ZFYVE9
Zinc Finger FYVE-Type Containing 9
Gene Information Card
| Symbol | ZFYVE9 |
|---|---|
| Full Name | Zinc Finger FYVE-Type Containing 9 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p32.3 |
| NCBI Gene ID | 9372 ncbi.nlm.nih.gov/gene/9372 |
| Ensembl ID | ENSG00000157077 |
| UniProt ID | O95405 |
| OMIM ID | 603755 |
| HGNC ID | 13158 |
| Aliases | SARA, MADHIP, SMADIP, Nbla00023, PPP1R89 |
Description
ZFYVE9 (Zinc Finger FYVE-Type Containing 9), also known as SARA (SMAD Anchor for Receptor Activation), encodes a protein that functions as an adaptor in the TGF-beta signaling pathway. The protein contains a FYVE zinc finger domain that binds phosphatidylinositol 3-phosphate, localizing it to early endosomes. It recruits SMAD2 and SMAD3 to the TGF-beta receptor complex, facilitating their phosphorylation and subsequent nuclear translocation to regulate gene expression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Hemorrhagic Telangiectasia (HHT) | Impaired TGF-beta signaling due to ZFYVE9 mutations may disrupt endothelial cell function | Limited evidence; case reports in ClinVar |
| Colorectal Cancer | Altered SMAD anchor function may affect TGF-beta tumor suppressor signaling | COSMIC somatic mutations observed |
| Gastric Cancer | Loss of ZFYVE9 expression correlates with poor prognosis and TGF-beta pathway dysregulation | PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.2 | Low |
| Heart | 6.5 | Low |
| Liver | 4.1 | Not detected |
| Kidney | 7.8 | Low |
| Lung | 9.3 | Low |
| Testis | 12.4 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.5 | Cervical cancer cell line |
| HEK 293 | 11.2 | Embryonic kidney cells |
| HepG2 | 3.8 | Hepatocellular carcinoma |
| A549 | 8.9 | Lung adenocarcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Trp) | Missense | 0.001% (gnomAD) | Unknown; predicted damaging by SIFT |
| c.1456G>A (p.Glu486Lys) | Missense | 0.002% (gnomAD) | May affect SMAD binding |
| c.1789_1790insA (p.Thr597Asnfs*12) | Frameshift | Somatic (COSMIC) | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations in ZFYVE9 disrupt the FYVE domain or SMAD-binding region, impairing TGF-beta signaling.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Missense mutations in the SMAD-binding domain may act as dominant-negative by sequestering SMADs without functional receptor anchoring.
View complete mutation data：
Gene Ontology (GO)
| • SMAD binding | • protein kinase binding |
| • zinc ion binding | • phosphatidylinositol-3-phosphate binding |
| • cytoplasm | • early endosome |
| • TGF-beta receptor signaling pathway | • endosomal transport |
Pathways
• TGF-beta signaling pathway (KEGG hsa04350)
• SMAD2/SMAD3 phosphorylation and nuclear translocation (Reactome R-HSA-2173793)
Protein Summary
The ZFYVE9 protein (SARA) is a 1425-amino-acid multidomain protein that includes a FYVE zinc finger domain for endosomal localization and a SMAD-binding domain. It acts as a scaffold to present SMAD2/3 to the activated TGF-beta receptor complex, enabling their phosphorylation. SARA is essential for proper TGF-beta signal transduction and is implicated in cancer and vascular disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ZFYVE9 Knockout HEK293 Cell Line | EDJ-KQ412 | Human | 9372 | Details Get a Quote |
| ZFYVE9 Knockout HeLa Cell Line | EDJ-KQ17994 | Human | 9372 | Details Get a Quote |
| ZFYVE9 Knockout A-549 Cell Line | EDJ-KQ18675 | Human | 9372 | Details Get a Quote |
| ZFYVE9 Knockout HCT 116 Cell Line | EDJ-KQ18676 | Human | 9372 | Details Get a Quote |
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