FNIP1 was first reported in relation to autosomal recessive FNIP1-associated syndrome in 2020 (Niehues T, et al., 2020, PMID: 32181500). Folliculin interacting protein 1 (FNIP1) encodes the FNIP1 protein, a regulator of adenosine monophosphate-activated protein (AMPK) and mammalian target of rapamycin (mTOR) cellular pathways. FNIP1 controls B cell development through regulation of mitochondrial autophagy (reviewed in PMID: 39013219). FNIP1 deficiency is associated with a syndromic disease that includes B cell immunodeficiency and cardiomyopathy. The latter is related to the important role of FNIP1 in controlling skeletal muscle functional angiogenesis, which is required for muscle revascularization during ischemia (PMID: 37932296). Seven variants (missense, nonsense, frameshift, and splice site) have been reported in seven probands, and one additional family member, in four publications (PMIDs: 32181500, 32905580, 37522988, 39537849). This gene-disease association is supported by its function in nutrient/energy sensing (PMID: 17028174), which is altered in patient cells (PMID: 32905580). Additionally, mouse models recapitulate the block at the pre-B-cell stage and dysregulation of metabolic regulators (PMIDs: 22608497, 22709692) as well as some key features of the disease (PMID: 27303042). In summary, there is definitive evidence to support the relationship between FNIP1 and autosomal recessive FNIP1-associated syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.
This gene-disease pair was originally evaluated by the Antibody Deficiencies GCEP on November, 16 2021. It was reevaluated on November 22, 2024. As a result of this reevaluation, the classification changed from Strong to Definitive due to the replication of this gene-disease relationship over time and two additional case reports (PMIDs: 37522988, 39537849).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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