal M-current that suppresses repetitive firing. Pathogenic variants cause a spectrum from self-limited familial neonatal epilepsy to severe developmental and epileptic encephalopathy.

  1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in KCNQ2 have source records linked to Infantile spasms. Association strength is not clinical gene validity.

• TUBA1A: Tubulin alpha-1A chain

  An alpha-tubulin chain that pairs with beta-tubulin to build microtubules. Microtubules provide tracks for transport and help shape dividing and migrating cells, making TUBA1A especially important for fetal brain development.

  1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in TUBA1A have source records linked to Infantile spasms. Association strength is not clinical gene validity.

• CDKL5: Cyclin-dependent kinase-like 5

  It phosphorylates neuronal substrates involved in synapse development, cytoskeletal organization, and signaling during early brain maturation. Loss-of-function variants cause CDKL5 deficiency disorder with very early epilepsy and severe developmental impairment.

  0 ClinVar pathogenic / likely pathogenic and 2 uncertain variants in CDKL5 have source records linked to Infantile spasms. Association strength is not clinical gene validity.

• GRIN2B: Glutamate receptor ionotropic, NMDA 2B

  The GluN2B subunit of NMDA glutamate receptors, ion channels that mediate excitatory signaling in the brain. Pathogenic variants can disrupt neuronal development and cause neurodevelopmental disorders, sometimes with epilepsy.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in GRIN2B have source records linked to Infantile spasms. Association strength is not clinical gene validity.

• SCN8A: Sodium channel protein type 8 subunit alpha

  The protein forms Nav1.6, a voltage-gated sodium channel that sets the threshold and propagation of neuronal action potentials. It is widely important for neuronal excitability, and SCN8A variants are associated with developmental and epileptic encephalopathies.

  1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in SCN8A have source records linked to Infantile spasms. Association strength is not clinical gene validity.

Weakly linked (only a few uncertain records): KCNT1, SCN1A and STXBP1.

Where Infantile spasms variants cluster

• SCN2A I (positions 111–456): 5 of 14 ClinVar pathogenic / likely pathogenic variants, 2.1× more than its size predicts.

ClinVar pathogenic and likely pathogenic variants linked to Infantile spasms

Which prediction tools work for Infantile spasms

Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.

• MetaLR: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaMissense: 93 out of 100
• EVE: 91 out of 100
• CATVariant: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• ESM1b (LLR): 89 out of 100
• SIFT: 89 out of 100
• MutPred2: 78 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 77 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Seizures, benign familial infantile, 3 also has ClinVar records linked to SCN2A variants; they fall mostly in different places as the Infantile spasms variants (167 pathogenic / likely pathogenic).
• Complex neurodevelopmental disorder also has ClinVar records linked to SCN2A variants; they fall mostly in different places as the Infantile spasms variants (22 pathogenic / likely pathogenic).
• Episodic ataxia type 2 also has ClinVar records linked to SCN2A variants; they fall mostly in different places as the Infantile spasms variants (15 pathogenic / likely pathogenic).
• Benign familial infantile epilepsy also has ClinVar records linked to SCN2A variants; they fall mostly in different places as the Infantile spasms variants (6 pathogenic / likely pathogenic).
• Malignant migrating partial seizures of infancy also has ClinVar records linked to SCN2A variants; they fall mostly in different places as the Infantile spasms variants (3 pathogenic / likely pathogenic).
• Early-infantile DEE also has ClinVar records linked to KCNQ2 variants; they fall mostly in different places as the Infantile spasms variants (199 pathogenic / likely pathogenic).
• Seizures, benign familial infantile, 3 also has ClinVar records linked to KCNQ2 variants; they fall mostly in different places as the Infantile spasms variants (57 pathogenic / likely pathogenic).
• Tubulinopathy also has ClinVar records linked to TUBA1A variants; they fall mostly in different places as the Infantile spasms variants (101 pathogenic / likely pathogenic).
• Lissencephaly due to TUBA1A mutation also has ClinVar records linked to TUBA1A variants; they fall mostly in different places as the Infantile spasms variants (62 pathogenic / likely pathogenic).
• Tubulinopathy-associated dysgyria also has ClinVar records linked to TUBA1A variants; they fall mostly in different places as the Infantile spasms variants (6 pathogenic / likely pathogenic).
• TUBA1A-associated tubulinopathy also has ClinVar records linked to TUBA1A variants; they fall mostly in different places as the Infantile spasms variants (3 pathogenic / likely pathogenic).
• Early-infantile DEE also has ClinVar records linked to SCN8A variants; they fall mostly in different places as the Infantile spasms variants (90 pathogenic / likely pathogenic).
• Cognitive impairment with or without cerebellar ataxia also has ClinVar records linked to SCN8A variants; they fall mostly in different places as the Infantile spasms variants (22 pathogenic / likely pathogenic).
• Seizures, benign familial infantile, 3 also has ClinVar records linked to SCN8A variants; they fall mostly in different places as the Infantile spasms variants (12 pathogenic / likely pathogenic).
• Complex neurodevelopmental disorder also has ClinVar records linked to SCN8A variants; they fall mostly in different places as the Infantile spasms variants (8 pathogenic / likely pathogenic).
• Autosomal recessive inheritance also has ClinVar records linked to SCN8A variants; they fall mostly in different places as the Infantile spasms variants (3 pathogenic / likely pathogenic).

Diseases related to Infantile spasms

• Epilepsy, also linked to GRIN2B, KCNQ2, SCN2A and SCN8A
• Seizures, benign familial infantile, 3, also linked to KCNQ2, SCN2A and SCN8A
• Complex neurodevelopmental disorder, also linked to GRIN2B, SCN2A and SCN8A
• Genetic developmental and epileptic encephalopathy, also linked to KCNQ2, SCN2A and SCN8A
• Early-infantile DEE, also linked to KCNQ2 and SCN8A
• Amyotrophic lateral sclerosis, also linked to SCN2A and SCN8A
• Cardiac arrhythmia, also linked to SCN2A and SCN8A
• Focal epilepsy, also linked to SCN2A and SCN8A
• Migraine, also linked to SCN2A and SCN8A
• Lennox-Gastaut syndrome, also linked to SCN2A and SCN8A
• Episodic ataxia type 2, also linked to SCN2A
• Alzheimer disease, also linked to GRIN2B

Frequently asked questions

Which genes have records linked to Infantile spasms?

This view contains 6 analyzed proteins: SCN2A, KCNQ2, TUBA1A, CDKL5, GRIN2B and 1 more. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.

What do the clinical classifications mean?

Linked records include 17 pathogenic or likely pathogenic variants, 2 variants of uncertain significance and 1 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.

Does the evidence score change a VUS classification?

No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.

Can I download the variant evidence?

Download the CSV for all 23 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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