DOCK11

Summary

DOCK11 (dedicator of cytokinesis 11, HGNC:23483) is a protein-coding gene on chromosome Xq24, encoding Dedicator of cytokinesis protein 11 (Q5JSL3). Guanine nucleotide-exchange factor (GEF) that activates CDC42 by exchanging bound GDP for free GTP.

Predicted to enable guanyl-nucleotide exchange factor activity. Involved in positive regulation of filopodium assembly. Predicted to be located in cytosol.

Source: NCBI Gene 139818 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autoinflammatory disease, multisystem, with immune dysregulation, X-linked (Strong, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 609 total — 9 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 50
• Druggable target: yes
• MANE Select transcript: NM_144658

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23483
Approved symbol	DOCK11
Name	dedicator of cytokinesis 11
Location	Xq24
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32122, FLJ43653, ZIZ2, ACG
Ensembl gene	ENSG00000147251
Ensembl biotype	protein_coding
OMIM	300681
Entrez	139818

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000276202, ENST00000276204, ENST00000632573, ENST00000633080, ENST00000924404, ENST00000966546

RefSeq mRNA: 1 — MANE Select: NM_144658 NM_144658

CCDS: CCDS35373

Canonical transcript exons

ENST00000276202 — 53 exons

Exon	Start	End
ENSE00000979325	118675936	118676049
ENSE00000979327	118680482	118680692
ENSE00000979329	118681694	118681794
ENSE00000979332	118588137	118588321
ENSE00000979333	118588413	118588478
ENSE00000979334	118590210	118590302
ENSE00000979335	118593214	118593337
ENSE00000979336	118597431	118597552
ENSE00000979337	118598030	118598116
ENSE00000979338	118599139	118599228
ENSE00000979339	118605238	118605356
ENSE00000979340	118608072	118608141
ENSE00000979341	118608231	118608356
ENSE00000979344	118614692	118614775
ENSE00000979346	118618550	118618728
ENSE00001037538	118654904	118654961
ENSE00001037555	118643457	118643594
ENSE00001037573	118627504	118627579
ENSE00001037590	118648945	118649127
ENSE00001037607	118654602	118654817
ENSE00001125722	118639435	118639577
ENSE00001125744	118628163	118628272
ENSE00001125748	118681058	118681248
ENSE00001125752	118662686	118662792
ENSE00001341309	118676591	118676737
ENSE00001341314	118671023	118671145
ENSE00001341323	118651964	118652077
ENSE00001341332	118641190	118641305
ENSE00001341335	118638080	118638127
ENSE00001341337	118636346	118636412
ENSE00001341339	118624539	118624655
ENSE00001341345	118615600	118615711
ENSE00001341348	118610272	118610418
ENSE00001341350	118609278	118609349
ENSE00001363921	118543511	118543593
ENSE00001366814	118542725	118542841
ENSE00001368460	118545323	118545392
ENSE00001370995	118542926	118543015
ENSE00001373054	118495815	118496073
ENSE00001373947	118561383	118561517
ENSE00001379004	118572323	118572463
ENSE00001379831	118566005	118566182
ENSE00001380806	118573806	118574018
ENSE00001384578	118566574	118566653
ENSE00001386540	118546021	118546116
ENSE00001387946	118578525	118578647
ENSE00001388912	118568079	118568162
ENSE00001456065	118630379	118630490
ENSE00001503791	118683079	118683217
ENSE00001914930	118685688	118686147
ENSE00003567049	118580097	118580179
ENSE00003631391	118584735	118584857
ENSE00003651389	118585041	118585117

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 98.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.2436 / max 327.9168, expressed in 1461 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197357	6.6406	1302
197355	6.0627	1160
197354	0.3371	182
197356	0.2032	97

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parietal pleura	UBERON:0002400	98.36	gold quality
germinal epithelium of ovary	UBERON:0001304	96.53	gold quality
calcaneal tendon	UBERON:0003701	95.31	gold quality
visceral pleura	UBERON:0002401	95.09	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.02	gold quality
adipose tissue	UBERON:0001013	94.84	gold quality
layer of synovial tissue	UBERON:0007616	94.47	gold quality
granulocyte	CL:0000094	93.57	gold quality
tendon	UBERON:0000043	93.16	gold quality
blood	UBERON:0000178	93.11	gold quality
synovial joint	UBERON:0002217	93.10	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.80	gold quality
leukocyte	CL:0000738	92.59	gold quality
omental fat pad	UBERON:0010414	92.52	gold quality
peritoneum	UBERON:0002358	92.44	gold quality
monocyte	CL:0000576	92.33	gold quality
trabecular bone tissue	UBERON:0002483	92.26	gold quality
superficial temporal artery	UBERON:0001614	92.01	gold quality
bone marrow	UBERON:0002371	91.63	gold quality
tendon of biceps brachii	UBERON:0008188	91.46	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.26	gold quality
lower esophagus	UBERON:0013473	91.19	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.89	gold quality
pericardium	UBERON:0002407	90.80	gold quality
spleen	UBERON:0002106	90.68	gold quality
lower lobe of lung	UBERON:0008949	90.61	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.28	gold quality
popliteal artery	UBERON:0002250	90.14	gold quality
tibial artery	UBERON:0007610	90.13	gold quality
mucosa of stomach	UBERON:0001199	89.97	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.94
E-CURD-119	yes	5.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

64 targeting DOCK11, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-1200	99.71	70.42	1838

Literature-anchored findings (GeneRIF, showing 4)

• DOCK11 and DENND2A play pivotal roles in the maintenance of hepatitis B virus in host cells. (PMID:33539396)
• DOCK11 deficiency in patients with X-linked actinopathy and autoimmunity. (PMID:36952639)
• Systemic Inflammation and Normocytic Anemia in DOCK11 Deficiency. (PMID:37342957)
• DOCK11 and Immune Disease. (PMID:37590454)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dock11	ENSDARG00000062485
mus_musculus	Dock11	ENSMUSG00000031093
rattus_norvegicus	Dock11	ENSRNOG00000013321
drosophila_melanogaster	Zir	FBGN0031216
caenorhabditis_elegans		WBGENE00000419
caenorhabditis_elegans		WBGENE00018520

Paralogs (10): DOCK9 (ENSG00000088387), DOCK3 (ENSG00000088538), DOCK8 (ENSG00000107099), DOCK7 (ENSG00000116641), DOCK4 (ENSG00000128512), DOCK6 (ENSG00000130158), DOCK2 (ENSG00000134516), DOCK10 (ENSG00000135905), DOCK5 (ENSG00000147459), DOCK1 (ENSG00000150760)

Protein

Protein identifiers

Dedicator of cytokinesis protein 11 — Q5JSL3 (reviewed: Q5JSL3)

Alternative names: Activated Cdc42-associated guanine nucleotide exchange factor, Zizimin-2

All UniProt accessions (4): Q5JSL3, A0A0J9YW64, A0A0J9YXQ7, A6NIW2

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with CDC42.

Disease relevance. Autoinflammatory disease, multisystem, with immune dysregulation, X-linked (ADMIDX) [MIM:301109] An X-linked recessive disorder apparent in infancy or early childhood, and characterized by immune dysregulation, variable cytopenias, and systemic or organ-specific autoinflammatory manifestations. Clinical features include systemic lupus erythematosus, panniculitis, inflammatory bowel disease, pulmonary disease, or arthritis associated with recurrent fever, leukocytosis, lymphoproliferation, and hepatosplenomegaly in the absence of an infectious agent. Death in childhood has been reported. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The DOCKER domain is necessary for the GEF activity. The DOCKER domain mediates interaction with activated CDC42 in conjunction with residues 66-126.

Miscellaneous. ‘Zizim’ means ‘spike’ in Hebrew.

Similarity. Belongs to the DOCK family.

RefSeq proteins (1): NP_653259* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
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
IPR037809	C2_Dock-D	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: PF00169, PF06920, PF11878, PF14429, PF20421, PF20422

UniProt features (28 total): modified residue 10, sequence variant 10, domain 3, sequence conflict 3, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JSL3-F1	79.65	0.37

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 (10): 306, 440, 445, 1237, 1240, 12, 16, 23, 161, 248

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

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

MSigDB gene sets: 312 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_B_CELL_HOMEOSTASIS, GOBP_B_CELL_ACTIVATION, GOBP_LYMPHOCYTE_HOMEOSTASIS, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOMF_GTPASE_BINDING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, COUP_01, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION

GO Biological Process (6): B cell homeostasis (GO:0001782), marginal zone B cell differentiation (GO:0002315), small GTPase-mediated signal transduction (GO:0007264), regulation of Rho protein signal transduction (GO:0035023), positive regulation of GTPase activity (GO:0043547), positive regulation of filopodium assembly (GO:0051491)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RHO GTPase cycle	2
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lymphocyte homeostasis	1
mature B cell differentiation involved in immune response	1
intracellular signaling cassette	1
Rho protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
GTPase activity	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
filopodium assembly	1
regulation of filopodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
GTPase binding	1
binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

978 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DOCK11	DHX37	Q8IY37	892
DOCK11	DHX8	Q14562	879
DOCK11	RHOJ	Q9H4E5	750
DOCK11	CDC42	P21181	700
DOCK11	DOCK2	Q92608	642
DOCK11	RHOQ	P17081	614
DOCK11	GLYAT	Q6IB77	613
DOCK11	TSHZ1	Q6ZSZ6	611
DOCK11	RABIF	P47224	562
DOCK11	GGCT	O75223	544
DOCK11	GGTLC3	B5MD39	529
DOCK11	GUCY2C	P25092	528
DOCK11	GGT1	P19440	527
DOCK11	GCG	P01275	511
DOCK11	DOCK1	Q14185	508

IntAct

54 interactions, top by confidence:

A	B	Type	Score
PAAT	CLTC	psi-mi:“MI:0914”(association)	0.740
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
CYGB	AKR7A2	psi-mi:“MI:0914”(association)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
UQCRH	DCTN6	psi-mi:“MI:0914”(association)	0.530
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAB	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	SHTN1	psi-mi:“MI:0914”(association)	0.530
DOCK11	ACSL3	psi-mi:“MI:0915”(physical association)	0.400
DOCK11	AHNAK	psi-mi:“MI:0915”(physical association)	0.400
DOCK11	HTT	psi-mi:“MI:0915”(physical association)	0.370
BFRF1A	SHTN1	psi-mi:“MI:0914”(association)	0.350
GORASP1	CLASP2	psi-mi:“MI:0914”(association)	0.350
ARHGAP22	KDM6A	psi-mi:“MI:0914”(association)	0.350
PAAT	EIF4E2	psi-mi:“MI:0914”(association)	0.350
DENR	ATG13	psi-mi:“MI:0914”(association)	0.350
GCHFR	OBSL1	psi-mi:“MI:0914”(association)	0.350
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
YWHAZ	SPEG	psi-mi:“MI:0914”(association)	0.350
DOCK9	CHD1	psi-mi:“MI:0914”(association)	0.350
YWHAH	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAQ	SHTN1	psi-mi:“MI:0914”(association)	0.350
CEP192	WASL	psi-mi:“MI:0914”(association)	0.350
DOCK11	DOCK9	psi-mi:“MI:0914”(association)	0.350
YWHAB	BRAF	psi-mi:“MI:0914”(association)	0.350

BioGRID (95): DOCK11 (Affinity Capture-MS), DOCK11 (Affinity Capture-MS), DOCK11 (Affinity Capture-MS), DOCK11 (Affinity Capture-MS), DOCK11 (Affinity Capture-MS), DOCK11 (Affinity Capture-MS), DOCK11 (Affinity Capture-MS), DOCK11 (Affinity Capture-MS), DOCK11 (Affinity Capture-MS), DOCK11 (Affinity Capture-MS), DOCK11 (Affinity Capture-RNA), DOCK11 (Affinity Capture-MS), DOCK11 (Proximity Label-MS), DOCK11 (Proximity Label-MS), DOCK11 (Proximity Label-MS)

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 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
Activation of BAD and translocation to mitochondria	7	136.7×	3e-12
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	120.6×	4e-12
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	120.6×	4e-12
Activation of BH3-only proteins	7	89.1×	4e-11
RHO GTPases activate PKNs	7	56.9×	1e-09
Intrinsic Pathway for Apoptosis	7	52.6×	1e-09
FOXO-mediated transcription	5	43.1×	1e-06
SARS-CoV-1-host interactions	8	36.0×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	39.8×	5e-05
intracellular protein localization	7	15.9×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	5
Uncertain significance	186
Likely benign	10
Benign	7

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
2444458	NM_144658.4(DOCK11):c.5120G>C (p.Trp1707Ser)	Pathogenic
2444459	NM_144658.4(DOCK11):c.1718+5G>A	Pathogenic
2444466	NM_144658.4(DOCK11):c.75dup (p.Glu26Ter)	Pathogenic
2499981	NM_144658.4(DOCK11):c.3893T>G (p.Leu1298Arg)	Pathogenic
2499982	NM_144658.4(DOCK11):c.4007A>G (p.His1336Arg)	Pathogenic
2499983	NM_144658.4(DOCK11):c.823A>T (p.Thr275Ser)	Pathogenic
2499984	NM_144658.4(DOCK11):c.1240G>T (p.Asp414Tyr)	Pathogenic
2499985	NM_144658.4(DOCK11):c.5117T>C (p.Leu1706Ser)	Pathogenic
2499986	NM_144658.4(DOCK11):c.4097G>A (p.Arg1366Gln)	Pathogenic
2444457	NM_144658.4(DOCK11):c.323A>G (p.Tyr108Cys)	Likely pathogenic
2499987	NM_144658.4(DOCK11):c.5653C>T (p.Arg1885Cys)	Likely pathogenic
4077363	NM_144658.4(DOCK11):c.4582-1G>A	Likely pathogenic
4527662	NM_144658.4(DOCK11):c.392+1G>A	Likely pathogenic
4819041	NM_144658.4(DOCK11):c.5377_5378del (p.Ser1793fs)	Likely pathogenic

SpliceAI

7179 predictions. Top by Δscore:

Variant	Effect	Δscore
X:118542719:A:AG	acceptor_gain	1.0000
X:118542720:T:G	acceptor_gain	1.0000
X:118542721:A:AG	acceptor_gain	1.0000
X:118542721:AAAG:A	acceptor_gain	1.0000
X:118542722:A:G	acceptor_gain	1.0000
X:118542722:AAG:A	acceptor_gain	1.0000
X:118542723:A:AG	acceptor_gain	1.0000
X:118542723:A:C	acceptor_loss	1.0000
X:118542723:AG:A	acceptor_gain	1.0000
X:118542724:G:A	acceptor_gain	1.0000
X:118542724:G:GA	acceptor_gain	1.0000
X:118542724:GGAA:G	acceptor_gain	1.0000
X:118542724:GGAAA:G	acceptor_gain	1.0000
X:118542830:G:GT	donor_gain	1.0000
X:118542837:TATCT:T	donor_gain	1.0000
X:118542838:ATCTG:A	donor_loss	1.0000
X:118542839:TCTG:T	donor_loss	1.0000
X:118542840:CT:C	donor_gain	1.0000
X:118542841:TGTG:T	donor_loss	1.0000
X:118542842:G:GG	donor_gain	1.0000
X:118542842:GTGA:G	donor_loss	1.0000
X:118542843:TGAGT:T	donor_loss	1.0000
X:118542844:GAG:G	donor_loss	1.0000
X:118542916:T:TA	acceptor_gain	1.0000
X:118542918:T:TA	acceptor_gain	1.0000
X:118542924:A:AG	acceptor_gain	1.0000
X:118542925:G:GA	acceptor_gain	1.0000
X:118542925:GA:G	acceptor_gain	1.0000
X:118542925:GAT:G	acceptor_gain	1.0000
X:118542925:GATC:G	acceptor_gain	1.0000

AlphaMissense

13771 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:118561438:T:C	L205P	1.000
X:118566036:T:C	L242P	1.000
X:118566098:T:A	W263R	1.000
X:118566098:T:C	W263R	1.000
X:118654714:T:C	L1603P	1.000
X:118654756:T:C	L1617P	1.000
X:118654767:T:A	W1621R	1.000
X:118654767:T:C	W1621R	1.000
X:118654771:T:C	L1622P	1.000
X:118654915:T:G	C1641W	1.000
X:118681214:T:C	L1943P	1.000
X:118681220:T:C	L1945P	1.000
X:118495990:T:C	F7L	0.999
X:118495991:T:C	F7S	0.999
X:118495991:T:G	F7C	0.999
X:118495992:C:A	F7L	0.999
X:118495992:C:G	F7L	0.999
X:118546069:T:A	W171R	0.999
X:118546069:T:C	W171R	0.999
X:118546073:T:C	L172S	0.999
X:118561396:G:C	R191P	0.999
X:118561438:T:A	L205H	0.999
X:118566030:T:C	F240S	0.999
X:118566036:T:A	L242H	0.999
X:118566066:T:C	L252P	0.999
X:118588417:G:C	R662T	0.999
X:118588417:G:T	R662M	0.999
X:118597431:T:A	V755D	0.999
X:118597433:G:A	G756R	0.999
X:118597433:G:C	G756R	0.999

dbSNP variants (sampled 300 via entrez): RS1000001374 (X:118513305 G>A,T), RS1000008050 (X:118526009 T>A,C,G), RS1000058548 (X:118645350 C>T), RS1000061380 (X:118668940 A>G), RS1000113199 (X:118586357 G>A,T), RS1000119626 (X:118572394 G>A), RS1000161567 (X:118581529 T>C,G), RS1000180956 (X:118641078 C>T), RS1000231297 (X:118586735 T>C), RS1000243442 (X:118649612 G>A), RS1000275231 (X:118571974 G>C), RS1000292262 (X:118673581 A>G), RS1000312148 (X:118550025 T>C), RS1000324488 (X:118515627 T>A), RS1000324908 (X:118510278 C>T)

Disease associations

OMIM: gene MIM:300681 | disease phenotypes: MIM:301109

GenCC curated gene-disease

Disease	Classification	Inheritance
autoinflammatory disease, multisystem, with immune dysregulation, X-linked	Strong	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
autoinflammatory disease, multisystem, with immune dysregulation, X-linked	Strong	XL

Mondo (1): autoinflammatory disease, multisystem, with immune dysregulation, X-linked (MONDO:0957494)

Orphanet (0):

HPO phenotypes

50 total (30 of 50 shown, HPO-id order):

HPO	Term
HP:0000100	Nephrotic syndrome
HP:0000155	Oral ulcer
HP:0000265	Mastoiditis
HP:0000403	Recurrent otitis media
HP:0000474	Thickened nuchal skin fold
HP:0001252	Hypotonia
HP:0001419	X-linked recessive inheritance
HP:0001508	Failure to thrive
HP:0001701	Pericarditis
HP:0001744	Splenomegaly
HP:0001890	Autoimmune hemolytic anemia
HP:0001904	Autoimmune neutropenia
HP:0001973	Autoimmune thrombocytopenia
HP:0001974	Increased total leukocyte count
HP:0002014	Diarrhea
HP:0002091	Restrictive ventilatory defect
HP:0002240	Hepatomegaly
HP:0002720	Decreased circulating IgA concentration
HP:0002725	Systemic lupus erythematosus
HP:0002837	Recurrent bronchitis
HP:0002850	Decreased circulating total IgM
HP:0002923	Rheumatoid factor positive
HP:0003212	Increased circulating IgE concentration
HP:0003262	Anti-smooth muscle antibody positivity
HP:0003493	Antinuclear antibody positivity
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0004315	Decreased circulating IgG concentration
HP:0004844	Coombs-positive hemolytic anemia

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002395_647	Mean platelet volume	2.000000e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067263 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.90	Kd	125.8	nM	CHEMBL5653589
6.90	ED50	125.8	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148258: Binding affinity to human DOCK11 incubated for 45 mins by Kinobead based pull down assay	kd	0.1258	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, increases methylation, affects cotreatment	5
bisphenol S	decreases methylation, increases expression, affects cotreatment	3
Dexamethasone	increases expression, affects cotreatment	2
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	increases expression	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
nickel sulfate	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
perfluoro-n-nonanoic acid	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
(+)-JQ1 compound	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation	1
Vorinostat	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651300	Binding	Binding affinity to human DOCK11 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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