• 30
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
DOCK8 (HGNC:19191) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
dedicator of cytokinesis 8
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
FLJ00026, FLJ00152, ZIR8, FLJ00346
%HI
35.69(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0(Read more about gnomAD pLI score)
LOEUF
0.48(Read more about gnomAD LOEUF score)
Cytoband
9p24.3
Genomic Coordinates
GRCh37/hg19: chr9:214865-465255 NCBI Ensembl UCSC
GRCh38/hg38: chr9:211257-465255 NCBI Ensembl UCSC
MANE Select Transcript
NM_203447.4 ENST00000432829.7 (Read more about MANE Select)
Function
Guanine nucleotide exchange factor (GEF) which specifically activates small GTPase CDC42 by exchanging bound GDP for free GTP (PubMed:28028151, PubMed:22461490). During immune responses, required for interstitial dendritic cell (DC) migration by locally activating CDC42 at the leading edge membrane of DC (By similarity). Required for CD4(+) T-cell migration in response to chemokine stimulation by promoting CDC42 activation at T cell leading edge membrane (PubMed:28028151). Is involved in NK cell... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-21882
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Gene Associated with Autosomal Recessive Phenotype (30)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
06/14/2023

Haploinsufficiency (HI) Score Details

HI Score:
30
HI Evidence Strength:
Gene Associated with Autosomal Recessive Phenotype (Disclaimer)
HI Disease:
  • combined immunodeficiency due to DOCK8 deficiency Monarch
HI Evidence Comments:
DOCK8 is associated with autosomal recessive hyper-IgE recurrent infection syndrome (OMIM 243700). While heterozygous microdeletions of only DOCK8 have not been reported, DOCK8 involvement has been reported in chromosome 9p terminal deletions, associated with intellectual disability and dysmorphic features, and is speculated as contributing to the phenotype and duplications of the 9p terminal region, partially overlapping DOCK8, have been reported in patients with language disability (PMIDs 3469792, 29191242). Benítez-Burraco (2020) (PMID 33510598) reported a de novo ~0.2 Mb intragenic duplication within 9p24.3 involving a portion of DOCK8 (detected by CGH array) in a 11-year old boy with marked expressive and receptive problems, which affect both structural and functional aspects of language. The author performed expression microarray and found that DOCK8 was slightly upregulated. The authors concluded that dysregulation of DOCK8 altered the interaction between DOCK8 and CDC42 which is acting as the hub component of the network encompassing language-related genes. Of importance, normal copy number variation has been described in this region. An association of DOCK8 haploinsufficiency and cancer predisposition is unclear although some studies have reported potential truncating heterozygous variants of DOCK8 in a variety of cancer phenotypes (PMIDs 34308104, 29625052).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Published Evidence:

Genomic View

Select assembly: (NC_000009.11) (NC_000009.12)