DOCK8 |
- 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)