KIF1B – Pheochromocytoma

Despite inclusion of KIF1B in multiple large cohort sequencing studies of pheochromocytoma (n=75) and paraganglioma (n=115), no pathogenic or likely pathogenic germline variants in KIF1B were reported (PMID:33777662, PMID:37529773). A single c.4723G>A (p.Val1575Met) variant was described in a 26-year-old proband with juvenile-onset pheochromocytoma but remained classified as a variant of uncertain significance due to lack of segregation data and absence in additional cases (PMID:35046208).

Functional insights include identification of a somatic c.2618C>T (p.Thr873Ile) in the hPheo1 pheochromocytoma cell line, which modulates cell adhesion yet lacks validation in vivo (PMID:33138083). A prior attribution of familial pheochromocytoma to a KIF1B variant was later reassigned to MAX, underscoring conflicting findings (PMID:35046208). The mechanistic role of KIF1B in catecholamine-secreting tumourigenesis remains speculative, informed predominantly by its motor protein functions in neuronal models. Key take-home: current evidence is insufficient to support routine clinical testing of KIF1B for pheochromocytoma predisposition.

References

• Journal of kidney cancer and VHL • 2021 • Germline Pathogenic Variants Identified by Targeted Next-Generation Sequencing of Susceptibility Genes in Pheochromocytoma and Paraganglioma. PMID:33777662
• Endocrine oncology (Bristol, England) • 2023 • Germline genetic variants in pheochromocytoma/paraganglioma: single-center experience. PMID:37529773
• Endocrine journal • 2022 • A case of juvenile-onset pheochromocytoma with KIF1B p.V1529M germline mutation. PMID:35046208
• International journal of molecular sciences • 2020 • Activation of RAS Signalling is Associated with Altered Cell Adhesion in Phaeochromocytoma. PMID:33138083

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