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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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DOK5
docking protein 5
Chromosome 20 · 20q13.2
NCBI Gene: 55816Ensembl: ENSG00000101134.13HGNC: HGNC:16173UniProt: Q9P104
33PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
regulation of neurotrophin TRK receptor signaling pathwaysignaling adaptor activitycell surface receptor protein tyrosine kinase signaling pathwaycytosoladolescent idiopathic scoliosisplacenta praeviatooth diseasepreeclampsia
✦AI Summary

DOK5 is a member of the DOK (downstream of tyrosine kinase/docking protein) family that functions as an enzymatically inert adaptor protein, providing a scaffolding platform for multimolecular signaling complexes 1. DOK5 serves as a substrate for TrkB and TrkC neurotrophin receptors, interacting through its PTB domain with the NPQY motif in a kinase-activity-dependent manner and competing with N-shc for the same binding site 2. The protein plays crucial roles in neurotrophin-induced MAPK pathway activation and is essential for NT-3 signaling that prevents TrkC-induced apoptosis by regulating caspase-3 activity 23. DOK5 expression is upregulated during osteoblast differentiation and regulates bone cell proliferation and differentiation through canonical Wnt/β-catenin signaling 4. The protein is also involved in fibrotic processes, being upregulated by IGFBP-5 in a MAPK-dependent manner and contributing to dermal thickening 5. Clinically, DOK5 variants show associations with type 2 diabetes and obesity susceptibility 6, and the gene has been identified as a potential diagnostic biomarker for intracranial aneurysms 7. These findings establish DOK5 as a versatile adaptor protein involved in neuronal survival, bone metabolism, fibrosis, and metabolic disorders.

Sources cited
1
DOK5 is a member of the DOK family of adaptor proteins expressed in human T cells
PMID: 12595900
2
DOK5 serves as substrate for TrkB/C receptors and is involved in neurotrophin-induced MAPK activation
PMID: 16647839
3
DOK5 is necessary for NT-3 signaling to block TrkC-induced apoptosis by regulating caspase-3 activity
PMID: 23954828
4
DOK5 regulates osteoblast proliferation and differentiation via canonical Wnt/β-catenin signaling
PMID: 35234166
5
DOK5 is upregulated by IGFBP-5 and contributes to fibrosis through MAPK signaling
PMID: 24551065
6
DOK5 variants are associated with type 2 diabetes and obesity susceptibility
PMID: 20187968
7
DOK5 is identified as a potential diagnostic biomarker for intracranial aneurysms
PMID: 41824480
Disease Associationsⓘ20
adolescent idiopathic scoliosisOpen Targets
0.32Weak
placenta praeviaOpen Targets
0.30Weak
tooth diseaseOpen Targets
0.30Weak
preeclampsiaOpen Targets
0.30Weak
vascular diseaseOpen Targets
0.28Weak
Phenotypic abnormalityOpen Targets
0.27Weak
benign urinary system neoplasmOpen Targets
0.24Weak
smoking initiationOpen Targets
0.23Weak
obesityOpen Targets
0.21Weak
mathematical abilityOpen Targets
0.19Weak
ovarian dysfunctionOpen Targets
0.18Weak
poisoningOpen Targets
0.17Weak
response to xenobiotic stimulusOpen Targets
0.17Weak
complex regional pain syndromeOpen Targets
0.17Weak
type 2 diabetes mellitusOpen Targets
0.16Weak
diabetes mellitusOpen Targets
0.16Weak
joint diseaseOpen Targets
0.15Weak
cervical carcinomaOpen Targets
0.14Weak
gastric cancerOpen Targets
0.07Suggestive
systemic sclerodermaOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PILRBShared pathway100%DOK4Shared pathway100%SAMD10Shared pathway100%GAB4Shared pathway100%RETProtein interaction80%GDNFProtein interaction71%
Tissue Expression6 tissues
Heart
100%
Brain
30%
Ovary
3%
Lung
2%
Liver
2%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
DOK5PILRBDOK4SAMD10GAB4RETGDNF
PROTEIN STRUCTURE
Preparing viewer…
PDB1J0W · 2.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.93LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.66 [0.47–0.93]
RankingsWhere DOK5 stands among ~20K protein-coding genes
  • #11,325of 20,598
    Most Researched33
  • #8,623of 17,882
    Most Constrained (LOEUF)0.93
Genes detectedDOK5
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
DOK4 and DOK5: new Dok-related genes expressed in human T cells.
PMID: 12595900
Genes Immun · 2003
1.00
2
Evaluation of DOK5 as a susceptibility gene for type 2 diabetes and obesity in North Indian population.
PMID: 20187968
BMC Med Genet · 2010
0.90
3
Dok5 regulates proliferation and differentiation of osteoblast via canonical Wnt/β-catenin signaling.
PMID: 35234166
J Musculoskelet Neuronal Interact · 2022
0.80
4
Genetics of Cardiac Aging Implicate Organ-Specific Variation.
PMID: 39148824
medRxiv · 2024
0.70
5
Dok5 is substrate of TrkB and TrkC receptors and involved in neurotrophin induced MAPK activation.
PMID: 16647839
Cell Signal · 2006
0.60