Angioedema, hereditary, 6

Summary

Angioedema, hereditary, 6 (MONDO:0023660) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	angioedema, hereditary, 6
Mondo ID	MONDO:0023660
OMIM	619363
UMLS	C5543516
MedGen	1785484
GARD	0025373
Is cancer (heuristic)	no

Also known as: HAE6

Data availability: 4 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › dermatitis › urticaria › angioedema › hereditary angioedema › angioedema, hereditary, 6

Related subtypes (9): hereditary angioedema type 3, angioedema, hereditary, 4, angioedema, hereditary, 7, angioedema, hereditary, 5, angioedema, hereditary, 8, hereditary angioedema with C1Inh deficiency, PLG-related hereditary angioedema with normal C1inh, hereditary angioedema with normal C1inh not related to F12 or PLG variant, hereditary angioedema with normal C1Inh

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

4 retrieved; paginated sample, class counts are floors:

2 pathogenic, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1162306	NM_001102416.3(KNG1):c.1136T>A (p.Met379Lys)	KNG1	Pathogenic	no assertion criteria provided
1162307	NM_001102416.3(KNG1):c.1720C>G (p.Pro574Ala)	KNG1	Pathogenic	no assertion criteria provided
225401	NM_001102416.3(KNG1):c.1866_1869del (p.Ser623fs)	KNG1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2431559	NM_001102416.3(KNG1):c.166T>G (p.Leu56Val)	KNG1	Uncertain significance	criteria provided, single submitter

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
KNG1	Moderate	Autosomal dominant	angioedema, hereditary, 6	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KNG1	Orphanet:483	Congenital high-molecular-weight kininogen deficiency
KNG1	Orphanet:599418	Hereditary angioedema with normal C1Inh not related to F12 or PLG variant

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
KNG1	HGNC:6383	ENSG00000113889	P01042	Kininogen-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KNG1	Kininogen-1	Kininogens are inhibitors of thiol proteases.

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)
KNG1	Other/Unknown	no		Cystatin_dom, Kininogen, Prot_inh_cystat_CS

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
liver	1
renal medulla	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KNG1	117	tissue_specific	marker	renal medulla, liver, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KNG1	4,126

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KNG1	P01042	19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 21. 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
R-HSA-140837	1	1427.5×	0.006	KNG1
Regulation of FXIIa and plasma kallikrein activity	1	1142.0×	0.006	KNG1
FXIIa, PKa-dependent activation of coagulation pathway	1	1142.0×	0.006	KNG1
R-HSA-140877	1	951.7×	0.006	KNG1
FXIIa activates plasma kallikrein-kinin system	1	173.0×	0.021	KNG1
Response to elevated platelet cytosolic Ca2+	1	163.1×	0.021	KNG1
Platelet activation, signaling and aggregation	1	105.7×	0.024	KNG1
Post-translational protein phosphorylation	1	100.2×	0.024	KNG1
Platelet degranulation	1	87.8×	0.024	KNG1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.024	KNG1
Class A/1 (Rhodopsin-like receptors)	1	74.2×	0.024	KNG1
Peptide ligand-binding receptors	1	74.2×	0.024	KNG1
GPCR ligand binding	1	64.2×	0.025	KNG1
G alpha (q) signalling events	1	57.4×	0.026	KNG1
GPCR downstream signalling	1	43.4×	0.032	KNG1
Signaling by GPCR	1	40.1×	0.032	KNG1
G alpha (i) signalling events	1	39.0×	0.032	KNG1
Hemostasis	1	36.0×	0.032	KNG1
Post-translational protein modification	1	19.2×	0.058	KNG1
Metabolism of proteins	1	12.4×	0.085	KNG1
Signal Transduction	1	10.2×	0.098	KNG1

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 blood coagulation	1	1203.7×	0.005	KNG1
negative regulation of proteolysis	1	674.1×	0.005	KNG1
negative regulation of cell adhesion	1	383.0×	0.005	KNG1
vasodilation	1	366.4×	0.005	KNG1
blood coagulation	1	173.7×	0.009	KNG1
positive regulation of cytosolic calcium ion concentration	1	117.0×	0.011	KNG1
positive regulation of apoptotic process	1	56.7×	0.020	KNG1
inflammatory response	1	37.7×	0.027	KNG1

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
KNG1	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	KNG1

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)
KNG1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.