Pathogenic variants (disease-causing) in the TMEM127 gene can predispose individuals to pheochromocytomas (adrenal gland tumor) and less commonly paragangliomas (head and neck tumor). Management of TMEM127–related tumor risk includes regular surveillance tailored to guidelines for hereditary paraganglioma–pheochromocytoma syndromes, typically involving periodic biochemical testing, whole-body or targeted MRI, and clinical evaluation to detect tumors early. TMEM127 variants are not known to be more common in the Ashkenazi Jewish population.
Pathogenic variants in TMEM127 exhibit autosomal dominant inheritance. This means there is a 50% chance the condition can be passed from generation-to-generation. First degree relatives (parents, siblings, children) have a 50% chance to have the same pathogenic variant whereas second degree relatives (grandparents, aunts/uncles, nieces/nephews, half-siblings) have a 25% chance. More distant relatives have lower chances of having the same pathogenic variant when one is identified in the family.
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Written December 2025
