FNIP1

Summary

FNIP1 (folliculin interacting protein 1, HGNC:29418) is a protein-coding gene on chromosome 5q31.1, encoding Folliculin-interacting protein 1 (Q8TF40). 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.

This gene encodes a protein that binds to the tumor suppressor protein folliculin and to AMP-activated protein kinase (AMPK). The encoded protein participates in the regulation of cellular metabolism and nutrient sensing by modulating the AMPK and target of rapamycin signaling pathways. This gene has a closely related paralog that encodes a protein with similar binding activities. Both related proteins also associate with the molecular chaperone heat shock protein-90 (Hsp90) and negatively regulate its ATPase activity and facilitate its association with folliculin.

Source: NCBI Gene 96459 — RefSeq curated summary.

At a glance

• Gene–disease (curated): FNIP1-associated syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 20
• Clinical variants (ClinVar): 500 total — 25 pathogenic, 3 likely-pathogenic (top 7% of genes corpus-wide)
• GTEx eGene: eQTL in 10 tissues, sQTL in 3 (q < 0.05)
• Phenotypes (HPO): 21
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.39 (moderately constrained)
• MANE Select transcript: NM_133372
• Interaction hub: 1,902 STRING partners (top 8% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29418
Approved symbol	FNIP1
Name	folliculin interacting protein 1
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1961
Ensembl gene	ENSG00000217128
Ensembl biotype	protein_coding
OMIM	610594
Entrez	96459

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 14 protein_coding, 1 TEC

MANE Select: ENST00000510461

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 5: 1

ENST00000510461, ENST00000307954, ENST00000307968, ENST00000511848, ENST00000623690, ENST00000934997, ENST00000985038, ENST00001034524, ENST00001074649, ENST00001095501, ENST00001110316, ENST00001110317, ENST00001110318, ENST00001112266, ENST00001133135

RefSeq mRNA: 4 — MANE Select: NM_133372 NM_001008738, NM_001346113, NM_001346114, NM_133372

CCDS: CCDS34226, CCDS34227, CCDS87320, CCDS87321

Canonical transcript exons

ENST00000510461 — 18 exons

Exon	Start	End
ENSE00000899265	131679029	131679175
ENSE00000899266	131698917	131699002
ENSE00000899267	131704065	131704266
ENSE00000899268	131706411	131706546
ENSE00001084000	131651802	131651999
ENSE00001171918	131647090	131647205
ENSE00001171934	131670463	131670631
ENSE00001171941	131671505	131672924
ENSE00001354197	131677703	131677872
ENSE00002067175	131796830	131797017
ENSE00002087554	131641714	131644763
ENSE00002467820	131710578	131710661
ENSE00002495750	131719317	131719417
ENSE00002500644	131716565	131716656
ENSE00002518147	131718986	131719060
ENSE00002519315	131709201	131709272
ENSE00002524130	131730904	131731038
ENSE00003709819	131744564	131744690

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 96.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.0298 / max 430.7187, expressed in 1813 samples.

Highest expression (Bgee): cardiac muscle of right atrium, ventricle myocardium, myocardium, layer of synovial tissue, skeletal muscle tissue of rectus abdominis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FNIP1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 10 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

13 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	4.9e-07	+0.59	5:131695268:T:C
Artery Aorta	eqtl	5.6e-04	-0.33	5:131678690:A:G
Whole Blood	eqtl	8.8e-04	-0.07	5:131555408:C:T
Esophagus Muscularis	eqtl	1.1e-03	-0.14	5:131905150:C:A
Spleen	eqtl	1.4e-02	+0.20	5:131402619:A:AAAG
Colon Transverse	sqtl	1.8e-02	+0.77	5:131154560:C:T
Esophagus Muscularis	sqtl	2.7e-02	-0.98	5:130826091:T:C
Cells Cultured fibroblasts	eqtl	2.9e-02	+0.08	5:131884317:C:G
Adipose Subcutaneous	eqtl	3.1e-02	+0.27	5:132477630:C:T
Artery Tibial	eqtl	3.5e-02	+0.31	5:132417792:C:T
Lung	eqtl	3.9e-02	+0.29	5:131339668:G:A
Brain Cortex	eqtl	4.2e-02	+0.38	5:132672519:T:C
Muscle Skeletal	eqtl	4.7e-02	+0.10	5:132008665:T:C

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
63273	18.9310	1813
63272	0.6093	264
63274	0.4895	220

Top tissues by expression

showing 100 of 257 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	96.03	gold quality
left ventricle myocardium	UBERON:0006566	95.68	gold quality
myocardium	UBERON:0002349	94.31	gold quality
layer of synovial tissue	UBERON:0007616	94.19	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.96	gold quality
corpus callosum	UBERON:0002336	93.85	gold quality
epithelial cell of pancreas	CL:0000083	93.80	gold quality
vastus lateralis	UBERON:0001379	93.45	gold quality
pancreatic ductal cell	CL:0002079	93.22	gold quality
deltoid	UBERON:0001476	93.05	gold quality
calcaneal tendon	UBERON:0003701	92.99	gold quality
quadriceps femoris	UBERON:0001377	92.94	gold quality
subthalamic nucleus	UBERON:0001906	92.91	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.71	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.65	gold quality
inferior vagus X ganglion	UBERON:0005363	92.55	gold quality
biceps brachii	UBERON:0001507	92.50	gold quality
synovial joint	UBERON:0002217	92.48	gold quality
tibia	UBERON:0000979	92.35	gold quality
lateral globus pallidus	UBERON:0002476	92.27	gold quality
dorsal plus ventral thalamus	UBERON:0001897	92.21	gold quality
heart right ventricle	UBERON:0002080	92.09	gold quality
substantia nigra pars compacta	UBERON:0001965	91.87	gold quality
saphenous vein	UBERON:0007318	91.73	gold quality
skeletal muscle tissue	UBERON:0001134	91.42	gold quality
medulla oblongata	UBERON:0001896	91.35	gold quality
tibialis anterior	UBERON:0001385	91.31	gold quality
penis	UBERON:0000989	91.26	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.07	gold quality
urethra	UBERON:0000057	91.02	gold quality
visceral pleura	UBERON:0002401	90.97	gold quality
cartilage tissue	UBERON:0002418	90.95	gold quality
ventral tegmental area	UBERON:0002691	90.90	gold quality
vena cava	UBERON:0004087	90.85	gold quality
muscle tissue	UBERON:0002385	90.71	gold quality
superior surface of tongue	UBERON:0007371	90.71	gold quality
globus pallidus	UBERON:0001875	90.69	gold quality
upper arm skin	UBERON:0004263	90.64	gold quality
cardia of stomach	UBERON:0001162	90.61	gold quality
superior vestibular nucleus	UBERON:0007227	90.55	gold quality
body of tongue	UBERON:0011876	90.52	gold quality
amniotic fluid	UBERON:0000173	90.45	gold quality
tongue	UBERON:0001723	90.42	gold quality
pericardium	UBERON:0002407	90.37	gold quality
kidney epithelium	UBERON:0004819	90.20	silver quality
blood	UBERON:0000178	90.07	gold quality
medial globus pallidus	UBERON:0002477	90.01	gold quality
pylorus	UBERON:0001166	89.81	gold quality
nasal cavity epithelium	UBERON:0005384	89.78	silver quality
bone marrow cell	CL:0002092	89.77	gold quality
parietal pleura	UBERON:0002400	89.75	gold quality
jejunum	UBERON:0002115	89.70	gold quality
pons	UBERON:0000988	89.62	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.40	gold quality
bone marrow	UBERON:0002371	89.26	gold quality
pharyngeal mucosa	UBERON:0000355	89.10	gold quality
tendon	UBERON:0000043	88.89	gold quality
trachea	UBERON:0003126	88.70	gold quality
parietal lobe	UBERON:0001872	88.63	gold quality
nipple	UBERON:0002030	88.50	gold quality
buccal mucosa cell	CL:0002336	88.48	gold quality
trabecular bone tissue	UBERON:0002483	88.42	gold quality
thymus	UBERON:0002370	88.40	gold quality
entorhinal cortex	UBERON:0002728	88.35	gold quality
palpebral conjunctiva	UBERON:0001812	88.33	gold quality
postcentral gyrus	UBERON:0002581	88.19	gold quality
renal medulla	UBERON:0000362	88.09	gold quality
trigeminal ganglion	UBERON:0001675	87.87	gold quality
seminal vesicle	UBERON:0000998	87.84	gold quality
adrenal tissue	UBERON:0018303	87.83	gold quality
oviduct epithelium	UBERON:0004804	87.78	gold quality
endothelial cell	CL:0000115	87.75	gold quality
mammalian vulva	UBERON:0000997	87.51	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.50	gold quality
jejunal mucosa	UBERON:0000399	87.48	gold quality
cauda epididymis	UBERON:0004360	87.42	gold quality
esophagus squamous epithelium	UBERON:0006920	87.41	gold quality
sperm	CL:0000019	87.11	gold quality
dorsal root ganglion	UBERON:0000044	86.90	gold quality
superficial temporal artery	UBERON:0001614	86.73	gold quality
eye	UBERON:0000970	86.70	gold quality
cerebellar vermis	UBERON:0004720	86.69	gold quality
skin of hip	UBERON:0001554	86.59	gold quality
superior frontal gyrus	UBERON:0002661	86.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.55	gold quality
colonic epithelium	UBERON:0000397	86.51	gold quality
germinal epithelium of ovary	UBERON:0001304	86.34	gold quality
parotid gland	UBERON:0001831	86.15	gold quality
occipital lobe	UBERON:0002021	86.12	gold quality
endometrium	UBERON:0001295	85.98	gold quality
islet of Langerhans	UBERON:0000006	85.97	gold quality
caput epididymis	UBERON:0004358	85.95	gold quality
mammary gland	UBERON:0001911	85.87	gold quality
thoracic mammary gland	UBERON:0005200	85.85	gold quality
middle temporal gyrus	UBERON:0002771	85.59	gold quality
corpus epididymis	UBERON:0004359	85.29	gold quality
decidua	UBERON:0002450	85.21	gold quality
gastrocnemius	UBERON:0001388	85.18	gold quality
muscle of leg	UBERON:0001383	85.06	gold quality
lower lobe of lung	UBERON:0008949	85.04	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-124858	no	522.50
E-MTAB-10290	no	127.78
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Corpus callosum	tissue	60.8
Nucleus accumbens	tissue	43.1
Putamen	tissue	41.7
Ventral forebrain	tissue	36.4
Postcentral gyrus	tissue	34.0
Hippocampus	tissue	33.6	low
Midbrain	tissue	31.2
Basal ganglia	tissue	30.7	low
Medulla oblongata	tissue	30.6
Locus coeruleus	tissue	30.6
Choroid plexus	tissue	30.5
Substantia nigra	tissue	30.5
Septum	tissue	30.4
Hippocampal formation	tissue	29.2
Thalamus	tissue	28.7
Spinal cord	tissue	28.5
Cerebellum	tissue	28.2	low
Cerebral cortex	tissue	28.1	low
Occipital cortex	tissue	28.1
Somatosensory cortex	tissue	27.9
Superior colliculi	tissue	27.8
Periaqueductal gray	tissue	27.7
Pons	tissue	27.3
Olfactory bulb	tissue	27.2
Hypothalamus	tissue	26.4
Retrosplenial cortex	tissue	26.4
Retrosplenial and cingulate cortex	tissue	26.0
Motor cortex	tissue	25.6
Entorhinal cortex	tissue	24.9
Amygdala	tissue	24.7
Insular cortex	tissue	24.1
Prefrontal cortex	tissue	23.8
Temporal cortex	tissue	23.3
Caudate putamen	tissue	22.7
Frontal cortex	tissue	18.9
Bone marrow	tissue	15.0	medium
Tongue	tissue	13.3
Testis	tissue	12.9	medium
Parathyroid gland	tissue	12.1	not detected
Skeletal muscle	tissue	11.8	medium
Liver	tissue	11.3	medium
Ovary	tissue	9.9	medium
Thyroid gland	tissue	9.8	low
Adipose tissue	tissue	9.5	low
Endometrium 1	tissue	8.6	medium
Breast	tissue	8.3	medium
Heart muscle	tissue	8.3	medium
Adrenal gland	tissue	7.9	medium
Prostate	tissue	7.7	low
Duodenum	tissue	7.6	high
Gallbladder	tissue	7.5	medium
Placenta	tissue	7.2	medium
Cervix	tissue	7.0	medium
Stomach 1	tissue	7.0	high
Kidney	tissue	7.0	medium
Smooth muscle	tissue	6.9	medium
Retina	tissue	6.6
Spleen	tissue	6.6	low
Small intestine	tissue	6.6	high
Skin 1	tissue	6.5	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Parieto-temporal junction (white matter) (80.0), Corpus callosum, splenium (white matter) (75.9), Corpus callosum, genu (white matter) (73.6), Temporal white matter (68.3), Angular gyrus (white matter) (63.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PRKAA1, PRKAB1, PRKAG1

miRNA regulators (miRDB)

Targeting FNIP1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 189 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4682	100.00	68.89	1258
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.394, missense Z 2.69 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000510461 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
5:131,644,688–131,651,903	67 / 115.2	0.58	no
5:131,651,904–131,796,921	1109 / 1288.5	0.86	no

Literature-anchored findings (GeneRIF, showing 12)

• Results suggest that FLCN, mutated in Birt-Hogg-Dube syndrome, and its interacting partner FNIP1 may be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways. (PMID:17028174)
• The FLCN-FNIP complex deregulated in Birt-Hogg-Dube syndrome is absolutely required for B-cell differentiation. (PMID:22709692)
• Based on previous studies and gene ontology database, we found that POLQ encoding DNA polymerase theta enzyme and FNIP1 encoding tumor suppressor folliculin-interacting protein might have contributed to the Interdigitating dendritic cell sarcoma (IDCS). Our study provides potential causative genetic factors of IDCS and plays a role in advancing the understanding of IDCS pathogenesis (PMID:30099721)
• casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90. (PMID:30699359)
• Mutations of the gene FNIP1 associated with a syndromic autosomal recessive immunodeficiency with cardiomyopathy and pre-excitation syndrome. (PMID:32181500)
• Absent B cells, agammaglobulinemia, and hypertrophic cardiomyopathy in folliculin-interacting protein 1 deficiency. (PMID:32905580)
• A Cellular Mechanism to Detect and Alleviate Reductive Stress. (PMID:32941802)
• Loss of FLCN-FNIP1/2 induces a non-canonical interferon response in human renal tubular epithelial cells. (PMID:33459596)
• Familial multiple discoid fibromas is linked to a locus on chromosome 5 including the FNIP1 gene. (PMID:36599954)
• Induction of lysosomal and mitochondrial biogenesis by AMPK phosphorylation of FNIP1. (PMID:37079666)
• Direct regulation of FNIP1 and FNIP2 by MEF2 sustains MTORC1 activation and tumor progression in pancreatic cancer. (PMID:37772772)
• Muscle-bone cross-talk through the FNIP1-TFEB-IGF2 axis is associated with bone metabolism in human and mouse. (PMID:38838134)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fnip1	ENSDARG00000102171
mus_musculus	Fnip1	ENSMUSG00000035992
rattus_norvegicus	Fnip1	ENSRNOG00000009104
drosophila_melanogaster	CG3764	FBGN0036684
caenorhabditis_elegans		WBGENE00020208

Paralogs (1): FNIP2 (ENSG00000052795)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2444668) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 91 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal skeletal muscle morphology	3
absent B cells	3
enlarged heart	2
small spleen	2
cardiac hypertrophy	2
arrested B cell differentiation	2
decreased IgM level	2
decreased B-1 B cell number	2
increased T cell number	2
decreased B cell number	2
increased CD4-positive, alpha-beta T cell number	2
increased B cell apoptosis	2
prolonged QRS complex duration	2
abnormal bone marrow cell number	1
increased neutrophil cell number	1
abnormal heart morphology	1
abnormal cecum morphology	1
abnormal mammary gland morphology	1
abnormal spleen morphology	1
abnormal thymus morphology	1
small thymus	1
enlarged thymus	1
decreased body weight	1
increased anxiety-related response	1
decreased locomotor activity	1

+66 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gallus gallus	Q5W4S4	76.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
IL3-AS1	ncRNA	105379174
ACSL6-AS2	ncRNA	124901062
ACSL6	protein-coding	23305
IL3	protein-coding	3562
MEIKIN	protein-coding	728637
RAPGEF6	protein-coding	51735
CDC42SE2	protein-coding	56990
LYRM7	protein-coding	90624
ACSL6-AS1	ncRNA	101927693
CSF2	protein-coding	1437
HINT1	protein-coding	3094

Protein

Protein identifiers

Folliculin-interacting protein 1 — Q8TF40 (reviewed: Q8TF40)

All UniProt accessions (2): Q8TF40, J3KNG8

UniProt curated annotations — full annotation on UniProt →

Function. 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. Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases, leading to activation of the non-canonical mTORC1 signaling. 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. 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. Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy. 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. Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90. Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins. 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. Required for B-cell development.

Subunit / interactions. Homodimer and homomultimer. Heterodimer and heteromultimer with FNIP2. Interacts with FLCN (via C-terminus). Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator. Interacts with HSPCA and with the PRKAA1, PRKAB1 and PRKAG1 subunits of 5’-AMP-activated protein kinase (AMPK). Phosphorylated FLCN and AMPK are preferentially bound. Interacts with HSP70, STIP1, PTGES3, CDC37, BRAF, GCR and CDK4. Interacts with HSP90AA1; the interaction inhibits HSP90AA1 ATPase activity. Interacts with ATP2A2.

Subcellular location. Lysosome membrane. Cytoplasm. Cytosol.

Tissue specificity. Strong expression is found in the heart, liver placenta, muscle, nasal mucosa, salivary gland and uvula and moderate expression in kidney and lung. Higher levels detected in clear cell renal cell carcinoma (RCC) and chromophobe RCC than in normal kidney tissue. Expressed in peripheral blood mononuclear cells.

Post-translational modifications. Phosphorylated by AMPK in response to energetic stress. Phosphorylation by AMPK in response to mitochondrial damage promotes inactivation of the non-canonical mTORC1 signaling, nuclear translocation of TFEB and TFE3, inducing transcription of lysosomal or autophagy genes. Sequential phosphorylation by CK2 promotes its gradual interaction with HSP90AA1/Hsp90. Priming phosphorylation at Ser-938 is followed by relay phosphorylation at Ser-939, Ser-941, Ser-946 and Ser-948, promoting its gradual interaction with HSP90AA1/Hsp90. This leads to incremental inhibition of HSP90AA1/Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients. Dephosphorylated by protein phosphatase 5 (PP5), promoting glycosylation by OGT. GlcNAcylation at Ser-938 by OGT following dephosphorylation by protein phosphatase 5 (PP5) promotes ubiquitination and degradation by the proteasome. Ubiquitinated through ‘Lys-11’ linkage of ubiquitin moieties at Lys-1119 following glycosylation by OGT, leading to its degradation by the proteasome. Ubiquitinated by the CRL2(FEM1B) complex in response to reductive stress: reductive stress causes reduction of the conserved Cys degron in FNIP1, followed by zinc-binding, zinc acting as a molecular glue for recognition by the CRL2(FEM1B) complex. Ubiquitination leads to FNIP1 degradation, and activation of mitochondria to recalibrate reactive oxygen species (ROS). Oxidation of the Cys degron in normal conditions promotes its stabilization by preventing recognition and ubiquitination by the CRL2(FEM1B) complex.

Disease relevance. Immunodeficiency 93 and hypertrophic cardiomyopathy (IMD93) [MIM:619705] An autosomal recessive disorder characterized by onset of recurrent viral and bacterial infections, particularly with encapsulated bacteria, and hypertrophic cardiomyopathy in the first months or years of life. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The KY-finger orients the Cys degron for ubiquitination by the CRL2(FEM1B) complex.

Similarity. Belongs to the FNIP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8TF40-1	1	yes
Q8TF40-2	2
Q8TF40-3	3

RefSeq proteins (4): NP_001008738, NP_001333042, NP_001333043, NP_588613* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026156	FNIP_fam	Family
IPR028084	FNIP_N_dom	Domain
IPR028085	FNIP_mid_dom	Domain
IPR028086	FNIP_C_dom	Domain
IPR037545	DENN_FNIP1/2	Domain

Pfam: PF14636, PF14637, PF14638

UniProt features (53 total): modified residue 15, mutagenesis site 10, sequence variant 7, binding site 5, region of interest 4, domain 3, splice variant 3, compositionally biased region 2, chain 1, glycosylation site 1, cross-link 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
8JE2	Cryo-EM structure of neddylated Cul2-Rbx1-EloBC-FEM1B complexed with FNIP1-FLCN	ELECTRON MICROSCOPY	3.63

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TF40-F1	55.41	0.16

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5)

Position	Role
608	Zn(2+)
610	Zn(2+)
613	Zn(2+)
615	Zn(2+)

Post-translational modifications (16)

Type	Positions
Phosphoserine	220, 230, 232, 261, 296, 593, 594, 760, 763, 938, 939, 941, 946, 948
Phosphothreonine	294
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in ubiquitin)	1119

Glycosylation sites (1)

Type	Positions
O-linked (glcnac) serine	938

Mutagenesis-validated functional residues (10)

Position	Phenotype
220	in sa5 mutant; abolishes phosphorylation by ampk, leading to activation of the non-canonical mtorc1 signaling; when associated with …
230–232	in sa5 mutant; abolishes phosphorylation by ampk, leading to activation of the non-canonical mtorc1 signaling; when associated with a-220 …
261	in sa5 mutant; abolishes phosphorylation by ampk, leading to activation of the non-canonical mtorc1 signaling; when associated with a-220 …
593	in sa5 mutant; abolishes phosphorylation by ampk, leading to activation of the non-canonical mtorc1 signaling; when associated with a-220 …
938–948	mimics phosphorylation status; leading to inhibit atpase activity of hsp90aa1/hsp90.
938	impaired phosphorylation by ck2 and interaction with hsp90aa1/hsp90.
982	no effect on ubiquitination and protein stability.
1117	no effect on ubiquitination and protein stability.
1119	impaired ubiquitination, leading to increased stability.
1134	no effect on ubiquitination and protein stability.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-9639288	Amino acids regulate mTORC1	curated
R-HSA-9711097	Cellular response to starvation	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—

MSigDB gene sets: 294 (showing top): GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS, ACTACCT_MIR196A_MIR196B, GOBP_VACUOLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_B_CELL_ACTIVATION, GOCC_VACUOLAR_MEMBRANE, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS, TATTATA_MIR374, GOBP_REGULATION_OF_VACUOLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (11): negative regulation of transcription by RNA polymerase II (GO:0000122), immature B cell differentiation (GO:0002327), positive regulation of B cell apoptotic process (GO:0002904), cellular response to starvation (GO:0009267), B cell differentiation (GO:0030183), positive regulation of protein-containing complex assembly (GO:0031334), negative regulation of TOR signaling (GO:0032007), positive regulation of TOR signaling (GO:0032008), positive regulation of TORC1 signaling (GO:1904263), negative regulation of lysosome organization (GO:1905672), regulation of pro-B cell differentiation (GO:2000973)

GO Molecular Function (6): enzyme activator activity (GO:0008047), enzyme binding (GO:0019899), ATPase inhibitor activity (GO:0042030), metal ion binding (GO:0046872), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), cytosol (GO:0005829)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Cellular response to starvation	1
Cellular responses to stimuli	1
Cellular responses to stress	1

GO top-level categories

41 GO namespaces:

Category	Terms
TOR signaling	2
regulation of TOR signaling	2
protein binding	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
B cell differentiation	1
B cell apoptotic process	1
regulation of B cell apoptotic process	1
positive regulation of lymphocyte apoptotic process	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
lymphocyte differentiation	1
B cell activation	1
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
negative regulation of intracellular signal transduction	1
positive regulation of intracellular signal transduction	1
positive regulation of TOR signaling	1
TORC1 signaling	1
regulation of TORC1 signaling	1
lysosome organization	1
negative regulation of organelle organization	1
regulation of lysosome organization	1
pro-B cell differentiation	1
regulation of lymphoid progenitor cell differentiation	1
catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
ATP-dependent activity	1
molecular function inhibitor activity	1
cation binding	1
binding	1
intracellular anatomical structure	1
lysosome	1
lytic vacuole membrane	1
cytoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 13 of 20 annotations. The rest are phylogenetic / computational / electronic (IEA).

13 experimentally-supported GO terms:

GO term	NS	Evidence
B cell differentiation	BP	mutant phenotype
negative regulation of lysosome organization	BP	direct assay
negative regulation of transcription by RNA polymerase II	BP	direct assay
positive regulation of TOR signaling	BP	direct assay
positive regulation of TORC1 signaling	BP	direct assay
positive regulation of protein-containing complex assembly	BP	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
lysosomal membrane	CC	direct assay
ATPase inhibitor activity	MF	direct assay
enzyme activator activity	MF	direct assay
enzyme binding	MF	physical interaction
protein-folding chaperone binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,902 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FNIP1	FLCN	Q8NFG4	978
FNIP1	PRKAG1	P54619	774
FNIP1	MTOR	P42345	771
FNIP1	PRKAA1	Q13131	711
FNIP1	PRKAB1	Q9Y478	691
FNIP1	RRAGC	Q9HB90	678
FNIP1	SLC38A9	Q8NBW4	634
FNIP1	NPRL3	Q12980	633
FNIP1	TSC2	P49815	614
FNIP1	RRAGD	Q9NQL2	611
FNIP1	WDR24	Q96S15	599
FNIP1	SMCR8	Q8TEV9	599
FNIP1	AGRP	O00253	598
FNIP1	FEM1B	Q9UK73	588
FNIP1	DEPDC5	O75140	571

IntAct

Human interaction partners of FNIP1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
FNIP2	physical association	0.620	4
FLCN	association	0.560	4
ORF	physical association	0.560	1
GABARAP	direct interaction	0.520	1
GABARAPL1	direct interaction	0.520	1
GABARAPL2	direct interaction	0.440	1
MAP1LC3B	direct interaction	0.440	1
MAP1LC3C	direct interaction	0.440	1
CFTR	physical association	0.370	1
PRKAG1	association	0.350	2

BioGRID (65 interactions; top human partners by supporting records): FLCN (Affinity Capture-Western; 11 records), HSP90AA1 (Affinity Capture-Western; 5 records), COPS5 (Affinity Capture-MS; 3 records), PRKAA1 (Reconstituted Complex; 3 records), BTRC (Affinity Capture-MS; 2 records), FBXW11 (Affinity Capture-MS; 2 records), FNIP2 (Affinity Capture-Western; 2 records), PRKAG1 (Affinity Capture-MS; 2 records), AGO2 (Affinity Capture-RNA), BRAF (Affinity Capture-Western), CDC37 (Affinity Capture-Western), CDK4 (Affinity Capture-Western), CFTR (PCA), CUL2 (Biochemical Activity), CUL3 (Affinity Capture-MS)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
FNIP1	“down-regulates activity”	HSP90AA1	binding
FNIP1	“down-regulates activity”	HSP90AB1	binding

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
★ FNIP1-FNIP2-HSP90AA1 complex	3	HSP90AA1, FNIP1, FNIP2
★ FNIP1-HSP90AA1-TSC1 complex	3	HSP90AA1, TSC1, FNIP1
★ FNIP1-HSP90AA1 complex	2	HSP90AA1, FNIP1

Disease & clinical

Genetic variants

Variant evidence for FNIP1: 500 ClinVar records (28 pathogenic / likely pathogenic); 20 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

500 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	25
Likely pathogenic	3
Uncertain significance	198
Likely benign	225
Benign	24

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 28 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1335873	NM_133372.3(FNIP1):c.868C>T (p.Arg290Ter)	Pathogenic	criteria provided, single submitter	2
1928651	NM_133372.3(FNIP1):c.157C>T (p.Arg53Ter)	Pathogenic	criteria provided, single submitter	1
2025700	NM_133372.3(FNIP1):c.2922dup (p.Glu975Ter)	Pathogenic	criteria provided, single submitter	1
2031591	NM_133372.3(FNIP1):c.2833dup (p.Asp945fs)	Pathogenic	criteria provided, single submitter	1
2114300	NM_133372.3(FNIP1):c.1243_1250del (p.Glu415fs)	Pathogenic	criteria provided, single submitter	1
2804561	NM_133372.3(FNIP1):c.2108_2109del (p.Glu703fs)	Pathogenic	criteria provided, single submitter	1
2809950	NM_133372.3(FNIP1):c.1666_1676dup (p.Asp559fs)	Pathogenic	criteria provided, single submitter	1
2839600	NM_133372.3(FNIP1):c.1174C>T (p.Arg392Ter)	Pathogenic	criteria provided, single submitter	1
3651218	NM_133372.3(FNIP1):c.1234C>T (p.Arg412Ter)	Pathogenic	criteria provided, single submitter	1
3653139	NM_133372.3(FNIP1):c.2889dup (p.Gly964fs)	Pathogenic	criteria provided, single submitter	1
3663844	NM_133372.3(FNIP1):c.225_226del (p.Gly76fs)	Pathogenic	criteria provided, single submitter	1
3669058	NM_133372.3(FNIP1):c.859C>T (p.Arg287Ter)	Pathogenic	criteria provided, single submitter	1
3670425	NM_133372.3(FNIP1):c.3372C>A (p.Tyr1124Ter)	Pathogenic	criteria provided, single submitter	1
3711756	NM_133372.3(FNIP1):c.2047del (p.Cys683fs)	Pathogenic	criteria provided, single submitter	1
4698435	NM_133372.3(FNIP1):c.2302C>T (p.Arg768Ter)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore FNIP1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 21 predictions of 1,665):

Position(s)	Effect	Δscore	Sites
5:131651882	donor_gain	1.0000
5:131651886	donor_gain	1.0000
5:131651899	donor_gain	1.0000
5:131670461–131670462	donor_loss	1.0000	5
5:131670632–131670633	acceptor_loss	1.0000	3
5:131679032	donor_gain	1.0000
5:131679047	donor_gain	1.0000
5:131699004	acceptor_gain	1.0000
5:131704063–131704064	donor_loss	1.0000	4
5:131704267–131704268	acceptor_loss	1.0000	3

AlphaMissense

2,946 missense substitutions predicted likely pathogenic (of 7,767 scored), across 647 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M132	9	0.986	0.999
M133	9	0.937	0.998
M139	9	0.933	0.999
M128	9	0.926	0.992
M1120	9	0.896	0.987
M158	9	0.895	0.999
M471	9	0.893	0.980
M1105	9	0.859	0.968
H149	8	0.997	1.000
D940	8	0.991	0.997
D1109	8	0.991	0.998
D1146	8	0.990	0.997
F134	8	0.989	1.000
D508	8	0.989	0.997
D49	8	0.987	0.998
D60	8	0.987	0.995
F163	8	0.981	0.999
H463	8	0.978	0.996
F753	8	0.978	0.999
F353	8	0.973	0.997

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	6.93e-05
Ovary Serous Cystadenocarcinoma (validation)	unfavorable	0.000536

Disease associations

OMIM: gene MIM:610594 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
immunodeficiency 93 and hypertrophic cardiomyopathy	Strong	Autosomal recessive	2

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
FNIP1-associated syndrome	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (3 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

3 panels:

Panel	Rating
Primary immunodeficiency or monogenic inflammatory bowel disease	green
Paediatric or syndromic cardiomyopathy	amber
Unexplained death in infancy and sudden unexplained death in childhood	amber

Mondo (1): (MONDO:0030528)

Orphanet (1): Agammaglobulinemia-early-onset hypertrophic cardiomyopathy-neutropenia syndrome (Orphanet:693647)

HPO phenotypes

21 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001263	Global developmental delay
HP:0001639	Hypertrophic cardiomyopathy
HP:0001716	Wolff-Parkinson-White syndrome
HP:0001875	Decreased total neutrophil count
HP:0002110	Bronchiectasis
HP:0002136	Broad-based gait
HP:0002194	Delayed gross motor development
HP:0002850	Decreased circulating IgM concentration
HP:0003593	Infantile onset
HP:0004315	Decreased circulating IgG concentration
HP:0004432	Agammaglobulinemia
HP:0005133	Right ventricular dilatation
HP:0005180	Tricuspid regurgitation
HP:0010862	Delayed fine motor development
HP:0010976	Decreased total B cell count
HP:0012389	Appendicular hypotonia
HP:0030252	Absent circulating B cells
HP:0030388	Decreased class-switched memory B cell proportion
HP:0033542	Bronchial wall thickening
HP:0100280	Crohn’s disease

GWAS associations

20 associations:

Study	Trait	p-value
GCST004132_104	Crohn’s disease	6e-36
GCST004861_47	Itch intensity from mosquito bite	1e-30
GCST004131_32	Inflammatory bowel disease	4e-27
GCST010701_3	Cortical surface area (MOSTest)	1e-20
GCST004862_233	Itch intensity from mosquito bite adjusted by bite size	1e-17
GCST004865_90	Itch intensity from mosquito bite adjusted by bite size	4e-17
GCST004863_127	Mosquito bite size	3e-16
GCST90013663_6	Alanine aminotransferase levels	2e-12
GCST004624_86	Sum eosinophil basophil counts	3e-10
GCST004606_56	Eosinophil count	4e-10
GCST004862_61	Itch intensity from mosquito bite adjusted by bite size	1e-9
GCST004862_175	Itch intensity from mosquito bite adjusted by bite size	3e-9
GCST010703_310	Brain morphology (MOSTest)	3e-9
GCST90013664_103	Aspartate aminotransferase levels	1e-8
GCST010702_71	Subcortical volume (MOSTest)	2e-8
GCST011956_122	Systemic lupus erythematosus	4e-8
GCST002817_2	Alzheimer’s disease in APOE e4- carriers	3e-7
GCST002817_1	Alzheimer’s disease in APOE e4- carriers	4e-7
GCST002875_45	Diisocyanate-induced asthma	1e-6
GCST004133_15	Ulcerative colitis	2e-6

EFO canonical traits (from GWAS)

7 canonical traits:

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0004842	eosinophil count
EFO:0005090	basophil count
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004346	neuroimaging measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5291519 (SINGLE PROTEIN), CHEMBL5291963 (PROTEIN-PROTEIN INTERACTION)

PharmGKB: 1 entry (CPIC guideline: no)

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.17	IC50	670	nM	CHEMBL5289726
5.66	IC50	2200	nM	CHEMBL5289726

PubChem BioAssay actives

3 with measured affinity, of 3 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-chloro-N-(2-cyanoethyl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)acetamide	1939927: Inhibition of FNIP1 in human HEK293T cells	ic50	0.6700	uM

CTD chemical–gene interactions

59 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases expression, decreases expression, affects cotreatment, increases abundance, increases oxidation	3
bisphenol A	decreases methylation, increases expression	2
arsenite	decreases reaction, affects expression, affects binding	2
Arsenic Trioxide	affects cotreatment, increases expression	2
Formaldehyde	increases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Dronabinol	decreases expression, increases expression	2
Asbestos, Crocidolite	affects expression, increases expression	2
Cadmium Chloride	increases expression	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
trichostatin A	increases expression	1
dodecyldimethylamine oxide	increases expression	1
sodium arsenite	increases expression	1
didecyldimethylammonium	increases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
pentabromodiphenyl ether	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
14-deoxy-11,12-didehydroandrographolide	increases expression	1
abrine	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5243421	Binding	Inhibition of FNIP1 in human HEK293T cells	A comprehensive review of BET-targeting PROTACs for cancer therapy. — *Bioorg Med Chem*

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_XN86	HAP1 FNIP1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

9 trials:

NCT	Phase	Status	Title
NCT07738107	Phase 1/2	RECRUITING	ATR 1072 in Participants With PRKAG2 Syndrome
NCT00251121	Not specified	COMPLETED	Routine Mini-invasive Electrophysiology Study for Patients Feeling Tachycardia, With a Negative Holter ECG
NCT00873470	Not specified	TERMINATED	Wolff-Parkinson-White Syndrome Anterograde Refractory Period of Accessory Duct
NCT03207373	Not specified	TERMINATED	Stress ECG Test for the Evaluation of the Risk of Sudden Cardiac Death in a Paediatric Cohort With WPW Pattern
NCT03301935	Not specified	COMPLETED	Risk Assessment in Patients With Symptomatic- and Asymptomatic Preexcitation
NCT03816033	Not specified	UNKNOWN	Cryotherapy Versus Radiofrequency Catheter Ablation Research Program
NCT04106622	Not specified	UNKNOWN	Accessory Pathway Antegrade Effective Refractory Period Among WPW Patients: the Risk in Relation to the Location
NCT06349109	Not specified	COMPLETED	Physical Activity in Children With Wolff-Parkinson-White Syndrome
NCT07435181	Not specified	NOT_YET_RECRUITING	Comparative Outcomes of Radiofrequency Ablation of Concealed and Manifest Accessory Pathways: a Single Center, Retrospective Observational Study

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for FNIP1 across ~30M SureChEMBL compounds — explore on Sugi Predict.