West syndrome: genes and variants

Genes linked to West syndrome

• 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 disease-causing and 0 uncertain variants in KCNQ2 are linked to West syndrome.

• 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 disease-causing and 0 uncertain variants in TUBA1A are linked to West syndrome.

• 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.

  11 disease-causing and 0 uncertain variants in SCN2A are linked to West syndrome.

Weakly linked (only a few uncertain records): CDKL5, GRIN2B and SCN1A.

Where West syndrome variants cluster

• SCN2A I (positions 111–456): 4 of 11 disease-causing changes, 2.1× more than its size predicts.

Known disease-causing variants in West syndrome

Which prediction tools work for West syndrome

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• EVE: 96 out of 100
• CATVariant: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaMissense: 95 out of 100
• MetaLR: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• ESM1b (LLR): 95 out of 100
• SIFT: 90 out of 100
• MutPred2: 78 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 76 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Seizures, benign familial infantile, 3 is also caused by SCN2A variants; they fall mostly in different places as the West syndrome variants (167 disease-causing).
• Complex neurodevelopmental disorder is also caused by SCN2A variants; they fall mostly in different places as the West syndrome variants (22 disease-causing).
• Episodic ataxia type 2 is also caused by SCN2A variants; they fall mostly in different places as the West syndrome variants (15 disease-causing).
• Benign familial infantile epilepsy is also caused by SCN2A variants; they fall mostly in different places as the West syndrome variants (6 disease-causing).
• Infantile spasms is also caused by SCN2A variants; they fall mostly in different places as the West syndrome variants (3 disease-causing).
• Early-infantile DEE is also caused by KCNQ2 variants; they fall mostly in different places as the West syndrome variants (199 disease-causing).
• Seizures, benign familial neonatal, 1 is also caused by KCNQ2 variants; they fall mostly in different places as the West syndrome variants (57 disease-causing).
• Tubulinopathy is also caused by TUBA1A variants; they fall mostly in different places as the West syndrome variants (101 disease-causing).
• Lissencephaly due to TUBA1A mutation is also caused by TUBA1A variants; they fall mostly in different places as the West syndrome variants (62 disease-causing).
• Tubulinopathy-associated dysgyria is also caused by TUBA1A variants; they fall mostly in different places as the West syndrome variants (6 disease-causing).
• TUBA1A-associated tubulinopathy is also caused by TUBA1A variants; they fall mostly in different places as the West syndrome variants (3 disease-causing).

Diseases related to West syndrome

• Epilepsy, also linked to KCNQ2 and SCN2A
• Genetic developmental and epileptic encephalopathy, also linked to KCNQ2 and SCN2A
• Early-infantile DEE, also linked to KCNQ2
• Seizures, benign familial infantile, 3, also linked to SCN2A
• Amyotrophic lateral sclerosis, also linked to SCN2A
• Episodic ataxia type 2, also linked to SCN2A
• Tubulinopathy, also linked to TUBA1A
• Cardiac arrhythmia, also linked to SCN2A
• Autosomal recessive limb-girdle muscular dystrophy, also linked to TUBA1A
• Seizures, benign familial neonatal, 1, also linked to KCNQ2
• Lissencephaly due to TUBA1A mutation, also linked to TUBA1A
• Complex neurodevelopmental disorder, also linked to SCN2A

Frequently asked questions

Which genes are linked to West syndrome?

In CATVariant, West syndrome is linked to 3 analyzed proteins: KCNQ2 (Potassium voltage-gated channel subfamily KQT member 2), TUBA1A (Tubulin alpha-1A chain) and SCN2A (Sodium channel protein type 2 subunit alpha).

How many genetic variants are linked to West syndrome?

16 variants: 13 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 2 are of uncertain significance or have conflicting reports.

Which uncertain variants in West syndrome look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for West syndrome?

Among tools not trained on clinical labels, EVE separates this disease's known disease-causing variants from harmless ones best (AUROC 0.96, based on 8 disease-causing and 43 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis 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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