DOCK1

Summary

DOCK1 (dedicator of cytokinesis 1, HGNC:2987) is a protein-coding gene on chromosome 10q26.2, encoding Dedicator of cytokinesis protein 1 (Q14185). Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility.

This gene encodes a member of the dedicator of cytokinesis protein family. Dedicator of cytokinesis proteins act as guanine nucleotide exchange factors for small Rho family G proteins. The encoded protein regulates the small GTPase Rac, thereby influencing several biological processes, including phagocytosis and cell migration. Overexpression of this gene has also been associated with certain cancers. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1793 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 409 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001290223

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2987
Approved symbol	DOCK1
Name	dedicator of cytokinesis 1
Location	10q26.2
Locus type	gene with protein product
Status	Approved
Aliases	DOCK180, ced5
Ensembl gene	ENSG00000150760
Ensembl biotype	protein_coding
OMIM	601403
Entrez	1793

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000280333, ENST00000464466, ENST00000473861, ENST00000484400, ENST00000495574, ENST00000623213, ENST00000871522, ENST00000871523, ENST00000939681, ENST00000939682, ENST00000939683, ENST00000961939, ENST00000961940

RefSeq mRNA: 13 — MANE Select: NM_001290223 NM_001290223, NM_001377543, NM_001377544, NM_001377546, NM_001377547, NM_001377548, NM_001377550, NM_001377553, NM_001377554, NM_001377556, NM_001377558, NM_001377560, NM_001380

CCDS: CCDS73222, CCDS76359

Canonical transcript exons

ENST00000623213 — 52 exons

Exon	Start	End
ENSE00000728235	127023200	127023324
ENSE00000987393	126981918	126981973
ENSE00000987394	126987521	126987617
ENSE00000987395	126990455	126990603
ENSE00000987396	126996748	126996883
ENSE00000987397	126998092	126998249
ENSE00000987398	126999354	126999435
ENSE00000987399	127000172	127000307
ENSE00000987400	127008732	127008804
ENSE00000987402	127018710	127018835
ENSE00000987403	127024685	127024783
ENSE00000987404	127026352	127026424
ENSE00000987405	127031650	127031753
ENSE00000987406	127032137	127032320
ENSE00000987407	127037719	127037816
ENSE00000987408	127042625	127042714
ENSE00000987409	127043064	127043164
ENSE00000987410	127052681	127052815
ENSE00000987411	127061668	127061776
ENSE00000987412	127106231	127106301
ENSE00000996152	127127669	127127764
ENSE00000996160	127410840	127410924
ENSE00000996162	127404325	127404429
ENSE00000996163	127381278	127381368
ENSE00000996164	127362064	127362212
ENSE00000996166	127447394	127447545
ENSE00000996167	127403055	127403144
ENSE00000996168	127373781	127373866
ENSE00000996169	127409037	127409178
ENSE00000996171	127419666	127419749
ENSE00000996172	127374058	127374214
ENSE00000996175	127425874	127426011
ENSE00000996176	127418365	127418541
ENSE00000996177	127409313	127409391
ENSE00000996178	127444126	127444279
ENSE00000996180	127433283	127433428
ENSE00000996181	127380082	127380122
ENSE00000996182	127415152	127415238
ENSE00000996184	127354669	127354727
ENSE00000996186	127384790	127384909
ENSE00001190649	127110248	127110354
ENSE00001307005	127439027	127439225
ENSE00001338090	126977948	126977988
ENSE00001338098	126970702	126970785
ENSE00003521287	127125474	127125601
ENSE00003551083	127339006	127339084
ENSE00003554285	127343646	127343746
ENSE00003581549	127248008	127248109
ENSE00003614612	127257335	127257429
ENSE00003757054	127012232	127012374
ENSE00003757621	126905428	126905563
ENSE00003758048	127451332	127452516

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 94.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.5427 / max 371.7705, expressed in 1574 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107596	24.5427	1574

Top tissues by expression

291 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	94.52	gold quality
medial globus pallidus	UBERON:0002477	93.30	gold quality
globus pallidus	UBERON:0001875	92.70	gold quality
olfactory bulb	UBERON:0002264	92.67	silver quality
stromal cell of endometrium	CL:0002255	92.52	gold quality
sural nerve	UBERON:0015488	92.34	gold quality
calcaneal tendon	UBERON:0003701	92.29	gold quality
inferior vagus X ganglion	UBERON:0005363	92.20	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.00	gold quality
amygdala	UBERON:0001876	91.86	gold quality
subthalamic nucleus	UBERON:0001906	91.84	gold quality
spinal cord	UBERON:0002240	91.60	gold quality
ventricular zone	UBERON:0003053	91.43	gold quality
putamen	UBERON:0001874	90.70	gold quality
cardia of stomach	UBERON:0001162	90.28	gold quality
skin of abdomen	UBERON:0001416	90.26	gold quality
ventral tegmental area	UBERON:0002691	90.12	gold quality
metanephros cortex	UBERON:0010533	89.72	gold quality
dorsal plus ventral thalamus	UBERON:0001897	89.55	gold quality
superior vestibular nucleus	UBERON:0007227	89.43	gold quality
popliteal artery	UBERON:0002250	89.38	gold quality
tibial artery	UBERON:0007610	89.38	gold quality
midbrain	UBERON:0001891	89.33	gold quality
skin of leg	UBERON:0001511	89.26	gold quality
substantia nigra	UBERON:0002038	89.24	gold quality
hypothalamus	UBERON:0001898	89.16	gold quality
peripheral nervous system	UBERON:0000010	89.01	gold quality
tibial nerve	UBERON:0001323	89.01	gold quality
ectocervix	UBERON:0012249	89.00	gold quality
medulla oblongata	UBERON:0001896	88.98	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	22.50
E-ANND-3	yes	8.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PTTG1

miRNA regulators (miRDB)

53 targeting DOCK1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-98-3P	100.00	74.08	3907
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-30A-3P	99.87	69.74	2928

Literature-anchored findings (GeneRIF, showing 40)

• Dock180 ELMO complex functions as an unconventional two-part exchange factor for Rac. (PMID:12134158)
• identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity (PMID:12432077)
• Rac activation by the ELMO.Dock180 complex at discrete intracellular locations mediated by the N-terminal 330 amino acids of ELMO1 plays a role in cell migration (PMID:14638695)
• while N-terminal SH3 of CrkII promotes assembly between CrkII and DOCK180, the C-terminal SH3 of CrkII regulates the stability and turnover of the DOCK180/ELMO complex (PMID:15700267)
• The N-terminal SH3 domain of Dock180 binds to the distant catalytic Docker domain and negatively regulates the function of Dock180. (PMID:15723800)
• DOCK180, via its DHR-1 and DHR-2 domains, couples PtdIns(3,4,5)P(3) signalling to Rac GTP-loading, which is essential for directional cell movement. (PMID:16025104)
• ARNO and ARF6 coordinate with the Dock180/Elmo complex to promote Rac activation at the leading edge of migrating cells. (PMID:16213822)
• LOX regulates cell motility/migration through changes in actin filament polymerization, which involve the regulation of the p130(Cas)/Crk/DOCK180 (PMID:16440329)
• The DOCK180 protein is ubiquitylated on the plasma membrane, and also that Elmo1 functions as an inhibitor of ubiquitylation of Dock180. (PMID:16495483)
• Using pulldown assays, we identified engulfment and cell motility (ELMO) protein as the IpgB1 binding partner. IpgB1 colocalized with ELMO and Dock180 in membrane ruffles induced by Shigella. (PMID:17173036)
• A significant percentage of the total endogenous Crk II partitions in the nucleus in mammalian cells, where it forms distinct complexes with DOCK180, Wee1, and Abl. (PMID:17764157)
• DOCK180 regulates CI-MPR trafficking via SNX5 and this function is independent of its guanine nucleotide exchange factor activity toward Rac1 (PMID:18596235)
• uPAR cooperates with integrin complexes containing beta(3) integrin to drive formation of the p130Cas-CrkII signaling complex and activation of Rac, resulting in a Rac-driven elongated-mesenchymal morphology, cell motility, and invasion. (PMID:18725541)
• The DOCK180-ELMO1 interaction is mapped to the N-terminal 200 amino acids of DOCK180, and to the C-terminal 200 amino acids of ELMO1, comprising the ELMO1 PH domain. (PMID:18768751)
• along with DOCK1, DOCK5 is an important mediator of CrkII/CrkL regulation of Caco-2 spreading and migration on collagen IV. (PMID:19004829)
• ANKRD28, a novel binding partner of DOCK180, promotes cell migration by regulating focal adhesion formation. (PMID:19118547)
• It regulates cell morphology and motility. (review) (PMID:19803396)
• protein-protein interaction mediated by ARNO coiled-coil domain required for ARNO induced motility; coiled-coil domain promotes assembly of multiprotein complex containing ARNO and Dock180; assembly of complex requires coiled-coil domain, GRASP and IPCEF (PMID:20016009)
• signal transfer of Crk/Dock180/Rac1 is implicated in actin cytoskeleton reorganization and thus in the cell proliferation, motility, invasion, and of human ovarian cancer cell line SKOV3. (PMID:20237902)
• DOCK180, an atypical Rac activator, links CXCR4 signaling to Rac activation in order to control endothelial cell migration during cardiovascular development. (PMID:20829512)
• Dock180 contributes to ovarian carcinogenesis and dissemination (PMID:22175896)
• EGFRvIII (also known as DeltaEGFR and de2-7EGFR), a constitutively active EGFR mutant that is frequently co-overexpressed with EGFR in human glioblastoma, promotes tumorigenesis through Src family kinase (SFK)-dependent phosphorylation of Dock180 (PMID:22323579)
• Solved is the solution structure of DOCK180 SH3 domain, which shares similar target binding features with the SH3 domain of DOCK2. (PMID:23239367)
• Dock180 could act as a pro-survival molecule in H9C2 cardiomyocytes via activation of its downstream pro-survival signaling molecule, AKT. (PMID:23314417)
• findings indicate that a chemokine-controlled pathway, consisting of Galphai2, ELMO1/Dock180, Rac1 and Rac2, regulates the actin cytoskeleton during breast cancer metastasis (PMID:23591873)
• DOCK1-Rac signaling as an HER2 effector pathway essential for HER2-mediated breast cancer progression to metastasis. (PMID:23592719)
• our findings describe a novel mechanism by which EGFRvIII drives glioma tumorigenesis and invasion through protein kinase A-dependent phosphorylation of Dock180 (PMID:23728337)
• High DOCK180 expression is associated with serous ovarian cancer. (PMID:24819662)
• Thus, Elmo1 and Dock180 facilitate blood vessel formation by stabilization of the endothelium during angiogenesis. (PMID:25586182)
• Dock1 modulation by miR-31 plays an important function in glioma invasion (PMID:26946516)
• stimulation of the DOCK180 pathway represents an alternative mechanism of PTP1B inhibitor-stimulated endothelial cell motility, which does not require concomitant VEGFR2 activation as a prerequisite. (PMID:27052191)
• one statistically significant common variant in the DOCK1 gene was associated with DeltaBMI in GI cancer and COPD cases providing support for at least partially shared aetiology of DeltaBMI in complex diseases. (PMID:28044437)
• In summary, this investigation identifies an EGFR-DOCK180-RAC1-MLK3-JNK signaling axis that drives glioblastoma cell migration and dissemination.IMPLICATIONS: On the basis of these findings, MLK3 emerges as a potential therapeutic target for the treatment of glioblastoma (PMID:28487380)
• Data suggest that GPR124 promotes cell adhesion via interaction with Elmo1-Dock180 and intersectin 1/2; this constitutes a previously unrecognized heteromeric complex that is putatively involved in GPR124-dependent adhesive/angiogenic responses in vascular endothelial cells. (GPR124 = G-protein coupled receptor 124; Elmo1 = ELMO domain-containing protein 1; Dock180 = dedicator of cytokinesis protein 1 180 kDa) (PMID:28600358)
• High DOCK1 expression is associated with Oral squamous cell carcinoma. (PMID:29286141)
• Taken together, these results indicate that DOCK1 is a critical regulator of the malignant phenotypes induced by Rac1(P29S), and suggest that targeting DOCK1 might be an effective approach to treat cancers associated with Rac1(P29S) mutation. (PMID:29432733)
• DOCK180 has an indispensable role in pregnancy establishment as knocking down Dock180 abrogates pregnancy by a consolidated impact on decidualization and angiogenesis by regulating AIRE nuclear entry. (PMID:29516628)
• CircDOCK1 affected the progression of BC via modulation of circDOCK1/hsa-miR-132-3p/Sox5 pathway. (PMID:30983072)
• Circular RNA DOCK1 downregulates microRNA-124 to induce the growth of human thyroid cancer cell lines. (PMID:32584497)
• TBOPP enhances the anticancer effect of cisplatin by inhibiting DOCK1 in renal cell carcinoma. (PMID:32626999)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dock1	ENSDARG00000099093
mus_musculus	Dock1	ENSMUSG00000058325
rattus_norvegicus	Dock1	ENSRNOG00000018683
caenorhabditis_elegans		WBGENE00000419

Paralogs (10): DOCK9 (ENSG00000088387), DOCK3 (ENSG00000088538), DOCK8 (ENSG00000107099), DOCK7 (ENSG00000116641), DOCK4 (ENSG00000128512), DOCK6 (ENSG00000130158), DOCK2 (ENSG00000134516), DOCK10 (ENSG00000135905), DOCK11 (ENSG00000147251), DOCK5 (ENSG00000147459)

Protein

Protein identifiers

Dedicator of cytokinesis protein 1 — Q14185 (reviewed: Q14185)

Alternative names: 180 kDa protein downstream of CRK

All UniProt accessions (2): Q14185, A0A096LNH6

UniProt curated annotations — full annotation on UniProt →

Function. Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Along with DOCK1, mediates CRK/CRKL regulation of epithelial and endothelial cell spreading and migration on type IV collagen. Functions as a guanine nucleotide exchange factor (GEF), which activates Rac Rho small GTPases by exchanging bound GDP for free GTP. Its GEF activity may be enhanced by ELMO1.

Subunit / interactions. Interacts with the SH3 domains of CRK and NCK2 via multiple sites. Interacts with nucleotide-free RAC1 via its DOCKER domain. Interacts with ELMO1, ELMO2 and probably ELMO3 via its SH3 domain. Interacts with ADGRB1. Identified in a complex with AUTS2 and ELMO2.

Subcellular location. Cytoplasm. Membrane.

Tissue specificity. Highly expressed in placenta, lung, kidney, pancreas and ovary. Expressed at intermediate level in thymus, testes and colon.

Domain organisation. The DOCKER domain is necessary and sufficient for the GEF activity.

Similarity. Belongs to the DOCK family.

RefSeq proteins (13): NP_001277152, NP_001364472, NP_001364473, NP_001364475, NP_001364476, NP_001364477, NP_001364479, NP_001364482, NP_001364483, NP_001364485, NP_001364487, NP_001364489, NP_001371 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR026791	DOCK	Family
IPR027007	C2_DOCK-type_domain	Domain
IPR027357	DOCKER_dom	Domain
IPR032376	DOCK_N	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR042455	DOCK_N_sub1	Homologous_superfamily
IPR043161	DOCK_C_lobe_A	Homologous_superfamily
IPR043162	DOCK_C_lobe_C	Homologous_superfamily
IPR046769	DOCKER_Lobe_A	Domain
IPR046770	DOCKER_Lobe_B	Domain
IPR046773	DOCKER_Lobe_C	Domain
IPR047025	DOCK1_5_SH3	Domain
IPR047026	DOCK1_C2	Domain
IPR056372	TPR_DOCK	Domain

Pfam: PF00018, PF06920, PF14429, PF16172, PF20421, PF20422, PF23554

UniProt features (43 total): modified residue 9, strand 8, compositionally biased region 7, region of interest 6, domain 3, helix 3, short sequence motif 2, mutagenesis site 2, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3L4C	X-RAY DIFFRACTION	2.37

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14185-F1	79.63	0.41

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (9): 1681, 1743, 1751, 1756, 1761, 1764, 1767, 1772, 1858

Mutagenesis-validated functional residues (2):

Position	Phenotype
1401–1402	abolishes rac gef activity.
1487–1489	abolishes rac gef activity.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-418885	DCC mediated attractive signaling
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-8849471	PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9664422	FCGR3A-mediated phagocytosis
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-9958810	SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)

MSigDB gene sets: 244 (showing top): TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, REACTOME_INNATE_IMMUNE_SYSTEM, MORF_MSH3, GOBP_SYNAPSE_ASSEMBLY, PID_NETRIN_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_EPITHELIAL_CELL_MIGRATION, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_VESICLE_MEDIATED_TRANSPORT, GOMF_GTPASE_BINDING, GOBP_POSITIVE_REGULATION_OF_SUBSTRATE_ADHESION_DEPENDENT_CELL_SPREADING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION

GO Biological Process (12): phagocytosis, engulfment (GO:0006911), apoptotic process (GO:0006915), signal transduction (GO:0007165), integrin-mediated signaling pathway (GO:0007229), small GTPase-mediated signal transduction (GO:0007264), myoblast fusion (GO:0007520), positive regulation of epithelial cell migration (GO:0010634), cell migration (GO:0016477), regulation of postsynapse assembly (GO:0150052), positive regulation of substrate adhesion-dependent cell spreading (GO:1900026), hematopoietic progenitor cell differentiation (GO:0002244), phagocytosis (GO:0006909)

GO Molecular Function (5): guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), SH3 domain binding (GO:0017124), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (7): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), guanyl-nucleotide exchange factor complex (GO:0032045), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
RHO GTPase cycle	3
Fcgamma receptor (FCGR) dependent phagocytosis	1
Netrin-1 signaling	1
Signaling by VEGF	1
Signaling by PTK6	1
Leishmania phagocytosis	1
Hemostasis	1
Activation of STAT3 by cadherin engagement	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
GTPase regulator activity	2
synapse	2
phagocytosis	1
plasma membrane invagination	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell surface receptor signaling pathway	1
intracellular signaling cassette	1
syncytium formation by cell-cell fusion	1
myotube differentiation	1
epithelial cell migration	1
regulation of epithelial cell migration	1
positive regulation of cell migration	1
cell motility	1
regulation of synapse assembly	1
postsynapse assembly	1
regulation of postsynapse organization	1
positive regulation of cell-substrate adhesion	1
substrate adhesion-dependent cell spreading	1
regulation of substrate adhesion-dependent cell spreading	1
hemopoiesis	1
cell differentiation	1
endocytosis	1
GTP binding	1
GDP binding	1
GTPase activity	1
enzyme activator activity	1
protein domain specific binding	1
GTPase binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1

Protein interactions and networks

STRING

1876 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DOCK1	ELMO2	Q96JJ3	999
DOCK1	CRK	P46108	999
DOCK1	ELMO1	Q92556	999
DOCK1	BCAR1	P56945	996
DOCK1	WDR35	Q9P2L0	991
DOCK1	ELMO3	Q96BJ8	991
DOCK1	RHOG	P35238	980
DOCK1	ADGRB1	O14514	959
DOCK1	SRC	P12931	955
DOCK1	PXN	P49023	954
DOCK1	DHX37	Q8IY37	942
DOCK1	AKT1	P31749	930
DOCK1	DHX8	Q14562	929
DOCK1	GULP1	Q9UBP9	925
DOCK1	CRKL	P46109	878

IntAct

99 interactions, top by confidence:

A	B	Type	Score
DOCK1	ELMO1	psi-mi:“MI:0915”(physical association)	0.940
ELMO1	DOCK1	psi-mi:“MI:0915”(physical association)	0.940
ELMO1	DOCK1	psi-mi:“MI:0914”(association)	0.940
ANKRD54	TULP3	psi-mi:“MI:0914”(association)	0.930
GRB2	DOCK1	psi-mi:“MI:0915”(physical association)	0.850
CRK	DOCK1	psi-mi:“MI:0915”(physical association)	0.770
CRK	DOCK1	psi-mi:“MI:0407”(direct interaction)	0.770
GRB2	WIPF3	psi-mi:“MI:0914”(association)	0.730
RAC1	DOCK1	psi-mi:“MI:0914”(association)	0.730
DOCK1	RAC1	psi-mi:“MI:0915”(physical association)	0.730
RAC1	DOCK1	psi-mi:“MI:0915”(physical association)	0.730

BioGRID (110): DOCK1 (Affinity Capture-Western), DOCK1 (Affinity Capture-MS), DOCK1 (Affinity Capture-MS), DOCK1 (Affinity Capture-MS), DOCK1 (Affinity Capture-MS), CRK (Co-fractionation), RAC1 (Co-fractionation), DOCK1 (Affinity Capture-MS), DOCK1 (Affinity Capture-MS), DOCK1 (Affinity Capture-MS), DOCK1 (Affinity Capture-MS), DOCK1 (Two-hybrid), ARL4A (Affinity Capture-Western), DOCK1 (Affinity Capture-Western), DOCK1 (Affinity Capture-MS)

ESM2 similar proteins: A1A5P5, A6H690, A6NCM1, A7SK48, B2RY04, E7EXT2, O70481, P97393, P97564, Q12874, Q13017, Q14185, Q14738, Q1LXZ7, Q24087, Q2KI89, Q2TAA8, Q3SYG4, Q3U0M1, Q45GW3, Q4R8Y5, Q5GJ77, Q5R629, Q5ZL77, Q68F70, Q6AX60, Q6AXQ7, Q6NU25, Q7ZYV9, Q811G0, Q86XH1, Q8BUR4, Q8BWR8, Q8C3J5, Q8CDK3, Q8CIM8, Q8IUC4, Q8IWV7, Q8T773, Q92608

Diamond homologs: B2RY04, E7F1U2, P53281, P59764, Q14185, Q8BUR4, Q8C3J5, Q8CIQ7, Q8IZD9, Q8N1I0, Q92608, Q9H7D0, M0R4F8, Q09822, Q5TCX8, Q62662, Q6XZF7, Q8VDG6, Q91X43, Q922K9

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
SNX5	“up-regulates activity”	DOCK1	binding
EGFR	“up-regulates activity”	DOCK1	phosphorylation
MAPK1	unknown	DOCK1	phosphorylation
AUTS2	“up-regulates activity”	DOCK1	binding
DOCK1	“up-regulates activity”	RAC1	“guanine nucleotide exchange factor”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Downstream signal transduction	7	52.2×	1e-08
FCGR3A-mediated phagocytosis	9	33.0×	3e-09
RHO GTPases Activate WASPs and WAVEs	5	31.1×	4e-05
EPHB-mediated forward signaling	5	26.0×	7e-05
Regulation of actin dynamics for phagocytic cup formation	7	25.3×	2e-06
Signaling by SCF-KIT	5	24.3×	8e-05
VEGFA-VEGFR2 Pathway	7	19.1×	9e-06
EPH-Ephrin signaling	5	16.2×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
Rac protein signal transduction	6	51.1×	1e-06
positive regulation of Rac protein signal transduction	5	49.1×	7e-06
positive regulation of substrate adhesion-dependent cell spreading	6	34.0×	7e-06
ephrin receptor signaling pathway	6	31.3×	7e-06
cellular response to transforming growth factor beta stimulus	5	20.9×	2e-04
epidermal growth factor receptor signaling pathway	5	18.8×	4e-04
actin filament organization	8	14.4×	1e-05
regulation of actin cytoskeleton organization	6	14.3×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

409 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	324
Likely benign	18
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
521686	NM_001290223.2(DOCK1):c.2053dup (p.Glu685fs)	Likely pathogenic

SpliceAI

13374 predictions. Top by Δscore:

Variant	Effect	Δscore
10:126970695:A:AG	acceptor_gain	1.0000
10:126970696:T:G	acceptor_gain	1.0000
10:126970697:CACA:C	acceptor_loss	1.0000
10:126970698:A:AG	acceptor_gain	1.0000
10:126970698:ACAGC:A	acceptor_loss	1.0000
10:126970699:C:G	acceptor_gain	1.0000
10:126970699:CA:C	acceptor_loss	1.0000
10:126970700:A:AG	acceptor_gain	1.0000
10:126970701:G:GT	acceptor_gain	1.0000
10:126970701:GC:G	acceptor_gain	1.0000
10:126970701:GCT:G	acceptor_gain	1.0000
10:126970701:GCTT:G	acceptor_gain	1.0000
10:126970701:GCTTT:G	acceptor_gain	1.0000
10:126970782:GAAG:G	donor_gain	1.0000
10:126970786:GT:G	donor_loss	1.0000
10:126970787:T:G	donor_loss	1.0000
10:126987517:CCA:C	acceptor_loss	1.0000
10:126987518:CA:C	acceptor_loss	1.0000
10:126987519:A:AG	acceptor_gain	1.0000
10:126987519:AGGC:A	acceptor_loss	1.0000
10:126987520:G:GA	acceptor_loss	1.0000
10:126987520:G:GG	acceptor_gain	1.0000
10:126987615:GTG:G	donor_gain	1.0000
10:126990452:T:G	acceptor_gain	1.0000
10:126990453:A:AG	acceptor_gain	1.0000
10:126990454:G:GG	acceptor_gain	1.0000
10:126990454:GC:G	acceptor_gain	1.0000
10:126990454:GCA:G	acceptor_gain	1.0000
10:126990454:GCAA:G	acceptor_gain	1.0000
10:126990599:AACAG:A	donor_loss	1.0000

AlphaMissense

12547 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:126977959:G:C	G48R	1.000
10:126977960:G:A	G48D	1.000
10:126987580:T:C	L96P	1.000
10:126987588:T:A	W99R	1.000
10:126987588:T:C	W99R	1.000
10:126990504:T:C	L125P	1.000
10:126990516:G:C	R129P	1.000
10:127000217:T:C	C299R	1.000
10:127000298:G:A	G326R	1.000
10:127000298:G:C	G326R	1.000
10:127000299:G:A	G326E	1.000
10:127000304:G:C	A328P	1.000
10:127000305:C:A	A328D	1.000
10:127008788:T:C	F348L	1.000
10:127008790:C:A	F348L	1.000
10:127008790:C:G	F348L	1.000
10:127012374:G:C	G380R	1.000
10:127018710:G:A	G380D	1.000
10:127018715:T:A	W382R	1.000
10:127018715:T:C	W382R	1.000
10:127023276:C:A	N447K	1.000
10:127023276:C:G	N447K	1.000
10:127024766:T:A	W491R	1.000
10:127024766:T:C	W491R	1.000
10:127026389:T:C	L509P	1.000
10:127026406:C:G	H515D	1.000
10:127032309:T:C	L613P	1.000
10:127037742:T:A	W625R	1.000
10:127037742:T:C	W625R	1.000
10:127042625:T:C	F650L	1.000

dbSNP variants (sampled 300 via entrez): RS1000002365 (10:127315149 G>A), RS1000006225 (10:126995803 A>G), RS1000007069 (10:127209294 C>T), RS1000009009 (10:127287602 T>C), RS1000009636 (10:127100149 C>A,T), RS1000022234 (10:127083103 T>A), RS1000026561 (10:126967334 C>T), RS1000032635 (10:126912725 C>T), RS1000037045 (10:127128014 T>C), RS1000039275 (10:127409212 C>T), RS1000042798 (10:127169157 C>T), RS1000044518 (10:127361572 G>A), RS1000054510 (10:127088713 C>A), RS1000054520 (10:127314956 A>G), RS1000055640 (10:127254309 T>C)

Disease associations

OMIM: gene MIM:601403 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): temporomandibular joint disorder (MONDO:0005473)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST001703_1	Apolipoprotein Levels	4.000000e-08
GCST002343_7	Response to cytidine analogues (gemcitabine)	4.000000e-06
GCST002367_2	Social communication problems	9.000000e-06
GCST002783_167	Body mass index	7.000000e-07
GCST002783_221	Body mass index	2.000000e-06
GCST002794_13	Airway wall thickness	9.000000e-06
GCST002794_15	Airway wall thickness	8.000000e-08
GCST002794_3	Airway wall thickness	8.000000e-06
GCST004100_1	Body mass index (change over time) in gastrointestinal cancer or chronic obstructive pulmonary disease	9.000000e-10
GCST004101_1	Body mass index (change over time) in gastrointestinal cancer	2.000000e-08
GCST006609_4	Response to TNF inhibitor in rheumatoid arthritis (change in tender 28-joint count)	7.000000e-08
GCST006610_1	Response to TNF inhibitor in rheumatoid arthritis (change in disease activity score)	5.000000e-06
GCST006719_9	BRCA1/2-negative high-risk breast cancer	1.000000e-06
GCST007576_253	Chronotype	5.000000e-09
GCST007756_1	Homeostasis model assessment of insulin resistance in less-fat diet	3.000000e-08
GCST008152_68	Weight	2.000000e-06
GCST010396_109	Gut microbiota (bacterial taxa, hurdle binary method)	5.000000e-07

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004732	lipoprotein measurement
EFO:0005427	social communication impairment
EFO:0004340	body mass index
EFO:0006898	airway wall thickness measurement
EFO:0005937	longitudinal BMI measurement
EFO:0004653	response to TNF antagonist
EFO:0005413	joint damage measurement
EFO:0009435	arthritis disease activity score measurement
EFO:0009443	BRCAX breast cancer
EFO:0008328	chronotype measurement
EFO:0004338	body weight
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D013705	Temporomandibular Joint Disorders	C05.500.607.221.897; C05.550.905; C05.651.243.897; C07.320.610.291.897; C07.678

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523288 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	7
Aflatoxin B1	decreases expression, increases methylation	3
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
Cisplatin	decreases expression, affects cotreatment	2
Tobacco Smoke Pollution	increases methylation, decreases expression	2
Valproic Acid	increases methylation, affects expression	2
aristolochic acid I	decreases expression	1
2,4,6-tribromophenol	increases expression	1
methyleugenol	decreases expression	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	decreases expression	1
arsenite	decreases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
bisphenol S	affects cotreatment, increases methylation	1
jinfukang	affects cotreatment, decreases expression	1
7-(benzylamino)-1,3,4,8-tetrahydropyrrolo(4,3,2-de)quinolin-8(1H)-one	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1
Acetaminophen	decreases expression	1
Arsenic	increases methylation	1
Atrazine	decreases expression	1
Caffeine	affects phosphorylation	1
Ivermectin	decreases expression	1
Menthol	decreases expression	1
Rotenone	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4335410	Binding	Binding affinity to DOCK1 in human Huh7.5.1 cell lysate infected with HCV at 0.1 to 10 uM incubated for 1 hr followed by 10000 mJ/cm2 UV irradiation for 10 mins and subsequent addition of biotin-N3 measured after 1 hr by ABPP Gel-based by L	Discovery, Optimization, and Target Identification of Novel Potent Broad-Spectrum Antiviral Inhibitors. — J Med Chem

Clinical trials (associated diseases)

215 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03522207	PHASE4	TERMINATED	Accuracy and Efficacy of Trazodone (Desyrel) on Sleep Quality and Pain Management of TMD Patient
NCT04110587	PHASE4	COMPLETED	Hyaluronic Acid Evaluation as Adjuvant to Temporomandibular Joint Arthroscopy
NCT04810429	PHASE4	COMPLETED	Comparison of Temporomandibular Joint Arthroscopy With Botulinum Toxin Injection Versus Placebo
NCT05817162	PHASE4	UNKNOWN	Temporomandibular Joint Arthrocentesis With Infiltration of PRP + Ropivacaine Versus PRP
NCT06044974	PHASE4	COMPLETED	Nd-YAG Laser Versus Epidermal Growth Factor For Myogenic Tempromandibular Disorder.
NCT06452134	PHASE4	NOT_YET_RECRUITING	Evaluation the Effect of Coenzyme Q10 on Tissue Healing Process in Patients Undergoing Wisdom Tooth Extraction
NCT06530745	PHASE4	COMPLETED	PRP vs HA Intra-articular Injections in TMDs
NCT07401745	PHASE4	ACTIVE_NOT_RECRUITING	Occlusal Splint Combined With Granisetron Injection for Management of Myofascial Pain Related to Temporomandibular Disorders
NCT00001955	PHASE2	COMPLETED	Study of Etanercept and Celecoxib to Treat Temporomandibular Disorders (Painful Joint Conditions)
NCT00009594	PHASE2	COMPLETED	Alternative Medicine Approaches for Women With Temporomandibular Disorders
NCT00010621	PHASE2	COMPLETED	Complementary Medicine Approaches to TMD Pain Management
NCT00066937	PHASE2	COMPLETED	Comparison of Psychological and Pharmacological Treatments for Pain Due to Temporomandibular Joint Disorder (TMD)
NCT02794922	PHASE2	COMPLETED	Effectiveness of Vitamin B in Reducing Temporomandibular Joint Disorder Pain
NCT04557878	PHASE2	COMPLETED	Role of Liquid Phase Concentrated Growth Factors vs. Hypertonic Dextrose Prolotherapy for Management of Patients With Disc Displacement Without Reduction
NCT04609748	PHASE2	UNKNOWN	Comparative Analysis of the Effectiveness of the Use of Nimesulide and CBD Oil in Patients With Pain in the Preauricular Region Due to the Pain-dysfunctional Syndrome of the Temporomandibular Joint.
NCT04724759	PHASE2	COMPLETED	The Effect of Opioid-Free Anesthesia in TMJ Surgery
NCT05883982	PHASE2	COMPLETED	Intra-articular I-PRF Injections in Patients With Temporomandibular Joint Dysfunction
NCT00870922	PHASE1	UNKNOWN	Effects of Masseter Manual Therapy on Temporomandibular Dysfunction
NCT01659372	PHASE1	UNKNOWN	Low Level Laser Therapy Versus Pharmacotherapy in in Improving Masticatory Muscle Pain
NCT02202070	PHASE1	WITHDRAWN	Botox for Treatment of TMJ Disorder With Bruxism
NCT03137914	PHASE1	COMPLETED	Nasal Septum Autologous Chondrocytes Transplantation for Condylar Resorption After Orthognathic Surgery
NCT06214637	PHASE1	UNKNOWN	Effectiveness of Melissa Officinalis for the Treatment of Probable Sleep Bruxism in Children and Adolescents
NCT01706172	PHASE2/PHASE3	COMPLETED	Treatment of Temporomandibular Dysfunction With Hypertonic Dextrose Injection
NCT02908568	PHASE2/PHASE3	UNKNOWN	Stimulation of the Proprioceptive Trigeminocardiac Reflex
NCT05214924	PHASE2/PHASE3	ENROLLING_BY_INVITATION	Effectiveness of iPRF Injections in Temporomandibular Joints Degeneration Management
NCT00899717	PHASE1/PHASE2	COMPLETED	Occlusal Adjustment as Treatment for Chronic Orofacial Pain
NCT02602483	PHASE1/PHASE2	COMPLETED	Exploratory Study To Assess the Efficacy and Safety of a Triple Combination for Acute Pain Treatment in Patients With Temporomandibular Joint Disorders (TMJD).
NCT05305833	PHASE1/PHASE2	UNKNOWN	Stem Cells and Stromal Vascular Fraction for Temporomandibular Joint Disease
NCT06694532	PHASE1/PHASE2	RECRUITING	EffIcacy Between Arthrocentesis With High Versus Low Molecular Weight Hyaluronic Acid in Treatment of TMJ Disorders
NCT03655275	EARLY_PHASE1	UNKNOWN	Effects of Platelet-rich Plasma Prolotherapy of Temporomandibular Joint Subluxation
NCT03675659	EARLY_PHASE1	UNKNOWN	Intra-articular Magnesium Sulfate for Tmj Dysfunction
NCT00001600	Not specified	COMPLETED	Diagnosis and Evaluation of Patients Needing Third Molar (Wisdom Tooth) Extraction and Patients With Chronic Facial Pain
NCT00001601	Not specified	COMPLETED	Evaluation and Treatment of Oral Soft Tissue Diseases
NCT00237042	Not specified	COMPLETED	Managing Temporomandibular Disorder (TMD) Symptoms
NCT00981149	Not specified	COMPLETED	Duloxetine for Treatment of Painful Temporomandibular Joint Disorder
NCT01113177	Not specified	COMPLETED	Effect of Functional Treatment on Mandibular Asymmetric Growth
NCT01187316	Not specified	COMPLETED	Treatment of Temporomandibular Disorders
NCT01333150	Not specified	UNKNOWN	Effect of Propranolol on the Autonomic Nervous System and Muscle Pain
NCT01417650	Not specified	UNKNOWN	The Effect of Low Level Laser Therapy on Improvement of Temporomandibular Joint Osteoarthritis
NCT01475630	Not specified	COMPLETED	Physical Therapy for Temporomandibular Joint (TMJ) Closed Lock