DOCK8

Summary

DOCK8 (dedicator of cytokinesis 8, HGNC:19191) is a protein-coding gene on chromosome 9p24.3, encoding Dedicator of cytokinesis protein 8 (Q8NF50). Guanine nucleotide exchange factor (GEF) which specifically activates small GTPase CDC42 by exchanging bound GDP for free GTP.

This gene encodes a member of the DOCK180 family of guanine nucleotide exchange factors. Guanine nucleotide exchange factors interact with Rho GTPases and are components of intracellular signaling networks. Mutations in this gene result in the autosomal recessive form of the hyper-IgE syndrome. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 81704 — RefSeq curated summary.

At a glance

• Gene–disease (curated): combined immunodeficiency due to DOCK8 deficiency (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 43
• Clinical variants (ClinVar): 3,362 total — 134 pathogenic, 73 likely-pathogenic
• Phenotypes (HPO): 51
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_203447

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19191
Approved symbol	DOCK8
Name	dedicator of cytokinesis 8
Location	9p24.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ00026, FLJ00152, ZIR8, FLJ00346
Ensembl gene	ENSG00000107099
Ensembl biotype	protein_coding
OMIM	611432
Entrez	81704

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 12 retained_intron, 6 protein_coding, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000382329, ENST00000382331, ENST00000382341, ENST00000432829, ENST00000453981, ENST00000454469, ENST00000462618, ENST00000469197, ENST00000469391, ENST00000474772, ENST00000478380, ENST00000479404, ENST00000483757, ENST00000487230, ENST00000493666, ENST00000495184, ENST00000524396, ENST00000682121, ENST00000682249, ENST00000682260, ENST00000683406, ENST00000684166, ENST00000684384, ENST00000684637, ENST00000685949

RefSeq mRNA: 3 — MANE Select: NM_203447 NM_001190458, NM_001193536, NM_203447

CCDS: CCDS55283, CCDS55284, CCDS6440

Canonical transcript exons

ENST00000432829 — 48 exons

Exon	Start	End
ENSE00001491727	464159	465255
ENSE00003458845	390471	390566
ENSE00003461470	340159	340321
ENSE00003469546	386331	386426
ENSE00003486781	399146	399259
ENSE00003497795	404918	405073
ENSE00003498626	304581	304704
ENSE00003502320	371428	371566
ENSE00003515082	449784	449927
ENSE00003515304	463517	463687
ENSE00003515422	443427	443516
ENSE00003517066	325671	325737
ENSE00003520772	414782	414951
ENSE00003526113	339006	339099
ENSE00003536561	370230	370300
ENSE00003545454	376210	376305
ENSE00003547922	334225	334384
ENSE00003554185	426885	426981
ENSE00003557090	420949	421078
ENSE00003561757	328022	328171
ENSE00003563396	406930	407069
ENSE00003574895	434783	434975
ENSE00003575900	286461	286636
ENSE00003578846	420401	420583
ENSE00003586952	432166	432324
ENSE00003591843	441875	442009
ENSE00003600796	372185	372286
ENSE00003606375	311954	312166
ENSE00003616475	439245	439388
ENSE00003618352	418068	418207
ENSE00003619285	396785	396934
ENSE00003630561	422048	422135
ENSE00003636130	336582	336718
ENSE00003646693	429702	429854
ENSE00003650003	379771	379935
ENSE00003650461	289510	289581
ENSE00003651205	317043	317128
ENSE00003656987	332398	332478
ENSE00003660054	368018	368135
ENSE00003669443	376977	377211
ENSE00003675404	271627	271729
ENSE00003678695	382513	382685
ENSE00003680841	446370	446606
ENSE00003681023	428362	428496
ENSE00003681539	433875	433975
ENSE00003682079	452011	452117
ENSE00003691321	441286	441417
ENSE00003722208	214865	215029

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 97.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.7569 / max 1313.9222, expressed in 1064 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95741	12.7866	840
95748	8.1063	435
95740	1.1727	559
95742	1.0918	419
95747	0.7709	203
95745	0.7516	243
95739	0.4312	246
95746	0.3266	140
95738	0.1956	86
95749	0.0398	7

Top tissues by expression

250 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	97.15	gold quality
leukocyte	CL:0000738	96.72	gold quality
monocyte	CL:0000576	96.71	gold quality
thymus	UBERON:0002370	96.30	gold quality
blood	UBERON:0000178	95.97	gold quality
spleen	UBERON:0002106	94.71	gold quality
granulocyte	CL:0000094	94.61	gold quality
lymph node	UBERON:0000029	94.02	gold quality
vermiform appendix	UBERON:0001154	93.97	gold quality
bone marrow	UBERON:0002371	93.78	gold quality
pancreatic ductal cell	CL:0002079	93.40	gold quality
epithelial cell of pancreas	CL:0000083	92.83	gold quality
ileal mucosa	UBERON:0000331	91.61	gold quality
epithelium of nasopharynx	UBERON:0001951	90.73	gold quality
tonsil	UBERON:0002372	89.91	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.08	gold quality
palpebral conjunctiva	UBERON:0001812	88.53	gold quality
placenta	UBERON:0001987	88.40	gold quality
lower lobe of lung	UBERON:0008949	88.14	gold quality
caecum	UBERON:0001153	87.55	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.34	gold quality
lower esophagus	UBERON:0013473	87.29	gold quality
superficial temporal artery	UBERON:0001614	86.98	gold quality
gall bladder	UBERON:0002110	86.97	gold quality
right testis	UBERON:0004534	86.85	gold quality
right adrenal gland cortex	UBERON:0035827	86.63	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.17	gold quality
trabecular bone tissue	UBERON:0002483	85.99	gold quality
right adrenal gland	UBERON:0001233	85.56	gold quality
right lung	UBERON:0002167	85.53	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1918.27
E-HCAD-35	yes	1770.84
E-CURD-119	yes	35.69
E-HCAD-25	yes	23.47
E-ANND-3	yes	18.25
E-HCAD-30	no	1510.21
E-GEOD-89232	no	449.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

67 targeting DOCK8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-150-3P	99.43	70.51	920
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-4312	99.34	67.30	511

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• involvement of DOCK8 in processes that affect the organisation of filamentous actin. (PMID:15304341)
• rare mutations in the DOCK8 gene may contribute to some cases of autosomal dominant mental retardation (PMID:18060736)
• Under-expression of DOCK8 is associated with hepatocellular carcinoma. (PMID:19640199)
• Autosomal recessive DOCK8 deficiency is associated with a novel variant of combined immunodeficiency. (PMID:19776401)
• Autosomal-recessive mutations in DOCK8 are responsible for many, although not all, cases of autosomal-recessive hyper-IgE syndrome. (PMID:20004785)
• Chromosome 9p loss is the hallmark of squamous cell carcinoma, and DMRT1, DMRT3 and DOCK8 genes at 9p24.3 might be of interest for the study of the pathophysiology of SCC as potential targets for therapeutic measures. (PMID:20596660)
• Several AR-HIES patients have recently been shown to harbour mutations in the gene for dedicator of cytokinesis 8 (DOCK8). Here, we present the long-term outcome of a girl having received a hematopoietic stem cell graft. (PMID:21058221)
• DOCK8 deficiency and clinical manifestations of hyper IgE syndromes (Review) (PMID:21178271)
• Mutations in DOCK8 lead to DOCK8 immunodeficiency syndrome characterized by recurrent viral infections, severe atopy, and early onset malignancy. (Review) (PMID:21178272)
• A 2-bp deletion at codon 510 in exon 14 causing a frameshift mutation was found in 3 homozygous siblings with Job syndrome and their heterozygous first-cousin parents. (PMID:21763205)
• Rates of malignancy and overall mortality in patients with DOCK8 deficiency were higher than in those with Job’s syndrome (PMID:21931011)
• Findings help to explain why DOCK8-deficient patients are susceptible to recurrent infections and provide new insights into how T-cell memory is sustained. (PMID:21969276)
• These findings highlight a key role for DOCK8 in the survival and function of human and mouse CD8 T cells. (PMID:22006977)
• DOCK8 deficiency (a newly described combined primary immunodeficiency disease) accounted for 15% of combined immune deficiency cases in the National Primary Immunodeficiency Disorders Registry in Kuwait, a country with high prevalence of consanguinity. (PMID:22534316)
• DOCK8 mediates an MyD88 signaling pathway essential for TLR9-driven B-cell proliferation aand immunoglobulin production. (PMID:22581261)
• DOCK8 encodes dedicator of cytokinesis 8. (PMID:22876580)
• We used this new approach to analyse exome data from 24 patients with primary immunodeficiencies. Our analysis identified two novel causative deletions in the genes GATA2 and DOCK8 (PMID:22942019)
• Three novel DOCK8 mutations and two large deletions are found in thirteen patients with autosomal recessive hyper-IgE syndrome in a single center experience. (PMID:22968740)
• nonsense mutation in the CLEC7A gene, p.Tyr238X, rs16910526 and a novel homozygous frameshift variant in exon 27 of the DOCK8 gene, c.3193delA were identified in brothers with an immunodeficiency syndrome characterized by severe eczema, milk and egg allergies, infections, diarrhea, failure to thrive and, in two of the three, lymphoma lymphoma. (PMID:23374272)
• DOCK8 deficiency results in severely impaired natural killer cell function because of an inability to form a mature lytic immunologic synapse through targeted synaptic F-actin accumulation (PMID:23380217)
• Dedicator of cytokinesis 8 interacts with talin and Wiskott-Aldrich syndrome protein to regulate NK cell cytotoxicity. (PMID:23455509)
• Two novel large deletions, del1-14 exons and del8-18 exons, of DOCK8 have been identified in two siblings with the adaptive immune deficiencies. (PMID:23859592)
• DOCK8 deficiency results in defective antibody responses and undirected plasma cell expansion in the lymph nodes, as part of a combined immunodeficiency cured by hematopoietic stem cell transplantation. (PMID:23891736)
• Clinical features of immunodeficiency syndrome are associated with DOCK8 mutations. (Review) (PMID:23911989)
• DOCK8 is required for the development and survival of mature NKT cells. (PMID:23929855)
• Biallelic mutations in the DOCK8 gene cause autosomal-recessive hyper-IgE syndrome. (PMID:24698323)
• Hyper-IgE syndromes and atopic dermatitis patients showed different sensitization pattern of serum IgE corresponding to the allergic disease manifestations and Th-cell subset data, suggesting a key role of DOCK8 in the development of food allergy (PMID:24898675)
• Dedicator of cytokinesis 8-deficient patients have a breakdown in peripheral B-cell tolerance and defective regulatory T cells (PMID:25218284)
• Mutations of DOCK8 in three children, two of whom developed sclerosing cholangitis, are reported. (PMID:25220305)
• This is a case of systemic lupus erythematosus with hyper-immunoglobulin E syndrome documented as DOCK8 deficiency. (PMID:25332498)
• DOCK8-regulated shape integrity of lymphocytes prevents cytothripsis and promotes antiviral immunity in the skin. (PMID:25422492)
• CD147 has a role in promoting Src-dependent activation of Rac1 signaling through STAT3/DOCK8 during the motility of hepatocellular carcinoma cells (PMID:25428919)
• DOCK8 deficiency is likely in patients with severe viral infections, allergies, and/or low IgM levels. (PMID:25724123)
• Letter/Case Report: DOCK8 homozygous mutation leading to primary immune deficiency. (PMID:26235511)
• comparative study provides a long-term observation of DOCK8- and STAT3-hyper-IgE syndrome patients with regard to clinical and laboratory findings, and assesses the activation and cytokine secretion of lymphocytes after in vitro stimulation (PMID:26592211)
• mutations in Chinese patients with hyper-IgE syndrome (PMID:26659092)
• Our results suggest that decreased expression of DOCK8 in response to CRH might disturb the immunosuppressive function of Tregs and contribute to stress-induced aggravation of AD symptoms. (PMID:26799599)
• A novel DOCK8 sequence insertion caused primary immunodeficiency in two siblings from a consanguineous family. (PMID:26883462)
• Our results showed that DOCK8-deficient patients have a profound defect in TH17 differentiation related to decreased STAT3 phosphorylation, translocation to the nucleus, and transcriptional activity (PMID:27350570)
• The CD4+ T-cell compartment is greatly altered in the absence of DOCK8. Specifically, DOCK8-deficient patients have increased TH2 cells and defects in TH1 and TH17 cell differentiation (PMID:27554822)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	dock8	ENSDARG00000055225
mus_musculus	Dock8	ENSMUSG00000052085
rattus_norvegicus	Dock8	ENSRNOG00000015894
drosophila_melanogaster	Zir	FBGN0031216
drosophila_melanogaster	Ziz	FBGN0260486
caenorhabditis_elegans		WBGENE00000419
caenorhabditis_elegans	F22G12.5	WBGENE00009065
caenorhabditis_elegans		WBGENE00018520

Paralogs (10): DOCK9 (ENSG00000088387), DOCK3 (ENSG00000088538), DOCK7 (ENSG00000116641), DOCK4 (ENSG00000128512), DOCK6 (ENSG00000130158), DOCK2 (ENSG00000134516), DOCK10 (ENSG00000135905), DOCK11 (ENSG00000147251), DOCK5 (ENSG00000147459), DOCK1 (ENSG00000150760)

Protein

Protein identifiers

Dedicator of cytokinesis protein 8 — Q8NF50 (reviewed: Q8NF50)

All UniProt accessions (8): Q8NF50, A0A804HK14, A0A8I5KQK5, A2A369, C9J7A3, E9PDJ4, E9PHZ4, F8WC95

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide exchange factor (GEF) which specifically activates small GTPase CDC42 by exchanging bound GDP for free GTP. During immune responses, required for interstitial dendritic cell (DC) migration by locally activating CDC42 at the leading edge membrane of DC. Required for CD4(+) T-cell migration in response to chemokine stimulation by promoting CDC42 activation at T cell leading edge membrane. Is involved in NK cell cytotoxicity by controlling polarization of microtubule-organizing center (MTOC), and possibly regulating CCDC88B-mediated lytic granule transport to MTOC during cell killing.

Subunit / interactions. Interacts (via DOCKER domain) with GTPase CDC42; the interaction activates CDC42 by exchanging GDP for GTP. The unphosphorylated form interacts (via DOCKER domain) with LRCH1 (via LRR repeats); the interaction prevents the association between DOCK8 and CDC42. Interacts with CCDC88B.

Subcellular location. Cytoplasm. Cell membrane. Cell projection. Lamellipodium membrane.

Tissue specificity. Expressed in peripheral blood mononuclear cells (PBMCs).

Post-translational modifications. In response to chemokine CXCL12/SDF-1-alpha stimulation, phosphorylated by PRKCA/PKC-alpha which promotes DOCK8 dissociation from LRCH1.

Disease relevance. Hyper-IgE syndrome 2, autosomal recessive, with recurrent infections (HIES2) [MIM:243700] A rare disorder characterized by immunodeficiency, recurrent infections, eczema, increased serum IgE, eosinophilia and lack of connective tissue and skeletal involvement. The disease is caused by variants affecting the gene represented in this entry. Intellectual developmental disorder, autosomal dominant 2 (MRD2) [MIM:614113] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration disrupting DOCK8 has been found in a patient with intellectual disability and ectodermal dysplasia. A balanced translocation, t(X;9) (q13.1;p24). A genomic deletion of approximately 230 kb in subtelomeric 9p has been detected in a patient with intellectual disability.

Domain organisation. The DOCKER domain is necessary and sufficient for the GEF activity.

Similarity. Belongs to the DOCK family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8NF50-1	1	yes
Q8NF50-2	2
Q8NF50-3	3
Q8NF50-4	4

RefSeq proteins (3): NP_001177387, NP_001180465, NP_982272* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016024	ARM-type_fold	Homologous_superfamily
IPR021816	DOCK_C/D_N	Domain
IPR026791	DOCK	Family
IPR027007	C2_DOCK-type_domain	Domain
IPR027357	DOCKER_dom	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR037808	C2_Dock-C	Domain
IPR043161	DOCK_C_lobe_A	Homologous_superfamily
IPR043162	DOCK_C_lobe_C	Homologous_superfamily
IPR046769	DOCKER_Lobe_A	Domain
IPR046770	DOCKER_Lobe_B	Domain
IPR046773	DOCKER_Lobe_C	Domain

Pfam: PF06920, PF11878, PF14429, PF20421, PF20422

UniProt features (36 total): sequence variant 9, modified residue 8, sequence conflict 8, mutagenesis site 6, domain 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NF50-F1	75.17	0.27

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (8): 2087, 20, 139, 451, 904, 936, 1145, 1243

Mutagenesis-validated functional residues (6):

Position	Phenotype
2077	abolishes phosphorylation. no migration in response to chemokine cxcl12/sdf-1-alpha stimulation; when associated with a-
2077	phosphomimetic mutant. enhances migration in response to chemokine cxcl12/sdf-1-alpha stimulation and reduces interactio
2082	abolishes phosphorylation. no migration in response to chemokine cxcl12/sdf-1-alpha stimulation; when associated with a-
2082	phosphomimetic mutant. enhances migration in response to chemokine cxcl12/sdf-1-alpha stimulation and reduces interactio
2087	abolishes phosphorylation. no migration in response to chemokine cxcl12/sdf-1-alpha stimulation; when associated with a-
2087	phosphomimetic mutant. enhances migration in response to chemokine cxcl12/sdf-1-alpha stimulation and reduces interactio

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013409	RHOJ GTPase cycle
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 334 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_DENDRITIC_CELL_MIGRATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOZGIT_ESR1_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_LYMPHOCYTE_MIGRATION, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS

GO Biological Process (11): immunological synapse formation (GO:0001771), small GTPase-mediated signal transduction (GO:0007264), regulation of Rho protein signal transduction (GO:0035023), dendritic cell migration (GO:0036336), positive regulation of GTPase activity (GO:0043547), regulation of small GTPase mediated signal transduction (GO:0051056), memory T cell proliferation (GO:0061485), negative regulation of T cell apoptotic process (GO:0070233), positive regulation of establishment of T cell polarity (GO:1903905), cellular response to chemokine (GO:1990869), positive regulation of T cell migration (GO:2000406)

GO Molecular Function (2): guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515)

GO Cellular Component (8): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), cell leading edge (GO:0031252), leading edge membrane (GO:0031256), lamellipodium membrane (GO:0031258), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RHO GTPase cycle	3
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cell-cell recognition	1
lymphocyte activation	1
intracellular signaling cassette	1
Rho protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
mononuclear cell migration	1
GTPase activity	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
T cell proliferation	1
negative regulation of lymphocyte apoptotic process	1
T cell apoptotic process	1
regulation of T cell apoptotic process	1
establishment of T cell polarity	1
positive regulation of T cell activation	1
regulation of establishment of T cell polarity	1
cellular response to cytokine stimulus	1
response to chemokine	1
T cell migration	1
positive regulation of lymphocyte migration	1
regulation of T cell migration	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
plasma membrane	1
cell leading edge	1
lamellipodium	1
cell projection membrane	1
leading edge membrane	1

Protein interactions and networks

STRING

1790 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DOCK8	CDC42	P21181	977
DOCK8	WAS	P42768	943
DOCK8	KANK1	Q14678	934
DOCK8	WIPF1	O43516	881
DOCK8	RHOJ	Q9H4E5	851
DOCK8	DMRT1	Q9Y5R6	846
DOCK8	RHOQ	P17081	769
DOCK8	TYK2	P29597	723
DOCK8	PGM3	O95394	677
DOCK8	ZNF341	Q9BYN7	609
DOCK8	LRCH1	Q9Y2L9	604
DOCK8	LRCH3	Q96II8	602
DOCK8	DHX8	Q14562	591
DOCK8	LRBA	P50851	582
DOCK8	STAT3	P40763	580

IntAct

71 interactions, top by confidence:

A	B	Type	Score
DOCK8	LRCH1	psi-mi:“MI:0915”(physical association)	0.740
DOCK8	LRCH2	psi-mi:“MI:0915”(physical association)	0.740
DOCK8	LRCH2	psi-mi:“MI:0914”(association)	0.740
ARPC3	ARPC2	psi-mi:“MI:0914”(association)	0.640
DOCK8	LRCH4	psi-mi:“MI:0914”(association)	0.620
DOCK8	LRCH4	psi-mi:“MI:0403”(colocalization)	0.620
DOCK8	MYD88	psi-mi:“MI:0915”(physical association)	0.580
MYD88	DOCK8	psi-mi:“MI:0915”(physical association)	0.580
MEOX2	DOCK8	psi-mi:“MI:0915”(physical association)	0.560
DOCK8	KRT40	psi-mi:“MI:0915”(physical association)	0.560
DOCK8	CARHSP1	psi-mi:“MI:0915”(physical association)	0.560
DOCK8	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
CARHSP1	DOCK8	psi-mi:“MI:0915”(physical association)	0.560
PIMREG	DOCK8	psi-mi:“MI:0915”(physical association)	0.560
LRCH3	LRCH2	psi-mi:“MI:0914”(association)	0.530
NTA1	DOCK8	psi-mi:“MI:0915”(physical association)	0.490
RRD1	DOCK8	psi-mi:“MI:0915”(physical association)	0.490
EUC1	DOCK8	psi-mi:“MI:0915”(physical association)	0.490
DOCK8	RRD1	psi-mi:“MI:0915”(physical association)	0.490

BioGRID (175): DOCK8 (Two-hybrid), DOCK8 (Two-hybrid), DOCK8 (Two-hybrid), DOCK8 (Two-hybrid), DOCK8 (Two-hybrid), DOCK8 (Two-hybrid), DOCK8 (Two-hybrid), DOCK8 (Two-hybrid), DOCK8 (Two-hybrid), DOCK8 (Two-hybrid), DOCK8 (Two-hybrid), DOCK8 (Two-hybrid), FAM161A (Two-hybrid), LRCH3 (Two-hybrid), MED30 (Two-hybrid)

ESM2 similar proteins: A2AF47, B0DOB4, B0R034, E9Q8I9, O02697, O15327, O75694, O94915, P37199, P42228, P48736, P59764, Q0VGW0, Q14B46, Q1JQ19, Q2TAF4, Q4QR86, Q4R4D7, Q5JSL3, Q5R8B7, Q5RA60, Q5U1Z0, Q5XGX5, Q62717, Q6AZT6, Q6GLR7, Q80TJ1, Q80TR8, Q86UW7, Q8BMG7, Q8BYR5, Q8BZN6, Q8C147, Q8N1I0, Q8NF50, Q8NFP9, Q8R1A4, Q8R3N6, Q91WS7, Q95JW3

Diamond homologs: A2AF47, B0R034, Q5JSL3, Q63603, Q8BIK4, Q8BZN6, Q8C147, Q8NF50, Q96BY6, Q9BZ29, Q9VZZ9, Q8R1A4, Q8VDR9, Q96HP0, Q96N67

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRKCA	“down-regulates activity”	DOCK8	phosphorylation
DOCK8	“up-regulates activity”	CDC42	“guanine nucleotide exchange factor”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 60 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
FCGR3A-mediated phagocytosis	5	26.7×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

3362 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	134
Likely pathogenic	73
Uncertain significance	1406
Likely benign	1268
Benign	289

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027955	NM_203447.4(DOCK8):c.5442del (p.Val1813_Tyr1814insTer)	Pathogenic
1069888	NM_203447.4(DOCK8):c.1498C>T (p.Arg500Ter)	Pathogenic
1070493	NC_000009.11:g.(?214977)(215049_?)del	Pathogenic
1070494	NC_000009.11:g.(?214957)(286656_?)del	Pathogenic
1071622	NM_203447.4(DOCK8):c.5161C>T (p.Gln1721Ter)	Pathogenic
1071623	NM_203447.4(DOCK8):c.5481dup (p.Arg1828Ter)	Pathogenic
1072705	NC_000009.11:g.(?271607)(334404_?)del	Pathogenic
1072707	NC_000009.11:g.(?271607)(370320_?)del	Pathogenic
1072708	NC_000009.11:g.(?426865)(429874_?)del	Pathogenic
1072709	NC_000009.11:g.(?289490)(399279_?)del	Pathogenic
1072710	NC_000009.11:g.(?325651)(386446_?)del	Pathogenic
1197276	NM_203447.4(DOCK8):c.4153+1G>A	Pathogenic
1301836	NM_203447.4(DOCK8):c.4241+1G>A	Pathogenic
1340719	GRCh37/hg19 9p24.3(chr9:285034-402280)x1	Pathogenic
1349421	NC_000009.11:g.(?271607)(289601_?)del	Pathogenic
1367934	NM_203447.4(DOCK8):c.6115C>T (p.Gln2039Ter)	Pathogenic
1390481	NM_203447.4(DOCK8):c.760del (p.Arg254fs)	Pathogenic
1421481	NM_203447.4(DOCK8):c.1271_1274dup (p.Ser426fs)	Pathogenic
1451221	NM_203447.4(DOCK8):c.4163del (p.Arg1388fs)	Pathogenic
1451629	NM_203447.4(DOCK8):c.851del (p.Leu284fs)	Pathogenic
1451794	NM_203447.4(DOCK8):c.2464G>T (p.Glu822Ter)	Pathogenic
1454702	NC_000009.11:g.(?271607)(332498_?)del	Pathogenic
1454704	NC_000009.11:g.(?325651)(332498_?)del	Pathogenic
1456361	NC_000009.11:g.(?214977)(377231_?)del	Pathogenic
1456362	NC_000009.11:g.(?214977)(399279_?)del	Pathogenic
1457132	NM_203447.4(DOCK8):c.27_28del (p.Ala11fs)	Pathogenic
1457238	NC_000009.11:g.(?271607)(434995_?)del	Pathogenic
1457993	NC_000009.11:g.(?271607)(382705_?)del	Pathogenic
1460365	NC_000009.11:g.(?386311)(422155_?)del	Pathogenic
1460425	NC_000009.11:g.(?271607)(328191_?)del	Pathogenic

SpliceAI

8233 predictions. Top by Δscore:

Variant	Effect	Δscore
9:215027:CAGGT:C	donor_loss	1.0000
9:215028:AGG:A	donor_loss	1.0000
9:215029:GGT:G	donor_loss	1.0000
9:215030:G:GC	donor_loss	1.0000
9:215031:T:A	donor_loss	1.0000
9:286598:GGAAT:G	donor_gain	1.0000
9:286599:G:GT	donor_gain	1.0000
9:286600:A:T	donor_gain	1.0000
9:286603:G:GG	donor_gain	1.0000
9:286632:G:GT	donor_gain	1.0000
9:286633:A:T	donor_gain	1.0000
9:286635:GG:G	donor_gain	1.0000
9:286636:GG:G	donor_gain	1.0000
9:289500:A:AG	acceptor_gain	1.0000
9:289501:C:G	acceptor_gain	1.0000
9:289505:A:AG	acceptor_gain	1.0000
9:289505:ATTAG:A	acceptor_gain	1.0000
9:289506:TTA:T	acceptor_loss	1.0000
9:289507:TAGGG:T	acceptor_loss	1.0000
9:289508:A:AG	acceptor_gain	1.0000
9:289508:A:T	acceptor_loss	1.0000
9:289508:AG:A	acceptor_gain	1.0000
9:289509:G:A	acceptor_gain	1.0000
9:289509:G:GT	acceptor_gain	1.0000
9:289509:GGGT:G	acceptor_gain	1.0000
9:289509:GGGTT:G	acceptor_gain	1.0000
9:289577:CGGAA:C	donor_gain	1.0000
9:289578:GGAA:G	donor_gain	1.0000
9:289578:GGAAG:G	donor_gain	1.0000
9:289579:G:GT	donor_gain	1.0000

AlphaMissense

13911 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:317110:T:A	V270D	0.999
9:325708:G:C	A289P	0.999
9:325714:T:G	Y291D	0.999
9:328025:T:C	S300P	0.999
9:334306:T:A	W403R	0.999
9:334306:T:C	W403R	0.999
9:422086:T:A	W1398R	0.999
9:422086:T:C	W1398R	0.999
9:422088:G:C	W1398C	0.999
9:422088:G:T	W1398C	0.999
9:449896:T:C	L1977P	0.999
9:325712:T:C	L290P	0.998
9:328128:T:C	F334S	0.998
9:328161:T:C	L345P	0.998
9:328167:T:A	V347D	0.998
9:334304:C:A	A402D	0.998
9:371493:T:C	L645P	0.998
9:372185:T:A	W670R	0.998
9:372185:T:C	W670R	0.998
9:372240:T:A	V688D	0.998
9:376240:T:A	W714R	0.998
9:376240:T:C	W714R	0.998
9:377089:T:C	L773P	0.998
9:441906:G:C	R1796P	0.998
9:441909:T:A	V1797D	0.998
9:442005:T:C	L1829P	0.998
9:452027:C:A	A1993D	0.998
9:463585:T:C	L2046P	0.998
9:463606:T:C	L2053P	0.998
9:463618:T:C	L2057P	0.998

dbSNP variants (sampled 300 via entrez): RS1000004589 (9:336630 T>C), RS1000021707 (9:408023 C>T), RS1000037292 (9:450050 C>A), RS1000041192 (9:256351 C>T), RS1000044666 (9:384235 T>G), RS1000059555 (9:286012 A>C), RS1000064110 (9:447851 C>T), RS1000068321 (9:268043 G>A), RS1000069742 (9:347500 T>C), RS1000071434 (9:357882 A>C,G), RS1000085158 (9:322969 T>A), RS1000087213 (9:325940 G>C), RS1000096905 (9:223769 G>T), RS1000102329 (9:412492 A>C,G), RS1000103912 (9:295830 C>T)

Disease associations

OMIM: gene MIM:611432 | disease phenotypes: MIM:243700, MIM:618282, MIM:181500, MIM:614113, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
combined immunodeficiency due to DOCK8 deficiency	Strong	Autosomal recessive
autosomal dominant non-syndromic intellectual disability	Supportive	Autosomal dominant
complex neurodevelopmental disorder	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
combined immunodeficiency due to DOCK8 deficiency	Definitive	AR

Mondo (11): combined immunodeficiency due to DOCK8 deficiency (MONDO:0009478), hyper-IgE recurrent infection syndrome 3, autosomal recessive (MONDO:0032654), severe combined immunodeficiency (MONDO:0015974), hepatoblastoma (MONDO:0018666), primary ovarian failure (MONDO:0005387), intellectual disability (MONDO:0001071), schizophrenia (MONDO:0005090), intellectual disability, autosomal dominant 2 (MONDO:0013581), autism (MONDO:0005260), complex neurodevelopmental disorder (MONDO:0100038), autosomal dominant non-syndromic intellectual disability (MONDO:0015802)

Orphanet (7): Combined immunodeficiency due to DOCK8 deficiency (Orphanet:217390), Autosomal recessive hyper-IgE syndrome due to ZNF341 deficiency (Orphanet:641368), Severe combined immunodeficiency (Orphanet:183660), Hepatoblastoma (Orphanet:449), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

51 total (30 of 51 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000389	Chronic otitis media
HP:0000403	Recurrent otitis media
HP:0000964	Eczematoid dermatitis
HP:0001047	Atopic dermatitis
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001880	Increased total eosinophil count
HP:0002090	Pneumonia
HP:0002099	Asthma
HP:0002110	Bronchiectasis
HP:0002138	Subarachnoid hemorrhage
HP:0002205	Recurrent respiratory infections
HP:0002301	Hemiplegia
HP:0002718	Recurrent bacterial infections
HP:0002754	Osteomyelitis
HP:0002841	Recurrent fungal infections
HP:0002850	Decreased circulating total IgM
HP:0002860	Squamous cell carcinoma
HP:0002960	Autoimmunity
HP:0003193	Allergic rhinitis
HP:0003212	Increased circulating IgE concentration
HP:0003237	Increased circulating IgG concentration
HP:0003593	Infantile onset
HP:0004429	Recurrent viral infections
HP:0005318	Cerebral vasculitis
HP:0005401	Recurrent candida infections
HP:0005403	Decreased total T cell count
HP:0005406	Recurrent bacterial skin infections
HP:0005425	Recurrent sinopulmonary infections

GWAS associations

43 associations (top):

Study	Trait	p-value
GCST001335_17	Mean platelet volume	4.000000e-12
GCST001762_639	Obesity-related traits	3.000000e-06
GCST003262_206	Post bronchodilator FEV1	3.000000e-06
GCST003262_962	Post bronchodilator FEV1	3.000000e-06
GCST004599_68	Mean platelet volume	4.000000e-09
GCST004599_69	Mean platelet volume	2.000000e-42
GCST004599_70	Mean platelet volume	7.000000e-11
GCST004599_71	Mean platelet volume	1.000000e-45
GCST004599_72	Mean platelet volume	5.000000e-33
GCST004603_79	Platelet count	5.000000e-14
GCST004608_111	Granulocyte percentage of myeloid white cells	2.000000e-09
GCST004610_173	White blood cell count	3.000000e-11
GCST004613_126	Sum neutrophil eosinophil counts	2.000000e-11
GCST004614_30	Granulocyte count	3.000000e-11
GCST004616_198	Platelet distribution width	5.000000e-15
GCST004620_25	Sum basophil neutrophil counts	2.000000e-11
GCST004626_70	Myeloid white cell count	2.000000e-10
GCST004629_82	Neutrophil count	1.000000e-11
GCST006979_151	Heel bone mineral density	1.000000e-10
GCST006988_13	Blond vs. brown/black hair color	7.000000e-27
GCST007504_3	Nevus count	2.000000e-08
GCST007505_25	Nevus count or cutaneous melanoma	1.000000e-12
GCST010303_44	Nevus count or cutaneous melanoma	4.000000e-12
GCST011011_12	Youthful appearance (self-reported)	1.000000e-58
GCST90002394_289	Monocyte percentage of white cells	8.000000e-09
GCST90002394_290	Monocyte percentage of white cells	5.000000e-18
GCST90002395_20	Mean platelet volume	7.000000e-14
GCST90002395_46	Mean platelet volume	6.000000e-17
GCST90002395_47	Mean platelet volume	1.000000e-20
GCST90002395_48	Mean platelet volume	1.000000e-64

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0004309	platelet count
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0007984	platelet component distribution width
EFO:0005090	basophil count
EFO:0009270	heel bone mineral density
EFO:0003924	hair color
EFO:0004632	nevus count
EFO:0007989	monocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0009188	Red cell distribution width

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D018197	Hepatoblastoma	C04.557.435.380
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
D016511	Severe Combined Immunodeficiency	C16.320.798.750; C16.614.815; C18.452.284.800; C20.673.795.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10491684	Toxicity	3	carboplatin;gemcitabine	Non-Small Cell Lung Carcinoma;Thrombocytopenia

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10491684	DOCK8	3	2.50	1	carboplatin;gemcitabine

CTD chemical–gene interactions

53 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	4
methylmercuric chloride	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	3
Nickel	decreases expression, increases expression	3
bisphenol A	decreases expression	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Doxorubicin	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	affects methylation, increases methylation	2
2,4,6-tribromophenol	decreases expression	1
methyleugenol	decreases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	decreases expression	1
arsenite	decreases methylation	1
sulforaphane	decreases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	increases methylation	1
nitazoxanide	affects response to substance	1
mercuric bromide	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
glycidamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, decreases expression, affects cotreatment	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1

Clinical trials (associated diseases)

202 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT01420627	PHASE3	COMPLETED	EZN-2279 in Patients With ADA-SCID
NCT06940570	PHASE3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT03017326	PHASE3	ACTIVE_NOT_RECRUITING	Paediatric Hepatic International Tumour Trial
NCT03533582	PHASE3	ACTIVE_NOT_RECRUITING	Cisplatin and Combination Chemotherapy in Treating Children and Young Adults With Hepatoblastoma or Liver Cancer After Surgery
NCT04478292	PHASE3	RECRUITING	A Multi-institutional Study for Treatment of Children With Newly Diagnosed Hepatoblastoma Using a Modified PHITT Strategy
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT01176006	PHASE2	ACTIVE_NOT_RECRUITING	Pilot Study of Reduced-Intensity Hematopoietic Stem Cell Transplant of DOCK8 Deficiency
NCT00000603	PHASE2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00794508	PHASE2	COMPLETED	MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID
NCT01182675	PHASE2	TERMINATED	Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim
NCT01529827	PHASE2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02177760	PHASE2	WITHDRAWN	Sirolimus Prophylaxis for aGVHD in TME SCID
NCT03619551	PHASE2	ACTIVE_NOT_RECRUITING	Conditioning SCID Infants Diagnosed Early
NCT01154816	PHASE2	COMPLETED	Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia
NCT02011126	PHASE2	WITHDRAWN	Imetelstat Sodium in Treating Younger Patients With Relapsed or Refractory Solid Tumors
NCT02867592	PHASE2	ACTIVE_NOT_RECRUITING	Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03210714	PHASE2	ACTIVE_NOT_RECRUITING	Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652	PHASE2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213665	PHASE2	COMPLETED	Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03213678	PHASE2	COMPLETED	Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213704	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03220035	PHASE2	COMPLETED	Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
NCT03233204	PHASE2	COMPLETED	Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
NCT03526250	PHASE2	COMPLETED	Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)
NCT03698994	PHASE2	ACTIVE_NOT_RECRUITING	Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)