C1 inhibitor deficiency

Summary

C1 inhibitor deficiency (MONDO:0007361) is a disease with 1 cohort gene and 6 clinical trials. Top therapeutic interventions include deucrictibant.

At a glance

• Cohort genes: 1
• ClinVar variants: 10
• Clinical trials: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	C1 inhibitor deficiency
Mondo ID	MONDO:0007361
OMIM	120790
Orphanet	459353
DOID	DOID:0060002
UMLS	C1852700
MedGen	343867
GARD	0024554
Is cancer (heuristic)	no

Also known as: Quincke oedema

Data availability: 10 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › complement deficiency › classic complement early component deficiency › C1 inhibitor deficiency

Related subtypes (12): complement component C1r/C1s deficiency, complement component 2 deficiency, complement component 5 deficiency, complement component 7 deficiency, complement component 6 deficiency, complement component 3 deficiency, complement component C1s deficiency, type II complement component 8 deficiency, type I complement component 8 deficiency, complement component 9 deficiency, complement component 4b deficiency, complement component 4a 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

10 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 2 pathogenic, 2 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1675130	NM_000062.3(SERPING1):c.1450C>T (p.Gln484Ter)	SERPING1	Pathogenic	criteria provided, multiple submitters, no conflicts
626349	NM_000062.3(SERPING1):c.106_107del (p.Ser36fs)	SERPING1	Pathogenic	criteria provided, multiple submitters, no conflicts
4526430	NM_000062.3(SERPING1):c.796del (p.Val266fs)	SERPING1	Likely pathogenic	criteria provided, single submitter
305016	NM_000062.3(SERPING1):c.5C>T (p.Ala2Val)	SERPING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3946	NM_000062.3(SERPING1):c.1397G>A (p.Arg466His)	SERPING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1379992	NM_000062.3(SERPING1):c.997G>A (p.Ala333Thr)	SERPING1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1675129	NM_000062.3(SERPING1):c.1147A>G (p.Met383Val)	SERPING1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2414593	NM_000062.3(SERPING1):c.155A>G (p.Lys52Arg)	SERPING1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2696776	NM_000062.3(SERPING1):c.884T>C (p.Leu295Pro)	SERPING1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2733011	NM_000062.3(SERPING1):c.1211C>T (p.Thr404Met)	SERPING1	Uncertain significance	criteria provided, multiple submitters, no conflicts

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	Supportive	Autosomal dominant	C1 inhibitor 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: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	2
PHASE2/PHASE3	1
PHASE3	1
PHASE1/PHASE2	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
NCT06343779	PHASE3	COMPLETED	Study of Oral Deucrictibant Soft Capsule for On-Demand Treatment of Angioedema Attacks in Adolescents and Adults With Hereditary Angioedema
NCT07046806	PHASE1/PHASE2	RECRUITING	Oral Deucrictibant for Prophylactic and Acute Treatment in Hereditary Angioedema Patients
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
NCT06210698	Not specified	UNKNOWN	Angioedema Biomarker Research Study

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DEUCRICTIBANT	2	3