autoinflammatory disease, multisystem, with immune dysregulation, X-linked

Summary

autoinflammatory disease, multisystem, with immune dysregulation, X-linked (MONDO:0957494) is a disease caused by DOCK11 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: DOCK11 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autoinflammatory disease, multisystem, with immune dysregulation, X-linked
Mondo ID	MONDO:0957494
OMIM	301109
UMLS	C5829577
MedGen	1840213
GARD	0026852
Is cancer (heuristic)	no

Data availability: 14 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › autoinflammatory syndrome › autoinflammatory disease, multisystem, with immune dysregulation, X-linked

Related subtypes (36): cherubism, chronic recurrent multifocal osteomyelitis, Pelger-Huet-like anomaly and episodic fever with abdominal pain, pyogenic arthritis-pyoderma gangrenosum-acne syndrome, psoriasis 14, pustular, autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation, periodic fever syndrome, infantile onset panniculitis with uveitis and systemic granulomatosis, idiopathic recurrent pericarditis, pyoderma gangrenosum-acne-suppurative hidradenitis syndrome, neonatal inflammatory skin and bowel disease, magic syndrome, autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis, Schnitzler syndrome, PFAPA syndrome, pyoderma gangrenosum, SAPHO syndrome, sarcoidosis, adult-onset Still disease, systemic-onset juvenile idiopathic arthritis, VEXAS syndrome, autoinflammatory syndrome, familial, Behcet-like, CEBPE-associated autoinflammation-immunodeficiency-neutrophil dysfunction syndrome, type 1 interferonopathy, autoinflammatory disease, X-linked, autoinflammatory syndrome with immunodeficiency, early-onset pulmonary and cutaneous vasculitis, autoinflammatory syndrome due to TBK1 deficiency, F12-associated cold autoinflammatory syndrome, neonatal-onset severe multisystemic autoinflammatory disease with increased IL18, SAMD9L-associated autoinflammatory syndrome, autoinflammatory syndrome of childhood, autoinflammatory disease, systemic, with vasculitis, granulomatous autoinflammatory syndrome of childhood, PAPASH syndrome, Sharpin-related autoinflammatory syndrome

Subtypes (2): early-onset autoimmune disorder due to DOCK11 partial deficiency, early-onset immune dysregulation due to DOCK11 complete deficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

14 retrieved; paginated sample, class counts are floors:

6 pathogenic, 5 uncertain significance, 2 likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2444458	NM_144658.4(DOCK11):c.5120G>C (p.Trp1707Ser)	DOCK11	Pathogenic	criteria provided, single submitter
2444466	NM_144658.4(DOCK11):c.75dup (p.Glu26Ter)	DOCK11	Pathogenic	criteria provided, single submitter
2499981	NM_144658.4(DOCK11):c.3893T>G (p.Leu1298Arg)	DOCK11	Pathogenic	no assertion criteria provided
2499983	NM_144658.4(DOCK11):c.823A>T (p.Thr275Ser)	DOCK11	Pathogenic	no assertion criteria provided
2499984	NM_144658.4(DOCK11):c.1240G>T (p.Asp414Tyr)	DOCK11	Pathogenic	no assertion criteria provided
2499986	NM_144658.4(DOCK11):c.4097G>A (p.Arg1366Gln)	DOCK11	Pathogenic	no assertion criteria provided
2499987	NM_144658.4(DOCK11):c.5653C>T (p.Arg1885Cys)	DOCK11	Likely pathogenic	criteria provided, single submitter
4819041	NM_144658.4(DOCK11):c.5377_5378del (p.Ser1793fs)	DOCK11	Likely pathogenic	criteria provided, single submitter
3362713	NM_144658.4(DOCK11):c.1388A>G (p.Gln463Arg)	DOCK11	Uncertain significance	criteria provided, single submitter
4082103	NM_144658.4(DOCK11):c.2696T>C (p.Ile899Thr)	DOCK11	Uncertain significance	criteria provided, single submitter
4082104	NM_144658.4(DOCK11):c.2185C>G (p.Leu729Val)	DOCK11	Uncertain significance	criteria provided, single submitter
4292921	NM_144658.4(DOCK11):c.4069C>T (p.Arg1357Ter)	DOCK11	Uncertain significance	criteria provided, single submitter
4532152	NM_144658.4(DOCK11):c.4019T>C (p.Leu1340Pro)	DOCK11	Uncertain significance	criteria provided, single submitter
3897941	NM_144658.4(DOCK11):c.2949+3A>T	DOCK11	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
DOCK11	Strong	X-linked	autoinflammatory disease, multisystem, with immune dysregulation, X-linked	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DOCK11	Orphanet:658946	Early-onset immune dysregulation with autoimmunity due to DOCK11 partial deficiency
DOCK11	Orphanet:658951	Early-onset immune dysregulation due to DOCK11 complete deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DOCK11	HGNC:23483	ENSG00000147251	Q5JSL3	Dedicator of cytokinesis protein 11	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DOCK11	Dedicator of cytokinesis protein 11	Guanine nucleotide-exchange factor (GEF) that activates CDC42 by exchanging bound GDP for free GTP.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DOCK11	Scaffold/PPI	no		PH_domain, PH-like_dom_sf, ARM-type_fold

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
germinal epithelium of ovary	1
parietal pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DOCK11	255	ubiquitous	marker	parietal pleura, germinal epithelium of ovary, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DOCK11	1,127

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DOCK11	Q5JSL3	79.65

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
CDC42 GTPase cycle	1	72.3×	0.016	DOCK11
Factors involved in megakaryocyte development and platelet production	1	66.4×	0.016	DOCK11
RAC1 GTPase cycle	1	61.1×	0.016	DOCK11

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
marginal zone B cell differentiation	1	1872.4×	0.003	DOCK11
B cell homeostasis	1	561.7×	0.003	DOCK11
positive regulation of filopodium assembly	1	561.7×	0.003	DOCK11
regulation of Rho protein signal transduction	1	510.7×	0.003	DOCK11
positive regulation of GTPase activity	1	276.3×	0.004	DOCK11
small GTPase-mediated signal transduction	1	183.2×	0.005	DOCK11

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DOCK11	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
DOCK11	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	DOCK11

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
DOCK11	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.