SPTBN4 (Q9H254) variants and mutations

SPTBN4 (also known as Q9H254) is a human protein-coding gene encoding a spectrin beta chain, non-erythrocytic 4 protein. It stabilizes axonal membrane domains and organizes ion channels and cytoskeletal complexes at nodes of Ranvier and neuromuscular structures. Biallelic pathogenic variants cause a severe neurodevelopmental disorder with congenital hypotonia, neuropathy, deafness, and respiratory insufficiency. This analysis covers 3,489 SPTBN4 variants and mutations. Of these, 75% have computational variant effect predictions. Disease context includes neurodevelopmental disorder with hypotonia, neuropathy, and deafness, hereditary disease, and neurodegenerative disease. Example SPTBN4 variants include A2T, A2V, and A2A.

Variant analysis overview

Gene: SPTBN4
Protein: Q9H254
UniProt accession: Q9H254
Organism: Homo sapiens
Variants analyzed: 3489
Variant scope: all variants
Completed: 2026-08-20

Variant and mutation evidence

Variant composition: 3,300 unspecified-consequence records; 91 synonymous variants; 80 missense variants; 2 in-frame deletions; 8 stop-gained variants; 4 frameshift variants; 4 splice-region variants
Prediction scores: 2,610 variants have prediction scores (75% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: neurodevelopmental disorder with hypotonia, neuropathy, and deafness, hereditary disease, neurodegenerative disease, deafness, essential tremor, hearing loss, autosomal recessive, autosomal dominant nonsyndromic hearing loss, Benign familial chorea, Global developmental delay, myoclonic epilepsy, Hypotonia, Flexion contracture.

Protein structure and variant hotspots

Protein features: 3 domains.
Structural context: 470 variants have structural context.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable SPTBN4 variants

Examples include A2T, A2V, A2A, Q3H, Q3R, Q3Q, V4A, V4G. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

SPTBN4 analysis run — SPTBN4 (3,489 variants) — completed 2026-08-20