DOCK7

dedicator of cytokinesis 7, the group of DOCK family Rho GEFs

Basic information

Region (hg38): 1:62454297-62688386

Links

ENSG00000116641 ∙ NCBI:85440 ∙ OMIM:615730 ∙ HGNC:19190 ∙ Uniprot:Q96N67 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 23 (Strong), mode of inheritance: AR
• developmental and epileptic encephalopathy, 23 (Moderate), mode of inheritance: AR
• developmental and epileptic encephalopathy, 23 (Supportive), mode of inheritance: AR
• developmental and epileptic encephalopathy, 23 (Strong), mode of inheritance: AR
• developmental and epileptic encephalopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 23	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	24814191
As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DOCK7 gene.

• Developmental and epileptic encephalopathy, 23 (1270 variants)
• not provided (312 variants)
• Inborn genetic diseases (77 variants)
• not specified (15 variants)
• Familial hypobetalipoproteinemia 2 (5 variants)
• Seizure (2 variants)
• Fetal akinesia deformation sequence 3 (1 variants)
• ANGPTL3-related condition (1 variants)
• DOCK7-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DOCK7 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			10	321	5	336
missense		1	613	11	1	626
nonsense	13	3				16
start loss						0
frameshift	23	4				27
inframe indel		1	6			7
splice donor/acceptor (+/-2bp)		13				13
splice region		3	37	57	4	101
non coding	3	1	41	239	95	379
Total	39	23	670	571	101

Highest pathogenic variant AF is 0.000388

Variants in DOCK7

This is a list of pathogenic ClinVar variants found in the DOCK7 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-62455259-G-A			Likely benign (Sep 11, 2021)
1-62455318-C-A			Likely benign (Jun 12, 2021)
1-62455415-T-G		Developmental and epileptic encephalopathy, 23	Uncertain significance (Oct 29, 2019)
1-62455425-T-C		Developmental and epileptic encephalopathy, 23	Uncertain significance (Jun 16, 2022)
1-62455430-C-T		Developmental and epileptic encephalopathy, 23 • Inborn genetic diseases	Uncertain significance (Apr 11, 2023)
1-62455436-C-T		Developmental and epileptic encephalopathy, 23	Uncertain significance (Sep 07, 2022)
1-62455442-C-T		Developmental and epileptic encephalopathy, 23	Uncertain significance (Oct 17, 2022)
1-62455443-G-T		Developmental and epileptic encephalopathy, 23	Likely benign (Feb 10, 2022)
1-62455448-A-C		Developmental and epileptic encephalopathy, 23 • Inborn genetic diseases	Uncertain significance (Feb 06, 2024)
1-62455450-G-A		Developmental and epileptic encephalopathy, 23	Likely benign (Feb 06, 2023)
1-62455452-A-G		Developmental and epileptic encephalopathy, 23	Uncertain significance (Nov 01, 2022)
1-62455456-T-C		Developmental and epileptic encephalopathy, 23	Uncertain significance (Apr 10, 2019)
1-62455458-T-TG		Developmental and epileptic encephalopathy, 23 • DOCK7-related disorder	Likely benign (Oct 22, 2023)
1-62455461-G-GA		Developmental and epileptic encephalopathy, 23 • DOCK7-related disorder	Benign/Likely benign (Jan 17, 2024)
1-62455462-A-G		Developmental and epileptic encephalopathy, 23	Likely benign (Jun 13, 2022)
1-62455466-A-T		Developmental and epileptic encephalopathy, 23	Likely benign (Jan 11, 2024)
1-62455470-G-A		Developmental and epileptic encephalopathy, 23	Likely benign (May 27, 2022)
1-62455475-G-A		Developmental and epileptic encephalopathy, 23	Benign (Jan 29, 2024)
1-62455475-GACATAGTTAGTTAA-G		Developmental and epileptic encephalopathy, 23	Likely benign (Apr 21, 2021)
1-62455751-T-C			Benign (Mar 18, 2021)
1-62457519-C-A		Developmental and epileptic encephalopathy, 23	Likely benign (Oct 02, 2023)
1-62457528-A-T		Developmental and epileptic encephalopathy, 23	Likely benign (Apr 01, 2023)
1-62457538-C-T		Developmental and epileptic encephalopathy, 23	Uncertain significance (Nov 27, 2023)
1-62457543-G-A		Developmental and epileptic encephalopathy, 23	Likely benign (Aug 28, 2023)
1-62457550-A-G		Developmental and epileptic encephalopathy, 23	Uncertain significance (Jun 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DOCK7	protein_coding	protein_coding	ENST00000340370	49	233571

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000636	1.00	125691	0	57	125748	0.000227

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.42	791	1.11e+3	0.711	0.0000598	13861
Missense in Polyphen		171	364.69	0.4689		4606
Synonymous	0.369	375	384	0.976	0.0000204	3994
Loss of Function	7.25	34	119	0.285	0.00000700	1438

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000550	0.000549
Ashkenazi Jewish	0.000205	0.000198
East Asian	0.000113	0.000109
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000285	0.000273
Middle Eastern	0.000113	0.000109
South Asian	0.000135	0.000131
Other	0.000854	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP. Does not have a GEF activity for CDC42. Required for STMN1 'Ser-15' phosphorylation during axon formation and consequently for neuronal polarization (PubMed:16982419). Has a role in pigmentation (By similarity). Involved in the regulation of cortical neurogenesis through the control of radial glial cells (RGCs) proliferation versus differentiation; negatively regulates the basal-to-apical interkinetic nuclear migration of RGCs by antagonizing the microtubule growth-promoting function of TACC3 (By similarity). {ECO:0000250|UniProtKB:Q8R1A4, ECO:0000269|PubMed:16982419}.
• Disease: DISEASE: Epileptic encephalopathy, early infantile, 23 (EIEE23) [MIM:615859]: A severe disease characterized by early-onset intractable epilepsy, dysmorphic features, intellectual disability, and cortical blindness. Brain imaging shows an abnormally marked pontobulbar sulcus with mild pontine hypoplasia, white matter abnormalities, and atrophy in the occipital lobe. {ECO:0000269|PubMed:24814191}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Factors involved in megakaryocyte development and platelet production;Integrin;Hemostasis;ErbB2/ErbB3 signaling events (Consensus)

Recessive Scores

• pRec: 0.137

Intolerance Scores

• loftool: 0.776
• rvis_EVS: -2.54
• rvis_percentile_EVS: 0.88

Haploinsufficiency Scores

• pHI: 0.105
• hipred: Y
• hipred_score: 0.637
• ghis: 0.601

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.766

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dock7
• Phenotype: limbs/digits/tail phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); pigmentation phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: microtubule cytoskeleton organization;small GTPase mediated signal transduction;axonogenesis;interkinetic nuclear migration;neuron projection development;positive regulation of peptidyl-serine phosphorylation;establishment of neuroblast polarity;regulation of neurogenesis;activation of GTPase activity;negative regulation of cold-induced thermogenesis;positive regulation of vascular associated smooth muscle cell migration
• Cellular component: focal adhesion;COP9 signalosome;axon;growth cone;neuron projection;basal part of cell
• Molecular function: guanyl-nucleotide exchange factor activity;protein binding;Rac GTPase binding