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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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WDR59
WD repeat domain 59
Chromosome 16 · 16q23.1
NCBI Gene: 79726Ensembl: ENSG00000103091.16HGNC: HGNC:25706UniProt: Q6PJI9
59PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein localization to plasma membraneprotein bindingcellular response to nutrient levelscellular response to amino acid starvationneurodegenerative diseasechronic laryngitisadolescent idiopathic scoliosisflatfoot
✦AI Summary

WDR59 functions as a key component of the GATOR2 complex, a pentameric protein assembly that regulates mTORC1 signaling in response to amino acid availability 1. The GATOR2 complex, containing WDR24, MIOS, WDR59, SEH1L, and SEC13, adopts a large cage-like architecture where WDR59 contributes to the octagonal scaffold structure through α-solenoids and helps orient WD40 β-propeller domains that mediate interactions with nutrient sensors 2. WDR59 exhibits context-dependent functions in TORC1 regulation: in some tissues it promotes TORC1 activity by stabilizing GATOR2 components and preventing their proteolytic degradation, while in others it inhibits TORC1 by opposing GATOR2's inhibition of GATOR1 3. The protein is essential for GATOR2-mediated interactions with mTORC2, facilitating Sestrin2-induced AKT activation through the GATOR2-mTORC2 axis 4. WDR59 also plays a role in proper lysosomal localization of the GATOR complex, which is crucial for nutrient sensing 5. Beyond metabolic regulation, genetic variants in WDR59 have been associated with sleep-related traits, particularly snoring, suggesting broader physiological roles 6.

Sources cited
1
WDR59 is a component of the GATOR2 complex that regulates mTORC1 signaling
PMID: 23723238
2
GATOR2 adopts a cage-like architecture with WDR59 contributing to the octagonal scaffold structure
PMID: 35831510
3
WDR59 has dual, context-dependent functions in TORC1 regulation
PMID: 36577058
4
WDR59 is essential for GATOR2-mTORC2 interactions and Sestrin2-induced AKT activation
PMID: 31915252
5
WDR59 is required for proper lysosomal localization of the GATOR complex
PMID: 28199315
6
WDR59 genetic variants are associated with snoring and sleep-related traits
PMID: 38177695
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.45Moderate
chronic laryngitisOpen Targets
0.27Weak
adolescent idiopathic scoliosisOpen Targets
0.22Weak
flatfootOpen Targets
0.22Weak
hemolytic anemiaOpen Targets
0.22Weak
myeloid leukemiaOpen Targets
0.22Weak
Non-Neoplastic Bile Duct DisorderOpen Targets
0.22Weak
Blackfan-Diamond anemiaOpen Targets
0.09Suggestive
inosine triphosphatase deficiencyOpen Targets
0.06Suggestive
primary familial polycythemia due to EPO receptor mutationOpen Targets
0.06Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.06Suggestive
Hereditary persistence of fetal hemoglobin - beta-thalassemiaOpen Targets
0.06Suggestive
alpha thalassemia-intellectual disability syndrome type 1Open Targets
0.06Suggestive
Alpha-thalassemia - intellectual disability syndrome linked to chromosome 16Open Targets
0.06Suggestive
Alpha-thalassemia - myelodysplastic syndromeOpen Targets
0.06Suggestive
alpha-thalassemia-myelodysplastic syndromeOpen Targets
0.06Suggestive
Autosomal dominant methemoglobinemiaOpen Targets
0.06Suggestive
hemoglobin D diseaseOpen Targets
0.06Suggestive
autosomal dominant sideroblastic anemiaOpen Targets
0.05Suggestive
Constitutional sideroblastic anemiaOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
LAMTOR3Protein interaction100%LAMTOR5Protein interaction100%SESN1Protein interaction100%LAMTOR2Protein interaction100%LAMTOR1Protein interaction100%LAMP1Protein interaction100%
Tissue Expression6 tissues
Liver
100%
Ovary
77%
Bone Marrow
55%
Heart
53%
Lung
38%
Brain
20%
Gene Interaction Network
Click a node to explore
WDR59LAMTOR3LAMTOR5SESN1LAMTOR2LAMTOR1LAMP1
PROTEIN STRUCTURE
Preparing viewer…
PDB9LWF · 3.41 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.91LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.76 [0.65–0.91]
RankingsWhere WDR59 stands among ~20K protein-coding genes
  • #7,832of 20,598
    Most Researched59
  • #8,204of 17,882
    Most Constrained (LOEUF)0.91
Genes detectedWDR59
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Structure of the nutrient-sensing hub GATOR2.
PMID: 35831510
Nature · 2022
1.00
2
Exome sequencing identifies genes associated with sleep-related traits.
PMID: 38177695
Nat Hum Behav · 2024
0.90
3
The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.
PMID: 28600779
Hum Genet · 2017
0.80
4
A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1.
PMID: 23723238
Science · 2013
0.70
5
Unveiling GATOR2 Function: Novel Insights from Drosophila Research.
PMID: 39513902
Cells · 2024
0.60