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FCGRT – Colon Carcinoma

In a familial cancer investigation, FCGRT (HGNC:3621) was noted as one of several candidate genes in patients with a spectrum of malignancies including colon carcinoma (MONDO_0002032) (PMID:27900359). Although the primary focus of the study was on a pathogenic event in CHEK2, FCGRT emerged from multi‐gene sequencing panels performed in affected individuals. The genetic evidence for FCGRT is therefore limited, as no recurrent or functionally disruptive variants were reported specifically for FCGRT in these cases. Moreover, segregation of FCGRT variants in affected relatives was not demonstrated, diminishing the weight of its genetic association with colon carcinoma.

Multiple functional studies have robustly characterized the neonatal Fc receptor encoded by FCGRT, demonstrating its critical role in IgG binding, transcytosis, and catabolism (PMID:8700168, PMID:9036967). However, while these experiments provide moderate functional evidence for the biological importance of FcRn activity, a clear mechanistic link between altered FcRn function and the pathogenesis of colon carcinoma remains unestablished. Additional research is needed to define the clinical relevance of FCGRT alterations in this cancer type.

Key take‑home: Although FCGRT has well‐documented roles in immunoglobulin regulation, its inclusion as a candidate gene in familial colon carcinoma is supported by limited genetic evidence and should be interpreted with caution in diagnostic and commercial settings.

References

  • Cold Spring Harbor molecular case studies • 2016 • Homozygous inactivation of CHEK2 is linked to a familial case of multiple primary lung cancer with accompanying cancers in other organs PMID:27900359
  • Molecular immunology • 1996 • The stoichiometry and affinity of the interaction of murine Fc fragments with the MHC class I-related receptor, FcRn PMID:8700168
  • Journal of immunology • 1997 • Delineation of the amino acid residues involved in transcytosis and catabolism of mouse IgG1 PMID:9036967

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

FCGRT was identified among candidate genes in familial cancer studies with minimal segregation data and no recurring disruptive variants reported (PMID:27900359).

Genetic Evidence

Limited

The gene was captured in a multi‐patient screening panel without direct evidence of pathogenic variants or robust segregation in colon carcinoma cases.

Functional Evidence

Moderate

Multiple studies have demonstrated that FcRn, encoded by FCGRT, plays a key role in IgG homeostasis (PMID:8700168, PMID:9036967), though a direct link to tumorigenesis has not been established.