Vibratory urticaria

Summary

Vibratory urticaria (MONDO:0006618) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	vibratory urticaria
Mondo ID	MONDO:0006618
EFO	EFO:1000775
DOID	DOID:1554
ICD-10-CM	L50.4
SNOMED CT	51247001
UMLS	C0157743
MedGen	510413
Is cancer (heuristic)	no

Data availability: 12 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › dermatitis › urticaria › physical urticaria › vibratory urticaria

Related subtypes (2): cholinergic urticaria, familial dermatographia

Subtypes (1): autosomal dominant vibratory urticaria

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

12 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 3 conflicting classifications of pathogenicity, 2 benign/likely benign, 1 benign, 1 likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3765553	NM_013447.4(ADGRE2):c.1276C>T (p.Gln426Ter)	ADGRE2	Likely pathogenic	criteria provided, single submitter
2074623	NM_013447.4(ADGRE2):c.56C>T (p.Pro19Leu)	ADGRE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
222005	NM_013447.4(ADGRE2):c.1475G>A (p.Cys492Tyr)	ADGRE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2978511	NM_013447.4(ADGRE2):c.1243G>A (p.Ala415Thr)	ADGRE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1301601	NM_013447.4(ADGRE2):c.457C>T (p.Leu153Phe)	ADGRE2	Uncertain significance	criteria provided, single submitter
1301602	NM_013447.4(ADGRE2):c.461A>T (p.Lys154Ile)	ADGRE2	Uncertain significance	criteria provided, single submitter
3892965	NM_013447.4(ADGRE2):c.31+2_31+3insGTCTTTCTC	ADGRE2	Uncertain significance	criteria provided, single submitter
4077844	NM_013447.4(ADGRE2):c.494A>G (p.Asn165Ser)	ADGRE2	Uncertain significance	criteria provided, single submitter
2068876	NM_013447.4(ADGRE2):c.1919A>G (p.Asn640Ser)	ADGRE2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
2126077	NM_013447.4(ADGRE2):c.1842G>C (p.Leu614Phe)	ADGRE2	Benign	criteria provided, multiple submitters, no conflicts
2168798	NM_013447.4(ADGRE2):c.920C>T (p.Ala307Val)	ADGRE2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
708623	NM_013447.4(ADGRE2):c.1693_1709del (p.Gln565fs)	ADGRE2	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ADGRE2	Orphanet:493342	Vibratory urticaria

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
ADGRE2	HGNC:3337	ENSG00000127507	Q9UHX3	Adhesion G protein-coupled receptor E2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ADGRE2	Adhesion G protein-coupled receptor E2	Cell surface receptor that binds to the chondroitin sulfate moiety of glycosaminoglycan chains and promotes cell attachment.

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
GPCR	1	23.9×	0.042

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ADGRE2	GPCR	yes		EGF-type_Asp/Asn_hydroxyl_site, GPS, EGF

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
blood	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADGRE2	179	ubiquitous	marker	monocyte, blood, mononuclear cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADGRE2	1,318

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ADGRE2	Q9UHX3	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Class B/2 (Secretin family receptors)	1	190.3×	0.021	ADGRE2
GPCR ligand binding	1	64.2×	0.031	ADGRE2
Signaling by GPCR	1	40.1×	0.033	ADGRE2
Signal Transduction	1	10.2×	0.098	ADGRE2

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
granulocyte chemotaxis	1	3370.4×	0.002	ADGRE2
regulation of mast cell degranulation	1	1872.4×	0.002	ADGRE2
cell surface receptor signaling pathway	1	64.1×	0.028	ADGRE2
cell migration	1	61.5×	0.028	ADGRE2
inflammatory response	1	37.7×	0.028	ADGRE2
cell adhesion	1	37.5×	0.028	ADGRE2
G protein-coupled receptor signaling pathway	1	36.2×	0.028	ADGRE2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ADGRE2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	ADGRE2
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)
ADGRE2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.