SF3B5
Chr 6splicing factor 3b subunit 5
Also known as: SF3b10, Ysf3
The protein functions as a component of the SF3B subcomplex within the U2 snRNP spliceosome, where it mediates recognition of intron branch sites and promotes selection of the branch-site adenosine during pre-mRNA splicing. Biallelic pathogenic variants cause microcephaly with simplified gyral pattern, abnormal corpus callosum, and seizures, inherited in an autosomal recessive manner. Affected individuals typically present in early infancy with developmental delays and neurological abnormalities.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
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
24 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 | 18 | 0 | 18 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 5 | 1 | 0 | 6 |
Likely Benign | 0 | 0 | 0 | 0 | 0 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 5 | 19 | 0 | 24 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SF3B5 · 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