Alt. symbols: KIAA1961

Approved name: folliculin interacting protein 1
Alt. names: folliculininteracting protein 1

Location: 5q31.1: 131641714 - 131797017 (-)
Gene type: protein_coding, 5 transcripts.

Scores: LoFtool: 0.431000 | pLI: 0.99981945 | LOEUF: 0.251

HGNC: 29418

NCBI: 96459, RefSeq: .0

Ensembl: ENSG00000217128.13

LRG_ | Status: none

OMIM: 610594

Expression | ProteinAtlas

FNIP1 encodes a protein that forms a complex with FNIP2 and folliculin (FLCN) to interact with and regulate the function of AMP-activated protein kinase (AMPK), a master sensor of energy utilization that activates key catabolic pathways upon energy deprivation and cellular stress.

In 2020, Niehuis et al. identified homozygous FNIP1 mutations in 3 patients from 2 consanguineous families with early onset recurrent sinopulmonary and GI infections (PMID: 3281500) - at least two showed hypogammaglobulinemia (IgG, IgM), reduced absolute and relative switched memory B cells, a pre-B cell stage differentiation block, and cardiac abnormalities reminiscent of FNIP1-deficient murine phenotypes (PMID: 22608497). But unlike the mouse model, all 3 patients showed peripheral T-cell lymp hocytosis and intermittent neutropenia. Saettini et al. (2021) subsequently identified biallelic mutations in 3 additional unrelated patients with agammaglobulinemia and absent circulating B cells, recurrent infections, and hypertrophic cardiomyopathy (PMID: 32905580). Again, some patients also showed intermittent or severe chronic neutropenia, as well as T-cell abnormalities (lymphocytosis and/or defective T-cell proliferation with increased apoptosis), another feature not seen in mouse models. Consistent with mouse data suggesting that FNIP1 may serve as part of a metabolic checkpoint during B cell development, the authors found evidence of altered cellular metabolism, including increased mitochondrial number and activity in Bcells and constitutive hyperactivation of downstream PI3K targets in B cell precursors. [Load More]