DOCK1 (dedicator of cytokinesis 1)

Gene

• Entrez ID: 1793
• Gene name: Dedicator of cytokinesis 1
• Gene symbol: DOCK1
• Synonyms (NCBI Gene): DOCK180, ced5
• Chromosome: 10
• Chromosome location: 10q26.2
• Summary: 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 influencin

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs767858333	->G	Likely-pathogenic	Coding sequence variant, frameshift variant, 5 prime UTR variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT047082	hsa-miR-183-5p	CLASH	23622248
MIRT038422	hsa-miR-296-3p	CLASH	23622248
MIRT054619	hsa-miR-155-5p	Immunocytochemistry, Immunohistochemistry, In situ hybridization, Luciferase reporter assay, Microarray, qRT-PCR, Western blot	24604078
MIRT574169	hsa-miR-6867-5p	PAR-CLIP	20371350
MIRT574168	hsa-miR-4455	PAR-CLIP	20371350
MIRT574167	hsa-miR-574-5p	PAR-CLIP	20371350
MIRT574169	hsa-miR-6867-5p	PAR-CLIP	20371350
MIRT574168	hsa-miR-4455	PAR-CLIP	20371350
MIRT574167	hsa-miR-574-5p	PAR-CLIP	20371350
MIRT942782	hsa-miR-105	CLIP-seq
MIRT942783	hsa-miR-1228	CLIP-seq
MIRT942784	hsa-miR-1271	CLIP-seq
MIRT942785	hsa-miR-1273f	CLIP-seq
MIRT942786	hsa-miR-1287	CLIP-seq
MIRT942787	hsa-miR-182	CLIP-seq
MIRT942788	hsa-miR-186	CLIP-seq
MIRT942789	hsa-miR-224	CLIP-seq
MIRT942790	hsa-miR-31	CLIP-seq
MIRT942791	hsa-miR-3150a-3p	CLIP-seq
MIRT942792	hsa-miR-3173-3p	CLIP-seq
MIRT942793	hsa-miR-3175	CLIP-seq
MIRT942794	hsa-miR-3184	CLIP-seq
MIRT942795	hsa-miR-3652	CLIP-seq
MIRT942796	hsa-miR-423-5p	CLIP-seq
MIRT942797	hsa-miR-4257	CLIP-seq
MIRT942798	hsa-miR-4430	CLIP-seq
MIRT942799	hsa-miR-4432	CLIP-seq
MIRT942800	hsa-miR-4492	CLIP-seq
MIRT942801	hsa-miR-4498	CLIP-seq
MIRT942802	hsa-miR-450b-5p	CLIP-seq
MIRT942803	hsa-miR-4688	CLIP-seq
MIRT942804	hsa-miR-4696	CLIP-seq
MIRT942805	hsa-miR-4714-5p	CLIP-seq
MIRT942806	hsa-miR-4728-5p	CLIP-seq
MIRT942807	hsa-miR-4779	CLIP-seq
MIRT942808	hsa-miR-486-3p	CLIP-seq
MIRT942809	hsa-miR-518a-5p	CLIP-seq
MIRT942810	hsa-miR-527	CLIP-seq
MIRT942811	hsa-miR-579	CLIP-seq
MIRT942812	hsa-miR-603	CLIP-seq
MIRT942813	hsa-miR-606	CLIP-seq
MIRT942814	hsa-miR-711	CLIP-seq
MIRT942815	hsa-miR-762	CLIP-seq
MIRT942816	hsa-miR-939	CLIP-seq
MIRT942817	hsa-miR-96	CLIP-seq
MIRT942811	hsa-miR-579	CLIP-seq
MIRT2387058	hsa-miR-4742-3p	CLIP-seq
MIRT942811	hsa-miR-579	CLIP-seq
MIRT2387059	hsa-miR-587	CLIP-seq
MIRT2387060	hsa-miR-630	CLIP-seq
MIRT2387061	hsa-miR-664	CLIP-seq
MIRT2518617	hsa-miR-1224-3p	CLIP-seq
MIRT2518618	hsa-miR-146a	CLIP-seq
MIRT2518619	hsa-miR-146b-5p	CLIP-seq
MIRT2518620	hsa-miR-3200-3p	CLIP-seq
MIRT2518621	hsa-miR-3680	CLIP-seq
MIRT942797	hsa-miR-4257	CLIP-seq
MIRT2518622	hsa-miR-4484	CLIP-seq
MIRT2518623	hsa-miR-4509	CLIP-seq
MIRT2518624	hsa-miR-4710	CLIP-seq
MIRT942805	hsa-miR-4714-5p	CLIP-seq
MIRT2518625	hsa-miR-4717-5p	CLIP-seq
MIRT2518626	hsa-miR-4753-5p	CLIP-seq
MIRT2518627	hsa-miR-4792	CLIP-seq
MIRT2518628	hsa-miR-483-3p	CLIP-seq
MIRT2518629	hsa-miR-548an	CLIP-seq
MIRT2518630	hsa-miR-589	CLIP-seq
MIRT942812	hsa-miR-603	CLIP-seq
MIRT942813	hsa-miR-606	CLIP-seq
MIRT942814	hsa-miR-711	CLIP-seq
MIRT2518617	hsa-miR-1224-3p	CLIP-seq
MIRT2518620	hsa-miR-3200-3p	CLIP-seq
MIRT942797	hsa-miR-4257	CLIP-seq
MIRT942805	hsa-miR-4714-5p	CLIP-seq
MIRT942812	hsa-miR-603	CLIP-seq
MIRT942813	hsa-miR-606	CLIP-seq
MIRT942814	hsa-miR-711	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
PTTG1	Activation	22081074

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IDA	12134158
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IEA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	TAS
GO:0005096	Function	GTPase activator activity	TAS	9808620
GO:0005515	Function	Protein binding	IPI	12134158, 15247908, 15723800, 17474147, 17515907, 18768751, 19118547, 20936779, 28514442, 30853625, 31980649, 32203420, 33961781, 35044719
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IDA	17515907
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	TAS	8661160
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IBA
GO:0006909	Process	Phagocytosis	IEA
GO:0006911	Process	Phagocytosis, engulfment	TAS	9548255
GO:0006915	Process	Apoptotic process	IEA
GO:0006915	Process	Apoptotic process	TAS	9548255
GO:0007165	Process	Signal transduction	TAS	8661160
GO:0007229	Process	Integrin-mediated signaling pathway	TAS	9808620
GO:0007264	Process	Small GTPase-mediated signal transduction	IEA
GO:0007264	Process	Small GTPase-mediated signal transduction	TAS	9808620
GO:0007520	Process	Myoblast fusion	IBA
GO:0010634	Process	Positive regulation of epithelial cell migration	IMP	19004829
GO:0016020	Component	Membrane	IEA
GO:0016477	Process	Cell migration	IBA
GO:0017124	Function	SH3 domain binding	IEA
GO:0031267	Function	Small GTPase binding	IBA
GO:0032045	Component	Guanyl-nucleotide exchange factor complex	IDA	12134158
GO:0098794	Component	Postsynapse	IDA	21900250
GO:0098794	Component	Postsynapse	IMP	21900250
GO:0098978	Component	Glutamatergic synapse	IDA	21900250
GO:0098978	Component	Glutamatergic synapse	IMP	21900250
GO:0150052	Process	Regulation of postsynapse assembly	IDA	21900250
GO:0150052	Process	Regulation of postsynapse assembly	IMP	21900250
GO:1900026	Process	Positive regulation of substrate adhesion-dependent cell spreading	IMP	19004829

Other IDs

• MIM: 601403
• HGNC: 2987
• e!Ensembl: ENSG00000150760

Protein

• UniProt ID: Q14185
• Protein name: Dedicator of cytokinesis protein 1 (180 kDa protein downstream of CRK) (DOCK180)
• Protein 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 (PubMed:1900482
• PDB: 3L4C
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00018	SH3_1	15 → 62	SH3 domain	Domain
  PF16172	DOCK_N	72 → 416	DOCK N-terminus	Family
  PF14429	DOCK-C2	421 → 618	C2 domain in Dock180 and Zizimin proteins	Domain
  PF06920	DHR-2	1111 → 1610	Dock homology region 2	Family

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

  MTRWVPTKREEKYGVAFYNYDARGADELSLQIGDTVHILETYEGWYRGYTLRKKSKKGIF
  PASYIHLKEAIVEGKGQHETVIPGDLPLIQEVTTTLREWSTIWRQLYVQDNREMFRSVRH
  MIYDLIEWRSQILSGTLPQDELKELKKKVTAKIDYGNRILDLDLVVRDEDGNILDPELTS
  TISLFRAHEIASKQVEERLQEEKSQKQNIDINRQAKFAATPSLALFVNLKNVVCKIGEDA
  EVLMSLYDPVESKFISENYLVRWSSSGLPKDIDRLHNLRAVFTDLGSKDLKREKISFVCQ
  IVRVGRMELRDNNTRKLTSGLRRPFGVAVMDVTDIINGKVDDEDKQHFIPFQPVAGENDF
  LQTVINKVIAAKEVNHKGQGLWVTLKLLPGDIHQIRKEFPHLVDRTTAVARKTGFPEIIM
  PGDVRNDIYVTLVQGDFDKGSKTTAKNVEVTVSVYDEDGKRLEHVIFPGAGDEAISEYKS
  VIYYQVKQPRWFETVKVAIPIEDVNRSHLRFTFRHRSSQDSKDKSEKIFALAFVKLMRYD
  GTTLRDGEHDLIVYKAEAKKLEDAATYLSLPSTKAELEEKGHSATGKSMQSLGSCTISKD
  SFQISTLVCSTKLTQNVDLLGLLKWRSNTSLLQQNLRQLMKVDGGEVVKFLQDTLDALFN
  IMMENSESETFDTLVFDALVFIIGLIADRKFQHFNPVLETYIKKHFSATLAYTKLTKVLK
  NYVDGAEKPGVNEQLYKAMKALESIFKFIVRSRILFNQLYENKGEADFVESLLQLFRSIN
  DMMSSMSDQTVRVKGAALKYLPTIVNDVKLVFDPKELSKMFTEFILNVPMGLLTIQKLYC
  LIEIVHSDLFTQHDCREILLPMMTDQLKYHLERQEDLEACCQLLSHILEVLYRKDVGPTQ
  RHVQIIMEKLLRTVNRTVISMGRDSELIGNFVACMTAILRQMEDYHYAHLIKTFGKMRTD
  VVDFLMETFIMFKNLIGKNVYPFDWVIMNMVQNKVFLRAINQYADMLNKKFLDQANFELQ
  LWNNYFHLAVAFLTQESLQLENFSSAKRAKILNKYGDMRRQIGFEIRDMWYNLGQHKIKF
  IPEMVGPILEMTLIPETELRKATIPIFFDMMQCEFHSTRSFQMFENEIITKLDHEVEGGR
  GDEQYKVLFDKILLEHCRKHKYLAKTGETFVKLVVRLMERLLDYRTIMHDENKENRMSCT
  VNVLNFYKEIEREEMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLLKWSEDVCVAHLTQ
  RDGYQATTQGQLKEQLYQEIIHYFDKGKMWEEAIALGKELAEQYENEMFDYEQLSELLKK
  QAQFYENIVKVIRPKPDYFAVGYYGQGFPTFLRGKVFIYRGKEYERREDFEARLLTQFPN
  AEKMKTTSPPGDDIKNSPGQYIQCFTVKPKLDLPPKFHRPVSEQIVSFYRVNEVQRFEYS
  RPIRKGEKNPDNEFANMWIERTIYTTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLT
  NDKINSMVQQHLDDPSLPINPLSMLLNGIVDPAVMGGFANYEKAFFTDRYLQEHPEAHEK
  IEKLKDLIAWQIPFLAEGIRIHGDKVTEALRPFHERMEACFKQLKEKVEKEYGVRIMPSS
  LDDRRGSRPRSMVRSFTMPSSSRPLSVASVSSLSSDSTPSRPGSDGFALEPLLPKKMHSR
  SQDKLDKDDLEKEKKDKKKEKRNSKHQEIFEKEFKPTDISLQQSEAVILSETISPLRPQR
  PKSQVMNVIGSERRFSVSPSSPSSQQTPPPVTPRAKLSFSMQSSLELNGMTGADVADVPP
  PLPLKGSVADYGNLMENQDLLGSPTPPPPPPHQRHLPPPLPSKTPPPPPPKTTRKQASVD
  SGIVQ

• Sequence length: 1865

Pathways

KEGG:

Efferocytosis
Focal adhesion
Fc gamma R-mediated phagocytosis
Regulation of actin cytoskeleton
Bacterial invasion of epithelial cells
Shigellosis
Yersinia infection

Reactome:

Regulation of actin dynamics for phagocytic cup formation
DCC mediated attractive signaling
VEGFA-VEGFR2 Pathway
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases
FCGR3A-mediated phagocytosis
Factors involved in megakaryocyte development and platelet production

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AMYOTROPHIC LATERAL SCLEROSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ASTROCYTOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BRCAX BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOMYOPATHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DOCK1-related disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DUCHENNE MUSCULAR DYSTROPHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EBV-positive nodal T- and NK-cell lymphoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INSOMNIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG ADENOCARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOYAMOYA DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OLIGODENDROGLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Temporomandibular joint disorder	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer Disease	Alzheimer disease	Pubtator	34440432	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Carcinoma	Breast Carcinoma	BEFREE	23592719, 29432733, 31528235		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	23591873, 25332238, 29432733	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	21698158, 22323579, 32626999, 36718103	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Adenoid Cystic	Adenoid cystic carcinoma	Pubtator	21692051	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	34184075	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	30983072		★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	32626999	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	22175896, 24819662		★☆☆☆☆ Found in Text Mining only
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	BEFREE	28044437		★☆☆☆☆ Found in Text Mining only
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	GWASCAT_DG	28044437		★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Cognition disorder	Pubtator	39976347	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	33685455	Associate	★☆☆☆☆ Found in Text Mining only
Congenital chromosomal disease	Congenital Chromosomal Disease	BEFREE	19558528		★☆☆☆☆ Found in Text Mining only
Dysmorphic features	Dysmorphic Features	CLINVAR_DG	17670792, 17765544, 18332221, 18591431, 18820033, 20829512, 25022758, 26527617, 27662902, 3372592		★☆☆☆☆ Found in Text Mining only
Gastrointestinal carcinoma	Gastrointestinal carcinoma	GWASCAT_DG	28044437		★☆☆☆☆ Found in Text Mining only
Gastrointestinal Neoplasms	Gastrointestinal neoplasm	Pubtator	28044437	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	22080864, 28487380, 30108175		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	22323579, 28487380, 30108175	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	28487380, 30108175		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	17671188, 22080864, 26946516		★☆☆☆☆ Found in Text Mining only
Heart Failure	Heart failure	Pubtator	34572079	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	33335013	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	33658535, 38077322	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	31114350, 31762818		★☆☆☆☆ Found in Text Mining only
Malignant Glioma	Glioma	BEFREE	17671188		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	23592719, 29432733, 31528235		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of gastrointestinal tract	Malignant gastrointestinal tract tumors	BEFREE	28044437		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	BEFREE	22175896, 24819662		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	21698158		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	17671188, 22175896, 28467910, 29432733, 30108175, 31717460		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	29432733	Associate	★☆☆☆☆ Found in Text Mining only
Melanoma Cutaneous Malignant	Melanoma	Pubtator	27914105	Associate	★☆☆☆☆ Found in Text Mining only
Multiple congenital anomalies	Multiple Congenital Anomalies	CLINVAR_DG	17670792, 17765544, 18332221, 18591431, 18820033, 20829512, 25022758, 26527617, 27662902, 3372592		★☆☆☆☆ Found in Text Mining only
Muscular Dystrophy, Duchenne	Duchenne Muscular Dystrophy	GWASCAT_DG	30014611		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	23592719, 30983072, 31528235		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	25772781	Associate	★☆☆☆☆ Found in Text Mining only
ovarian neoplasm	Ovarian neoplasm	BEFREE	22175896, 24819662		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	20237902, 24819662	Associate	★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic Ovary Syndrome	BEFREE	27662902		★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	28044437	Associate	★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	28645778		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	29286141	Associate	★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	21698158		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	21698158, 24260584	Associate	★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple Negative Breast Neoplasms	BEFREE	30127952, 31717460		★☆☆☆☆ Found in Text Mining only