DOCK2 (dedicator of cytokinesis 2)

Gene

• Entrez ID: 1794
• Gene name: Dedicator of cytokinesis 2
• Gene symbol: DOCK2
• Synonyms (NCBI Gene): IMD40
• Chromosome: 5
• Chromosome location: 5q35.1
• Summary: The protein encoded by this gene belongs to the CDM protein family. It is specifically expressed in hematopoietic cells and is predominantly expressed in peripheral blood leukocytes. The protein is involved in remodeling of the actin cytoskeleton required

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs149411090	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant, non coding transcript variant
rs762909359	C>T	Pathogenic	Genic downstream transcript variant, coding sequence variant, stop gained, non coding transcript variant
rs1561585424	G>A	Likely-pathogenic	Splice donor variant
rs1561898523	G>A	Likely-pathogenic	Genic downstream transcript variant, splice donor variant
rs1581049599	A>T	Likely-pathogenic	Stop gained, coding sequence variant, non coding transcript variant
rs1581090174	G>T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1581531492	T>C	Likely-pathogenic	Splice donor variant, genic downstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT2214272	hsa-miR-1263	CLIP-seq
MIRT2214273	hsa-miR-3200-3p	CLIP-seq
MIRT2387062	hsa-miR-150	CLIP-seq
MIRT2387063	hsa-miR-3156-3p	CLIP-seq
MIRT2387064	hsa-miR-3921	CLIP-seq
MIRT2387065	hsa-miR-4301	CLIP-seq
MIRT2387066	hsa-miR-4639-3p	CLIP-seq
MIRT2387067	hsa-miR-4653-5p	CLIP-seq
MIRT2387068	hsa-miR-4713-5p	CLIP-seq
MIRT2387069	hsa-miR-532-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001766	Process	Membrane raft polarization	IEA
GO:0001768	Process	Establishment of T cell polarity	IEA
GO:0001771	Process	Immunological synapse formation	IEA
GO:0002277	Process	Myeloid dendritic cell activation involved in immune response	IEA
GO:0002277	Process	Myeloid dendritic cell activation involved in immune response	ISS
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IBA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IDA	10559471
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IEA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	TAS
GO:0005096	Function	GTPase activator activity	IEA
GO:0005515	Function	Protein binding	IPI	12134158, 15723800, 25416956, 32296183, 32814053
GO:0005576	Component	Extracellular region	TAS
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005856	Component	Cytoskeleton	IEA
GO:0005886	Component	Plasma membrane	IBA
GO:0006935	Process	Chemotaxis	IEA
GO:0007010	Process	Cytoskeleton organization	IEA
GO:0007264	Process	Small GTPase-mediated signal transduction	IEA
GO:0007520	Process	Myoblast fusion	IBA
GO:0012505	Component	Endomembrane system	IEA
GO:0016020	Component	Membrane	HDA	19946888
GO:0016020	Component	Membrane	IEA
GO:0016477	Process	Cell migration	IBA
GO:0030036	Process	Actin cytoskeleton organization	IEA
GO:0030036	Process	Actin cytoskeleton organization	TAS	12176041
GO:0031267	Function	Small GTPase binding	IBA
GO:0035580	Component	Specific granule lumen	TAS
GO:0042098	Process	T cell proliferation	IEA
GO:0042110	Process	T cell activation	IEA
GO:0042608	Function	T cell receptor binding	IDA	12176041
GO:0044351	Process	Macropinocytosis	IEA
GO:0044351	Process	Macropinocytosis	ISS
GO:0045059	Process	Positive thymic T cell selection	IEA
GO:0045060	Process	Negative thymic T cell selection	IEA
GO:0046631	Process	Alpha-beta T cell activation	IEA
GO:0046633	Process	Alpha-beta T cell proliferation	IEA
GO:0050766	Process	Positive regulation of phagocytosis	IEA
GO:0050766	Process	Positive regulation of phagocytosis	ISS
GO:0051056	Process	Regulation of small GTPase mediated signal transduction	TAS
GO:0070062	Component	Extracellular exosome	HDA	20458337

Other IDs

• MIM: 603122
• HGNC: 2988
• e!Ensembl: ENSG00000134516

Protein

• UniProt ID: Q92608
• Protein name: Dedicator of cytokinesis protein 2
• Protein function: Involved in cytoskeletal rearrangements required for lymphocyte migration in response of chemokines. Activates RAC1 and RAC2, but not CDC42, by functioning as a guanine nucleotide exchange factor (GEF), which exchanges bound GDP for free GTP. Ma
• PDB: 2RQR, 2YIN, 3A98, 3B13, 6TGB, 6TGC
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07653	SH3_2	12 → 66	Variant SH3 domain	Domain
  PF16172	DOCK_N	71 → 414	DOCK N-terminus	Family
  PF14429	DOCK-C2	419 → 616	C2 domain in Dock180 and Zizimin proteins	Domain
  PF06920	DHR-2	1116 → 1615	Dock homology region 2	Family

• Tissue specificity: TISSUE SPECIFICITY: Specifically expressed in hematopoietic cells. Highly expressed in peripheral blood leukocytes, and expressed at intermediate level in thymus and spleen. Expressed at very low level in the small intestine and colon. {ECO:0000269|PubMed
• Sequence:

  MAPWRKADKERHGVAIYNFQGSGAPQLSLQIGDVVRIQETCGDWYRGYLIKHKMLQGIFP
  KSFIHIKEVTVEKRRNTENIIPAEIPLAQEVTTTLWEWGSIWKQLYVASKKERFLQVQSM
  MYDLMEWRSQLLSGTLPKDELKELKQKVTSKIDYGNKILELDLIVRDEDGNILDPDNTSV
  ISLFHAHEEATDKITERIKEEMSKDQPDYAMYSRISSSPTHSLYVFVRNFVCRIGEDAEL
  FMSLYDPNKQTVISENYLVRWGSRGFPKEIEMLNNLKVVFTDLGNKDLNRDKIYLICQIV
  RVGKMDLKDTGAKKCTQGLRRPFGVAVMDITDIIKGKAESDEEKQHFIPFHPVTAENDFL
  HSLLGKVIASKGDSGGQGLWVTMKMLVGDIIQIRKDYPHLVDRTTVVARKLGFPEIIMPG
  DVRNDIYITLLQGDFDKYNKTTQRNVEVIMCVCAEDGKTLPNAICVGAGDKPMNEYRSVV
  YYQVKQPRWMETVKVAVPIEDMQRIHLRFMFRHRSSLESKDKGEKNFAMSYVKLMKEDGT
  TLHDGFHDLVVLKGDSKKMEDASAYLTLPSYRHHVENKGATLSRSSSSVGGLSVSSRDVF
  SISTLVCSTKLTQNVGLLGLLKWRMKPQLLQENLEKLKIVDGEEVVKFLQDTLDALFNIM
  MEHSQSDEYDILVFDALIYIIGLIADRKFQHFNTVLEAYIQQHFSATLAYKKLMTVLKTY
  LDTSSRGEQCEPILRTLKALEYVFKFIVRSRTLFSQLYEGKEQMEFEESMRRLFESINNL
  MKSQYKTTILLQVAALKYIPSVLHDVEMVFDAKLLSQLLYEFYTCIPPVKLQKQKVQSMN
  EIVQSNLFKKQECRDILLPVITKELKELLEQKDDMQHQVLERKYCVELLNSILEVLSYQD
  AAFTYHHIQEIMVQLLRTVNRTVITMGRDHILISHFVACMTAILNQMGDQHYSFYIETFQ
  TSSELVDFLMETFIMFKDLIGKNVYPGDWMAMSMVQNRVFLRAINKFAETMNQKFLEHTN
  FEFQLWNNYFHLAVAFITQDSLQLEQFSHAKYNKILNKYGDMRRLIGFSIRDMWYKLGQN
  KICFIPGMVGPILEMTLIPEAELRKATIPIFFDMMLCEYQRSGDFKKFENEIILKLDHEV
  EGGRGDEQYMQLLESILMECAAEHPTIAKSVENFVNLVKGLLEKLLDYRGVMTDESKDNR
  MSCTVNLLNFYKDNNREEMYIRYLYKLRDLHLDCDNYTEAAYTLLLHTWLLKWSDEQCAS
  QVMQTGQQHPQTHRQLKETLYETIIGYFDKGKMWEEAISLCKELAEQYEMEIFDYELLSQ
  NLIQQAKFYESIMKILRPKPDYFAVGYYGQGFPSFLRNKVFIYRGKEYERREDFQMQLMT
  QFPNAEKMNTTSAPGDDVKNAPGQYIQCFTVQPVLDEHPRFKNKPVPDQIINFYKSNYVQ
  RFHYSRPVRRGTVDPENEFASMWIERTSFVTAYKLPGILRWFEVVHMSQTTISPLENAIE
  TMSTANEKILMMINQYQSDETLPINPLSMLLNGIVDPAVMGGFAKYEKAFFTEEYVRDHP
  EDQDKLTHLKDLIAWQIPFLGAGIKIHEKRVSDNLRPFHDRMEECFKNLKMKVEKEYGVR
  EMPDFDDRRVGRPRSMLRSYRQMSIISLASMNSDCSTPSKPTSESFDLELASPKTPRVEQ
  EEPISPGSTLPEVKLRRSKKRTKRSSVVFADEKAAAESDLKRLSRKHEFMSDTNLSEHAA
  IPLKASVLSQMSFASQSMPTIPALALSVAGIPGLDEANTSPRLSQTFLQLSDGDKKTLTR
  KKVNQFFKTMLASKSAEEGKQIPDSLSTDL

• Sequence length: 1830

Pathways

KEGG:

Chemokine signaling pathway

Reactome:

Nef and signal transduction
Neutrophil degranulation
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)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Acute myeloid leukemia	Likely pathogenic	rs1429834722	RCV005926777	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
DOCK2 deficiency	Likely pathogenic; Pathogenic	rs1757824003, rs2113355272, rs2113291833, rs1761023588, rs2113874830, rs142830212, rs2113279864, rs1035797449, rs2532626798, rs2113843664, rs762909359, rs780318765, rs1581090174, rs2113559002, rs2532467695, rs1429834722, rs2532522791, rs755691445, rs2532490041, rs2532560930, rs1561585424, rs1561898523, rs1581531492, rs1756328793, rs1761749097	RCV001329974 RCV001375630 RCV001388658 RCV001382558 RCV001382895 RCV001383943 RCV001941940 RCV001994115 RCV003083703 RCV000180780 RCV000180781 RCV000180782 RCV000180783 RCV000180784 RCV002828651 RCV003019098 RCV003340886 RCV003754266 RCV003754393 RCV003754452 RCV003988956 RCV000685405 RCV000701898 RCV000797236 RCV001036774 RCV001050161	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Associated with severe COVID-19 disease	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ASTROCYTOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CENTRAL NERVOUS SYSTEM CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED IMMUNODEFICIENCY DUE TO DEDICATOR OF CYTOKINESIS 2 PROTEIN DEFICIENCY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED IMMUNODEFICIENCY DUE TO DOCK2 DEFICIENCY	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ANEURYSM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIGESTIVE SYSTEM DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DOCK2-related disorder	Likely benign; Benign; Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IMMUNODEFICIENCY 40	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INFLAMMATORY BOWEL DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUMINAL A BREAST CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEUROBLASTOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pancreatic adenocarcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostate cancer	Uncertain significance	ClinVar GWAS catalog	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
PROSTATE CANCER, FAMILIAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TRIPLE-NEGATIVE BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ULCERATIVE COLITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma Of Esophagus	Esophageal Cancer	CTD_human_DG	23525077		★☆☆☆☆ Found in Text Mining only
Adult Diffuse Large B-Cell Lymphoma	B-cell Lymphoma	BEFREE	20350533		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	Pubtator	36883952	Associate	★☆☆☆☆ Found in Text Mining only
B-Cell Lymphomas	B-Cell Lymphoma	BEFREE	20350533		★☆☆☆☆ Found in Text Mining only
Brain Neoplasms	Brain neoplasms	Pubtator	32867782	Associate	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	32867782	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	36965814	Associate	★☆☆☆☆ Found in Text Mining only
Chronic Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	29678828		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	24951259, 30076747		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	24951259, 40001597	Associate	★☆☆☆☆ Found in Text Mining only
Combined immunodeficiency	Severe combined immunodeficiency disease	BEFREE	29509960		★☆☆☆☆ Found in Text Mining only
Coronary Stenosis	Coronary stenosis	Pubtator	32327445	Stimulate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes mellitus	Pubtator	32327445	Stimulate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	37680885	Associate	★☆☆☆☆ Found in Text Mining only
Diffuse Large B-Cell Lymphoma	Diffuse Lymphoma	BEFREE	20350533		★☆☆☆☆ Found in Text Mining only
DOCK2 deficiency	DOCK2 Deficiency	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hematopoietic Neoplasms	Hematopoietic Neoplasms	BEFREE	20350533		★☆☆☆☆ Found in Text Mining only
Immune System Diseases	Immune system disease	Pubtator	35486341, 36952639	Associate	★☆☆☆☆ Found in Text Mining only
IMMUNODEFICIENCY 40	Immunodeficiency	ORPHANET_DG	26083206		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IMMUNODEFICIENCY 40	Immunodeficiency	UNIPROT_DG	26083206		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IMMUNODEFICIENCY 40	Immunodeficiency	CLINVAR_DG	26083206		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IMMUNODEFICIENCY 40	Immunodeficiency	GENOMICS_ENGLAND_DG	29503648		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IMMUNODEFICIENCY 40	Immunodeficiency	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	HPO_DG			★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	LHGDN	12393632		★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	12393632	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	27748370, 30975911, 31762818		★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	GWASCAT_DG	27903959		★☆☆☆☆ Found in Text Mining only
Lymphoma, Follicular	Lymphoma	BEFREE	20350533		★☆☆☆☆ Found in Text Mining only
Lymphopenia	Lymphopenia	BEFREE	31405607		★☆☆☆☆ Found in Text Mining only
Lymphopenia	Lymphopenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	24951259, 29509960		★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	30826364	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	30076747		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	19729484		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	28716822		★☆☆☆☆ Found in Text Mining only
Post-Traumatic Stress Disorder	Stress Disorder	BEFREE	28795405		★☆☆☆☆ Found in Text Mining only
Prostate cancer, familial	Prostate cancer	CTD_human_DG	29892016		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CANCER, HEREDITARY, 1	Prostate Cancer, Hereditary	CTD_human_DG	29892016		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	GWASCAT_DG	29892016		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	20412587, 30866497, 32486483	Associate	★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	BEFREE	30643265		★☆☆☆☆ Found in Text Mining only
Severe Combined Immunodeficiency	Severe combined immunodeficiency	Pubtator	30838481, 36380073, 36947335	Associate	★☆☆☆☆ Found in Text Mining only
Severe Combined Immunodeficiency	Severe combined immunodeficiency disease	BEFREE	31630188		★☆☆☆☆ Found in Text Mining only
Synovitis	Synovitis	BEFREE	29940858		★☆☆☆☆ Found in Text Mining only