SF3A3

Chr 1

splicing factor 3a subunit 3

Also known as: PRP9, PRPF9, SAP61, SF3a60

NCBI Gene: 10946ENSG00000183431UniProt: Q12874OMIM: 605596

The protein is a component of the SF3A subcomplex within the U2 snRNP spliceosome, where it participates in pre-mRNA splicing by mediating recognition of intron branch sites and promoting spliceosome assembly. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, developmental delay, and seizures, typically with onset in infancy or early childhood. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.12), indicating that heterozygous loss is not well tolerated.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.12
Clinical Summary— SF3A3
⚡
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
5 unique Pathogenic / Likely Pathogenic· 36 VUS of 67 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.12LOEUF
pLI 1.000
Z-score 5.70
OE 0.03 (0.01–0.12)
Highly constrained

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

Missense Constraint
3.62Z-score
OE missense 0.37 (0.32–0.44)
99 obs / 264.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.03 (0.01–0.12)
0≤0.351.4
Missense OE0.37 (0.32–0.44)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 1 / 39.8Missense obs/exp: 99 / 264.6Syn Z: 0.22
DN
0.2997th %ile
GOF
0.3887th %ile
LOF
0.72top 10%

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

LOFprediction above median · LOEUF 0.12

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

67 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS36
Likely Benign2
4
Pathogenic
1
Likely Pathogenic
36
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
1
0
1
VUS
0
33
3
0
36
Likely Benign
0
1
1
0
2
Benign
0
0
0
0
0
Total0349043

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

View in ClinVar →

Protein Context — Lollipop Plot

SF3A3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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