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SF3A1 – Colorectal Cancer

The current evidence linking SF3A1 to colorectal cancer is limited. In one family study of gastric- and rectal cancer, a set of 12 novel non‑synonymous variants was identified among 5 affected members (PMID:26872740), with SF3A1 included as a candidate gene; however, no individual variant meeting stringent pathogenic criteria was definitively established. Furthermore, a hospital‑based case‑control study involving 801 colorectal cancer patients and 817 controls investigated four candidate SF3A1 SNPs and found no significant association with colorectal cancer risk (PMID:26079486). These observations contribute to a gene‑disease association rated as Limited from a clinical validity perspective.

Functional studies, however, have consistently demonstrated that SF3A1 plays a critical role in pre‑mRNA splicing through its participation in prespliceosome assembly and specific RNA binding via its ubiquitin‑like domain. Experimental findings from multiple studies (PMID:8341697, PMID:31383795, PMID:35101980) reinforce the biological relevance of SF3A1 in RNA processing. Despite its well‑characterized splicing function, the genetic evidence does not currently support SF3A1 as a robust diagnostic marker for colorectal cancer.

Key Take‑Home: SF3A1 remains an essential splicing factor with moderate functional evidence but limited genetic evidence for colorectal cancer predisposition, warranting further research before clinical implementation.

References

  • BMC genetics • 2016 • Exome sequencing in one family with gastric‑ and rectal cancer PMID:26872740
  • PloS one • 2015 • The Associations between RNA Splicing Complex Gene SF3A1 Polymorphisms and Colorectal Cancer Risk in a Chinese Population PMID:26079486
  • Proceedings of the National Academy of Sciences of the United States of America • 1993 • The Saccharomyces cerevisiae PRP21 gene product is an integral component of the prespliceosome PMID:8341697
  • RNA (New York, N.Y.) • 2019 • Identification of a noncanonical RNA binding domain in the U2 snRNP protein SF3A1 PMID:31383795
  • Proceedings of the National Academy of Sciences of the United States of America • 2022 • Sequence‑specific RNA recognition by an RGG motif connects U1 and U2 snRNP for spliceosome assembly PMID:35101980

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Evidence from 5 affected individuals in a family study (PMID:26872740) alongside a large case‑control study showing no significant association (PMID:26079486) supports a limited association between SF3A1 and colorectal cancer.

Genetic Evidence

Limited

Candidate SF3A1 variants have not been definitively linked to colorectal cancer, and segregation data are sparse, reducing the strength of genetic evidence.

Functional Evidence

Moderate

Multiple studies have clearly delineated the role of SF3A1 in prespliceosome assembly and RNA binding, underscoring its biological relevance, although these functional insights do not directly translate to a strong disease association (PMID:8341697, PMID:31383795, PMID:35101980).