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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
DOCK3
dedicator of cytokinesis 3
Chromosome 3 Β· 3p21.2
NCBI Gene: 1795Ensembl: ENSG00000088538.14HGNC: HGNC:2989UniProt: Q8IZD9
45PubMed Papers
21Diseases
0Drugs
11Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cytosolprotein bindingcytoplasmsmall GTPase bindingneurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxiasyndromic intellectual disabilitygenetic disorderGlobal developmental delay
✦AI Summary

DOCK3 is a guanine nucleotide exchange factor (GEF) predominantly expressed in neurons and skeletal muscle that regulates small GTPase-mediated signaling 1. As a GEF, DOCK3 activates RAC1 and other small GTPases to control actin cytoskeleton dynamics and cell adhesion 2. DOCK3 functions through multiple mechanisms: it interacts with HAUS7 to facilitate microtubule assembly and axon regeneration following nerve injury 3, and it directly binds NMDA receptors to promote their internalization and reduce excitotoxic damage in retinal ganglion cells 4. In skeletal muscle, DOCK3 regulates myogenic differentiation and glucose metabolism through interaction with SORBS1 5. Biallelic loss-of-function variants in DOCK3 cause a neurodevelopmental disorder characterized by intellectual disability, hypotonia, and ataxia 16. DOCK3 expression is dosage-sensitive; moderate reduction improves outcomes in Duchenne muscular dystrophy, while complete loss impairs muscle function 7. Additionally, DOCK3 dysregulation contributes to osteoporosis pathogenesis through Wnt signaling modulation 8. These findings identify DOCK3 as a critical regulator of neurological development, axonal regeneration, muscle health, and metabolic homeostasis, with therapeutic potential for neurodevelopmental disorders and muscle diseases.

Sources cited
1
DOCK3 is highly expressed in neurons, essential for cell adhesion and neuronal outgrowth, and biallelic loss-of-function variants cause neurodevelopmental disorder with intellectual disability and muscle hypotonia
PMID: 37895289
2
DOCK3 activates the RAC1/PI3K/AKT signaling pathway and protects against sepsis-induced muscle atrophy
PMID: 37551034
3
HAUS7 is a DOCK3 binding partner necessary for microtubule assembly and axon regeneration after optic nerve injury
PMID: 40712007
4
DOCK3 directly binds GluN2B subunit of NMDA receptors and promotes their internalization to reduce excitotoxic damage in retinal ganglion cells
PMID: 27615513
5
DOCK3 is essential for skeletal muscle regeneration and glucose metabolism through interaction with SORBS1
PMID: 37742307
6
DOCK3 is dosage-sensitive; haploinsufficiency improves dystrophic pathologies while complete loss impairs muscle function and myogenic differentiation
PMID: 32766788
7
Biallelic DOCK3 variants cause neurodevelopmental disorder with intellectual disability, hypotonia, and ataxia
PMID: 40151040
8
DOCK3 dysregulation contributes to osteoporosis by modulating Wnt signaling in bone marrow mesenchymal stem cells
PMID: 36764273
Disease Associationsβ“˜21
neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxiaOpen Targets
0.70Moderate
syndromic intellectual disabilityOpen Targets
0.62Moderate
genetic disorderOpen Targets
0.47Moderate
Global developmental delayOpen Targets
0.42Moderate
HypotoniaOpen Targets
0.42Moderate
complex neurodevelopmental disorderOpen Targets
0.37Weak
Alzheimer diseaseOpen Targets
0.35Weak
schizophreniaOpen Targets
0.34Weak
asthmaOpen Targets
0.32Weak
septic shockOpen Targets
0.31Weak
placental retentionOpen Targets
0.28Weak
anemia (phenotype)Open Targets
0.28Weak
multinodular goiterOpen Targets
0.28Weak
Abnormality of the skeletal systemOpen Targets
0.27Weak
radiculitisOpen Targets
0.27Weak
Abruptio PlacentaeOpen Targets
0.25Weak
obesityOpen Targets
0.25Weak
gallbladder diseaseOpen Targets
0.24Weak
liver diseaseOpen Targets
0.23Weak
mathematical abilityOpen Targets
0.21Weak
Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxiaUniProt
Pathogenic Variants11
NM_004947.5(DOCK3):c.1766_1767del (p.Lys589fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2024β†’ Residue 589
NM_004947.5(DOCK3):c.4231del (p.Leu1411fs)Pathogenic
Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia
β˜…β˜†β˜†β˜†2024β†’ Residue 1411
NM_004947.5(DOCK3):c.1038-2A>GLikely pathogenic
Hypotonia;Global developmental delay|Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia
β˜…β˜†β˜†β˜†2024
NM_004947.5(DOCK3):c.4217del (p.Pro1406fs)Likely pathogenic
DOCK3-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 1406
NM_004947.5(DOCK3):c.1084C>T (p.Arg362Ter)Likely pathogenic
DOCK3-related disorder
β˜…β˜†β˜†β˜†2022β†’ Residue 362
NM_004947.5(DOCK3):c.1037+1G>ALikely pathogenic
DOCK3-related disorder
β˜…β˜†β˜†β˜†2022
NM_004947.5(DOCK3):c.152_158dup (p.Gly55fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 55
NM_004947.5(DOCK3):c.214del (p.Arg72fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 72
NM_004947.5(DOCK3):c.382C>T (p.Gln128Ter)Pathogenic
Inborn genetic diseases|Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia
β˜…β˜†β˜†β˜†2017β†’ Residue 128
NM_004947.5(DOCK3):c.2535_2538dup (p.Ser847fs)Likely pathogenic
DOCK3-related disorder
β˜†β˜†β˜†β˜†2024β†’ Residue 847
NM_004947.5(DOCK3):c.3107_3110del (p.Tyr1036fs)Pathogenic
Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia|Hypotonia;Global developmental delay
β˜†β˜†β˜†β˜†2020β†’ Residue 1036
View on ClinVar β†—
Related Genes
ELMO1Protein interaction98%ELMO2Protein interaction97%FYNProtein interaction96%CDC42Protein interaction94%NEDD9Protein interaction94%ELMO3Protein interaction91%
Tissue Expression6 tissues
Brain
100%
Heart
25%
Bone Marrow
8%
Lung
3%
Ovary
3%
Liver
1%
Gene Interaction Network
Click a node to explore
DOCK3ELMO1ELMO2FYNCDC42NEDD9ELMO3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q8IZD9
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.30Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.24 [0.19–0.30]
RankingsWhere DOCK3 stands among ~20K protein-coding genes
  • #9,438of 20,598
    Most Researched45
  • #2,787of 5,498
    Most Pathogenic Variants11
  • #1,128of 17,882
    Most Constrained (LOEUF)0.30 Β· top 10%
Genes detectedDOCK3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
PMID: 37895289
Genes (Basel) Β· 2023
1.00
2
Loss of ZBED6 Protects Against Sepsis-Induced Muscle Atrophy by Upregulating DOCK3-Mediated RAC1/PI3K/AKT Signaling Pathway in Pigs.
PMID: 37551034
Adv Sci (Weinh) Β· 2023
0.90
3
Role of HAUS7 as a DOCK3 binding partner in facilitating axon regeneration.
PMID: 40712007
Sci Adv Β· 2025
0.80
4
Dock3-NMDA receptor interaction as a target for glaucoma therapy.
PMID: 27615513
Histol Histopathol Β· 2017
0.70
5
DOCK3 regulates normal skeletal muscle regeneration and glucose metabolism.
PMID: 37742307
FASEB J Β· 2023
0.60