SF3B4
Chr 1ADsplicing factor 3b subunit 4
Also known as: AFD1, Hsh49, SAP49, SF3b49
The protein is a component of the SF3B subcomplex within the U2 snRNP spliceosome that recognizes branch sites and promotes pre-mRNA splicing. Mutations cause acrofacial dysostosis 1 (Nager type), which primarily affects craniofacial and limb development, following an autosomal dominant inheritance pattern. The gene is highly constrained against loss-of-function variants, indicating that heterozygous mutations are likely sufficient to cause disease.
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%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SF3B4 · 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