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): 415 total — 1 pathogenic, 1 likely-pathogenic (top 8% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 9 regions constrained (≈1% of expected missense variation)
• GTEx eGene: eQTL in 30 tissues, sQTL in 11 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.64 (unconstrained)
• MANE Select transcript: NM_001290223
• Notable: 415 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 25 — 18 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 2 retained_intron

MANE Select: ENST00000623213

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 4

ENST00000623213, ENST00000280333, ENST00000464466, ENST00000473861, ENST00000484400, ENST00000495574, ENST00000871522, ENST00000871523, ENST00000939681, ENST00000939682, ENST00000939683, ENST00000961939, ENST00000961940, ENST00000984874, ENST00000984875, ENST00001011248, ENST00001011249, ENST00001106411, ENST00001106412, ENST00001114244, ENST00001117700, ENST00001117701, ENST00001126825, ENST00001126826, ENST00001139846

RefSeq mRNA: 14 — 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_001377561, 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.

Highest expression (Bgee): corpus callosum, medial globus pallidus, globus pallidus, olfactory bulb, stromal cell of endometrium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DOCK1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 30 tissues and its splicing (sQTL) in 11 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 41 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	1.2e-52	-0.51	10:126798592:C:T
Skin Not Sun Exposed Suprapubic	sqtl	5.7e-29	-0.85	10:127026137:C:T
Cells Cultured fibroblasts	eqtl	4.2e-12	-0.21	10:126906570:C:T
Skin Sun Exposed Lower leg	sqtl	1.4e-11	-0.37	10:127270711:G:C
Artery Tibial	eqtl	1.8e-10	-0.15	10:127451661:T:C
Testis	eqtl	2.4e-10	+0.34	10:127412836:G:C
Colon Sigmoid	eqtl	1.3e-08	-0.27	10:127452665:G:A
Nerve Tibial	eqtl	4.3e-08	+0.30	10:127409165:C:T
Brain Putamen basal ganglia	eqtl	6.5e-06	-0.17	10:127452665:G:A
Skin Not Sun Exposed Suprapubic	eqtl	7.2e-06	+0.24	10:126941528:G:A
Esophagus Muscularis	eqtl	8.9e-06	-0.13	10:127451412:C:T
Thyroid	sqtl	1.1e-05	-0.31	10:127409922:G:A
Adipose Subcutaneous	eqtl	1.5e-05	+0.29	10:127412836:G:C
Brain Substantia nigra	eqtl	3.0e-05	-0.22	10:127451650:T:C
Esophagus Mucosa	sqtl	3.3e-05	+0.27	10:127250239:C:T
Brain Hippocampus	eqtl	5.8e-04	-0.16	10:127451429:G:A
Pancreas	eqtl	6.5e-04	-0.37	10:126952957:A:AT
Artery Tibial	sqtl	7.6e-04	+0.37	10:127387732:C:T
Lung	eqtl	1.1e-03	+0.18	10:126917308:C:G
Heart Atrial Appendage	eqtl	1.5e-03	-0.18	10:126906570:C:T

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
107596	24.5427	1574

Top tissues by expression

showing 100 of 291 tissues 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
left lobe of thyroid gland	UBERON:0001120	88.92	gold quality
lateral globus pallidus	UBERON:0002476	88.89	gold quality
renal medulla	UBERON:0000362	88.87	gold quality
aorta	UBERON:0000947	88.75	gold quality
caudate nucleus	UBERON:0001873	88.72	gold quality
thyroid gland	UBERON:0002046	88.66	gold quality
Ammon’s horn	UBERON:0001954	88.52	gold quality
smooth muscle tissue	UBERON:0001135	88.48	gold quality
right coronary artery	UBERON:0001625	88.27	gold quality
nucleus accumbens	UBERON:0001882	88.26	gold quality
descending thoracic aorta	UBERON:0002345	88.25	gold quality
endocervix	UBERON:0000458	88.23	gold quality
tendon	UBERON:0000043	88.18	gold quality
zone of skin	UBERON:0000014	88.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.09	gold quality
right lobe of thyroid gland	UBERON:0001119	88.09	gold quality
thoracic aorta	UBERON:0001515	87.96	gold quality
ascending aorta	UBERON:0001496	87.87	gold quality
lower esophagus mucosa	UBERON:0035834	87.86	gold quality
transverse colon	UBERON:0001157	87.82	gold quality
gall bladder	UBERON:0002110	87.81	gold quality
left ovary	UBERON:0002119	87.80	gold quality
colonic epithelium	UBERON:0000397	87.58	gold quality
dorsal root ganglion	UBERON:0000044	87.51	gold quality
body of uterus	UBERON:0009853	87.49	gold quality
trigeminal ganglion	UBERON:0001675	87.47	gold quality
mammary duct	UBERON:0001765	87.44	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.38	gold quality
CA1 field of hippocampus	UBERON:0003881	87.36	gold quality
middle frontal gyrus	UBERON:0002702	87.32	gold quality
postcentral gyrus	UBERON:0002581	87.26	gold quality
mucosa of transverse colon	UBERON:0004991	87.20	gold quality
temporal lobe	UBERON:0001871	87.18	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	87.03	gold quality
right ovary	UBERON:0002118	87.02	gold quality
left coronary artery	UBERON:0001626	86.99	gold quality
mucosa of urinary bladder	UBERON:0001259	86.97	silver quality
peritoneum	UBERON:0002358	86.90	gold quality
omental fat pad	UBERON:0010414	86.89	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.86	gold quality
minor salivary gland	UBERON:0001830	86.84	gold quality
coronary artery	UBERON:0001621	86.73	gold quality
epithelium of mammary gland	UBERON:0003244	86.66	gold quality
lower esophagus	UBERON:0013473	86.60	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.59	gold quality
mucosa of stomach	UBERON:0001199	86.58	gold quality
esophagus	UBERON:0001043	86.52	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.51	gold quality
uterine cervix	UBERON:0000002	86.49	gold quality
parietal lobe	UBERON:0001872	86.45	gold quality
synovial joint	UBERON:0002217	86.44	gold quality
esophagus mucosa	UBERON:0002469	86.37	gold quality
right uterine tube	UBERON:0001302	86.26	gold quality
adipose tissue of abdominal region	UBERON:0007808	86.22	gold quality
islet of Langerhans	UBERON:0000006	86.18	gold quality
urinary bladder	UBERON:0001255	86.10	gold quality
ovary	UBERON:0000992	86.01	gold quality
Brodmann (1909) area 46	UBERON:0006483	85.90	gold quality
colon	UBERON:0001155	85.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.83	gold quality
left uterine tube	UBERON:0001303	85.79	gold quality
vagina	UBERON:0000996	85.71	gold quality
type B pancreatic cell	CL:0000169	85.70	gold quality
mouth mucosa	UBERON:0003729	85.69	gold quality
pons	UBERON:0000988	85.59	gold quality
large intestine	UBERON:0000059	85.55	gold quality
lower lobe of lung	UBERON:0008949	85.55	gold quality
adult mammalian kidney	UBERON:0000082	85.52	gold quality
rectum	UBERON:0001052	85.51	gold quality
cingulate cortex	UBERON:0003027	85.49	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Locus coeruleus	tissue	49.1
Nucleus accumbens	tissue	48.8
Spinal cord	tissue	45.3
Hippocampus	tissue	44.3	low
Corpus callosum	tissue	38.7
Choroid plexus	tissue	38.0
Medulla oblongata	tissue	38.0
Substantia nigra	tissue	36.9
Midbrain	tissue	35.7
Thalamus	tissue	35.0
Postcentral gyrus	tissue	34.0
Putamen	tissue	32.4
Superior colliculi	tissue	31.9
Skin 1	tissue	31.5	low
Cerebral cortex	tissue	30.4	low
Somatosensory cortex	tissue	30.4
Pons	tissue	30.1
Ventral forebrain	tissue	29.1
Occipital cortex	tissue	29.0
Periaqueductal gray	tissue	28.8
Motor cortex	tissue	27.7
Hypothalamus	tissue	27.4
Prefrontal cortex	tissue	25.7
Olfactory bulb	tissue	25.4
Thyroid gland	tissue	24.9	high
Septum	tissue	24.6
Insular cortex	tissue	24.4
Parathyroid gland	tissue	24.0	low
Temporal cortex	tissue	23.9
Ovary	tissue	23.8	low
Hippocampal formation	tissue	23.3
Entorhinal cortex	tissue	23.3
Retrosplenial cortex	tissue	23.0
Retrosplenial and cingulate cortex	tissue	22.8
Amygdala	tissue	22.2
Cervix	tissue	21.9	medium
Basal ganglia	tissue	20.8	medium
Placenta	tissue	18.4	medium
Adipose tissue	tissue	18.3	low
Vagina	tissue	18.0	medium
Smooth muscle	tissue	18.0	low
Endometrium 1	tissue	18.0	medium
Kidney	tissue	18.0	medium
Seminal vesicle	tissue	17.4
Breast	tissue	17.3	high
Fallopian tube	tissue	17.0	medium
Salivary gland	tissue	16.7	medium
Gallbladder	tissue	16.1	not detected
Prostate	tissue	15.5	low
Epididymis	tissue	14.6	medium
Small intestine	tissue	14.2	medium
Urinary bladder	tissue	14.0	medium
Heart muscle	tissue	13.3	low
Esophagus	tissue	13.3	low
Rectum	tissue	13.0	not detected
Lung	tissue	12.9	medium
Duodenum	tissue	12.6	medium
Colon	tissue	12.5	low
Pancreas	tissue	11.2	medium
Caudate putamen	tissue	11.2

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Globus pallidus, externus (103.9), Globus pallidus, internus (100.3), Red nucleus (99.5), Temporal white matter (93.8), Cerebellar white matter (93.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PTTG1

miRNA regulators (miRDB)

Targeting DOCK1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 53 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 1.96e-18, LOEUF 0.637, missense Z 3.37 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000623213 splits into 9 regions with different missense tolerance; 1 is missense-constrained (≈1% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
10:126,905,518–126,998,154	227 / 254.1	0.89	no
10:126,998,155–126,998,200	3 / 17.6	0.17	yes (p 5.1e-04)
10:126,998,201–127,012,247	102 / 154.9	0.66	no
10:127,012,248–127,012,334	57 / 39.7	1.44	no
10:127,012,335–127,052,691	294 / 439.9	0.67	no
10:127,052,692–127,374,135	518 / 575.1	0.90	no
10:127,374,136–127,415,182	267 / 366.3	0.73	no
10:127,415,183–127,419,666	57 / 103.1	0.55	no
10:127,419,667–127,451,424	383 / 420.1	0.91	no

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2429765) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 30 distinct phenotype terms.

Mouse phenotype (MP)	Records
ventricular septal defect	2
abnormal heart morphology	1
double outlet right ventricle	1
short snout	1
hydronephrosis	1
abnormal myogenesis	1
abnormal muscle development	1
thin diaphragm muscle	1
atelectasis	1
cyanosis	1
abnormal vasculogenesis	1
edema	1
thymus hypoplasia	1
abnormal muscle physiology	1
hydrops fetalis	1
abnormal diaphragm morphology	1
abnormal intercostal muscle morphology	1
persistent truncus arteriosus	1
micrognathia	1
abnormal vascular endothelial cell migration	1
decreased skeletal muscle mass	1
pulmonary valve atresia	1
decreased skeletal muscle fiber diameter	1
decreased birth body size	1
atrioventricular septal defect	1

+5 more (showing top 25).

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
C10orf90	protein-coding	118611
DOCK1-AS1	ncRNA	105378552
NPS	protein-coding	594857
INSYN2A	protein-coding	642938
FOXI2	protein-coding	399823
CLRN3	protein-coding	119467

Protein

Protein identifiers

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

Alternative names: 180 kDa protein downstream of CRK

All UniProt accessions (2): A0A096LNH6, Q14185

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 (14): 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_001364490, 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 by resolution:

PDB	Title	Method	Resolution (Å)
3L4C	Structural basis of membrane-targeting by Dock180	X-RAY DIFFRACTION	2.37

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nucleoplasm; actin filaments; focal adhesion sites; nucleoli; plasma membrane

Antibody reliability (HPA): IH approved · IF approved

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)

Type	Positions
Phosphoserine	1681, 1743, 1751, 1756, 1761, 1764, 1858
Phosphothreonine	1767, 1772

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

9 curated (TAS) of 32; 7 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

32 pathways:

ID	Pathway	Evidence
R-HSA-9664422	FCGR3A-mediated phagocytosis ⚕	curated
R-HSA-983231	Factors involved in megakaryocyte development and platelet production	curated
R-HSA-8849471	PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases	curated
R-HSA-9013149	RAC1 GTPase cycle	curated
R-HSA-9013404	RAC2 GTPase cycle	curated
R-HSA-9013408	RHOG GTPase cycle	curated
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation	curated
R-HSA-9958810	SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	curated
R-HSA-4420097	VEGFA-VEGFR2 Pathway	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-9658195	Leishmania infection ⚕	—
R-HSA-9664417	Leishmania phagocytosis ⚕	—
R-HSA-9664407	Parasite infection ⚕	—
R-HSA-9824443	Parasitic Infection Pathways ⚕	—
R-HSA-422475	Axon guidance	—
R-HSA-418885	DCC mediated attractive signaling	electronic
R-HSA-1266738	Developmental Biology	—
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis	—
R-HSA-109582	Hemostasis	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-9675108	Nervous system development	—
R-HSA-373752	Netrin-1 signaling	—
R-HSA-9012999	RHO GTPase cycle	—
R-HSA-162582	Signal Transduction	—
R-HSA-9006927	Signaling by Non-Receptor Tyrosine Kinases	—
R-HSA-8848021	Signaling by PTK6	—
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—
R-HSA-194138	Signaling by VEGF	—

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 (11): 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), 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

13 top-level categories:

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
Immune System	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Innate Immune System	1
Axon guidance	1

GO top-level categories

40 GO namespaces:

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
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
cell periphery	1
intracellular protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 23 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
positive regulation of epithelial cell migration	BP	mutant phenotype
positive regulation of substrate adhesion-dependent cell spreading	BP	mutant phenotype
regulation of postsynapse assembly	BP	direct assay
cytoplasm	CC	direct assay
glutamatergic synapse	CC	direct assay
guanyl-nucleotide exchange factor complex	CC	direct assay
postsynapse	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,460 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DOCK1	ELMO1	Q92556	956
DOCK1	ELMO2	Q96JJ3	951
DOCK1	ELMO3	Q96BJ8	946
DOCK1	CRK	P46108	943
DOCK1	WDR35	Q9P2L0	927
DOCK1	DHX37	Q8IY37	890
DOCK1	ADGRB1	O14514	887
DOCK1	RHOG	P35238	873
DOCK1	GULP1	Q9UBP9	863
DOCK1	DHX8	Q14562	837
DOCK1	C10orf90	Q96M02	833
DOCK1	BCAR1	P56945	779
DOCK1	IFT122	Q9HBG6	746
DOCK1	AKT1	P31749	707
DOCK1	RABIF	P47224	688

IntAct

Human interaction partners of DOCK1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

15 partners by confidence:

Partner	Interaction type	MIscore	Records
ELMO1	physical association	0.940	17
GRB2	physical association	0.850	2
CRK	physical association	0.770	2
RAC1	association	0.730	10
NCK2	physical association	0.590	3
DOCK5	association	0.500	2
ANKRD28	physical association	0.400	4
CEBPE	physical association	0.400	1
FYN	physical association	0.400	1
NCK1	physical association	0.400	1
SRC	physical association	0.400	1
ELMO3	association	0.350	2
NUAK1	association	0.350	1
RHOG	association	0.350	1
SURF4	association	0.350	1

BioGRID (113 interactions; top human partners by supporting records): CRK (Co-fractionation; 14 records), ELMO1 (Affinity Capture-MS; 11 records), GRB2 (Affinity Capture-MS; 7 records), RAC1 (Co-fractionation; 5 records), GRASP (Affinity Capture-Western; 4 records), BCAR1 (Reconstituted Complex; 3 records), DOCK5 (Affinity Capture-Western; 3 records), FBXW11 (Affinity Capture-Western; 3 records), ANKRD54 (Affinity Capture-MS; 2 records), BTRC (Affinity Capture-MS; 2 records), CRKL (Affinity Capture-MS; 2 records), CYTH2 (Affinity Capture-Western; 2 records), ELMO3 (Affinity Capture-MS; 2 records), PFN1 (Proximity Label-MS; 2 records), RAC2 (Affinity Capture-MS; 2 records)

SIGNOR signaling

5 signaling 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”

Protein complexes (CORUM) (6)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

6 complexes by size:

Complex	Subunits	Members
ADGRA2-DOCK1-ELMO2-GNB1-GNG2 complex	5	ADGRA2, DOCK1, ELMO2, GNB1, GNG2
★ AXL-DOCK1-ELMO2-MET complex	4	AXL, DOCK1, ELMO2, MET
CRK-BCAR1-DOCK1 complex	3	BCAR1, CRK, DOCK1
ELMO1-DOCK1-RAC1 complex	3	DOCK1, ELMO1, RAC1
ELMO1-DOCK1-CRKII complex	3	CRK, DOCK1, ELMO1
ELMO1-DOCK1 complex	2	DOCK1, ELMO1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 15 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	5	135.9×	2e-08
FCGR3A-mediated phagocytosis	7	93.6×	8e-11
VEGFA-VEGFR2 Pathway	7	69.6×	4e-10
Regulation of actin dynamics for phagocytic cup formation	5	65.8×	4e-07
Constitutive Signaling by Aberrant PI3K in Cancer	5	45.3×	2e-06
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	34.6×	6e-06
PIP3 activates AKT signaling	5	23.9×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
Rac protein signal transduction	5	187.2×	1e-08
ephrin receptor signaling pathway	5	114.6×	8e-08
actin filament organization	6	47.5×	2e-07
actin cytoskeleton organization	5	26.4×	4e-05
cell migration	5	20.5×	1e-04

Disease & clinical

Genetic variants

Variant evidence for DOCK1: 415 ClinVar records (2 pathogenic / likely pathogenic); 17 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	327
Likely benign	18
Benign	0

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
521686	NM_001290223.2(DOCK1):c.2053dup (p.Glu685fs)	Likely pathogenic	criteria provided, single submitter	1
3061841	GRCh38/hg38 10q26.2-26.3(chr10:125976998-133427130)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore DOCK1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 6,523):

Position(s)	Effect	Δscore	Sites
10:126970699	acceptor_gain	1.0000
10:126970700–126970701	acceptor_loss	1.0000	6
10:126970786–126970787	donor_loss	1.0000	5
10:126987519–126987520	acceptor_loss	1.0000	6
10:126990452	acceptor_gain	1.0000
10:126990604–126990605	donor_loss	1.0000	5
10:126996884–126996885	donor_loss	1.0000	5
10:126998085	acceptor_gain	1.0000
10:126998089	acceptor_gain	1.0000
10:126999352	acceptor_gain	1.0000

AlphaMissense

5,770 missense substitutions predicted likely pathogenic (of 12,547 scored), across 1,306 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M1197	9	0.977	0.999
M1215	9	0.967	0.998
M1110	9	0.962	0.998
M307	9	0.955	0.997
M966	9	0.940	0.995
M1535	9	0.931	0.992
M537	9	0.890	0.984
M663	9	0.885	0.986
M942	9	0.849	0.984
D1133	8	0.999	1.000
D653	8	0.998	0.999
D656	8	0.998	0.999
H515	8	0.995	1.000
D427	8	0.994	0.998
N447	8	0.994	1.000
F659	8	0.991	0.999
F348	8	0.990	1.000
D1109	8	0.990	0.998
H1227	8	0.990	0.998
D284	8	0.989	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.85e-06
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	0.000476

Disease associations

OMIM: gene MIM:601403 | disease phenotypes:

GWAS associations

17 associations:

Study	Trait	p-value
GCST004100_1	Body mass index (change over time) in gastrointestinal cancer or chronic obstructive pulmonary disease	9e-10
GCST007576_260	Chronotype	5e-9
GCST004101_1	Body mass index (change over time) in gastrointestinal cancer	2e-8
GCST007756_1	Homeostasis model assessment of insulin resistance in less-fat diet	3e-8
GCST001703_1	Apolipoprotein Levels	4e-8
GCST006609_4	Response to TNF inhibitor in rheumatoid arthritis (change in tender 28-joint count)	7e-8
GCST002794_15	Airway wall thickness	8e-8
GCST010396_159	Gut microbiota (bacterial taxa, hurdle binary method)	5e-7
GCST002783_217	Body mass index	7e-7
GCST006719_9	BRCA1/2-negative high-risk breast cancer	1e-6
GCST002783_596	Body mass index	2e-6
GCST008152_93	Weight	2e-6
GCST002343_7	Response to cytidine analogues (gemcitabine)	4e-6
GCST006610_1	Response to TNF inhibitor in rheumatoid arthritis (change in disease activity score)	5e-6
GCST002794_3	Airway wall thickness	8e-6
GCST002367_2	Social communication problems	9e-6
GCST002794_13	Airway wall thickness	9e-6

EFO canonical traits (from GWAS)

12 canonical traits:

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523288 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

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	decreases methylation, decreases expression, affects cotreatment	2
Cisplatin	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	increases methylation, decreases expression	2
Valproic Acid	affects expression, increases methylation	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	affects binding, decreases reaction	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 221 trials:

NCT	Phase	Status	Title
NCT03522207	Phase 4	TERMINATED	Accuracy and Efficacy of Trazodone (Desyrel) on Sleep Quality and Pain Management of TMD Patient
NCT04110587	Phase 4	COMPLETED	Hyaluronic Acid Evaluation as Adjuvant to Temporomandibular Joint Arthroscopy
NCT04810429	Phase 4	COMPLETED	Comparison of Temporomandibular Joint Arthroscopy With Botulinum Toxin Injection Versus Placebo
NCT05817162	Phase 4	UNKNOWN	Temporomandibular Joint Arthrocentesis With Infiltration of PRP + Ropivacaine Versus PRP
NCT06044974	Phase 4	COMPLETED	Nd-YAG Laser Versus Epidermal Growth Factor For Myogenic Tempromandibular Disorder.
NCT06452134	Phase 4	UNKNOWN	Evaluation the Effect of Coenzyme Q10 on Tissue Healing Process in Patients Undergoing Wisdom Tooth Extraction
NCT06530745	Phase 4	COMPLETED	PRP vs HA Intra-articular Injections in TMDs
NCT07401745	Phase 4	ACTIVE_NOT_RECRUITING	Occlusal Splint Combined With Granisetron Injection for Management of Myofascial Pain Related to Temporomandibular Disorders
NCT00001955	Phase 2	COMPLETED	Study of Etanercept and Celecoxib to Treat Temporomandibular Disorders (Painful Joint Conditions)
NCT00009594	Phase 2	COMPLETED	Alternative Medicine Approaches for Women With Temporomandibular Disorders
NCT00010621	Phase 2	COMPLETED	Complementary Medicine Approaches to TMD Pain Management
NCT00066937	Phase 2	COMPLETED	Comparison of Psychological and Pharmacological Treatments for Pain Due to Temporomandibular Joint Disorder (TMD)
NCT02794922	Phase 2	COMPLETED	Effectiveness of Vitamin B in Reducing Temporomandibular Joint Disorder Pain
NCT04557878	Phase 2	COMPLETED	Role of Liquid Phase Concentrated Growth Factors vs. Hypertonic Dextrose Prolotherapy for Management of Patients With Disc Displacement Without Reduction
NCT04609748	Phase 2	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	Phase 2	COMPLETED	The Effect of Opioid-Free Anesthesia in TMJ Surgery
NCT05883982	Phase 2	COMPLETED	Intra-articular I-PRF Injections in Patients With Temporomandibular Joint Dysfunction
NCT07798258	Phase 2	ACTIVE_NOT_RECRUITING	Assessment of Injectable PRF Versus Dextrose Injection in Temporomandibular Joint in Anterior Disc Displacement With Reduction
NCT00870922	Phase 1	UNKNOWN	Effects of Masseter Manual Therapy on Temporomandibular Dysfunction
NCT01659372	Phase 1	UNKNOWN	Low Level Laser Therapy Versus Pharmacotherapy in in Improving Masticatory Muscle Pain
NCT02202070	Phase 1	WITHDRAWN	Botox for Treatment of TMJ Disorder With Bruxism
NCT03137914	Phase 1	COMPLETED	Nasal Septum Autologous Chondrocytes Transplantation for Condylar Resorption After Orthognathic Surgery
NCT06214637	Phase 1	UNKNOWN	Effectiveness of Melissa Officinalis for the Treatment of Probable Sleep Bruxism in Children and Adolescents
NCT01706172	Phase 2/3	COMPLETED	Treatment of Temporomandibular Dysfunction With Hypertonic Dextrose Injection
NCT02908568	Phase 2/3	UNKNOWN	Stimulation of the Proprioceptive Trigeminocardiac Reflex
NCT05214924	Phase 2/3	ENROLLING_BY_INVITATION	Effectiveness of iPRF Injections in Temporomandibular Joints Degeneration Management
NCT00899717	Phase 1/2	COMPLETED	Occlusal Adjustment as Treatment for Chronic Orofacial Pain
NCT02602483	Phase 1/2	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	Phase 1/2	UNKNOWN	Stem Cells and Stromal Vascular Fraction for Temporomandibular Joint Disease
NCT06694532	Phase 1/2	RECRUITING	EffIcacy Between Arthrocentesis With High Versus Low Molecular Weight Hyaluronic Acid in Treatment of TMJ Disorders
NCT03655275	Early Phase 1	UNKNOWN	Effects of Platelet-rich Plasma Prolotherapy of Temporomandibular Joint Subluxation
NCT03675659	Early Phase 1	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
NCT01502709	Not specified	TERMINATED	Neurostimulation in Temporomandibular Disorders (TMD) Patients
NCT01617356	Not specified	COMPLETED	Treatment of Temporomandibular Dysfunction With Hypertonic Dextrose Injection
NCT01676129	Not specified	UNKNOWN	Nocipoint Therapy Versus Standard Physical Therapy Using Electrical Stimulation in Treating Pain From TMJ Disorder
NCT01679821	Not specified	COMPLETED	Prevalence of Signs and Symptoms of TMD in Patients Wearing Double Complete Dentures, RPD and in Dentistry Students.
NCT01794624	Not specified	COMPLETED	Biobehavioral Pain Management in TMD
NCT02139735	Not specified	COMPLETED	Therapeutic Response of Ultrasound and Muscular Stretching in Temporomandibular Disorder Patients
NCT02164630	Not specified	COMPLETED	Optimizing Resilience In Orofacial Pain and Nociception
NCT02247063	Not specified	COMPLETED	Motor Cortex as a Research & Therapeutic Target in TMD
NCT02292355	Not specified	COMPLETED	Effect of the Method Pilates in Women With Temporomandibular Disorders
NCT02324712	Not specified	WITHDRAWN	Cytokine and Growth Factor Changes and Correlation With Clinical Outcomes Following Acupuncture for TMD
NCT02397070	Not specified	UNKNOWN	Effectiveness of a Jaw Exercise Program in Temporomandibular Disorders Patients
NCT02427113	Not specified	UNKNOWN	What Are the Effects of Music on Temporomandibular Disorder Symptoms?
NCT02490605	Not specified	UNKNOWN	Effect of the Use of an Occlusal Plate on the Postural Alignment
NCT02540863	Not specified	COMPLETED	Miofascial Release and Exercises Therapy in the Treatment of Temporomandibular Disorders
NCT02630771	Not specified	COMPLETED	Multimodal Assessment of Sensory Processing and Brain Features in Patients With Chronic Orofacial Pain
NCT02928809	Not specified	UNKNOWN	Effect of Low-level Laser Prior to the Induction of Fatigue
NCT02946645	Not specified	COMPLETED	Efficiency of Neuromuscular Bite vs Physiotherapy in TMD Patients
NCT02997410	Not specified	UNKNOWN	Ozone Therapy for Masticatory Muscle Pain (OTMMP)
NCT03065608	Not specified	COMPLETED	Evaluation of C-reactive Protein Level in the Group of Patient With Pain Form of Temporomandibular Joint Dysfunction