Variant Synonymizer: Platform to identify mutations defined in different ways is available now!
Over 2,000 gene–disease validation summaries are now available—no login required!
This summary evaluates the association between EPB41L4B (HGNC:19818) and colorectal cancer (MONDO_0005575). The evidence is drawn primarily from a single exome sequencing study examining a family with both rectal and gastric cancers, where a total of five affected members were found to share a set of novel non‑synonymous variants. Although the affected individuals demonstrated an autosomal dominant segregation pattern in this family (PMID:26872740), the contribution of EPB41L4B remains unclear because no gene‑specific variant was definitively established.
Genetic evidence indicates that EPB41L4B was among a panel of 12 candidate genes identified in the study. The inheritance mode appears to be autosomal dominant with the segregation analysis revealing four additional affected relatives carrying the variant. However, the absence of a unique, reportable HGVS variant for EPB41L4B reduces the strength of genetic evidence despite the observed familial clustering (PMID:26872740).
In terms of variant spectrum, while the study reported a missense change in another gene, no specific EPB41L4B variant was provided for inclusion. This limitation constrains the ability to directly correlate a functional change in EPB41L4B with the colorectal cancer phenotype.
Functional evidence supporting a role for EPB41L4B comes from independent studies in other cancer contexts. Investigations in prostate cancer models demonstrated that EPB41L4B (also known as Ehm2) is overexpressed and correlates with increased cellular motility and metastatic potential (PMID:16927306). Similarly, in lung adenocarcinoma, differential expression of EPB41L4B transcript variants was linked to alterations in cell adhesion and invasion (PMID:30816447). Although these studies do not directly address colorectal cancer, they provide a plausible mechanistic rationale by which EPB41L4B might influence tumor progression.
It is important to note that the reported association is derived from a single family study, and the possibility of complex or multigenic inheritance cannot be excluded. The overall evidence for EPB41L4B in colorectal cancer is therefore limited, and the current findings should be considered as preliminary until further independent validation is available.
In summary, while both genetic and functional studies offer intriguing insights into the potential role of EPB41L4B in oncogenesis, the limited genetic evidence and the absence of a specific pathogenic variant necessitate cautious interpretation. Additional studies focusing on EPB41L4B variants and their functional consequences in colorectal cancer are required to further substantiate its clinical utility.
Key Take‑home sentence: EPB41L4B represents a promising candidate in colorectal cancer that, despite limited current evidence, may eventually inform diagnostic and therapeutic strategies.
Gene–Disease AssociationLimitedBased on the identification of variants in 5 affected individuals (PMID:26872740) from a single family with a dominant segregation pattern, the association remains tentative given the absence of gene‑specific variant evidence and the possibility of complex inheritance. Genetic EvidenceLimitedAlthough candidate non‑synonymous variants in EPB41L4B were identified in a family with rectal and gastric cancer (PMID:26872740), the lack of a definitive, reportable HGVS variant limits the strength of genetic evidence. Functional EvidenceModerateFunctional assays in prostate cancer and lung adenocarcinoma models demonstrate that EPB41L4B influences key oncogenic processes such as cell adhesion and migration, offering mechanistic plausibility even though these studies pertain to different cancer types (PMID:16927306, PMID:30816447). |