SF3A1

Chr 22

splicing factor 3a subunit 1

Also known as: PRP21, PRPF21, SAP114, SF3A120

NCBI Gene: 10291ENSG00000099995UniProt: Q15459

This gene encodes a subunit of the splicing factor 3a protein complex. The splicing factor 3a heterotrimer is a component of the mature U2 small nuclear ribonucleoprotein particle (snRNP). U2 small nuclear ribonucleoproteins play a critical role in spliceosome assembly and pre-mRNA splicing. [provided by RefSeq, Aug 2014]

83
ClinVar variants
20
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— SF3A1
⚡
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
20 Pathogenic / Likely Pathogenic· 49 VUS of 83 total submissions

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.
0.30LOEUF
pLI 0.988
Z-score 4.96
OE 0.15 (0.08–0.30)
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.
4.16Z-score
OE missense 0.45 (0.40–0.50)
203 obs / 452.1 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.0.15 (0.08–0.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.45 (0.40–0.50)
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.1.03
0≤1.21.6
LoF obs/exp: 6 / 39.7Missense obs/exp: 203 / 452.1Syn Z: -0.29

ClinVar Variant Classifications

83 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic1
VUS49
Likely Benign1
Benign1
19
Pathogenic
1
Likely Pathogenic
49
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
18
0
19
Likely Pathogenic
0
0
1
0
1
VUS
0
46
3
0
49
Likely Benign
0
0
0
1
1
Benign
0
0
1
0
1
Total14623171

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

View in ClinVar →

Protein Context — Lollipop Plot

SF3A1 · 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
The Associations between RNA Splicing Complex Gene SF3A1 Polymorphisms and Colorectal Cancer Risk in a Chinese Population.
Chen X et al.·PLoS One
2015
Structural basis for the interaction between the first SURP domain of the SF3A1 subunit in U2 snRNP and the human splicing factor SF1.
Nameki N et al.·Protein Sci
2022
SF3A1 and pancreatic cancer: new evidence for the association of the spliceosome and cancer.
Tian J et al.·Oncotarget
2015
Integrative identification of non-coding regulatory regions driving metastatic prostate cancer.
Woo BJ et al.·Cell Rep
2024
Intramolecular autoinhibition regulates the selectivity of PRPF40A tandem WW domains for proline-rich motifs.
Martínez-Lumbreras S et al.·Nat Commun
2024
Hydroxysafflor yellow A alleviates ischemic myocardial injury by targeting SF3A1 to improve mitochondrial energy metabolism.
Wang BK et al.·Eur J Pharmacol
2025
Synergistic roles for human U1 snRNA stem-loops in pre-mRNA splicing.
Martelly W et al.·RNA Biol
2021
Identification of a noncanonical RNA binding domain in the U2 snRNP protein SF3A1.
Martelly W et al.·RNA
2019
Lactylome analyses suggest systematic lysine-lactylated substrates in oral squamous cell carcinoma under normoxia and hypoxia.
Song F et al.·Cell Signal
2024
Sequence-specific RNA recognition by an RGG motif connects U1 and U2 snRNP for spliceosome assembly.
de Vries T et al.·Proc Natl Acad Sci U S A
2022
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools