Hereditary angioedema type 2

Summary

Hereditary angioedema type 2 (MONDO:0015054) is a disease with 1 cohort gene and 7 clinical trials. Top therapeutic interventions include deucrictibant.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 6
• Clinical trials: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hereditary angioedema type 2
Mondo ID	MONDO:0015054
Orphanet	100051
UMLS	C0398776
MedGen	585077
GARD	0016934
Is cancer (heuristic)	no

Also known as: HAE 2 · HAE-II · hereditary angioneurotic edema type 2 · hereditary angioneurotic oedema type 2

Data availability: 6 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › dermatitis › urticaria › angioedema › hereditary angioedema › hereditary angioedema with C1Inh deficiency › hereditary angioedema type 2

Related subtypes (1): hereditary angioedema type 1

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

6 retrieved; paginated sample, class counts are floors:

5 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
3945	NM_000062.3(SERPING1):c.1372G>A (p.Ala458Thr)	SERPING1	Pathogenic	no assertion criteria provided
3947	NM_000062.3(SERPING1):c.1396C>T (p.Arg466Cys)	SERPING1	Pathogenic	criteria provided, multiple submitters, no conflicts
3948	NM_000062.3(SERPING1):c.1396C>A (p.Arg466Ser)	SERPING1	Pathogenic	no assertion criteria provided
3953	NM_000062.3(SERPING1):c.1361T>A (p.Val454Glu)	SERPING1	Pathogenic	no assertion criteria provided
3954	NM_000062.3(SERPING1):c.1357_1358insTGT (p.Gly453delinsValTrp)	SERPING1	Pathogenic	no assertion criteria provided
3946	NM_000062.3(SERPING1):c.1397G>A (p.Arg466His)	SERPING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

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
SERPING1	Strong	Autosomal dominant	hereditary angioedema with C1Inh deficiency	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SERPING1	Orphanet:100050	Hereditary angioedema type 1
SERPING1	Orphanet:100051	Hereditary angioedema type 2

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
SERPING1	HGNC:1228	ENSG00000149131	P05155	Plasma protease C1 inhibitor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SERPING1	Plasma protease C1 inhibitor	Serine protease inhibitor, which acrs as a regulator of the classical complement pathway.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SERPING1	Other/Unknown	no		Serpin_fam, Serpin_CS, Serpin_dom

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
right coronary artery	1
right lobe of liver	1
right lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SERPING1	299	ubiquitous	marker	right lobe of liver, right lung, right coronary artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SERPING1	2,104

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SERPING1	P05155	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Defective SERPING1 causes hereditary angioedema	1	2855.0×	0.002	SERPING1
Regulation of FXIIa and plasma kallikrein activity	1	1142.0×	0.002	SERPING1
Regulation of clotting cascade	1	233.1×	0.005	SERPING1
Regulation of Complement cascade	1	233.1×	0.005	SERPING1
Platelet degranulation	1	87.8×	0.011	SERPING1

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
negative regulation of complement activation, lectin pathway	1	8426.0×	5e-04	SERPING1
fibrinolysis	1	842.6×	0.002	SERPING1
blood circulation	1	510.7×	0.003	SERPING1
blood coagulation	1	173.7×	0.006	SERPING1

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
SERPING1	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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SERPING1

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)
SERPING1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 7.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	3
PHASE2	2
PHASE2/PHASE3	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05396105	PHASE2/PHASE3	ENROLLING_BY_INVITATION	Extension Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema
NCT06960213	PHASE3	RECRUITING	STOP-HAE: A Phase 3 Study of ADX-324 in HAE
NCT07428499	PHASE3	RECRUITING	Phase 3 Extension Study of ADX-324 in Participants With Hereditary Angioedema (HAE)
NCT06343779	PHASE3	COMPLETED	Study of Oral Deucrictibant Soft Capsule for On-Demand Treatment of Angioedema Attacks in Adolescents and Adults With Hereditary Angioedema
NCT04618211	PHASE2	COMPLETED	Dose-ranging Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema
NCT05047185	PHASE2	COMPLETED	Dose-ranging Study of Oral PHA-022121 for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Type I or Type II
NCT07448181	Not specified	RECRUITING	Real-life Ecological Momentary Assessment of Lived Burden in Hereditary AngioEdema

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DEUCRICTIBANT	2	3