Hypocomplementemic urticarial vasculitis

disease

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Also known as anti-C1q vasculitisMac Duffie hypocomplementemic urticarial vasculitisMac Duffie syndromeMcDuffie hypocomplementemic urticarial vasculitisMcDuffie syndrome

Summary

Hypocomplementemic urticarial vasculitis (MONDO:0018227) is a disease with 1 cohort gene.

At a glance

Prevalence: Unknown (Worldwide) [Orphanet-validated]
Cohort genes: 1
Phenotypes (HPO): 47

Clinical features

Signs & symptoms

Clinical features (HPO)

47 HPO clinical features (Orphanet curated; top 47 by frequency):

HPO ID	Term	Frequency
HP:0000988	Skin rash	Very frequent (80-99%)
HP:0000989	Pruritus	Very frequent (80-99%)
HP:0004431	Complement deficiency	Very frequent (80-99%)
HP:0011944	Small vessel vasculitis	Very frequent (80-99%)
HP:0000083	Renal insufficiency	Frequent (30-79%)
HP:0000093	Proteinuria	Frequent (30-79%)
HP:0000509	Conjunctivitis	Frequent (30-79%)
HP:0000554	Uveitis	Frequent (30-79%)
HP:0000790	Hematuria	Frequent (30-79%)
HP:0001369	Arthritis	Frequent (30-79%)
HP:0002017	Nausea and vomiting	Frequent (30-79%)
HP:0002027	Abdominal pain	Frequent (30-79%)
HP:0002094	Dyspnea	Frequent (30-79%)
HP:0002105	Hemoptysis	Frequent (30-79%)
HP:0002960	Autoimmunity	Frequent (30-79%)
HP:0007400	Irregular hyperpigmentation	Frequent (30-79%)
HP:0012735	Cough	Frequent (30-79%)
HP:0100533	Inflammatory abnormality of the eye	Frequent (30-79%)
HP:0100534	Episcleritis	Frequent (30-79%)
HP:0100665	Angioedema	Frequent (30-79%)
HP:0100820	Glomerulopathy	Frequent (30-79%)
HP:0000407	Sensorineural hearing impairment	Occasional (5-29%)
HP:0000763	Sensory neuropathy	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001287	Meningitis	Occasional (5-29%)
HP:0001315	Reduced tendon reflexes	Occasional (5-29%)
HP:0001373	Joint dislocation	Occasional (5-29%)
HP:0001541	Ascites	Occasional (5-29%)
HP:0001654	Abnormal heart valve morphology	Occasional (5-29%)
HP:0001698	Pericardial effusion	Occasional (5-29%)
HP:0001744	Splenomegaly	Occasional (5-29%)
HP:0002014	Diarrhea	Occasional (5-29%)
HP:0002091	Restrictive ventilatory defect	Occasional (5-29%)
HP:0002097	Emphysema	Occasional (5-29%)
HP:0002202	Pleural effusion	Occasional (5-29%)
HP:0002240	Hepatomegaly	Occasional (5-29%)
HP:0002665	Lymphoma	Occasional (5-29%)
HP:0002716	Lymphadenopathy	Occasional (5-29%)
HP:0002718	Recurrent bacterial infections	Occasional (5-29%)
HP:0003326	Myalgia	Occasional (5-29%)
HP:0004374	Hemiplegia/hemiparesis	Occasional (5-29%)
HP:0006536	Airway obstruction	Occasional (5-29%)
HP:0006824	Cranial nerve paralysis	Occasional (5-29%)
HP:0009830	Peripheral neuropathy	Occasional (5-29%)
HP:0100021	Cerebral palsy	Occasional (5-29%)
HP:0100326	Immunologic hypersensitivity	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	hypocomplementemic urticarial vasculitis
Mondo ID	MONDO:0018227
Orphanet	36412
ICD-11	629572966
SNOMED CT	239945009
UMLS	C0343206
MedGen	83360
GARD	0006725
Is cancer (heuristic)	no

Also known as: anti-C1q vasculitis · Mac Duffie hypocomplementemic urticarial vasculitis · Mac Duffie syndrome · McDuffie hypocomplementemic urticarial vasculitis · McDuffie syndrome

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › vasculitis › immune complex mediated vasculitis › hypocomplementemic urticarial vasculitis

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
DNASE1L3	Supportive	Autosomal recessive	hypocomplementemic urticarial vasculitis	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNASE1L3	Orphanet:300345	Autosomal systemic lupus erythematosus
DNASE1L3	Orphanet:36412	Hypocomplementemic urticarial vasculitis

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
DNASE1L3	HGNC:2959	ENSG00000163687	Q13609	Deoxyribonuclease gamma	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNASE1L3	Deoxyribonuclease gamma	Has DNA hydrolytic activity.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Phosphatase	1	83.9×	0.012

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNASE1L3	Phosphatase	yes		Endo/exonuclease/phosphatase, DNase_I, Deoxyribonuclease-1_AS

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
gingival epithelium	1
periodontal ligament	1
spleen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNASE1L3	228	broad	marker	periodontal ligament, spleen, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DNASE1L3	891

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DNASE1L3	Q13609	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
programmed cell death involved in cell development	1	8426.0×	4e-04	DNASE1L3
regulation of neutrophil mediated cytotoxicity	1	8426.0×	4e-04	DNASE1L3
regulation of acute inflammatory response	1	4213.0×	5e-04	DNASE1L3
neutrophil activation involved in immune response	1	1872.4×	8e-04	DNASE1L3
apoptotic DNA fragmentation	1	1203.7×	9e-04	DNASE1L3
DNA metabolic process	1	1053.2×	9e-04	DNASE1L3

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
DNASE1L3	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
DNASE1L3	5	Binding:5

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	1	DNASE1L3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
DNASE1L3	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: DNASE1L3