FCHO2
protein-codingFCH and mu domain containing endocytic adaptor 2, the group of F-BAR domain containing
Gene summary
Enables identical protein binding activity. Involved in clathrin coat assembly and clathrin-dependent endocytosis. Located in clathrin-coated pit and clathrin-coated vesicle. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~134.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FCHO2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_138782.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 1 | 1 | 5 | ||
| missense | 86 | 1 | 87 | |||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 96 | 2 | 1 | 99 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_620137.2 | 26 | MANE Select | |
| Ensembl | ENSP00000393776.2 | 26 | MANE Select | |
| RefSeq | NP_001139504.1 | 25 | Standard | |
| Ensembl | ENSP00000287761.6 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| fcho2 | Danio rerio | Structure: ventral fin fold Quality: decreased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vesicle-mediated transport
- Membrane Trafficking
- Clathrin-mediated endocytosis
- Cargo recognition for clathrin-mediated endocytosis
Biological Process
- membrane invagination
- clathrin coat assembly
- synaptic vesicle endocytosis
- membrane organization
- clathrin-dependent endocytosis
Molecular Function
- phosphatidylserine binding
- protein binding
- phospholipid binding
- phosphatidylinositol-4,5-bisphosphate binding
- microtubule binding
Cellular Component
- cytoplasm
- cytosol
- cytoskeleton
- plasma membrane
- clathrin-coated pit
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000430046
- Coding exons
- 26
- Length
- 134542
- Individuals with no LoFs
- 124622
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 124629
- p
- 0.0000281
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.02 | 251 | 359 | 0.700 | 0.0000169 | 5199 |
| Missense (PolyPhen) | 62 | 107.01 | 0.5794 | 1491 | ||
| Synonymous | 1.41 | 103 | 123 | 0.838 | 0.00000578 | 1489 |
| Loss of Function | 5.37 | 4 | 41.2 | 0.0971 | 0.00000191 | 632 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000034 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00011 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000048 | 0.000046 | rare |
| European (Non-Finnish) | 0.000019 | 0.000018 | rare |
| South Asian | 0.000073 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions in an early step of clathrin-mediated endocytosis. Has both a membrane binding/bending activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. Has a lipid-binding activity with a preference for membranes enriched in phosphatidylserine and phosphoinositides (Pi(4,5) biphosphate) like the plasma membrane. Its membrane-bending activity might be important for the subsequent action of clathrin and adaptors in the formation of clathrin-coated vesicles. Involved in adaptor protein complex AP- 2-dependent endocytosis of the transferrin receptor, it also functions in the AP-2-independent endocytosis of the LDL receptor. {ECO:0000269|PubMed:17540576, ECO:0000269|PubMed:20448150, ECO:0000269|PubMed:21762413, ECO:0000269|PubMed:22323290}.;
Recessive Scores
- pRec
- 0.0988
Intolerance Scores
- LoFtool
- 0.328
- RVIS EVS
- 0.06
- RVIS percentile EVS
- 58.85
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.229
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |