FLOT2

Summary

FLOT2 (flotillin 2, HGNC:3758) is a protein-coding gene on chromosome 17q11.2, encoding Flotillin-2 (Q14254). May act as a scaffolding protein within caveolar membranes, functionally participating in formation of caveolae or caveolae-like vesicles.

Caveolae are small domains on the inner cell membrane involved in vesicular trafficking and signal transduction. This gene encodes a caveolae-associated, integral membrane protein, which is thought to function in neuronal signaling.

Source: NCBI Gene 2319 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 84 total
• MANE Select transcript: NM_004475

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3758
Approved symbol	FLOT2
Name	flotillin 2
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	ESA, ESA1, ECS-1, ECS1
Ensembl gene	ENSG00000132589
Ensembl biotype	protein_coding
OMIM	131560
Entrez	2319

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 11 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000394906, ENST00000394908, ENST00000465427, ENST00000577789, ENST00000580313, ENST00000580805, ENST00000581509, ENST00000582174, ENST00000584569, ENST00000585169, ENST00000586827, ENST00000593158, ENST00000856824, ENST00000856825, ENST00000912298, ENST00000912299, ENST00000912300, ENST00000946599, ENST00000946600

RefSeq mRNA: 2 — MANE Select: NM_004475 NM_001330170, NM_004475

CCDS: CCDS11245, CCDS82097

Canonical transcript exons

ENST00000394908 — 11 exons

Exon	Start	End
ENSE00002779819	28897526	28897733
ENSE00003491605	28882118	28882237
ENSE00003541961	28882337	28882450
ENSE00003558618	28888945	28889026
ENSE00003578438	28884225	28884315
ENSE00003618140	28881814	28882028
ENSE00003662058	28883108	28883231
ENSE00003667163	28881192	28881375
ENSE00003669364	28880713	28880862
ENSE00003670531	28882573	28882691
ENSE00003845045	28879339	28880599

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 98.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.2695 / max 550.3691, expressed in 1819 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165093	30.8797	1819
165092	0.3096	144
165090	0.0758	16
165089	0.0044	2

Top tissues by expression

292 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.19	gold quality
monocyte	CL:0000576	97.19	gold quality
spleen	UBERON:0002106	97.18	gold quality
leukocyte	CL:0000738	97.17	gold quality
mononuclear cell	CL:0000842	97.06	gold quality
blood	UBERON:0000178	96.85	gold quality
mucosa of stomach	UBERON:0001199	96.48	gold quality
apex of heart	UBERON:0002098	96.43	gold quality
metanephros cortex	UBERON:0010533	96.34	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.15	gold quality
lymph node	UBERON:0000029	96.11	gold quality
minor salivary gland	UBERON:0001830	95.98	gold quality
right lung	UBERON:0002167	95.98	gold quality
lower esophagus	UBERON:0013473	95.95	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.95	gold quality
popliteal artery	UBERON:0002250	95.83	gold quality
tibial artery	UBERON:0007610	95.83	gold quality
descending thoracic aorta	UBERON:0002345	95.79	gold quality
upper lobe of left lung	UBERON:0008952	95.79	gold quality
left coronary artery	UBERON:0001626	95.74	gold quality
ventricular zone	UBERON:0003053	95.66	gold quality
tonsil	UBERON:0002372	95.65	gold quality
aorta	UBERON:0000947	95.51	gold quality
right uterine tube	UBERON:0001302	95.50	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.47	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.41	gold quality
esophagus	UBERON:0001043	95.37	gold quality
coronary artery	UBERON:0001621	95.36	gold quality
right lobe of liver	UBERON:0001114	95.31	gold quality
upper lobe of lung	UBERON:0008948	95.31	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7606	no	1588.91
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
BACE1	Repression

Upstream regulators (CollecTRI, top): TAF1, TP53, TP63

miRNA regulators (miRDB)

90 targeting FLOT2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-4306	99.72	70.50	3630

Literature-anchored findings (GeneRIF, showing 40)

• Flot-2 overexpression is associated with melanoma progression, with increased PAR-1 expression, and with transformation of SB2 melanoma cells to a highly metastatic line. (PMID:15492257)
• flotillin-2 identified and immunolocalized in the caveola-vesicle complexes (CVC )present in erythrocytes infected with P. vivax (PMID:16521037)
• flotillin-2 has a role in lymph node metastasis in melanoma (PMID:17013097)
• The results showed that flotillin-1 can interact with arginase1, and hence arginase activity was up-regulated by 26.8%. (PMID:17113085)
• These lines of evidence suggested that a Gq-coupled receptor activates specifically p38 MAPK through lipid rafts and Src kinase activation, in which flotillins positively modulate the Gq signaling. (PMID:17307333)
• Coassembly of flotillin1 and flotillin2 into microdomains induces membrane curvature, the formation of plasma-membrane invaginations morphologically similar to caveolae, and the accumulation of intracellular vesicles. (PMID:17600709)
• Reggie-1/flotillin-2 microdomains form independent of actin (PMID:17854803)
• deletion mutants of reggie-1/flotillin-2 accumulate in the Golgi complex in HeLa and Jurkat cells, suggesting Golgi-dependent trafficking of reggie-1/flotillin-2 (PMID:18237819)
• Flotillin 2 is a direct transcriptional target of the p53 family member genes in human cancer cells. (PMID:18296650)
• The interaction of flotillin-2 with amyloid precursor protein (APP) promotes the clustering of APP at the cell surface. (PMID:18337418)
• Epidermal Growth Factor stimulation of cells, flotillin 2 is tyrosine phosphorylated by Src kinases and endocytosed into late endosomes. (PMID:19318123)
• Flotillin-1 and -2 associate with PSGL-1 in resting and in stimulated neutrophils are importantly involved in neutrophil uropod formation and/or stabilization (PMID:19404397)
• copper modulates flotillin-2 association with cholesterol-rich lipid raft domains, and consequently Abeta synthesis is attenuated via copper-mediated inhibition of APP endocytosis (PMID:19542222)
• These results show that basolateral endocytosis of GPI-anchored proteins in hepatic cells occurs via a clathrin-independent flotillin-2-dependent pathway. (PMID:19605558)
• In hematopoietic cells, flotillins provide intrinsic cues that govern segregation of certain microdomain-associated molecules during immune cell polarization. (PMID:20027317)
• Studies indicate that spatial link between PrP and the microdomain-forming protein flotillins may contribute to PrP signaling, leading to thelocal assembly of membrane protein complexes at sites involved in cellular communication. (PMID:20515742)
• Reggie-1 (flotillin-2) dynamically colocalizes with KIF9 in living cells (PMID:21119006)
• flotillins have a role in NPC1L1-mediated cholesterol uptake and NPC1L1-flotillins-postive cholesterol-enriched membrane microdomains are involved in the mechanism for efficient cholesterol absorption (PMID:21187433)
• potentially relevant protein substrates of DHHC5 (PMID:22081607)
• by promoting EGFR internalization, reggie-1 restricts EGFR signaling involved in E-cadherin macropinocytosis and recycling and regulate adherens junction formation (PMID:22438585)
• Report role for flotillin 1/2 in interactions of lung epithelial cells with silica nanoparticles. (PMID:22669515)
• we describe how flotillin-1 and -2 contribute to the stabilization of ErbB2 at the cell surface in breast cancer tissue (PMID:22869152)
• results support predominant formation of flotillin-1 and -2 hetero-oligomers in resting and chemokine-stimulated human T-cells which may importantly contribute to structuring of the uropod. (PMID:23012365)
• The FLOT2 is abundantly expressed in term villous placental CTs and endothelial cells, and in comparison, expression of these proteins in the ST is reduced. (PMID:23064789)
• Flot2 is an important regulator of mammary tumor-derived lung metastasis (PMID:23146906)
• a positive correlation exists between flotillin2 and erbB2 expression levels (PMID:23658725)
• Results identify reggie-1 as a regulator of the Rab11a/SNX4-controlled sorting and recycling pathway. (PMID:23825023)
• High FLOT2 protein expression was associated with poor outcomes in patients with breast cancer. (PMID:23945257)
• By virtue of its abundant expression in enterocytes, flotillin-2 must have an essential function in intestinal physiology, especially in the colon. (PMID:23983584)
• We have identified flotillin 1 and 2 as new partners of the cadherin complexes (PMID:24046456)
• Flotillins directly interact with gamma-catenin and regulate epithelial cell-cell adhesion. (PMID:24391950)
• Depletion of either flotillin-1 or flotillin-2 resulted in downregulation of ErbB3 and a selective reduction of ErbB2-ErbB3 receptor complexes. (PMID:24747692)
• Study suggests the Flot2 protein expression is correlated with cancer progression and poor prognosis in gastric carcinomas, probably due to its role in the regulation of cell proliferation, migration, and invasion in gastric carcinoma cells. (PMID:24854103)
• results suggest that the increased expression of Flot-2 protein is a novel higher sensitivity biomarker that can predict lymph node metastases in NPC. (PMID:25014228)
• Our data suggest that FLOT2 is a novel molecule involved in renal cell carcinoma progression (PMID:25053596)
• Flotillin-2 is plays a role in the initial steps of skeletal myogenesis. (PMID:25105415)
• Flotillin 2 (FLOT2) is a direct target of microRNA-34a and the miR-34a/FLOT2 pathway plays a key role in melanoma proliferation and metastasis. (PMID:25403318)
• Knockdown of FLOT2 decreases breast cancer cell proliferation. Silencing of FLOT2 enhanced the transcriptional activity of FOXO factors by decreasing its phosphorylation through inhibiting the PI3K/Akt signaling pathway. (PMID:25738752)
• Our findings provided that high FLOT2 expression was associated with poor outcomes in non-small cell lung cancer patients (PMID:25755751)
• FLOT2 may serve as an oncogene in the development of cervical cancer (PMID:25755754)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	flot2a	ENSDARG00000004830
danio_rerio	flot2b	ENSDARG00000069774
mus_musculus	Flot2	ENSMUSG00000061981
rattus_norvegicus	Flot2	ENSRNOG00000009681
drosophila_melanogaster	Flo2	FBGN0264078

Paralogs (1): FLOT1 (ENSG00000137312)

Protein

Protein identifiers

Flotillin-2 — Q14254 (reviewed: Q14254)

Alternative names: Epidermal surface antigen, Membrane component chromosome 17 surface marker 1

All UniProt accessions (6): Q14254, E7EMK3, J3QKZ4, J3QLD9, K7EJ47, K7EKW9

UniProt curated annotations — full annotation on UniProt →

Function. May act as a scaffolding protein within caveolar membranes, functionally participating in formation of caveolae or caveolae-like vesicles. May be involved in epidermal cell adhesion and epidermal structure and function.

Subunit / interactions. Heterooligomeric complex of flotillin-1 and flotillin-2 and caveolin-1 and caveolin-2. Interacts with ECPAS.

Subcellular location. Cell membrane. Membrane. Caveola. Endosome.

Tissue specificity. In skin, expressed in epidermis and epidermal appendages but not in dermis. Expressed in all layers of the epidermis except the basal layer. In hair follicles, expressed in the suprabasal layer but not the basal layer. Also expressed in melanoma and carcinoma cell lines, fibroblasts and foreskin melanocytes.

Post-translational modifications. ZDHHC5-catalyzed palmitoylation predominantly occurs at Cys-4. ZDHHC5-catalyzed palmitoylation may be required for the formation of higher-order complexes and for neurite outgrowth in cultured neural stem cells.

Similarity. Belongs to the band 7/mec-2 family. Flotillin subfamily.

RefSeq proteins (2): NP_001317099, NP_004466* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001107	Band_7	Domain
IPR027705	Flotillin_fam	Family
IPR036013	Band_7/SPFH_dom_sf	Homologous_superfamily

Pfam: PF01145

UniProt features (12 total): lipid moiety-binding region 4, mutagenesis site 3, initiator methionine 1, chain 1, sequence conflict 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9L3G	ELECTRON MICROSCOPY	3.58

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14254-F1	82.39	0.38

Functional residue map

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

Post-translational modifications (5): 405, 2, 4, 19, 20

Mutagenesis-validated functional residues (3):

Position	Phenotype
20	loss of zdhhc5-catalyzed palmitoylation; when associated with s-4. partial loss of zdhhc5-catalyzed palmitoylation; when
4	loss of zdhhc5-catalyzed palmitoylation; when associated with s-20. partial loss of zdhhc5-catalyzed palmitoylation; whe
19	partial loss of zdhhc5-catalyzed palmitoylation; when associated with s-4 or s-20. complete loss of palmitoylation; when

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-5213460	RIPK1-mediated regulated necrosis
R-HSA-5675482	Regulation of necroptotic cell death
R-HSA-8849932	Synaptic adhesion-like molecules
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9696264	RND3 GTPase cycle
R-HSA-9696273	RND1 GTPase cycle

MSigDB gene sets: 286 (showing top): GGGACCA_MIR133A_MIR133B, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOCC_SECRETORY_GRANULE, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, chr17q11, BOYLAN_MULTIPLE_MYELOMA_D_DN, CEBPB_01, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, GTGCCTT_MIR506, GOBP_ESTABLISHMENT_OF_CELL_POLARITY

GO Biological Process (13): cell adhesion (GO:0007155), epidermis development (GO:0008544), negative regulation of gene expression (GO:0010629), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), protein localization to plasma membrane raft (GO:0044860), regulation of myoblast differentiation (GO:0045661), protein stabilization (GO:0050821), protein localization to plasma membrane (GO:0072659), anterograde dendritic transport (GO:0098937), regulation of postsynaptic membrane neurotransmitter receptor levels (GO:0099072), negative regulation of amyloid precursor protein catabolic process (GO:1902992), positive regulation of establishment of T cell polarity (GO:1903905), positive regulation of cell-cell adhesion (GO:0022409)

GO Molecular Function (2): protease binding (GO:0002020), protein binding (GO:0005515)

GO Cellular Component (21): uropod (GO:0001931), acrosomal membrane (GO:0002080), endosome (GO:0005768), plasma membrane (GO:0005886), caveola (GO:0005901), adherens junction (GO:0005912), focal adhesion (GO:0005925), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), flotillin complex (GO:0016600), lamellipodium (GO:0030027), endocytic vesicle (GO:0030139), cytoplasmic vesicle (GO:0031410), vesicle (GO:0031982), dendrite cytoplasm (GO:0032839), cell-cell contact zone (GO:0044291), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), glutamatergic synapse (GO:0098978), cortical actin cytoskeleton (GO:0030864), membrane raft (GO:0045121)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	5
Regulated Necrosis	1
RIPK1-mediated regulated necrosis	1
Protein-protein interactions at synapses	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein localization to cell periphery	2
plasma membrane bounded cell projection	2
cytoplasmic vesicle	2
cell-cell junction	2
cellular anatomical structure	2
cytoplasm	2
cellular process	1
tissue development	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
protein localization to membrane raft	1
myoblast differentiation	1
regulation of cell differentiation	1
regulation of protein stability	1
protein localization to membrane	1
dendrite cytoplasm	1
dendritic transport	1
regulation of biological quality	1
amyloid precursor protein catabolic process	1
negative regulation of protein metabolic process	1
regulation of amyloid precursor protein catabolic process	1
establishment of T cell polarity	1
positive regulation of T cell activation	1
regulation of establishment of T cell polarity	1
regulation of cell-cell adhesion	1
positive regulation of cell adhesion	1
cell-cell adhesion	1
enzyme binding	1
binding	1
cell trailing edge	1
acrosomal vesicle	1
secretory granule membrane	1
endomembrane system	1
membrane	1
cell periphery	1
plasma membrane raft	1

Protein interactions and networks

STRING

1440 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FLOT2	CAV1	Q03135	919
FLOT2	STOM	P27105	787
FLOT2	PTOV1	Q86YD1	768
FLOT2	FLOT1	O75955	762
FLOT2	CD81	P18582	761
FLOT2	CBL	P22681	755
FLOT2	CD63	P08962	742
FLOT2	RAB11A	P24410	603
FLOT2	FYN	P06241	591
FLOT2	TSG101	Q99816	574
FLOT2	ANXA2	P07355	556
FLOT2	ZDHHC5	Q9C0B5	548
FLOT2	PARK7	Q99497	543
FLOT2	HSP90AB1	P08238	540
FLOT2	CD9	P21926	537

IntAct

261 interactions, top by confidence:

A	B	Type	Score
FLOT2	FLOT1	psi-mi:“MI:0915”(physical association)	0.770
ETV6	LRP6	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CDCA3	CTDSPL	psi-mi:“MI:0914”(association)	0.670
TCIRG1	ATP6AP2	psi-mi:“MI:0914”(association)	0.640
SLC4A1	FLOT1	psi-mi:“MI:0914”(association)	0.530
FLOT2	MPC2	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	SEC16A	psi-mi:“MI:0914”(association)	0.530
SYNJ2BP	FLOT1	psi-mi:“MI:0914”(association)	0.530
CUL3	ACOT7	psi-mi:“MI:0914”(association)	0.500
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
FLOT2	sifA	psi-mi:“MI:0915”(physical association)	0.470
SLC4A1	SLC2A1	psi-mi:“MI:0403”(colocalization)	0.460
FLOT2	PSEN1	psi-mi:“MI:0914”(association)	0.420
PSEN1	FLOT2	psi-mi:“MI:2364”(proximity)	0.420

BioGRID (533): FLOT2 (Affinity Capture-MS), FLOT2 (Affinity Capture-MS), FLOT2 (Affinity Capture-MS), FLOT2 (Affinity Capture-MS), FLOT2 (Affinity Capture-MS), FLOT2 (Affinity Capture-MS), FLOT2 (Affinity Capture-MS), TMEM79 (Affinity Capture-MS), ABCB6 (Affinity Capture-MS), TBC1D15 (Affinity Capture-MS), MPZL3 (Affinity Capture-MS), DEGS1 (Affinity Capture-MS), MPC2 (Affinity Capture-MS), SLC26A6 (Affinity Capture-MS), FLOT2 (Proximity Label-MS)

ESM2 similar proteins: A3DDR3, A6L6E5, A6LDT3, A6QLR4, A6TSK9, A8MG60, B0K165, B0K9H8, B5YD74, B8DZW4, D2XNQ8, D2XNQ9, D2XNR0, D2XNR1, D2XNR2, O08917, O13127, O26788, O32076, O42305, O61491, O61492, O75955, P63694, P72655, P72929, P9WPR8, P9WPR9, Q08DN8, Q14254, Q21190, Q4V3D6, Q501E6, Q5LG75, Q5RBL4, Q5SJG0, Q5TM70, Q60634, Q64X50, Q67S38

Diamond homologs: A6QLR4, O08917, O13127, O32076, O42305, O61491, O61492, O75955, Q08DN8, Q14254, Q5RBL4, Q5TM70, Q60634, Q767L6, Q7YR41, Q98TZ8, Q9Z1E1, Q9Z2S9, Q8LNW4, Q8LNW6, D2XNR0, Q4V3D6, Q501E6, Q9LV90

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 238 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	6	20.9×	1e-04
EPHA-mediated growth cone collapse	6	15.3×	4e-04
Downstream signal transduction	5	12.8×	3e-03
EPH-ephrin mediated repulsion of cells	8	11.8×	1e-04
Signaling by SCF-KIT	6	10.0×	2e-03
EPH-Ephrin signaling	8	8.9×	4e-04
RHOD GTPase cycle	6	8.2×	6e-03
Extra-nuclear estrogen signaling	7	8.0×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	7	12.3×	1e-03
macroautophagy	7	8.6×	8e-03
protein transport	16	3.6×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2055 predictions. Top by Δscore:

Variant	Effect	Δscore
17:28880708:CATA:C	donor_loss	1.0000
17:28880709:ATAC:A	donor_loss	1.0000
17:28880710:TA:T	donor_loss	1.0000
17:28880711:A:AC	donor_gain	1.0000
17:28880711:ACC:A	donor_loss	1.0000
17:28880712:C:CC	donor_gain	1.0000
17:28880712:C:CG	donor_loss	1.0000
17:28880858:GCAAT:G	acceptor_gain	1.0000
17:28880859:CAAT:C	acceptor_gain	1.0000
17:28880859:CAATC:C	acceptor_gain	1.0000
17:28880860:AAT:A	acceptor_gain	1.0000
17:28880861:AT:A	acceptor_gain	1.0000
17:28880862:TCTAG:T	acceptor_loss	1.0000
17:28880863:C:CC	acceptor_gain	1.0000
17:28880870:G:C	acceptor_gain	1.0000
17:28880870:G:GC	acceptor_gain	1.0000
17:28881188:TCA:T	donor_loss	1.0000
17:28881189:CAC:C	donor_loss	1.0000
17:28881190:A:AC	donor_gain	1.0000
17:28881191:C:CC	donor_gain	1.0000
17:28881191:C:CG	donor_loss	1.0000
17:28881810:TCACT:T	donor_loss	1.0000
17:28881812:A:AC	donor_gain	1.0000
17:28881813:C:CA	donor_gain	1.0000
17:28881871:A:AC	donor_gain	1.0000
17:28881872:C:CC	donor_gain	1.0000
17:28882024:GCTGT:G	acceptor_loss	1.0000
17:28882025:CTGT:C	acceptor_gain	1.0000
17:28882026:TGT:T	acceptor_gain	1.0000
17:28882027:GT:G	acceptor_gain	1.0000

AlphaMissense

2783 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:28882234:C:G	A195P	1.000
17:28882353:C:G	R188P	1.000
17:28882360:C:G	A186P	1.000
17:28882381:C:G	A179P	1.000
17:28882585:G:C	S151R	1.000
17:28882585:G:T	S151R	1.000
17:28882587:T:G	S151R	1.000
17:28883122:A:G	L111P	1.000
17:28883129:C:G	G109R	1.000
17:28883129:C:T	G109R	1.000
17:28883134:A:G	L107P	1.000
17:28882348:C:G	A190P	0.999
17:28882366:C:G	A184P	0.999
17:28882399:C:G	A173P	0.999
17:28882425:A:G	L164P	0.999
17:28882577:A:C	I154S	0.999
17:28882577:A:T	I154N	0.999
17:28882601:C:T	G146D	0.999
17:28882602:C:G	G146R	0.999
17:28882625:G:T	A138E	0.999
17:28882626:C:G	A138P	0.999
17:28882649:A:G	F130S	0.999
17:28882685:A:G	L118P	0.999
17:28882691:C:T	G116E	0.999
17:28883120:G:T	R112S	0.999
17:28883128:C:T	G109E	0.999
17:28884229:G:T	A73D	0.999
17:28884236:C:G	G71R	0.999
17:28881937:C:G	R264P	0.998
17:28882019:C:G	A237P	0.998

dbSNP variants (sampled 300 via entrez): RS1000087723 (17:28893859 T>C,G), RS1000197598 (17:28897409 G>A,T), RS1000237236 (17:28887297 G>A), RS1000336539 (17:28893504 C>T), RS1000708204 (17:28893744 C>A), RS1000791877 (17:28887706 T>C,G), RS1000926644 (17:28887844 A>G), RS1001284609 (17:28882264 A>AG), RS1001483613 (17:28888172 C>A), RS1001527761 (17:28881938 G>A), RS1001546248 (17:28888235 G>A), RS1001613644 (17:28894643 T>A,C,G), RS1001695174 (17:28887777 G>A,C), RS1001781137 (17:28894460 C>T), RS1001978566 (17:28881668 G>A)

Disease associations

OMIM: gene MIM:131560 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004601_144	Red blood cell count	2.000000e-12
GCST005993_13	Mean corpuscular hemoglobin	1.000000e-16
GCST012147_10	Declining hemoglobin trajectory in blood donors	1.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0600027	hemoglobin change measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
bisphenol A	decreases expression, increases expression, affects cotreatment	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	3
Air Pollutants	increases oxidation, decreases expression, affects cotreatment, increases abundance, increases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Acetaminophen	decreases expression	2
Cadmium Chloride	increases abundance, increases palmitoylation, increases expression, decreases reaction	2
aristolochic acid I	increases expression	1
napabucasin	decreases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases oxidation, increases abundance	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	decreases expression, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
2-palmitoylglycerol	increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2X8	Abcam HEK293T FLOT2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.