DOCK11

dedicator of cytokinesis 11, the group of DOCK family Rho GEFs|Armadillo like helical domain containing|Pleckstrin homology domain containing

Basic information

Region (hg38): X:118495815-118686163

Links

ENSG00000147251 ∙ NCBI:139818 ∙ OMIM:300681 ∙ HGNC:23483 ∙ Uniprot:Q5JSL3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autoinflammatory disease, multisystem, with immune dysregulation, X-linked (Limited), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Autoimmune disease, multisystem, with immune dysregulation, X-linked	XL	Allergy/Immunology/Infectious	The condition can manifest with a variety of autoimmune sequelae, and medical management (eg, with immune-modulating therapy) has been described as beneficial	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Pulmonary	36952639

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DOCK11 gene.

• Inborn error of hematopoiesis and immunity with systemic inflammation and normocytic anemia (3 variants)
• Autoinflammatory disease, multisystem, with immune dysregulation, X-linked (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DOCK11 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6	3	9
missense	1	1	59	4	2	67
nonsense	1					1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region	1				1	2
non coding						0
Total	2	1	59	10	5

Variants in DOCK11

This is a list of pathogenic ClinVar variants found in the DOCK11 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-118495995-C-T			Likely benign (Sep 01, 2022)
X-118496036-A-G		not specified	Uncertain significance (Dec 16, 2022)
X-118496045-C-CT		Inborn error of hematopoiesis and immunity with systemic inflammation and normocytic anemia • Autoinflammatory disease, multisystem, with immune dysregulation, X-linked	Pathogenic (Mar 15, 2023)
X-118496048-A-T		not specified	Uncertain significance (Dec 16, 2022)
X-118542740-G-T		not specified	Uncertain significance (Jul 14, 2021)
X-118542743-G-C		not specified	Uncertain significance (Nov 23, 2024)
X-118542797-G-A		not specified	Uncertain significance (Dec 28, 2023)
X-118542821-T-C		not specified	Uncertain significance (Sep 12, 2023)
X-118542930-C-T		not specified	Uncertain significance (Apr 18, 2023)
X-118542942-G-A			Likely benign (Dec 01, 2022)
X-118542948-G-A		not specified	Uncertain significance (Sep 08, 2024)
X-118543524-A-G		Inborn error of hematopoiesis and immunity with systemic inflammation and normocytic anemia	Likely pathogenic (-)
X-118545366-A-G		not specified	Uncertain significance (Sep 30, 2024)
X-118546056-G-C			Benign (Mar 29, 2018)
X-118561443-T-C		not specified	Uncertain significance (Nov 24, 2024)
X-118561464-T-A		not specified	Uncertain significance (Feb 06, 2024)
X-118561497-G-T		not specified	Uncertain significance (Oct 12, 2021)
X-118566008-C-T		not specified	Uncertain significance (Dec 04, 2024)
X-118566060-A-G		not specified	Conflicting classifications of pathogenicity (Jun 10, 2024)
X-118566065-C-T			Benign (Mar 29, 2018)
X-118566134-A-T		DOCK11 deficiency • Autoinflammatory disease, multisystem, with immune dysregulation, X-linked	Pathogenic (Jul 12, 2023)
X-118566165-C-T		not specified	Uncertain significance (Mar 18, 2024)
X-118566173-A-G		not specified	Uncertain significance (Sep 28, 2022)
X-118572441-A-G		not specified	Uncertain significance (Nov 09, 2024)
X-118573830-G-T		DOCK11-related disorder	Uncertain significance (Dec 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DOCK11	protein_coding	protein_coding	ENST00000276202	53	190266

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0121	0.988	125706	17	21	125744	0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.68	519	722	0.719	0.0000532	13711
Missense in Polyphen		114	220.1	0.51796		4485
Synonymous	0.731	243	258	0.942	0.0000198	3727
Loss of Function	6.08	20	78.0	0.257	0.00000571	1546

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000212	0.000212
Ashkenazi Jewish	0.00	0.00
East Asian	0.000147	0.000109
Finnish	0.000255	0.000185
European (Non-Finnish)	0.000312	0.000220
Middle Eastern	0.000147	0.000109
South Asian	0.0000607	0.0000327
Other	0.000269	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Guanine nucleotide-exchange factor (GEF) that activates CDC42 by exchanging bound GDP for free GTP. Required for marginal zone (MZ) B-cell development, is associated with early bone marrow B-cell development, MZ B-cell formation, MZ B-cell number and marginal metallophilic macrophages morphology. Facilitates filopodia formation through the activation of CDC42. {ECO:0000250|UniProtKB:A2AF47}.
• Pathway: Factors involved in megakaryocyte development and platelet production;Hemostasis;Regulation of CDC42 activity (Consensus)

Intolerance Scores

• loftool: 0.620
• rvis_EVS: -0.08
• rvis_percentile_EVS: 47.26

Haploinsufficiency Scores

• pHI: 0.403
• hipred: Y
• hipred_score: 0.575
• ghis: 0.502

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.254

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dock11

Gene ontology

• Biological process: B cell homeostasis;marginal zone B cell differentiation;small GTPase mediated signal transduction;blood coagulation;positive regulation of GTPase activity;positive regulation of filopodium assembly
• Cellular component: cytosol
• Molecular function: guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;protein binding