SPTBN4
Chr 19ARspectrin beta, non-erythrocytic 4
Also known as: CMND, NEDHND, QV, SPNB4, SPTBN3
Spectrin beta 4 is an actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton and localizes to the nuclear matrix, PML nuclear bodies, and cytoplasmic vesicles. Mutations cause a neurodevelopmental disorder with hypotonia, neuropathy, and deafness inherited in an autosomal recessive pattern. This gene is extremely intolerant to loss-of-function variants (pLI >0.99, LOEUF 0.19), indicating that complete loss of protein function is likely deleterious.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
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
400 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 | 2 | 0 | 0 | 0 | 2 |
Likely Pathogenic | 8 | 1 | 0 | 0 | 9 |
VUS | 0 | 337 | 4 | 0 | 341 |
Likely Benign | 0 | 7 | 2 | 17 | 26 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 2 | |||
| Total | 10 | 345 | 6 | 17 | 380 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SPTBN4 · 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