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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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FCHO2
FCH and mu domain containing endocytic adaptor 2
Chromosome 5 · 5q13.2
NCBI Gene: 115548Ensembl: ENSG00000157107.15HGNC: HGNC:25180UniProt: Q0JRZ9
58PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
clathrin-dependent endocytosisprotein bindingclathrin coat assemblyclathrin-coated vesiclecornea transplantationbrain cancerkidney diseasehypothyroidism
✦AI Summary

FCHO2 (FCH and mu domain containing endocytic adaptor 2) is a membrane-binding protein that functions as a critical early-stage regulator of clathrin-mediated endocytosis (CME). The protein contains an F-BAR domain that enables both membrane binding and curvature generation, with specific lipid-binding preferences for phosphatidylserine and phosphoinositides, particularly PI(4,5)P2 1. FCHO2 assembles into ring-like patches at the plasma membrane where it recruits and organizes essential endocytic proteins including AP-2 adaptors, EPS15, and dynamin2 2. Mechanistically, FCHO2's BAR domain-generated membrane curvature drives multiple functional outcomes: it promotes PI(4,5)P2 clustering to enhance clathrin assembly 1, couples endocytic pit growth and lifetime through controlled membrane invagination 3, and activates the Nedd4L ubiquitin ligase for selective cargo sorting during endocytosis 4. FCHO2 mediates both AP-2-dependent transferrin receptor endocytosis and AP-2-independent LDL receptor internalization. Beyond canonical endocytic functions, dysregulated FCHO2 expression associates with disease: elevated FCHO2 correlates with poor pancreatic cancer survival 5, and circular RNA circFCHO2 promotes airway remodeling in COPD through indirect NF-κB pathway activation 6. These findings establish FCHO2 as a multifunctional endocytic organizer whose membrane-sculpting capacity integrates cargo selection with vesicle biogenesis.

Sources cited
1
FCHO2 binds PI(4,5)P2 domains, promotes PI(4,5)P2 clustering at membrane regions, and assembles into ring-like protein patches
PMID: 35044298
2
FCHO2 serves as an early CME initiation protein that is recruited and organized by ITSN1 scaffold protein
PMID: 39580802
3
FCHO2 BAR domain-generated membrane curvature recruits and activates the Nedd4L ubiquitin ligase for cargo sorting
PMID: 39402328
4
FCHO2 assembles at CCP rims to couple endocytic pit invagination to clathrin lattice assembly and control growth/lifetime
PMID: 31807703
5
High FCHO2 expression correlates with low pancreatic cancer survival and is reduced by GPER activation
PMID: 36077069
6
Circular RNA circFCHO2 promotes COPD airway remodeling by regulating PTBP1 nuclear translocation and GRN splicing
PMID: 41184265
7
FCHO2 F-BAR domain forms an intrinsically curved antiparallel dimer that binds liposomes and deforms membranes into tubules
PMID: 17540576
Disease Associationsⓘ20
cornea transplantationOpen Targets
0.35Weak
brain cancerOpen Targets
0.25Weak
kidney diseaseOpen Targets
0.24Weak
hypothyroidismOpen Targets
0.23Weak
squamous cell carcinomaOpen Targets
0.22Weak
nervous system cancerOpen Targets
0.19Weak
migraine disorderOpen Targets
0.11Weak
celiac diseaseOpen Targets
0.11Weak
venous thromboembolismOpen Targets
0.10Weak
bladder calculusOpen Targets
0.08Suggestive
urticariaOpen Targets
0.07Suggestive
Ischemic strokeOpen Targets
0.06Suggestive
Hemoglobin E - beta-thalassemiaOpen Targets
0.06Suggestive
hemoglobin E-beta-thalassemia syndromeOpen Targets
0.06Suggestive
Adult-onset autosomal recessive sideroblastic anemiaOpen Targets
0.06Suggestive
preeclampsiaOpen Targets
0.05Suggestive
hemoglobin D diseaseOpen Targets
0.05Suggestive
atrial fibrillationOpen Targets
0.05Suggestive
IRIDA syndromeOpen Targets
0.05Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
AP2A1Protein interaction92%CLTBProtein interaction85%DAB2Protein interaction85%PICALMProtein interaction85%EPN2Protein interaction85%NECAP1Protein interaction85%
Tissue Expression6 tissues
Lung
100%
Heart
77%
Bone Marrow
72%
Ovary
72%
Liver
50%
Brain
39%
Gene Interaction Network
Click a node to explore
FCHO2AP2A1CLTBDAB2PICALMEPN2NECAP1
PROTEIN STRUCTURE
Preparing viewer…
PDB7OIT · 1.65 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.55Moderately Constrained
pLIⓘ
0.79Intermediate
Observed/Expected LoF0.37 [0.26–0.55]
RankingsWhere FCHO2 stands among ~20K protein-coding genes
  • #7,865of 20,598
    Most Researched58
  • #3,523of 17,882
    Most Constrained (LOEUF)0.55 · top quartile
Genes detectedFCHO2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Identification and characterization of human FCHO2 and mouse Fcho2 genes in silico.
PMID: 15254787
Int J Mol Med · 2004
1.00
2
The Nedd4L ubiquitin ligase is activated by FCHO2-generated membrane curvature.
PMID: 39402328
EMBO J · 2024
0.90
3
Intersectin1 promotes clathrin-mediated endocytosis by organizing and stabilizing endocytic protein interaction networks.
PMID: 39580802
Cell Rep · 2024
0.80
4
Structural organization and dynamics of FCHo2 docking on membranes.
PMID: 35044298
Elife · 2022
0.70
5
Nanoscale coupling of endocytic pit growth and stability.
PMID: 31807703
Sci Adv · 2019
0.60