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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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FCHSD2
FCH and double SH3 domains 2
Chromosome 11 · 11q13.4
NCBI Gene: 9873Ensembl: ENSG00000137478.16HGNC: HGNC:29114UniProt: O94868
45PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingphosphatidylinositol-3,4,5-trisphosphate bindingclathrin-dependent endocytosisclathrin-coated pitneurodegenerative diseasetype 2 diabetes mellituscervical carcinomacholelithiasis
✦AI Summary

FCHSD2 is an F-BAR adapter protein that orchestrates clathrin-mediated endocytosis and membrane trafficking through coordinated actin polymerization. Its primary function is to facilitate the internalization of cell surface receptors, including integrin ITGB1 and transferrin receptor, by promoting progression from U-shaped to omega-shaped clathrin-coated pits 1. FCHSD2 is recruited to clathrin-coated pits by the scaffold protein intersectin 1 and to endosomal membranes by MICAL-L1 2. Once membrane-bound to regions enriched in phosphatidylinositol 3,4-bisphosphate or 3,4,5-trisphosphate, FCHSD2 activates Arp2/3-mediated branched actin polymerization through direct interaction with WASP/N-WASP, driving both pit maturation and endosomal fission 1, 2. In hair cells, FCHSD2 localizes to stereocilia and interacts with deafness-related protein PDZD7, linking cytoskeletal dynamics to stereociliary development 3, 4. Clinically, FCHSD2 regulates receptor tyrosine kinase trafficking in cancer cells; its loss promotes lysosomal degradation of EGFR and MET, triggering compensatory ERK1/2 signaling associated with worse prognosis in non-small-cell lung cancer 5.

Sources cited
1
FCHSD2 is recruited to clathrin-coated pits, binds phosphoinositides, activates actin polymerization via N-WASP/Arp2/3, and promotes pit maturation
PMID: 29887380
2
MICAL-L1 recruits FCHSD2 to endosomal membranes for ARP2/3-mediated actin branching, endosome fission, and receptor recycling
PMID: 39382837
3
FCHSD2 localizes to hair cell stereocilia, interacts with WASP/N-WASP, and stimulates F-actin assembly in vitro
PMID: 23437151
4
FCHSD2 interacts with deafness-related protein PDZD7 to regulate stereociliary development
PMID: 35695292
5
FCHSD2 loss in NSCLC promotes EGFR/MET degradation and aberrant ERK1/2 signaling; high FCHSD2 expression correlates with improved survival
PMID: 32678845
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.37Weak
type 2 diabetes mellitusOpen Targets
0.32Weak
cervical carcinomaOpen Targets
0.30Weak
cholelithiasisOpen Targets
0.27Weak
response to xenobiotic stimulusOpen Targets
0.27Weak
placenta praeviaOpen Targets
0.26Weak
partial epilepsyOpen Targets
0.26Weak
device complicationOpen Targets
0.26Weak
irritable bowel syndromeOpen Targets
0.25Weak
Lower limb asymmetryOpen Targets
0.19Weak
non-small cell lung carcinomaOpen Targets
0.04Suggestive
systemic lupus erythematosusOpen Targets
0.04Suggestive
coronary artery diseaseOpen Targets
0.04Suggestive
cancerOpen Targets
0.03Suggestive
alcohol drinkingOpen Targets
0.02Suggestive
Crohn's diseaseOpen Targets
0.02Suggestive
acute myeloid leukemiaOpen Targets
0.02Suggestive
preeclampsiaOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
lung adenocarcinomaOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
WASProtein interaction92%SORBS1Protein interaction91%ITSN1Protein interaction91%KIR3DL1Protein interaction88%STACProtein interaction88%TRIM45Protein interaction88%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
94%
Lung
78%
Ovary
70%
Brain
69%
Liver
41%
Gene Interaction Network
Click a node to explore
FCHSD2WASSORBS1ITSN1KIR3DL1STACTRIM45
PROTEIN STRUCTURE
Preparing viewer…
PDB6GBU · 3.44 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.47Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.31 [0.21–0.47]
RankingsWhere FCHSD2 stands among ~20K protein-coding genes
  • #9,448of 20,598
    Most Researched45
  • #2,658of 17,882
    Most Constrained (LOEUF)0.47 · top quartile
Genes detectedFCHSD2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Endosomal actin branching, fission, and receptor recycling require FCHSD2 recruitment by MICAL-L1.
PMID: 39382837
Mol Biol Cell · 2024
1.00
2
Identification and characterization of human FCHSD1 and FCHSD2 genes in silico.
PMID: 15067381
Int J Mol Med · 2004
0.90
3
PMID: 34520816
0.80
4
FCHSD1 and FCHSD2 are expressed in hair cell stereocilia and cuticular plate and regulate actin polymerization in vitro.
PMID: 23437151
PLoS One · 2013
0.70
5
Deafness-related protein PDZD7 forms complex with the C-terminal tail of FCHSD2.
PMID: 35695292
Biochem J · 2022
0.60