WDR59: WD Repeat Domain 59
A subunit of the GATOR2 complex involved in mTORC1 signaling and autophagy regulation
Gene Information Card
| Symbol | WDR59 |
|---|---|
| Full Name | WD Repeat Domain 59 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q23.1 |
| NCBI Gene ID | 79726 ncbi.nlm.nih.gov/gene/79726 |
| Ensembl ID | ENSG00000103024 |
| UniProt ID | Q6PJI9 |
| OMIM ID | 617862 |
| HGNC ID | 25541 |
| Aliases | FLJ10706, MGC138499, MGC138500 |
Description
WDR59 encodes a WD40 repeat-containing protein that is a component of the GATOR2 complex. GATOR2 negatively regulates the GATOR1 complex, which in turn inhibits the mTORC1 signaling pathway. Through this mechanism, WDR59 plays a role in amino acid sensing, cell growth, and autophagy regulation. The gene is located on chromosome 16q23.1 and is broadly expressed in human tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (general) | Dysregulation of mTORC1 signaling via GATOR2 complex alterations | COSMIC database reports somatic mutations in various cancers; limited direct evidence |
| Intellectual disability (potential) | Loss-of-function variants may disrupt mTORC1 signaling during neurodevelopment | ClinVar lists uncertain significance variants; no confirmed disease association |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain (cerebellum) | 10.2 | Medium |
| Heart | 8.1 | Medium |
| Liver | 6.3 | Low |
| Lung | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.3 | High expression |
| HeLa | 11.0 | Medium expression |
| K562 | 7.8 | Medium expression |
| A549 | 6.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Trp) | Missense | <0.01% | Unknown; predicted damaging by in silico tools |
| c.567del (p.Glu189fs) | Frameshift | <0.01% | Likely loss of function; no clinical data |
Mutation functional classification
Loss of Function (LOF)
Frameshift or nonsense variants predicted to truncate the protein, likely disrupting GATOR2 complex assembly and mTORC1 regulation.
Gain of Function (GOF)
Not reported for WDR59.
Dominant Negative (DN)
Not reported for WDR59.
View complete mutation data：
Gene Ontology (GO)
| • cellular response to amino acid starvation (GO:0034198) | • regulation of TOR signaling (GO:0032006) |
| • protein binding (GO:0005515) | • cytoplasm (GO:0005737) |
Pathways
• mTORC1 signaling (Reactome: R-HSA-165159)
• GATOR2 complex (Reactome: R-HSA-9639288)
Protein Summary
WDR59 is a 964-amino acid protein containing multiple WD40 repeats, which typically mediate protein-protein interactions. It is a core component of the GATOR2 complex, which functions as a negative regulator of GATOR1. By inhibiting GATOR1, WDR59 indirectly promotes mTORC1 activity in response to amino acid availability. The protein is localized in the cytoplasm and is ubiquitously expressed.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| WDR59 Knockout HEK293 Cell Line | EDJ-KQ1162 | Human | 79726 | Details Get a Quote |
| WDR59 Knockout HCT 116 Cell Line | EDJ-KQ19063 | Human | 79726 | Details Get a Quote |
| WDR59 Knockout A-549 Cell Line | EDJ-KQ20409 | Human | 79726 | Details Get a Quote |
| WDR59 Knockout HeLa Cell Line | EDJ-KQ20411 | Human | 79726 | Details Get a Quote |
