SRSF3

Chr 6

serine and arginine rich splicing factor 3

Also known as: SFRS3, SRp20

NCBI Gene: 6428ENSG00000112081UniProt: P84103

The protein encoded by this gene is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. Each of these factors contains an RNA recognition motif (RRM) for binding RNA and an RS domain for binding other proteins. The RS domain is rich in serine and arginine residues and facilitates interaction between different SR splicing factors. In addition to being critical for mRNA splicing, the SR proteins have also been shown to be involved in mRNA export from the nucleus and in translation. Two transcript variants, one protein-coding and the other non-coding, have been found for this gene. [provided by RefSeq, Sep 2010]

12
ClinVar variants
8
Pathogenic / LP
0.96
pLI score· haploinsufficient
0
Active trials
Clinical Summary— SRSF3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 4 VUS of 12 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.29LOEUF
pLI 0.963
Z-score 2.97
OE 0.00 (0.00–0.29)
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.
3.07Z-score
OE missense 0.17 (0.12–0.25)
18 obs / 107.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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 (0.00–0.29)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.17 (0.12–0.25)
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.1.22
0≤1.21.6
LoF obs/exp: 0 / 10.3Missense obs/exp: 18 / 107.5Syn Z: -1.00

ClinVar Variant Classifications

12 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS4
7
Pathogenic
1
Likely Pathogenic
4
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
1
0
1
VUS
0
2
2
0
4
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0210012

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

View in ClinVar →

Protein Context — Lollipop Plot

SRSF3 · 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
Proteomic Characterization Identifies Clinically Relevant Subgroups of Gastrointestinal Stromal Tumors.
Sun M et al.·Gastroenterology
2024
Regulatory interplay between SR proteins governs CLK1 kinase splice variants production.
Shkreta L et al.·RNA
2024
Prognostic and predictive value of super-enhancer-derived signatures for survival and lung metastasis in osteosarcoma.
Huang G et al.·J Transl Med
2024
Homeobox B9 Promotes Colon Cancer Progression by Targeting SRSF3.
Yuan L et al.·Dig Dis Sci
2023
SRSF3-Regulated RNA Alternative Splicing Promotes Glioblastoma Tumorigenicity by Affecting Multiple Cellular Processes.
Song X et al.·Cancer Res
2019
SRSF3 and HNRNPH1 Regulate Radiation-Induced Alternative Splicing of Protein Arginine Methyltransferase 5 in Hepatocellular Carcinoma.
Wen C et al.·Int J Mol Sci
2022
SRSF3 knockdown-induced cellular senescence as a possible therapeutic strategy for non-small cell lung cancer.
Nakamichi S et al.·Carcinogenesis
2025
Underexpression of SRSF3 and its target gene RBMX predicts good prognosis in patients with head and neck cancer.
Guo J et al.·J Oral Sci
2020Cohort
Dysregulation of SRSF3/circSAMD4/CIRBP Axis Promotes Iodinated Contrast-induced Acute Kidney Injury.
Wu X et al.·Int J Biol Sci
2025
B7-H3 is spliced by SRSF3 in colorectal cancer.
Zhang C et al.·Cancer Immunol Immunother
2021
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