U2AF1

Chr 21

U2 small nuclear RNA auxiliary factor 1

Also known as: FP793, RN, RNU2AF1, U2AF35, U2AFBP

NCBI Gene: 7307ENSG00000160201UniProt: Q01081

This gene belongs to the splicing factor SR family of genes. U2 auxiliary factor, comprising a large and a small subunit, is a non-snRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site. This gene encodes the small subunit which plays a critical role in both constitutive and enhancer-dependent RNA splicing by directly mediating interactions between the large subunit and proteins bound to the enhancers. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtMyelodysplastic syndrome
107
ClinVar variants
87
Pathogenic / LP
0.99
pLI score· haploinsufficient
4
Active trials
Clinical Summary— U2AF1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
87 Pathogenic / Likely Pathogenic· 17 VUS of 107 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

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.
0.22LOEUF
pLI 0.990
Z-score 3.44
OE 0.00 (0.00–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
3.85Z-score
OE missense 0.19 (0.14–0.25)
34 obs / 178.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.00 (0.00–0.22)
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 (0.14–0.25)
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.0.89
0≤1.21.6
LoF obs/exp: 0 / 13.8Missense obs/exp: 34 / 178.8Syn Z: 0.71

ClinVar Variant Classifications

107 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic83
Likely Pathogenic4
VUS17
Benign1
Conflicting2
83
Pathogenic
4
Likely Pathogenic
17
VUS
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————83
Likely Pathogenic
————4
VUS
————17
Likely Benign
————0
Benign
————1
Conflicting
—2
Total—107

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

U2AF1 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Primary myelofibrosis: 2023 update on diagnosis, risk-stratification, and management.
Tefferi A·Am J Hematol
2023Review
Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients.
Kahles A et al.·Cancer Cell
2018Cohort
Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management.
Tefferi A·Am J Hematol
2021Review
Chronic neutrophilic leukemia and atypical chronic myeloid leukemia: 2024 update on diagnosis, genetics, risk stratification, and management.
Szuber N et al.·Am J Hematol
2024Review
Acute myeloid leukemia ontogeny is defined by distinct somatic mutations.
Lindsley RC et al.·Blood
2015
Evolutionary landscape of clonal hematopoiesis in 3,359 individuals from the general population.
van Zeventer IA et al.·Cancer Cell
2023
Molecular impact of mutations in RNA splicing factors in cancer.
Zhang Q et al.·Mol Cell
2024Review
Mis-splicing-derived neoantigens and cognate TCRs in splicing factor mutant leukemias.
Kim WJ et al.·Cell
2025
Clonal Hematopoiesis of Indeterminate Potential Predicts Adverse Outcomes in Patients With Atherosclerotic Cardiovascular Disease.
Gumuser ED et al.·J Am Coll Cardiol
2023Cohort
U2AF1 pathogenic variants in myeloid neoplasms and precursor states: distribution of co-mutations and prognostic heterogeneity.
Badar T et al.·Blood Cancer J
2023
Top 10 resultsSearch PubMed ↗
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
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
Chronic Myeloid Leukemia, Chronic PhaseWithdrawal;Drug

Efficacy and Safety of TKIs' Withdrawal After a Two-step Dose Reduction in Patients with Chronic Myeloid Leukemia

ACTIVE NOT RECRUITING
NCT04147533Phase PHASE2Masaryk UniversityStarted 2020-06-16
Imatinib withdrawalDasatinibNilotinib

External Resources

Links to major genomics databases and tools