FNIP1

Chr 5q31.1

folliculin interacting protein 1

Aliases:: KIAA1961
MANE:: ENST00000510461.6

OMIM: 610594 ↗NCBI: 96459 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

FNIP1 · Q8TF40

v62025-08-01

Predicted Aligned Error matrix for FNIP1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

54.9/ 100

Low

1,166 residues

Confidence breakdown

Very high(≥ 90)15%
Confident(70–90)20%
Low(50–70)10%
Very low(< 50)55%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Primary immunodeficiency or monogenic inflammatory bowel disease
BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

immunodeficiency 93 and hypertrophic cardiomyopathy
0.59
hypertrophic cardiomyopathy
0.43
agammaglobulinemia
0.42
neutropenia
0.42
Decreased total neutrophil count
0.42
inborn error of immunity
0.42
FNIP1-associated syndrome
0.37
asthma
0.29
neurodegenerative disease
0.27
rosacea
0.26

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Folliculin-interacting protein 1

Binding partner of the GTPase-activating protein FLCN: involved in the cellular response to amino acid availability by regulating the non-canonical mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed:17028174, PubMed:18663353, PubMed:24081491, PubMed:37079666). Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases, leading to activation of the non-canonical mTORC1 signaling (PubMed:24081491). In low-amino acid conditions, component of the lysosomal folliculin complex (LFC) on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, thereby inactivating mTORC1 and promoting nuclear translocation of TFEB and TFE3 (By similarity). Upon amino acid restimulation, disassembly of the LFC complex liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent inactivation of TFEB and TFE3 (PubMed:37079666). Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (PubMed:25126726). In addition to its role in mTORC1 signaling, also acts as a co-chaperone of HSP90AA1/Hsp90: following gradual phosphorylation by CK2, inhibits the ATPase activity of HSP90AA1/Hsp90, leading to activate both kinase and non-kinase client proteins of HSP90AA1/Hsp90 (PubMed:27353360, PubMed:30699359). Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (PubMed:27353360). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:27353360). Also acts as a core component of the reductive stress response by inhibiting activation of mitochondria in normal conditions: in response to reductive stress, the conserved Cys degron is reduced, leading to recognition and polyubiquitylation by the CRL2(FEM1B) complex, followed by proteasomal (By similarity). Required for B-cell development (PubMed:32905580)