SH3D21
Chr 1manchette microtubule inner protein 1
Also known as: C1orf113, SH3D21
The SH3D21 protein is predicted to organize actin filaments and regulate cell migration. Mutations cause neurodevelopmental disorders with intellectual disability, developmental delay, and seizures, following an autosomal recessive inheritance pattern. This gene shows very low constraint against loss-of-function variants, consistent with recessive disease causation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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.
ClinVar Variant Classifications
183 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 | 0 | 0 | 6 | 0 | 6 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 143 | 4 | 0 | 147 |
Likely Benign | 0 | 16 | 0 | 2 | 18 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 159 | 12 | 2 | 173 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SH3D21 · 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