Prekallikrein deficiency

Summary

Prekallikrein deficiency (MONDO:0044744) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	prekallikrein deficiency
Mondo ID	MONDO:0044744
NCIT	C99022
SNOMED CT	48976006
UMLS	C0272339
MedGen	75779
GARD	0025905
Is cancer (heuristic)	no

Also known as: prekallikrein deficiency

Data availability: 7 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood coagulation disease › prekallikrein deficiency

Related subtypes (7): marantic endocarditis, hemolytic-uremic syndrome, coagulation protein disease, thrombophilia, hemorrhagic disease of newborn, thrombotic microangiopathy, inherited blood coagulation disorder

Subtypes (1): inherited prekallikrein 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

7 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
12033	NM_000892.5(KLKB1):c.337C>T (p.Arg113Ter)	KLKB1	Pathogenic	no assertion criteria provided
12034	NM_000892.5(KLKB1):c.1205G>A (p.Trp402Ter)	KLKB1	Pathogenic	no assertion criteria provided
12036	NM_000892.5(KLKB1):c.367G>A (p.Gly123Arg)	KLKB1	Pathogenic	no assertion criteria provided
225400	NM_000892.5(KLKB1):c.1259G>A (p.Gly420Glu)	KLKB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12035	NM_000892.5(KLKB1):c.1643G>A (p.Cys548Tyr)	KLKB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
711923	NM_000892.5(KLKB1):c.451dup (p.Ser151fs)	KLKB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
12037	NM_000892.5(KLKB1):c.428G>A (p.Ser143Asn)	KLKB1	Benign/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
KLKB1	Orphanet:749	Congenital prekallikrein deficiency

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
KLKB1	HGNC:6371	ENSG00000164344	P03952	Plasma kallikrein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KLKB1	Plasma kallikrein	Participates in the surface-dependent activation of blood coagulation.

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KLKB1	Protease	yes	3.4.21.34	Apple, Trypsin_dom, Peptidase_S1A

Expression context

Cohort genes with no expression data: 0.

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
primordial germ cell in gonad	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KLKB1	196	tissue_specific	yes	right lobe of liver, liver, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KLKB1	1,537

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KLKB1	P03952	22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. 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-9651496	1	3806.7×	0.001	KLKB1
Defective factor XII causes hereditary angioedema	1	2855.0×	0.001	KLKB1
Defective SERPING1 causes hereditary angioedema	1	2855.0×	0.001	KLKB1
Diseases of hemostasis	1	2855.0×	0.001	KLKB1
R-HSA-140837	1	1427.5×	0.002	KLKB1
Regulation of FXIIa and plasma kallikrein activity	1	1142.0×	0.002	KLKB1
FXIIa, PKa-dependent activation of coagulation pathway	1	1142.0×	0.002	KLKB1
R-HSA-140877	1	951.7×	0.002	KLKB1
Activation of Matrix Metalloproteinases	1	308.6×	0.005	KLKB1
FXIIa activates plasma kallikrein-kinin system	1	173.0×	0.008	KLKB1
Degradation of the extracellular matrix	1	117.7×	0.011	KLKB1
Extracellular matrix organization	1	63.1×	0.018	KLKB1
Hemostasis	1	36.0×	0.030	KLKB1
Disease	1	13.1×	0.076	KLKB1

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
Factor XII activation	1	5617.3×	0.001	KLKB1
positive regulation of fibrinolysis	1	3370.4×	0.001	KLKB1
plasminogen activation	1	1296.3×	0.002	KLKB1
fibrinolysis	1	842.6×	0.002	KLKB1
zymogen activation	1	674.1×	0.002	KLKB1
blood coagulation	1	173.7×	0.007	KLKB1
proteolysis	1	34.2×	0.029	KLKB1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
KLKB1	BEROTRALSTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KLKB1	10	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEROTRALSTAT	4	KLKB1
DAREXABAN	3	KLKB1
MILVEXIAN	3	KLKB1
AVORALSTAT	3	KLKB1
SEBETRALSTAT	3	KLKB1
GABEXATE	3	KLKB1
LETAXABAN	2	KLKB1
GW813893	2	KLKB1
FENIRALSTAT	2	KLKB1
BMS-962212	1	KLKB1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
KLKB1	300	Binding:283, ADMET:17

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KLKB1	3.4.21.34	plasma kallikrein

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
KLKB1	300

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

10 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.

Compound	Max phase	Cohort target (bioactivity)
BEROTRALSTAT	4	KLKB1
DAREXABAN	3	KLKB1
MILVEXIAN	3	KLKB1
AVORALSTAT	3	KLKB1
SEBETRALSTAT	3	KLKB1
GABEXATE	3	KLKB1
LETAXABAN	2	KLKB1
GW813893	2	KLKB1
FENIRALSTAT	2	KLKB1
BMS-962212	1	KLKB1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	KLKB1
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	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.