SF3B1

Chr 2

splicing factor 3b subunit 1

Also known as: Hsh155, MDS, PRP10, PRPF10, SAP155, SF3b155

NCBI Gene: 23451ENSG00000115524UniProt: O75533

This gene encodes subunit 1 of the splicing factor 3b protein complex. Splicing factor 3b, together with splicing factor 3a and a 12S RNA unit, forms the U2 small nuclear ribonucleoproteins complex (U2 snRNP). The splicing factor 3b/3a complex binds pre-mRNA upstream of the intron's branch site in a sequence independent manner and may anchor the U2 snRNP to the pre-mRNA. Splicing factor 3b is also a component of the minor U12-type spliceosome. The carboxy-terminal two-thirds of subunit 1 have 22 non-identical, tandem HEAT repeats that form rod-like, helical structures. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Myelodysplastic syndrome, somaticMIM #614286
137
ClinVar variants
40
Pathogenic / LP
1.00
pLI score· haploinsufficient
5
Active trials
Clinical Summary— SF3B1
⚡
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.
📋
ClinVar Variants
40 Pathogenic / Likely Pathogenic· 50 VUS of 137 total submissions
💊
Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.01 (0.00–0.07)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.19 (0.17–0.22)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 1 / 72.1Missense obs/exp: 141 / 723.9Syn Z: 0.28

ClinVar Variant Classifications

137 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic5
VUS50
Likely Benign9
Benign12
Conflicting1
35
Pathogenic
5
Likely Pathogenic
50
VUS
9
Likely Benign
12
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
4
1
0
5
VUS
4
41
5
0
50
Likely Benign
0
0
3
6
9
Benign
0
0
2
10
12
Conflicting
—1
Total4454616112

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Myelodysplastic syndrome, somatic

MIM #614286

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Myeloproliferative Neoplasm

Impact of Epigenetic Age on Clinic-biological Presentation and Prognosis in Myeloproliferative Neoplasms Epigenetic Age in Myeloproliferative Neoplasms (EpiC)

RECRUITING
NCT06022328University Hospital, BordeauxStarted 2023-12-15
Assessment of the epigenetic age
Myelodysplastic SyndromesMyeloproliferative NeoplasmAnemia

Luspatercept for Anemia in Lower Risk MDS or Non-proliferative MDS/MPN Neoplasms

RECRUITING
NCT05732961Phase PHASE2H. Lee Moffitt Cancer Center and Research InstituteStarted 2023-02-21
Luspatercept
AMLMDS

Molecular Genetics Guide the Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation

RECRUITING
NCT06972641Phase PHASE2, PHASE3Ruijin HospitalStarted 2025-06-10
DecitabineSorafenib (BAY-43-9006)，giritinibAvastinib
Metastatic Solid TumorSF3B1 Gene MutationSpliceosome Mutation

Patient Response to Immunotherapy Using Spliceosome Mutational Markers (PRISMM)

ACTIVE NOT RECRUITING
NCT04447651Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsStarted 2020-09-17
Recommendation for treatment with immunotherapy
Myelodysplastic Syndromes

Monitoring Mutational Burden in Low Risk MDS Patients Using Sequential Peripheral Blood Samples

RECRUITING
NCT04251078Josep Carreras Leukaemia Research InstituteStarted 2019-01-01

External Resources

Links to major genomics databases and tools