Capillary leak syndrome

Summary

Capillary leak syndrome (MONDO:0001956) is a disease with 1 cohort gene and 4 clinical trials.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 23
• Clinical trials: 4

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		150	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

23 HPO clinical features (Orphanet curated; top 23 by frequency):

HPO ID	Term	Frequency
HP:0001974	Leukocytosis	Very frequent (80-99%)
HP:0010741	Pedal edema	Very frequent (80-99%)
HP:0001733	Pancreatitis	Frequent (30-79%)
HP:0001824	Weight loss	Frequent (30-79%)
HP:0002014	Diarrhea	Frequent (30-79%)
HP:0002027	Abdominal pain	Frequent (30-79%)
HP:0002615	Hypotension	Frequent (30-79%)
HP:0003326	Myalgia	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0025142	Constitutional symptom	Frequent (30-79%)
HP:0031417	Rhinorrhea	Frequent (30-79%)
HP:0100598	Pulmonary edema	Frequent (30-79%)
HP:0000083	Renal insufficiency	Occasional (5-29%)
HP:0000091	Abnormal renal tubule morphology	Occasional (5-29%)
HP:0001701	Pericarditis	Occasional (5-29%)
HP:0002202	Pleural effusion	Occasional (5-29%)
HP:0004936	Venous thrombosis	Occasional (5-29%)
HP:0006543	Cardiorespiratory arrest	Occasional (5-29%)
HP:0006775	Multiple myeloma	Occasional (5-29%)
HP:0011675	Arrhythmia	Occasional (5-29%)
HP:0012735	Cough	Occasional (5-29%)
HP:0012819	Myocarditis	Occasional (5-29%)
HP:0100520	Oliguria	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	capillary leak syndrome
Mondo ID	MONDO:0001956
EFO	EFO:1001284
MeSH	D019559
Orphanet	188
DOID	DOID:14400
NCIT	C62578
SNOMED CT	87730004
UMLS	C0343084
MedGen	137987
GARD	0001084
MedDRA	10007196
Is cancer (heuristic)	no

Also known as: acute vascular leak syndrome · AVLS · capillary hyperpermeability syndrome · capillary leak syndrome · capillary leak syndrome with monoclonal gammopathy · Clarkson disease · CLS · idiopathic capillary leak syndrome · periodic systemic capillary leak syndrome · SCLS · Systemic Capillary Leak Syndrome · systemic capillary leak syndrome

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › capillary disorder › capillary leak syndrome

Related subtypes (3): breast angiomatosis, capillary lymphangioma, gastric antral vascular ectasia

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

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1691453	NM_006289.4(TLN1):c.7188+2T>C	TLN1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
TLN1	HGNC:11845	ENSG00000137076	Q9Y490	Talin-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TLN1	Talin-1	High molecular weight cytoskeletal protein concentrated at regions of cell-matrix and cell-cell contacts.

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)
TLN1	Other/Unknown	no		FERM_domain, IRS_PTB, ILWEQ_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
ascending aorta	1
popliteal artery	1
tibial artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TLN1	269	ubiquitous	marker	popliteal artery, tibial artery, ascending aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TLN1	3,215

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TLN1	Q9Y490	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. 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
p130Cas linkage to MAPK signaling for integrins	1	761.3×	0.005	TLN1
SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion	1	761.3×	0.005	TLN1
GRB2:SOS provides linkage to MAPK signaling for Integrins	1	713.8×	0.005	TLN1
Integrin signaling	1	423.0×	0.005	TLN1
Signaling by high-kinase activity BRAF mutants	1	317.2×	0.005	TLN1
MAP2K and MAPK activation	1	285.5×	0.005	TLN1
Signaling by RAF1 mutants	1	278.5×	0.005	TLN1
Smooth Muscle Contraction	1	265.6×	0.005	TLN1
Signaling by moderate kinase activity BRAF mutants	1	253.8×	0.005	TLN1
Paradoxical activation of RAF signaling by kinase inactive BRAF	1	253.8×	0.005	TLN1
Signaling downstream of RAS mutants	1	253.8×	0.005	TLN1
XBP1(S) activates chaperone genes	1	215.5×	0.006	TLN1
Signaling by BRAF and RAF1 fusions	1	170.4×	0.007	TLN1
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	1	160.8×	0.007	TLN1
Platelet degranulation	1	87.8×	0.011	TLN1

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
cell-substrate junction assembly	1	2808.7×	0.002	TLN1
cortical microtubule organization	1	1872.4×	0.002	TLN1
integrin activation	1	1404.3×	0.002	TLN1
cortical actin cytoskeleton organization	1	601.9×	0.003	TLN1
regulation of focal adhesion assembly	1	601.9×	0.003	TLN1
cell-cell junction assembly	1	443.5×	0.004	TLN1
platelet aggregation	1	337.0×	0.004	TLN1
integrin-mediated signaling pathway	1	160.5×	0.008	TLN1
cell-cell adhesion	1	101.5×	0.011	TLN1
actin cytoskeleton organization	1	79.1×	0.013	TLN1

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
TLN1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TLN1	1	Binding:1

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	TLN1

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)
TLN1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00936325	Not specified	COMPLETED	Studies in the Pathogenesis of Systemic Capillary Leak Syndrome
NCT02853682	Not specified	UNKNOWN	Characterization of Endothelial Dysfunction as a Function of Hyperaemia of the Brachial Artery During Cardiac Surgery
NCT03410771	Not specified	COMPLETED	Bioelectrical Impedance Analysis as a Bedside Tool to Estimate Volume of Distribution of Hydrophilic Antimicrobials in Critically Ill Patients
NCT03480529	Not specified	COMPLETED	Monitoring the IMmUological TOXicity of Drugs