SF3B1

Chr 2

splicing factor 3b subunit 1

ENSG00000115524UniProt: O75533OMIM: 605590

This gene encodes subunit 1 of the splicing factor 3b protein complex, which is essential for pre-mRNA splicing by recognizing branch sites and anchoring U2 snRNP to pre-mRNA during spliceosome assembly. The gene is extremely intolerant to loss-of-function variants (pLI ~1.0, LOEUF 0.066), suggesting that heterozygous mutations would likely cause severe developmental disorders, though specific Mendelian phenotypes have not yet been established in OMIM. Currently, SF3B1 mutations are only documented in somatic myelodysplastic syndrome, but the high constraint scores indicate this gene may be associated with uncharacterized neurodevelopmental conditions.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismLOEUF 0.071 OMIM phenotype
Clinical Summary— SF3B1
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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.07LOEUF
pLI 1.000
Z-score 7.76
OE 0.01 (0.00–0.07)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
7.70Z-score
OE missense 0.19 (0.17–0.22)
141 obs / 723.9 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.01 (0.00–0.07)
0≤0.351.4
Missense OE0.19 (0.17–0.22)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 1 / 72.1Missense obs/exp: 141 / 723.9Syn Z: 0.28
DN
0.3197th %ile
GOF
0.3590th %ile
LOF
0.82top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.07

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

ClinVar

Protein Context — Lollipop Plot

SF3B1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Post-transplant ring sideroblasts are common in haploidentical peripheral blood stem cell transplantation but not linked to SF3B1 mutations.
Hollenstein M et al.·Clin Chem Lab Med
2026
Concurrent SF3B1 Mutation and BCR::ABL1 Demonstrating a Myelodysplastic Syndrome Phenotype: A Case Report.
Brailovski E et al.·EJHaem
2026Open AccessCase report
Oncogenic SF3B1 mutations alter the splicing of mRNA noncoding regions to induce a novel therapeutic vulnerability.
Sekrecki M et al.·Blood
2026
Phosphorylation of SF3B1 by CDK11 orchestrates spliceosome activation via SNIP1-dependent RES complex recruitment.
Gajdušková P et al.·Nat Commun
2026
Overexpression of the TGF-β target CCN2 in megakaryocytes: a common feature of MDS with mutated SF3B1 : Uncovering novelinsights into the bone marrow microenvironment in MDS.
Leguit RJ et al.·Virchows Arch
2026
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients