SPTBN1
Chr 2ADspectrin beta, non-erythrocytic 1
Also known as: DDISBA, ELF, HEL102, SPTB2, betaSpII
Spectrin beta chain, non-erythrocytic 1 is an actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton and plays a critical role in central nervous system development and function. Mutations cause autosomal dominant developmental delay with impaired speech and behavioral abnormalities. This gene is extremely intolerant to loss-of-function variants (pLI ~1.0), indicating that even single pathogenic variants can cause disease.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
630 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 12 | 1 | 7 | 0 | 20 |
Likely Pathogenic | 17 | 9 | 1 | 0 | 27 |
VUS | 12 | 410 | 14 | 2 | 438 |
Likely Benign | 0 | 33 | 5 | 43 | 81 |
Benign | 0 | 1 | 2 | 7 | 10 |
Conflicting | — | 3 | |||
| Total | 41 | 454 | 29 | 52 | 579 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SPTBN1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools